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Sample records for chp-pak-pix pathway maintains

  1. Sex determination in honeybees: two separate mechanisms induce and maintain the female pathway

    DEFF Research Database (Denmark)

    Gempe, Tanja; Hasselmann, Martin; Schiøtt, Morten

    2009-01-01

    Organisms have evolved a bewildering diversity of mechanisms to generate the two sexes. The honeybee (Apis mellifera) employs an interesting system in which sex is determined by heterozygosity at a single locus (the Sex Determination Locus) harbouring the complementary sex determiner (csd) gene....... Bees heterozygous at Sex Determination Locus are females, whereas bees homozygous or hemizygous are males. Little is known, however, about the regulation that links sex determination to sexual differentiation. To investigate the control of sexual development in honeybees, we analyzed the functions...... and the regulatory interactions of genes involved in the sex determination pathway. We show that heterozygous csd is only required to induce the female pathway, while the feminizer (fem) gene maintains this decision throughout development. By RNAi induced knockdown we show that the fem gene is essential for entire...

  2. ICOS and Bcl6-dependent pathways maintain a CD4 T cell population with memory-like properties during tuberculosis

    Science.gov (United States)

    Moguche, Albanus O.; Shafiani, Shahin; Clemons, Corey; Larson, Ryan P.; Dinh, Crystal; Higdon, Lauren E.; Cambier, C.J.; Sissons, James R.; Gallegos, Alena M.; Fink, Pamela J.

    2015-01-01

    Immune control of persistent infection with Mycobacterium tuberculosis (Mtb) requires a sustained pathogen-specific CD4 T cell response; however, the molecular pathways governing the generation and maintenance of Mtb protective CD4 T cells are poorly understood. Using MHCII tetramers, we show that Mtb-specific CD4 T cells are subject to ongoing antigenic stimulation. Despite this chronic stimulation, a subset of PD-1+ cells is maintained within the lung parenchyma during tuberculosis (TB). When transferred into uninfected animals, these cells persist, mount a robust recall response, and provide superior protection to Mtb rechallenge when compared to terminally differentiated Th1 cells that reside preferentially in the lung-associated vasculature. The PD-1+ cells share features with memory CD4 T cells in that their generation and maintenance requires intrinsic Bcl6 and intrinsic ICOS expression. Thus, the molecular pathways required to maintain Mtb-specific CD4 T cells during ongoing infection are similar to those that maintain memory CD4 T cells in scenarios of antigen deprivation. These results suggest that vaccination strategies targeting the ICOS and Bcl6 pathways in CD4 T cells may provide new avenues to prevent TB. PMID:25918344

  3. The experience of seeking, gaining and maintaining employment after traumatic spinal cord injury and the vocational pathways involved.

    Science.gov (United States)

    Hilton, Gillean; Unsworth, Carolyn A; Stuckey, Ruth; Murphy, Gregory C

    2018-01-01

    Vocational potential in people with spinal cord injury (SCI) are unrealised with rates of employment substantially lower than in the labour force participation of the general population and the pre-injury employment rates. To understand the experience and pathway of people achieving employment outcome after traumatic spinal cord injury by; classifying participants into employment outcome groups of stable, unstable and without employment; identifying pre and post-injury pathways for participants in each group and, exploring the experiences of people of seeking, gaining and maintaining employment. Thirty-one participants were interviewed. Mixed methods approach including interpretive phenomenological analysis and vocational pathway mapping of quantitative data. The most common pathway identified was from study and work pre-injury to stable employment post-injury. Four super-ordinate themes were identified from the interpretive phenomenological analysis; expectations of work, system impacts, worker identity and social supports. Implications for clinical practice include fostering cultural change, strategies for system navigation, promotion of worker identity and optimal use of social supports. The findings increase insight and understanding of the complex experience of employment after spinal cord injury. There is opportunity to guide experimental research, policy development and education concerning the complexity of the return to work experience and factors that influence pathways.

  4. Optical angular constancy is maintained as a navigational control strategy when pursuing robots moving along complex pathways.

    Science.gov (United States)

    Wang, Wei; McBeath, Michael K; Sugar, Thomas G

    2015-03-24

    The optical navigational control strategy used to intercept moving targets was explored using a real-world object that travels along complex, evasive pathways. Fielders ran across a gymnasium attempting to catch a moving robot that varied in speed and direction, while ongoing position was measured using an infrared motion-capture system. Fielder running paths were compared with the predictions of three lateral control models, each based on maintaining a particular optical angle relative to the robotic target: (a) constant alignment angle (CAA), (b) constant eccentricity angle (CEA), and (c) linear optical trajectory (LOT). Findings reveal that running pathways were most consistent with maintenance of LOT and least consistent with CEA. This supports that fielders use the same optical control strategy of maintaining angular constancy using a LOT when navigating toward targets moving along complex pathways as when intercepting simple ballistic trajectories. In those cases in which a target dramatically deviates from its optical path, fielders appear to simply reset LOT parameters using a new constant angle value. Maintenance of such optical angular constancy has now been shown to work well with ballistic, complex, and evasive moving targets, confirming the LOT strategy as a robust, general-purpose optical control mechanism for navigating to intercept catchable targets, both airborne and ground based. © 2015 ARVO.

  5. Alternative oxidase: a respiratory electron transport chain pathway essential for maintaining photosynthetic performance during drought stress.

    Science.gov (United States)

    Vanlerberghe, Greg C; Martyn, Greg D; Dahal, Keshav

    2016-07-01

    Photosynthesis and respiration are the hubs of energy metabolism in plants. Drought strongly perturbs photosynthesis as a result of both diffusive limitations resulting from stomatal closure, and in some cases biochemical limitations that are associated with a reduced abundance of key photosynthetic components. The effects of drought on respiration, particularly respiration in the light (RL ), are less understood. The plant mitochondrial electron transport chain includes a non-energy conserving terminal oxidase called alternative oxidase (AOX). Several studies have shown that drought increases AOX transcript, protein and maximum capacity. Here we review recent studies comparing wild-type (WT) tobacco to transgenic lines with altered AOX protein amount. Specifically during drought, RL was compromised in AOX knockdown plants and enhanced in AOX overexpression plants, compared with WT. Significantly, these differences in RL were accompanied by dramatic differences in photosynthetic performance. Knockdown of AOX increased the susceptibility of photosynthesis to drought-induced biochemical limitations, while overexpression of AOX delayed the development of such biochemical limitations, compared with WT. Overall, the results indicate that AOX is essential to maintaining RL during drought, and that this non-energy conserving respiration maintains photosynthesis during drought by promoting energy balance in the chloroplast. This review also outlines several areas for future research, including the possibility that enhancement of non-energy conserving respiratory electron sinks may be a useful biotechnological approach to increase plant performance during stress. © 2016 Scandinavian Plant Physiology Society.

  6. Histone methyltransferase SETDB1 maintains survival of mouse spermatogonial stem/progenitor cells via PTEN/AKT/FOXO1 pathway.

    Science.gov (United States)

    Liu, Tiantian; Chen, Xiaoxu; Li, Tianjiao; Li, Xueliang; Lyu, Yinghua; Fan, Xiaoteng; Zhang, Pengfei; Zeng, Wenxian

    2017-10-01

    Spermatogonial stem cells (SSCs) possess the capacity of self-renewal and differentiation, which are the basis of spermatogenesis. In maintenance of SSC homeostasis, intrinsic/extrinsic factors and various signaling pathways tightly control the fate of SSCs. Methyltransferase SETDB1 (Set domain, bifurcated 1) catalyzes histone H3 lysine 9 (H3K9) trimethylation and represses gene expression. SETDB1 is required for maintaining the survival of spermatogonial stem cells in mice. However, the underlying molecular mechanism remains unclear. In the present study, we found that Setdb1 regulates PTEN/AKT/FOXO1 pathway to inhibit SSC apoptosis. Co-immunoprecipitation and reporter gene assay revealed that SETDB1 interacted and coordinated with AKT to regulate FOXO1 activity and expression of the downstream target genes Bim and Puma. Among the SETDB1-bound genes, the H3K9me3 levels on the promoter regions of Bim and Pten decreased in Setdb1-KD group; in contrast, H3K9me3 status on promoters of Bax and Puma remained unchanged. Therefore, SETDB1 was responsible for regulating the transcription activity of genes in the apoptotic pathway at least in part through modulating H3K9me3. This study replenishes the research on the epigenetic regulation of SSC survival, and provides a new insight for the future study of epigenetic regulation of spermatogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways.

    Science.gov (United States)

    Haverkamp, Jessica M; Smith, Amber M; Weinlich, Ricardo; Dillon, Christopher P; Qualls, Joseph E; Neale, Geoffrey; Koss, Brian; Kim, Young; Bronte, Vincenzo; Herold, Marco J; Green, Douglas R; Opferman, Joseph T; Murray, Peter J

    2014-12-18

    Nonresolving inflammation expands a heterogeneous population of myeloid suppressor cells capable of inhibiting T cell function. This heterogeneity has confounded the functional dissection of individual myeloid subpopulations and presents an obstacle for antitumor immunity and immunotherapy. Using genetic manipulation of cell death pathways, we found the monocytic suppressor-cell subset, but not the granulocytic subset, requires continuous c-FLIP expression to prevent caspase-8-dependent, RIPK3-independent cell death. Development of the granulocyte subset requires MCL-1-mediated control of the intrinsic mitochondrial death pathway. Monocytic suppressors tolerate the absence of MCL-1 provided cytokines increase expression of the MCL-1-related protein A1. Monocytic suppressors mediate T cell suppression, whereas their granulocytic counterparts lack suppressive function. The loss of the granulocytic subset via conditional MCL-1 deletion did not alter tumor incidence implicating the monocytic compartment as the functionally immunosuppressive subset in vivo. Thus, death pathway modulation defines the development, survival, and function of myeloid suppressor cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Latency-Associated Expression of Human Cytomegalovirus US28 Attenuates Cell Signaling Pathways To Maintain Latent Infection

    Directory of Open Access Journals (Sweden)

    Benjamin A. Krishna

    2017-12-01

    Full Text Available Reactivation of human cytomegalovirus (HCMV latent infection from early myeloid lineage cells constitutes a threat to immunocompromised or immune-suppressed individuals. Consequently, understanding the control of latency and reactivation to allow targeting and killing of latently infected cells could have far-reaching clinical benefits. US28 is one of the few viral genes that is expressed during latency and encodes a cell surface G protein-coupled receptor (GPCR, which, during lytic infection, is a constitutive cell-signaling activator. Here we now show that in monocytes, which are recognized sites of HCMV latency in vivo, US28 attenuates multiple cell signaling pathways, including mitogen-activated protein (MAP kinase and NF-κB, and that this is required to establish a latent infection; viruses deleted for US28 initiate a lytic infection in infected monocytes. We also show that these monocytes then become potent targets for the HCMV-specific host immune response and that latently infected cells treated with an inverse agonist of US28 also reactivate lytic infection and similarly become immune targets. Consequently, we suggest that the use of inhibitors of US28 could be a novel immunotherapeutic strategy to reactivate the latent viral reservoir, allowing it to be targeted by preexisting HCMV-specific T cells.

  9. Alternative Oxidase: A Mitochondrial Respiratory Pathway to Maintain Metabolic and Signaling Homeostasis during Abiotic and Biotic Stress in Plants

    Directory of Open Access Journals (Sweden)

    Greg C. Vanlerberghe

    2013-03-01

    Full Text Available Alternative oxidase (AOX is a non-energy conserving terminal oxidase in the plant mitochondrial electron transport chain. While respiratory carbon oxidation pathways, electron transport, and ATP turnover are tightly coupled processes, AOX provides a means to relax this coupling, thus providing a degree of metabolic homeostasis to carbon and energy metabolism. Beside their role in primary metabolism, plant mitochondria also act as “signaling organelles”, able to influence processes such as nuclear gene expression. AOX activity can control the level of potential mitochondrial signaling molecules such as superoxide, nitric oxide and important redox couples. In this way, AOX also provides a degree of signaling homeostasis to the organelle. Evidence suggests that AOX function in metabolic and signaling homeostasis is particularly important during stress. These include abiotic stresses such as low temperature, drought, and nutrient deficiency, as well as biotic stresses such as bacterial infection. This review provides an introduction to the genetic and biochemical control of AOX respiration, as well as providing generalized examples of how AOX activity can provide metabolic and signaling homeostasis. This review also examines abiotic and biotic stresses in which AOX respiration has been critically evaluated, and considers the overall role of AOX in growth and stress tolerance.

  10. Creating and maintaining a successful geoscience pathway from 2YC to 4YC for Native Hawaiian Students: First Steps

    Science.gov (United States)

    Guidry, M.; Eschenberg, A.; McCoy, F. W.; McManus, M. A.; Lee, K.; DeLay, J. K.; Taylor, S. V.; Dire, J.; Krupp, D.

    2017-12-01

    In the Fall of 2015, the two four year (4YC) institutions within the University of Hawaii (UH) system offering baccalaureate degrees in geosciences enrolled only six Native Hawaiian (NH) students out of a total of 194 students in geoscience degree programs. This percentage (3%) of NH students enrolled in geosciences is far lower than the percentage of NH students enrolled at any single institution in the UH system, which ranges from 14 to 42%. At the same time, only six (3%) of the 194 students enrolled in geoscience baccalaureate programs were transfer students from the UH community colleges. Of these six transfer students, three were NH. This reflects the need for increased transfer of NH in the geosciences from two year (2YC) to 4YC. In the Fall of 2015, UH Manoa's (UHM) School of Ocean and Earth Science and Technology (SOEST) accounted for only 0.14% of transfer students from UH community colleges. This compares to 5% in the UHM School of Engineering and 27% in the UHM College of Arts and Sciences. As part of the first year of a multi-institutional five-year NSF TCUP-PAGE (Tribal Colleges and Universities Program - PArtnerships for Geoscience Education) award, we review our first steps and strategies for building a successful and sustainable geoscience transfer pathway for Native Hawaiian and community college students into the three undergraduate geoscience programs (Atmospheric Sciences, Environmental Sciences, and Geology & Geophysics) within SOEST.

  11. Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer’s disease transgenic mice

    Science.gov (United States)

    Currais, Antonio; Prior, Marguerite; Dargusch, Richard; Armando, Aaron; Ehren, Jennifer; Schubert, David; Quehenberger, Oswald; Maher, Pamela

    2014-01-01

    Alzheimer’s disease (AD) is the most common type of dementia. It is the only one of the top ten causes of death in the USA for which prevention strategies have not been developed. Although AD has traditionally been associated with the deposition of amyloid β plaques and tau tangles, it is becoming increasingly clear that it involves disruptions in multiple cellular systems. Therefore, it is unlikely that hitting a single target will result in significant benefits to patients with AD. An alternative approach is to identify molecules that have multiple biological activities that are relevant to the disease. Fisetin is a small, orally active molecule which can act on many of the target pathways implicated in AD. We show here that oral administration of fisetin to APPswe/PS1dE9 double transgenic AD mice from 3 to 12 months of age prevents the development of learning and memory deficits. This correlates with an increase in ERK phosphorylation along with a decrease in protein carbonylation, a marker of oxidative stress. Importantly, fisetin also reduces the levels of the cyclin-dependent kinase 5 (Cdk5) activator p35 cleavage product, p25, in both control and AD brains. Elevated levels of p25 relative to p35 cause dysregulation of Cdk5 activity leading to neuroinflammation and neurodegeneration. These fisetin-dependent changes correlate with additional anti-inflammatory effects, including alterations in global eicosanoid synthesis, and the maintenance of markers of synaptic function in the AD mice. Together, these results suggest that fisetin may provide a new approach to the treatment of AD. PMID:24341874

  12. Probiotic-derived polyphosphate enhances the epithelial barrier function and maintains intestinal homeostasis through integrin-p38 MAPK pathway.

    Directory of Open Access Journals (Sweden)

    Shuichi Segawa

    Full Text Available Probiotics exhibit beneficial effects on human health, particularly in the maintenance of intestinal homeostasis in a complex manner notwithstanding the diversity of an intestinal flora between individuals. Thus, it is highly probable that some common molecules secreted by probiotic and/or commensal bacteria contribute to the maintenance of intestinal homeostasis and protect the intestinal epithelium from injurious stimuli. To address this question, we aimed to isolate the cytoprotective compound from a lactobacillus strain, Lactobacillus brevis SBC8803 which possess the ability to induce cytoprotective heat shock proteins in mouse small intestine. L. brevis was incubated in MRS broth and the supernatant was passed through with a 0.2-µm filter. Caco2/bbe cells were treated with the culture supernatant, and HSP27 expression was evaluated by Western blotting. HSP27-inducible components were separated by ammonium sulfate precipitation, DEAE anion exchange chromatography, gel filtration, and HPLC. Finally, we identified that the HSP27-inducible fraction was polyphosphate (poly P, a simple repeated structure of phosphates, which is a common product of lactobacilli and other bacteria associated with intestinal microflora without any definitive physiological functions. Then, poly P was synthesized by poly P-synthesizing enzyme polyphosphate kinase. The synthesized poly P significantly induced HSP27 from Caco2/BBE cells. In addition, Poly P suppressed the oxidant-induced intestinal permeability in the mouse small intestine and pharmacological inhibitors of p38 MAPK and integrins counteract its protective effect. Daily intrarectal administration of poly P (10 µg improved the inflammation grade and survival rate in 4% sodium dextran sulfate-administered mice. This study, for the first time, demonstrated that poly P is the molecule responsible for maintaining intestinal barrier actions which are mediated through the intestinal integrin β1-p38 MAPK.

  13. A novel differentiation pathway from CD4⁺ T cells to CD4⁻ T cells for maintaining immune system homeostasis.

    Science.gov (United States)

    Zhao, X; Sun, G; Sun, X; Tian, D; Liu, K; Liu, T; Cong, M; Xu, H; Li, X; Shi, W; Tian, Y; Yao, J; Guo, H; Zhang, D

    2016-04-14

    CD4(+) T lymphocytes are key players in the adaptive immune system and can differentiate into a variety of effector and regulatory T cells. Here, we provide evidence that a novel differentiation pathway of CD4(+) T cells shifts the balance from a destructive T-cell response to one that favors regulation in an immune-mediated liver injury model. Peripheral CD4(-)CD8(-)NK1.1(-) double-negative T cells (DNT) was increased following Concanavalin A administration in mice. Adoptive transfer of DNT led to significant protection from hepatocyte necrosis by direct inhibition on the activation of lymphocytes, a process that occurred primarily through the perforin-granzyme B route. These DNT converted from CD4(+) rather than CD8(+) T cells, a process primarily regulated by OX40. DNT migrated to the liver through the CXCR3-CXCL9/CXCL10 interaction. In conclusion, we elucidated a novel differentiation pathway from activated CD4(+) T cells to regulatory DNT cells for maintaining homeostasis of the immune system in vivo, and provided key evidence that utilizing this novel differentiation pathway has potential application in the prevention and treatment of autoimmune diseases.

  14. The sonic hedgehog signaling pathway maintains the cancer stem cell self-renewal of anaplastic thyroid cancer by inducing snail expression.

    Science.gov (United States)

    Heiden, Katherine B; Williamson, Ashley J; Doscas, Michelle E; Ye, Jin; Wang, Yimin; Liu, Dingxie; Xing, Mingzhao; Prinz, Richard A; Xu, Xiulong

    2014-11-01

    Cancer stem cells (CSCs) have been recently identified in thyroid neoplasm. Anaplastic thyroid cancer (ATC) contains a higher percentage of CSCs than well-differentiated thyroid cancer. The signaling pathways and the transcription factors that regulate thyroid CSC self-renewal remain poorly understood. The objective of this study is to use two ATC cell lines (KAT-18 and SW1736) as a model to study the role of the sonic hedgehog (Shh) pathway in maintaining thyroid CSC self-renewal and to understand its underlying molecular mechanisms. The expression and activity of aldehyde dehydrogenase (ALDH), a marker for thyroid CSCs, was analyzed by Western blot and ALDEFLUOR assay, respectively. The effect of three Shh pathway inhibitors (cyclopamine, HhAntag, GANT61), Shh, Gli1, Snail knockdown, and Gli1 overexpression on thyroid CSC self-renewal was analyzed by ALDEFLUOR assay and thyrosphere formation. The sensitivity of transfected KAT-18 cells to radiation was evaluated by a colony survival assay. Western blot analysis revealed that ALDH protein levels in five thyroid cancer cell lines (WRO82, a follicular thyroid cancer cell line; BCPAP and TPC1, two papillary thyroid cancer cell lines; KAT-18 and SW1736, two ATC cell lines) correlated with the percentage of the ALDH(High) cells as well as Gli1 and Snail expression. The Shh pathway inhibitors, Shh and Gli1 knockdown, in KAT-18 cells decreased thyroid CSC self-renewal and increased radiation sensitivity. In contrast, Gli1 overexpression led to increased thyrosphere formation, an increased percentage of ALDH(High) cells, and increased radiation resistance in KAT-18 cells. Inhibition of the Shh pathway by three specific inhibitors led to decreased Snail expression and a decreased number of ALDH(High) cells in KAT-18 and SW1736. Snail gene knockdown decreased the number of ALDH(High) cells in KAT-18 and SW1736 cells. The Shh pathway promotes the CSC self-renewal in ATC cell lines by Gli1-induced Snail expression.

  15. Somatotropinomas, but not nonfunctioning pituitary adenomas, maintain a functional apoptotic RET/Pit1/ARF/p53 pathway that is blocked by excess GDNF.

    Science.gov (United States)

    Diaz-Rodriguez, Esther; Garcia-Rendueles, Angela R; Ibáñez-Costa, Alejandro; Gutierrez-Pascual, Ester; Garcia-Lavandeira, Montserrat; Leal, Alfonso; Japon, Miguel A; Soto, Alfonso; Venegas, Eva; Tinahones, Francisco J; Garcia-Arnes, Juan A; Benito, Pedro; Angeles Galvez, Maria; Jimenez-Reina, Luis; Bernabeu, Ignacio; Dieguez, Carlos; Luque, Raul M; Castaño, Justo P; Alvarez, Clara V

    2014-11-01

    Acromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]), which secrete GH. Human and rodent somatotroph cells express the RET receptor. In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis that was prevented in the presence of GDNF. Apoptosis was accompanied by RET processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1) directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPα) consensus-binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters. Deletion of 1 cEBPα site prevented the RET-induced increase in hPit1 promoter expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF, steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the tumors was positively correlated with RET and negatively correlated with p53. In conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that is inhibited by GDNF. Disruption of GDNF's survival function might constitute a new therapeutic route in

  16. Zebrafish diras1 Promoted Neurite Outgrowth in Neuro-2a Cells and Maintained Trigeminal Ganglion Neurons In Vivo via Rac1-Dependent Pathway.

    Science.gov (United States)

    Yeh, Chi-Wei; Hsu, Li-Sung

    2016-12-01

    The small GTPase Ras superfamily regulates several neuronal functions including neurite outgrowth and neuron proliferation. In this study, zebrafish diras1a and diras1b were identified and were found to be mainly expressed in the central nervous system and dorsal neuron ganglion. Overexpression of green fluorescent protein (GFP)-diras1a or GFP-diras1b triggered neurite outgrowth of Neuro-2a cells. The wild types, but not the C terminus truncated forms, of diras1a and diras1b elevated the protein level of Ras-related C3 botulinum toxin substrate 1 (Rac1) and downregulated Ras homologous member A (RhoA) expression. Glutathione S-transferase (GST) pull-down assay also revealed that diras1a and diras1b enhanced Rac1 activity. Interfering with Rac1, Pak1, or cyclin-dependent kinase 5 (CDK5) activity or with the Arp2/3 inhibitor prevented diras1a and diras1b from mediating the neurite outgrowth effects. In the zebrafish model, knockdown of diras1a and/or diras1b by morpholino antisense oligonucleotides not only reduced axon guidance but also caused the loss of trigeminal ganglion without affecting the precursor markers, such as ngn1 and neuroD. Co-injection with messenger RNA (mRNA) derived from mouse diras1 or constitutively active human Rac1 restored the population of trigeminal ganglion. In conclusion, we provided preliminary evidence that diras1 is involved in neurite outgrowth and maintains the number of trigeminal ganglions through the Rac1-dependent pathway.

  17. Maintainability allocation

    International Nuclear Information System (INIS)

    Guyot, Christian.

    1980-06-01

    The author gives the general lines of a method for the allocation and for the evaluation of maintainability of complex systems which is to be developed during the conference. The maintainability objective is supposed to be formulated under the form of a mean time to repair (M.T.T.R.) [fr

  18. Maintaining positive

    OpenAIRE

    Gheorghe Gh. IONESCU; Adina Letitia NEGRUSA

    2004-01-01

    Maintaining positive work-force relationships includes in effective labor-management relations and making appropriate responses to current employee issues. Among the major current employee issues are protection from arbitrary dismissal, drug and alcohol abuse, privacy rights and family maters and they impact work. In our paper we discus two problems: first, the meanings of industrial democracy; second, the three principal operational concepts of industrial democracy (1) industrial democracy t...

  19. Transcriptomic studies reveal a key metabolic pathway contributing to a well-maintained photosynthetic system under drought stress in foxtail millet (Setaria italica L.

    Directory of Open Access Journals (Sweden)

    Weiping Shi

    2018-05-01

    Full Text Available Drought stress is one of the most important abiotic factors limiting crop productivity. A better understanding of the effects of drought on millet (Setaria italica L. production, a model crop for studying drought tolerance, and the underlying molecular mechanisms responsible for drought stress responses is vital to improvement of agricultural production. In this study, we exposed the drought resistant F1 hybrid, M79, and its parental lines E1 and H1 to drought stress. Subsequent physiological analysis demonstrated that M79 showed higher photosynthetic energy conversion efficiency and drought tolerance than its parents. A transcriptomic study using leaves collected six days after drought treatment, when the soil water content was about ∼20%, identified 3066, 1895, and 2148 differentially expressed genes (DEGs in M79, E1 and H1 compared to the respective untreated controls, respectively. Further analysis revealed 17 Gene Ontology (GO enrichments and 14 Kyoto Encyclopedia of Genes and Genomes (KEGG pathways in M79, including photosystem II (PSII oxygen-evolving complex, peroxidase (POD activity, plant hormone signal transduction, and chlorophyll biosynthesis. Co-regulation analysis suggested that these DEGs in M79 contributed to the formation of a regulatory network involving multiple biological processes and pathways including photosynthesis, signal transduction, transcriptional regulation, redox regulation, hormonal signaling, and osmotic regulation. RNA-seq analysis also showed that some photosynthesis-related DEGs were highly expressed in M79 compared to its parental lines under drought stress. These results indicate that various molecular pathways, including photosynthesis, respond to drought stress in M79, and provide abundant molecular information for further analysis of the underlying mechanism responding to this stress.

  20. Transcriptomic studies reveal a key metabolic pathway contributing to a well-maintained photosynthetic system under drought stress in foxtail millet (Setaria italica L.).

    Science.gov (United States)

    Shi, Weiping; Cheng, Jingye; Wen, Xiaojie; Wang, Jixiang; Shi, Guanyan; Yao, Jiayan; Hou, Liyuan; Sun, Qian; Xiang, Peng; Yuan, Xiangyang; Dong, Shuqi; Guo, Pingyi; Guo, Jie

    2018-01-01

    Drought stress is one of the most important abiotic factors limiting crop productivity. A better understanding of the effects of drought on millet ( Setaria italica L.) production, a model crop for studying drought tolerance, and the underlying molecular mechanisms responsible for drought stress responses is vital to improvement of agricultural production. In this study, we exposed the drought resistant F 1 hybrid, M79, and its parental lines E1 and H1 to drought stress. Subsequent physiological analysis demonstrated that M79 showed higher photosynthetic energy conversion efficiency and drought tolerance than its parents. A transcriptomic study using leaves collected six days after drought treatment, when the soil water content was about ∼20%, identified 3066, 1895, and 2148 differentially expressed genes (DEGs) in M79, E1 and H1 compared to the respective untreated controls, respectively. Further analysis revealed 17 Gene Ontology (GO) enrichments and 14 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in M79, including photosystem II (PSII) oxygen-evolving complex, peroxidase (POD) activity, plant hormone signal transduction, and chlorophyll biosynthesis. Co-regulation analysis suggested that these DEGs in M79 contributed to the formation of a regulatory network involving multiple biological processes and pathways including photosynthesis, signal transduction, transcriptional regulation, redox regulation, hormonal signaling, and osmotic regulation. RNA-seq analysis also showed that some photosynthesis-related DEGs were highly expressed in M79 compared to its parental lines under drought stress. These results indicate that various molecular pathways, including photosynthesis, respond to drought stress in M79, and provide abundant molecular information for further analysis of the underlying mechanism responding to this stress.

  1. Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype through activation of Hedgehog signaling pathway in colon cancer.

    Science.gov (United States)

    Wang, Rong; Wei, Jinlai; Zhang, Shouru; Wu, Xingye; Guo, Jinbao; Liu, Maoxi; Du, Kunli; Xu, Jun; Peng, Linglong; Lv, Zhenbing; You, Wenxian; Xiong, Yongfu; Fu, Zhongxue

    2016-12-27

    Cancer stem cells (CSCs) are a key target for reducing tumor growth, metastasis, and recurrence. Redox status is a critical factor in the maintenance of CSCs, and the antioxidant enzyme Peroxiredoxin 2 (Prdx2) plays an important role in the development of colon cancer. Therefore, we investigated the contribution of Prdx2 to the maintenance of stemness of colon CSCs. Here, we used short-hairpin RNAs and a Prdx2-overexpression vector to determine the effects of Prdx2. We demonstrated that knockdown of Prdx2 reduced the self-renewal and sphere formation and resulted in increased 5-FU-induced apoptosis in human colon CSCs. Prdx2 overexpression induced reversion of the self-renewal and sphere formation. Furthermore, the effects of Prdx2 resulted in an altered expression of stemness associated with the Hh/Gli1 signaling pathway. Finally, knockdown of Prdx2 in CD133+ cells reduced the volume of xenograft tumors in BALB/c-nu mice. Taken together, colon CSCs overexpress Prdx2, which promotes their stem cell properties via the Hh/Gli1 signaling pathway. The results suggest that Prdx2 may be an effective therapeutic target for the elimination of CSCs in colorectal cancer.

  2. Maintaining evolvability.

    Science.gov (United States)

    Crow, James F

    2008-12-01

    Although molecular methods, such as QTL mapping, have revealed a number of loci with large effects, it is still likely that the bulk of quantitative variability is due to multiple factors, each with small effect. Typically, these have a large additive component. Conventional wisdom argues that selection, natural or artificial, uses up additive variance and thus depletes its supply. Over time, the variance should be reduced, and at equilibrium be near zero. This is especially expected for fitness and traits highly correlated with it. Yet, populations typically have a great deal of additive variance, and do not seem to run out of genetic variability even after many generations of directional selection. Long-term selection experiments show that populations continue to retain seemingly undiminished additive variance despite large changes in the mean value. I propose that there are several reasons for this. (i) The environment is continually changing so that what was formerly most fit no longer is. (ii) There is an input of genetic variance from mutation, and sometimes from migration. (iii) As intermediate-frequency alleles increase in frequency towards one, producing less variance (as p --> 1, p(1 - p) --> 0), others that were originally near zero become more common and increase the variance. Thus, a roughly constant variance is maintained. (iv) There is always selection for fitness and for characters closely related to it. To the extent that the trait is heritable, later generations inherit a disproportionate number of genes acting additively on the trait, thus increasing genetic variance. For these reasons a selected population retains its ability to evolve. Of course, genes with large effect are also important. Conspicuous examples are the small number of loci that changed teosinte to maize, and major phylogenetic changes in the animal kingdom. The relative importance of these along with duplications, chromosome rearrangements, horizontal transmission and polyploidy

  3. SC1 Promotes MiR124-3p Expression to Maintain the Self-Renewal of Mouse Embryonic Stem Cells by Inhibiting the MEK/ERK Pathway.

    Science.gov (United States)

    Wei, Qing; Liu, Hongliang; Ai, Zhiying; Wu, Yongyan; Liu, Yingxiang; Shi, Zhaopeng; Ren, Xuexue; Guo, Zekun

    2017-01-01

    Self-renewal is one of the most important features of embryonic stem (ES) cells. SC1 is a small molecule modulator that effectively maintains the self-renewal of mouse ES cells in the absence of leukemia inhibitory factor (LIF), serum and feeder cells. However, the mechanism by which SC1 maintains the undifferentiated state of mouse ES cells remains unclear. In this study, microarray and small RNA deep-sequencing experiments were performed on mouse ES cells treated with or without SC1 to identify the key genes and microRNAs that contributed to self-renewal. SC1 regulates the expressions of pluripotency and differentiation factors, and antagonizes the retinoic acid (RA)-induced differentiation in the presence or absence of LIF. SC1 inhibits the MEK/ERK pathway through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and pathway reporting experiments. Small RNA deep-sequencing revealed that SC1 significantly modulates the expression of multiple microRNAs with crucial functions in ES cells. The expression of miR124-3p is upregulated in SC1-treated ES cells, which significantly inhibits the MEK/ERK pathway by targeting Grb2, Sos2 and Egr1. SC1 enhances the self-renewal capacity of mouse ES cells by modulating the expression of key regulatory genes and pluripotency-associated microRNAs. SC1 significantly upregulates miR124-3p expression to further inhibit the MEK/ ERK pathway by targeting Grb2, Sos2 and Egr1. © 2017 The Author(s). Published by S. Karger AG, Basel.

  4. EGCG Maintains Th1/Th2 Balance and Mitigates Ulcerative Colitis Induced by Dextran Sulfate Sodium through TLR4/MyD88/NF-κB Signaling Pathway in Rats

    Directory of Open Access Journals (Sweden)

    Xue Bing

    2017-01-01

    Full Text Available Objective. To observe the protective effect of epigallocatechin gallate (EGCG on dextran sulfate sodium- (DSS- induced ulcerative colitis in rats and to explore the roles of TLR4/MyD88/NF-κB signaling pathway. Methods. Rat models of ulcerative colitis were established by giving DSS. EGCG (50 mg/kg/d was given to assess disease activity index. HE staining was applied to observe histological changes. ELISA and qPCR detected the expression of inflammatory factors. Flow cytometry was used to measure the percentage of CD4+IFN-γ+ and CD4+IL-4+ in the spleen and colon. TLR4 antagonist E5564 was given in each group. Flow cytometry was utilized to detect CD4+IFN-γ+ and CD4+IL-4+ cells. Immunohistochemistry, qPCR, and western blot assay were applied to measure the expression of TLR4, MyD88, and NF-κB. Results. EGCG improved the intestinal mucosal injury in rats, inhibited production of inflammatory factors, maintained the balance of Th1/Th2, and reduced the expression of TLR4, MyD88, and NF-κB. After TLR4 antagonism, the protective effect of EGCG on intestinal mucosal injury was weakened in rats with ulcerative colitis, and the expressions of inflammatory factors were upregulated. Conclusion. EGCG can inhibit the intestinal inflammatory response by reducing the severity of ulcerative colitis and maintaining the Th1/Th2 balance through the TLR4/MyD88/NF-κB signaling pathway.

  5. How Do Positive Views Maintain Life Satisfaction?

    Science.gov (United States)

    Wu, Chia-Huei; Tsai, Ying-Mei; Chen, Lung Hung

    2009-01-01

    This study proposes three mediation pathways to explain how the positive views (perceived control, optimism and self-enhancement) proposed by Cummins and Nistico (Journal of Happiness Studies 3:37-69 2002) maintain life satisfaction. The three pathways were enhancing self-esteem, reducing have-want discrepancy and changing importance perceptions.…

  6. Maintaining protein composition in cilia.

    Science.gov (United States)

    Stephen, Louise A; Elmaghloob, Yasmin; Ismail, Shehab

    2017-12-20

    The primary cilium is a sensory organelle that is vital in regulating several signalling pathways. Unlike most organelles cilia are open to the rest of the cell, not enclosed by membranes. The distinct protein composition is crucial to the function of cilia and many signalling proteins and receptors are specifically concentrated within distinct compartments. To maintain this composition, a mechanism is required to deliver proteins to the cilium whilst another must counter the entropic tendency of proteins to distribute throughout the cell. The combination of the two mechanisms should result in the concentration of ciliary proteins to the cilium. In this review we will look at different cellular mechanisms that play a role in maintaining the distinct composition of cilia, including regulation of ciliary access and trafficking of ciliary proteins to, from and within the cilium.

  7. Ergonomics Contribution in Maintainability

    Science.gov (United States)

    Teymourian, Kiumars; Seneviratne, Dammika; Galar, Diego

    2017-09-01

    The objective of this paper is to describe an ergonomics contribution in maintainability. The economical designs, inputs and training helps to increase the maintainability indicators for industrial devices. This analysis can be helpful, among other cases, to compare systems, to achieve a better design regarding maintainability requirements, to improve this maintainability under specific industrial environment and to foresee maintainability problems due to eventual changes in a device operation conditions. With this purpose, this work first introduces the notion of ergonomics and human factors, maintainability and the implementation of assessment of human postures, including some important postures to perform maintenance activities. A simulation approach is used to identify the critical posture of the maintenance personnel and implements the defined postures with minimal loads on the personnel who use the equipment in a practical scenario. The simulation inputs are given to the designers to improve the workplace/equipment in order to high level of maintainability. Finally, the work concludes summarizing the more significant aspects and suggesting future research.

  8. Maintaining dignity in vulnerability

    DEFF Research Database (Denmark)

    Høy, Bente

    2016-01-01

    to understand the meaning of the narrated text. Results. The meaning of maintaining dignity was constituted in a sense of vulnerability to the self, and elucidated in three major interrelated themes: Being involved as a human being, being involved as the person one is and strives to become, and being involved...

  9. Constructability and maintainability

    International Nuclear Information System (INIS)

    Hart, R.S.

    1985-01-01

    A set of principles for minimizing the construction schedule was established at the outset of the CANDU 300 programme. Consideration of these principles and other factors led to the development of the unique CANDU 300 station layout. The paper discusses the CANDU 300 station layout and construction methods. In summary, the station layout provides 360 deg. construction access to all buildings, separation of nuclear and non-nuclear systems, precise and minimal physical interfaces between buildings, accommodation of many contractors and construction activities without interference, and maximum flexibility in terms of constructional, financial and supply arrangements. The CANDU 300 further employs modularization, shop fabrication and advanced instrumentation (multiplexers, remote processors, data highways) to minimize construction time. Many of the CANDU 300 features that enhance constructability also contribute to maintainability. These include the 360 deg. access to all principal buildings, the uncluttered and spacious building layouts, the simplification of systems and the high level of modularization. The CANDU 300 has also been designed to facilitate the replacement of all key components, thereby offering an essentially unlimited station life. A prime example is a reduction in the fuel channel inlet end-fitting diameter such that the fuel channels can be shop assembled and easily replaced after the initial 40 years of operation, without an extended unit outage. Maintainability within the reactor building has been given particular attention in the CANDU 300 design; key features of other CANDU reactors (the ability to replace a heat transport system pump motor at power, for example) have been incorporated, while accessibility and maintainability of all systems and components have been enhanced. These and other aspects of maintainability are discussed. (author)

  10. Reliability and maintainability

    International Nuclear Information System (INIS)

    1994-01-01

    Several communications in this conference are concerned with nuclear plant reliability and maintainability; their titles are: maintenance optimization of stand-by Diesels of 900 MW nuclear power plants; CLAIRE: an event-based simulation tool for software testing; reliability as one important issue within the periodic safety review of nuclear power plants; design of nuclear building ventilation by the means of functional analysis; operation characteristic analysis for a power industry plant park, as a function of influence parameters

  11. Seamless service: maintaining momentum.

    Science.gov (United States)

    Grinstead, N; Timoney, R

    1994-01-01

    Describes the process used by the Mater Infirmorum Hospital in Belfast in 1992-1994 to achieve high quality care (Seamless Service), motivate staff to deliver and measure performance. Aims of the project include focusing the organization on the customer, improving teamwork and motivation at all levels. After comprehensive data collection from GPs, patients and staff management forums developed a full TQM strategy to gain support and maintain momentum including innovative staff events (every staff member was given the opportunity to attend) where multilevel, multidisciplinary workshops enabled staff to design customer care standards, develop teams and lead customer-driven change.

  12. Gestures maintain spatial imagery.

    Science.gov (United States)

    Wesp, R; Hesse, J; Keutmann, D; Wheaton, K

    2001-01-01

    Recent theories suggest alternatives to the commonly held belief that the sole role of gestures is to communicate meaning directly to listeners. Evidence suggests that gestures may serve a cognitive function for speakers, possibly acting as lexical primes. We observed that participants gestured more often when describing a picture from memory than when the picture was present and that gestures were not influenced by manipulating eye contact of a listener. We argue that spatial imagery serves a short-term memory function during lexical search and that gestures may help maintain spatial images. When spatial imagery is not necessary, as in conditions of direct visual stimulation, reliance on gestures is reduced or eliminated.

  13. Maintainability design guide

    International Nuclear Information System (INIS)

    Pack, R.W.

    1985-01-01

    The Human Factors Design Guide for Maintainability provides guidance for systematically incorporating good human factors techniques into the design of power plants. The guide describes a means of developing a comprehensive program plan to ensure compliance with the human factors approaches specified by the utility. The guide also provides specific recommendations for design practices, with examples, bases, and references. The recommendations are formatted for easy use by nuclear power plant design teams and by utility personnel involved in specification and design review. The guide was developed under EPRI research project RP2166-4 and is currently being published

  14. Maintaining Relationship Based Procurement

    Directory of Open Access Journals (Sweden)

    Peter Davis

    2012-11-01

    Full Text Available Alliance and relationship projects are increasingin number and represent a large pool of work. Tobe successful relationship style contracts dependon soft-dollar factors, particularly the participants'ability to work together within an agreedframework, generally they are not based on lowbid tendering. Participants should be prepared todo business in an open environment based ontrust and mutually agreed governance. Theresearch evaluates relationship maintenance inthe implementation phase of constructionalliances - a particular derivative of relationshipstyle contracts. To determine the factors thatcontribute to relationship maintenance forty-nineexperienced Australian alliance projectmanagers were interviewed. The main findingswere; the development of relationships early inthe project form building blocks of success fromwhich relationships are maintained and projectvalue added; quality facilitation plays animportant part in relationship maintenance and ahybrid organisation created as a result of alliancedevelopment overcomes destructiveorganisational boundaries. Relationshipmaintenance is integral to alliance project controland failure to formalise it and pay attention toprocess and past outcomes will undermine analliance project's potential for success.

  15. Maintaining Web Cache Coherency

    Directory of Open Access Journals (Sweden)

    2000-01-01

    Full Text Available Document coherency is a challenging problem for Web caching. Once the documents are cached throughout the Internet, it is often difficult to keep them coherent with the origin document without generating a new traffic that could increase the traffic on the international backbone and overload the popular servers. Several solutions have been proposed to solve this problem, among them two categories have been widely discussed: the strong document coherency and the weak document coherency. The cost and the efficiency of the two categories are still a controversial issue, while in some studies the strong coherency is far too expensive to be used in the Web context, in other studies it could be maintained at a low cost. The accuracy of these analysis is depending very much on how the document updating process is approximated. In this study, we compare some of the coherence methods proposed for Web caching. Among other points, we study the side effects of these methods on the Internet traffic. The ultimate goal is to study the cache behavior under several conditions, which will cover some of the factors that play an important role in the Web cache performance evaluation and quantify their impact on the simulation accuracy. The results presented in this study show indeed some differences in the outcome of the simulation of a Web cache depending on the workload being used, and the probability distribution used to approximate updates on the cached documents. Each experiment shows two case studies that outline the impact of the considered parameter on the performance of the cache.

  16. ADAS Update and Maintainability

    Science.gov (United States)

    Watson, Leela R.

    2010-01-01

    Since 2000, both the National Weather Service Melbourne (NWS MLB) and the Spaceflight Meteorology Group (SMG) have used a local data integration system (LOIS) as part of their forecast and warning operations. The original LOIS was developed by the Applied Meteorology Unit (AMU) in 1998 (Manobianco and Case 1998) and has undergone subsequent improvements. Each has benefited from three-dimensional (3-D) analyses that are delivered to forecasters every 15 minutes across the peninsula of Florida. The intent is to generate products that enhance short-range weather forecasts issued in support of NWS MLB and SMG operational requirements within East Central Florida. The current LDIS uses the Advanced Regional Prediction System (ARPS) Data Analysis System (AD AS) package as its core, which integrates a wide variety of national, regional, and local observational data sets. It assimilates all available real-time data within its domain and is run at a finer spatial and temporal resolution than current national or regional-scale analysis packages. As such, it provides local forecasters with a more comprehensive understanding of evolving fine-scale weather features. Over the years, the LDIS has become problematic to maintain since it depends on AMU-developed shell scripts that were written for an earlier version of the ADAS software. The goals of this task were to update the NWS MLB/SMG LDIS with the latest version of ADAS, incorporate new sources of observational data, and upgrade and modify the AMU-developed shell scripts written to govern the system. In addition, the previously developed ADAS graphical user interface (GUI) was updated. Operationally, these upgrades will result in more accurate depictions of the current local environment to help with short-range weather forecasting applications, while also offering an improved initialization for local versions of the Weather Research and Forecasting (WRF) model used by both groups.

  17. Maintaining Healthy Skin -- Part 2

    Science.gov (United States)

    ... and SCI • Depression and SCI • Taking Care of Pressure Sores • Maintaining Healthy Skin (Part I) • Maintaining Healthy Skin ( ... For information on establishing skin tolerance, see our “Pressure Sores” pamphlet.) Pressure releases in a wheelchair can be ...

  18. AECL's reliability and maintainability program

    International Nuclear Information System (INIS)

    Wolfe, W.A.; Nieuwhof, G.W.E.

    1976-05-01

    AECL's reliability and maintainability program for nuclear generating stations is described. How the various resources of the company are organized to design and construct stations that operate reliably and safely is shown. Reliability and maintainability includes not only special mathematically oriented techniques, but also the technical skills and organizational abilities of the company. (author)

  19. Maintainability effectiveness evaluations and enhancement

    International Nuclear Information System (INIS)

    Seminara, J.L.

    1985-01-01

    In the mid-seventies EPRI initiated a research project to review the human factors aspects of nuclear power plant control rooms. In the course of investigating operator-control room interfaces in five operational control rooms, it became evident that many plant outages had either been caused or prolonged by human factors problems associated with maintenance activities. Consequently, as one of several follow-on projects, EPRI sponsored a review of nine power plants (five nuclear and four fossil) to examine the human factors aspects of plant maintainability. This survey revealed a wide variety of generic human factors problems that could negatively impact the effectiveness of plant maintenance personnel. It was clear that plant maintainability features deserved no less attention to human factors concerns than the operational features of the control room. This paper describes subsequent EPRI-initiated efforts to assist the utilities in conducting self-reviews of maintainability effectiveness and effect needed enhancements

  20. Developing and maintaining nuclear competencies

    International Nuclear Information System (INIS)

    Gobert, C.

    2004-01-01

    The paper discusses the following aspects on the nuclear knowledge management: assimilation of knowledge management, recognition of the nuclear specificity, attracting young talents. Another feature which, possibly, differentiates nuclear from other high-tech industries is that time constraints in some nuclear development may very well exceed the duration of a generation of professionals. That means, not only maintaining scientific and technical knowledge, which, as a minimum, leads to maintain: a rigorous supervision of human resources in quality and quantity; anticipatory planning of human resources, with a special focus on succession planning concerning expertise positions; a steady and continuous effort in training and retraining programs. Maintaining the safety culture is also one of the major managerial duties. Taking full account of the nuclear specificity in knowledge maintenance and development in the AREVA group, requests a multifunctional approach, which combines efforts of Research and Innovation, and Human Resources departments, plus the group Nuclear inspectorate. It is acknowledged that the industry, basically, would readily rely on the capabilities of the academic world and research centers in ensuring that training and education in nuclear science and technologies are attuned to the evolving needs of the industry, in maintaining the proper educational programs and in fostering fruitful cooperations between them

  1. [Maintaining patients' autonomy at home].

    Science.gov (United States)

    Niang, Bénédicte; Coudre, Jean Pierre

    2015-01-01

    To maintain the flow of hospital discharges, the patient's return home with support from a home nursing service is important. If any difficulties are identified, there are various programmes or good practices which can be put into place. The future law on adapting society to ageing also comprises a scheme combining home assistance and nursing care.

  2. Maintaining steam/condensate lines

    International Nuclear Information System (INIS)

    Russum, S.A.

    1992-01-01

    Steam and condensate systems must be maintained with the same diligence as the boiler itself. Unfortunately, they often are not. The water treatment program, critical to keeping the boiler at peak efficiency and optimizing operating life, should not stop with the boiler. The program must encompass the steam and condensate system as well. A properly maintained condensate system maximizes condensate recovery, which is a cost-free energy source. The fuel needed to turn the boiler feedwater into steam has already been provided. Returning the condensate allows a significant portion of that fuel cost to be recouped. Condensate has a high heat content. Condensate is a readily available, economical feedwater source. Properly treated, it is very pure. Condensate improves feedwater quality and reduces makeup water demand and pretreatment costs. Higher quality feedwater means more reliable boiler operation

  3. Disturbance maintains alternative biome states.

    Science.gov (United States)

    Dantas, Vinícius de L; Hirota, Marina; Oliveira, Rafael S; Pausas, Juli G

    2016-01-01

    Understanding the mechanisms controlling the distribution of biomes remains a challenge. Although tropical biome distribution has traditionally been explained by climate and soil, contrasting vegetation types often occur as mosaics with sharp boundaries under very similar environmental conditions. While evidence suggests that these biomes are alternative states, empirical broad-scale support to this hypothesis is still lacking. Using community-level field data and a novel resource-niche overlap approach, we show that, for a wide range of environmental conditions, fire feedbacks maintain savannas and forests as alternative biome states in both the Neotropics and the Afrotropics. In addition, wooded grasslands and savannas occurred as alternative grassy states in the Afrotropics, depending on the relative importance of fire and herbivory feedbacks. These results are consistent with landscape scale evidence and suggest that disturbance is a general factor driving and maintaining alternative biome states and vegetation mosaics in the tropics. © 2015 John Wiley & Sons Ltd/CNRS.

  4. Improving versus maintaining nuclear safety

    International Nuclear Information System (INIS)

    2002-01-01

    The concept of improving nuclear safety versus maintaining it has been discussed at a number of nuclear regulators meetings in recent years. National reports have indicated that there are philosophical differences between NEA member countries about whether their regulatory approaches require licensees to continuously improve nuclear safety or to continuously maintain it. It has been concluded that, while the actual level of safety achieved in all member countries is probably much the same, this is difficult to prove in a quantitative way. In practice, all regulatory approaches require improvements to be made to correct deficiencies and when otherwise warranted. Based on contributions from members of the NEA Committee on Nuclear Regulatory Activities (CNRA), this publication provides an overview of current nuclear regulatory philosophies and approaches, as well as insights into a selection of public perception issues. This publication's intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

  5. Developing and maintaining instructor capabilities

    International Nuclear Information System (INIS)

    Flynn, W.P.; Smith, G.

    1985-01-01

    The New York Power Authority, after surveying available courses, decided to develop an in-house instructor training program. Following the principles of the Systems Approach to Training the course embodied the results of a job analysis resulting in a program containing instruction in Educational Philosophy, the Systems Approach to Training, Methods and Media, and Testing. The course content is covered through classroom instruction, on-the-job training, instructor evaluations, and assignments. Instructors completing the program continue to maintain skills with inservice training

  6. Maintaining consistency in distributed systems

    Science.gov (United States)

    Birman, Kenneth P.

    1991-01-01

    In systems designed as assemblies of independently developed components, concurrent access to data or data structures normally arises within individual programs, and is controlled using mutual exclusion constructs, such as semaphores and monitors. Where data is persistent and/or sets of operation are related to one another, transactions or linearizability may be more appropriate. Systems that incorporate cooperative styles of distributed execution often replicate or distribute data within groups of components. In these cases, group oriented consistency properties must be maintained, and tools based on the virtual synchrony execution model greatly simplify the task confronting an application developer. All three styles of distributed computing are likely to be seen in future systems - often, within the same application. This leads us to propose an integrated approach that permits applications that use virtual synchrony with concurrent objects that respect a linearizability constraint, and vice versa. Transactional subsystems are treated as a special case of linearizability.

  7. Building and maintaining media contacts

    International Nuclear Information System (INIS)

    Fenton, Bob

    2000-01-01

    This presentation is answering the question: 'how does British Energy build and maintain its relationships with journalists in so many areas', not only the basic industrial correspondents that you would expect to have to deal with an industry British Energy, but those dealing with science and technology, the environment, personnel and training, city and financial, political, and on and on, and that is just the national press. Then add the local and regional media around power station sites - literally hundreds of contacts and you start to get an idea about the size of our media contact database. But it is managed it rather well. Every six months British Energy takes part in a survey run by one of the UK's leading market research companies who conducts a poll among journalists and then rate each company's performance. In the last three years British Energy has not been outside the top five in most categories, and in the top two in several. The answer is a lot of work over a long period of time. You cannot expect to build trusting relationships with a journalist overnight. At British Energy the key is being open and honest, and always available. Of course good media relations is not a one-way street, and there has to be some element of compromise if you are to achieve a relationship based on mutual trust

  8. Maintaining quality in blood banking.

    Science.gov (United States)

    Harvey, E; Hewison, C; Nevalainen, D E; Lloyd, H L

    1995-03-01

    component will warrant redress. The degree of fault attributed to the producer will in part depend on whether they have met the best available standards at all stages in the preparation of the product. If a Transfusion Service can show that it's operation has external accreditation, particularly to an internationally recognised standard such as ISO 9000 and they can show that staff have been properly trained, that equipment is properly supplied and maintained and that the facility is appropriate to the work being carried out, then the liability that exists when something goes wrong will be reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

  9. Ubiquitylation and the Fanconi Anemia Pathway

    Science.gov (United States)

    Garner, Elizabeth; Smogorzewska, Agata

    2012-01-01

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

  10. Building and maintaining media relations

    International Nuclear Information System (INIS)

    Oesterberg, Anders

    2000-01-01

    Full text: In my opinion good media relations are among the most valuable investments regarding the communications and Public Relations operations within an Organisation. This means, that all the work you put up in building and maintaining media relations, is worth all the efforts. It can mean the difference between success or failure. Although a reporter never would admit that he or she is easily influenced, the fact is that you would get better press in an emergency case if you have a positive personal relation to the reporter. So, in my opinion there is nothing more important, in building and maintaining media relations, than the face-to-face-contact. My experience of good personal relations to reporters is also that you're not only getting better press in emergency cases. You are more successful in getting published when you have something positive to say, too. Honesty and openness are two key-words in this context. I have never tried to manipulate and delude a reporter, since that definitely would ruin the relationship. I always try to be as straight forward as possible and underline what I can say and what I can't. That instead of presenting some forced lies. For me, it is also very important to create some kind of mid-field ground, where the reporter and I can meet unprejudiced. Sense of humour and distance, both to yourself and your organisation, are two main characteristics that are invaluable in order to create a good personal relationship with a reporter. But, I'm very accurate in emphasizing when I enter my role as a company representative. All in order to be regarded as correct, yet obliging. To be quick when it comes to returning calls is another vital component that gives the reporter a feeling that he or she is important enough to be contacted as soon as possible. This service-minded attitude is of course good for the relationship. Besides the more personal relation it's important to have a business-like relation, where you show a great deal of

  11. Mitochondrial quality control pathways as determinants of metabolic health

    NARCIS (Netherlands)

    Held, Ntsiki M.; Houtkooper, Riekelt H.

    2015-01-01

    Mitochondrial function is key for maintaining cellular health, while mitochondrial failure is associated with various pathologies, including inherited metabolic disorders and age-related diseases. In order to maintain mitochondrial quality, several pathways of mitochondrial quality control have

  12. Evolution of maintainability in France since 1971

    International Nuclear Information System (INIS)

    Guyot, Christian.

    1975-01-01

    The purpose of the paper is to make the point of maintainability in France since 1971. The importance of maintainability is recalled. Publications in France from 1971 to 1975 show the interest arose by maintainability; their analysis permits to make clear the general plan followed by the studies and gives indications on the directions of actual efforts. Conclusion is drawn on the orientation of work at short, medium and long term [fr

  13. Space maintainers in dentistry: past to present.

    Science.gov (United States)

    Setia, Vikas; Pandit, Inder Kumar; Srivastava, Nikhil; Gugnani, Neeraj; Sekhon, Harveen Kaur

    2013-10-01

    Early orthodontic interventions are often initiated in the developing dentition to promote favourable developmental changes. Interceptive orthodontic can eliminate or reduce the severity of a developing malocclusion, the complexity of orthodontic treatment, overall treatment time and cost. The safest way to prevent future malocclusions from tooth loss is to place a space maintainer that is effective and durable. An appropriate use of space maintainer is advocated to hold the space until the eruption of permanent teeth. This case report describes the various changing trends in use of space maintainers: conventional band and loop, prefabricated band with custom made loop and glass fibre reinforced composite resins as space maintainers.

  14. Molecular Pathways

    Science.gov (United States)

    Lok, Benjamin H.; Powell, Simon N.

    2012-01-01

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

  15. The Cost of Maintaining Educational Communications Equipment.

    Science.gov (United States)

    Humphrey, David A.

    Tentative formulas for calculating the cost of maintaining educational communications equipment are proposed. The formulas are based on a survey of campuses of the State University of New York. The survey analyzed the types of equipment to be maintained, types of maintenance, who uses the equipment, who services the equipment, and the cost…

  16. Coastal Maintained Channels in US waters

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This layer shows coastal channels and waterways that are maintained and surveyed by the U.S. Army Corps of Engineers (USACE). These channels are necessary...

  17. Marshal: Maintaining Evolving Models, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — SIFT proposes to design and develop the Marshal system, a mixed-initiative tool for maintaining task models over the course of evolving missions. Marshal-enabled...

  18. Maintaining Contour Trees of Dynamic Terrains

    DEFF Research Database (Denmark)

    Agarwal, Pankaj K.; Mølhave, Thomas; Revsbæk, Morten

    2015-01-01

    We study the problem of maintaining the contour tree T of a terrain Sigma, represented as a triangulated xy-monotone surface, as the heights of its vertices vary continuously with time. We characterize the combinatorial changes in T and how they relate to topological changes in Sigma. We present ...

  19. Maintaining Contour Trees of Dynamic Terrains

    DEFF Research Database (Denmark)

    Agarwal, Pankaj K.; Arge, Lars; Mølhave, Thomas

    We consider maintaining the contour tree T of a piecewise-linear triangulation M that is the graph of a time varying height function h:R2→R. We carefully describe the combinatorial change in T that happen as h varies over time and how these changes relate to topological changes in M. We present a...

  20. Maintainability of manpower system with restricted recruitment ...

    African Journals Online (AJOL)

    The maintainability of a manpower system is studied under a Markov framework. The classical method of controlling only one factor of flow is extended to highlight the case in which two factors are under control simultaneously. One special case of this extension, where recruitment of units faces partial embargo, is given, ...

  1. Competence in radiation protection - acquisition, maintaining, extending

    International Nuclear Information System (INIS)

    Breckow, J.; Geringer, T.; Radiation Protection Academy Seibersdorf; Haug, T.

    2007-01-01

    A survey is given on current initiatives, supranational in the EU and national in Germany and Switzerland, for education and training in radiation protection with the aim of maintaining and enlarging professional competence. Successively, individual studying possibilities and courses as well as some experiences with guidelines for professional knowledge in Germany are described. (orig.)

  2. PHOTOBIOMODULATION-MEDIATED PATHWAY DIAGNOSTICS

    Directory of Open Access Journals (Sweden)

    TIMON CHENG-YI LIU

    2013-01-01

    Full Text Available Cellular pathways are ordinarily diagnosed with pathway inhibitors, related gene regulation, or fluorescent protein markers. They are also suggested to be diagnosed with pathway activation modulation of photobiomodulation (PBM in this paper. A PBM on a biosystem function depends on whether the biosystem is in its function-specific homeostasis (FSH. An FSH, a negative feedback response for the function to be performed perfectly, is maintained by its FSH-essential subfunctions and its FSH-non-essential subfunctions (FNSs. A function in its FSH or far from its FSH is called a normal or dysfunctional function. A direct PBM may self-adaptatively modulate a dysfunctional function until it is normal so that it can be used to discover the optimum pathways for an FSH to be established. An indirect PBM may self-adaptatively modulate a dysfunctional FNS of a normal function until the FNS is normal, and the normal function is then upgraded so that it can be used to discover the redundant pathways for a normal function to be upgraded.

  3. Breeding and maintaining high-quality insects

    DEFF Research Database (Denmark)

    Jensen, Kim; Kristensen, Torsten Nygård; Heckmann, Lars-Henrik

    2017-01-01

    Insects have a large potential for sustainably enhancing global food and feed production, and commercial insect production is a rising industry of high economic value. Insects suitable for production typically have fast growth, short generation time, efficient nutrient utilization, high...... reproductive potential, and thrive at high density. Insects may cost-efficiently convert agricultural and industrial food by-products into valuable protein once the technology is finetuned. However, since insect mass production is a new industry, the technology needed to efficiently farm these animals is still...... in a starting phase. Here, we discuss the challenges and precautions that need to be considered when breeding and maintaining high-quality insect populations for food and feed. This involves techniques typically used in domestic animal breeding programs including maintaining genetically healthy populations...

  4. Maintaining Respiratory Health in Cystic Fibrosis Patients

    Directory of Open Access Journals (Sweden)

    MR Modaresi

    2014-04-01

    Full Text Available Cystic fibrosis (CF is an inherited disease that primarily affects the lungs and the digestive system, however, it also affects a number of other organs and systems. More than 90% of mortality of  CF patients is due to lung complications.  Healthy lungs are important for a long life for people with CF, We will discuss two important topics for maintaining respiratory health. Chronic use of drugs for maintaining respiratory health There are a number of drugs available to keep CF lungs healthy. We will discuss the science behind the recommendations for use of: Inhaled antibiotics Dornase alfa Azithromycin Hypertonic saline High-dose ibuprofen Ivacaftor CF Airway Clearance Therapies Airway Clearance therapy is very important to keeping CF lungs healthy. Our discussions cover the following topics such as the: Daily airway clearance Different techniques of airway clearance Effect of aerobic exercise on airway clearance  

  5. Pathways towards the proliferation of avoidance in anxiety and implications for treatment

    NARCIS (Netherlands)

    Arnaudova, I.; Kindt, M.; Fanselow, M.; Beckers, T.

    Avoidance is a key symptom of anxiety disorders. Maladaptive avoidance impairs general functioning acutely and maintains chronic anxiety. A better understanding of the mechanisms that elicit and maintain excessive avoidance might provide opportunities to improve treatment. Here, we discuss pathways

  6. Maintaining the Identify of Dynamically Embodied Agents

    OpenAIRE

    Martin, Alan; O'Hare, Gregory; Duffy, Brian; Schoen-Phelan, Bianca; Bradley, John

    2005-01-01

    Virtual agents are traditionally constrained in their embod- iment, as they are restricted to one form of body. We propose allowing them to change their embodiment in order to expand their capabili- ties. This presents users with a number of di±culties in maintaining the identity of the agents, but these can be overcome by using identity cues, certain features that remain constant across embodiment forms. This pa- per outlines an experiment that examines these identity cues, and shows that th...

  7. Pathway Distiller - multisource biological pathway consolidation.

    Science.gov (United States)

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

    2012-01-01

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

  8. Water quality maintaining device of power plant

    International Nuclear Information System (INIS)

    Kobayashi, Minoru; Inami, Ichiro.

    1994-01-01

    The device of the present invention reduces the amount of leaching materials of ion exchange resins from a water processing system of a BWR tyep plant, improves the water quality of reactor water to maintain the water at high purity. That is, steams used for power generation are condensated in a condensate system. A condensate filter and a condensate desalter for cleaning the condensates are disposed. A resin storage hopper is disposed for supplying the ion exchange resins to the water processing system. A device for supplying a nitrogen gas or an inert gas is disposed in the hopper. With such a constitution, the ion exchange resins in the water processing system are maintained in a nitrogen gas or inert gas atmosphere or at a low dissolved oxygen level in an operation stage in the power plant. Accordingly, degradation of the ion exchange resins in the water processing system is suppressed and the amount of the leaching material from the resins is reduced. As a result, the amount of the resins leached into the reactor is reduced, so that the reactor water quality can be maintained at high purity. (I.S.)

  9. Asada-Halliwell pathway maintains redox status in Dioscorea alata tuber which helps in germination.

    Science.gov (United States)

    Sharma, Shruti; Sehrawat, Ankita; Deswal, Renu

    2016-09-01

    Reactive Oxygen Species (ROS) are important regulatory molecules governing physiological processes. In the present study a biochemical and proteome level comparison of two contrasting growth stages of Dioscorea alata tuber namely germinating and mature tuber was performed in order to understand the tuber physiology and biochemistry. Existence of all the component enzymes [APx (ascorbate peroxidase), GR (glutathione reductase), DHAR (dehydroascorbate reductase), MDHAR (mono-dehydroascorbate reductase)] and major products [ascorbate (ASC) and glutathione (GSH)] of the cycle showed an operational Asada-Halliwell cycle in the tuber. A 2.65 fold increase in ASC content & a 3.8 fold increase in GR activity fortified the redox milieu during germination. In contrast a 5 fold higher H2O2 content (due to 3.08 fold lower APx activity) and accumulation of reactive nitrogen species (RNS) such as nitric oxide (NO, 2.4-fold) and S-nitrosothiol (SNO, 2.08 fold) contributed to overall oxidative conditions in the mature tuber. The carbonic anhydrase (CA, 7.5 fold), DHAR (5.31 fold) and MDHAR (7 fold) activities were higher in the germinating tuber in comparison with the mature tuber. GSNO negatively regulated the CA (3.6 & 3.95 fold), MDHAR (7.5 & 1.5 fold) and APx (2.3 & 1.81 fold) while another NO donor, CysNO negatively regulated the DHAR (2.24 & 1.32 fold) activity in the mature and germinating stages respectively indicating again that the lesser inhibition by NO (via nitrosylation) may be because of overall reducing environment in the germinating tuber. Increased SNO leading to S-nitrosylation of dioscorin was confirmed by Biotin switch assay. This is the first report showing dioscorin nitrosylation. The present analysis showed differential redox regulation and also suggests the physiological relevance of CA, DHAR, MDHAR, APx & GR in tuber germination for the first time. These enzymes may be used as potential markers of tuber germination in future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Identifying crucial parameter correlations maintaining bursting activity.

    Directory of Open Access Journals (Sweden)

    Anca Doloc-Mihu

    2014-06-01

    Full Text Available Recent experimental and computational studies suggest that linearly correlated sets of parameters (intrinsic and synaptic properties of neurons allow central pattern-generating networks to produce and maintain their rhythmic activity regardless of changing internal and external conditions. To determine the role of correlated conductances in the robust maintenance of functional bursting activity, we used our existing database of half-center oscillator (HCO model instances of the leech heartbeat CPG. From the database, we identified functional activity groups of burster (isolated neuron and half-center oscillator model instances and realistic subgroups of each that showed burst characteristics (principally period and spike frequency similar to the animal. To find linear correlations among the conductance parameters maintaining functional leech bursting activity, we applied Principal Component Analysis (PCA to each of these four groups. PCA identified a set of three maximal conductances (leak current, [Formula: see text]Leak; a persistent K current, [Formula: see text]K2; and of a persistent Na+ current, [Formula: see text]P that correlate linearly for the two groups of burster instances but not for the HCO groups. Visualizations of HCO instances in a reduced space suggested that there might be non-linear relationships between these parameters for these instances. Experimental studies have shown that period is a key attribute influenced by modulatory inputs and temperature variations in heart interneurons. Thus, we explored the sensitivity of period to changes in maximal conductances of [Formula: see text]Leak, [Formula: see text]K2, and [Formula: see text]P, and we found that for our realistic bursters the effect of these parameters on period could not be assessed because when varied individually bursting activity was not maintained.

  11. Store operations to maintain cache coherence

    Energy Technology Data Exchange (ETDEWEB)

    Evangelinos, Constantinos; Nair, Ravi; Ohmacht, Martin

    2017-08-01

    In one embodiment, a computer-implemented method includes encountering a store operation during a compile-time of a program, where the store operation is applicable to a memory line. It is determined, by a computer processor, that no cache coherence action is necessary for the store operation. A store-without-coherence-action instruction is generated for the store operation, responsive to determining that no cache coherence action is necessary. The store-without-coherence-action instruction specifies that the store operation is to be performed without a cache coherence action, and cache coherence is maintained upon execution of the store-without-coherence-action instruction.

  12. Store operations to maintain cache coherence

    Energy Technology Data Exchange (ETDEWEB)

    Evangelinos, Constantinos; Nair, Ravi; Ohmacht, Martin

    2017-09-12

    In one embodiment, a computer-implemented method includes encountering a store operation during a compile-time of a program, where the store operation is applicable to a memory line. It is determined, by a computer processor, that no cache coherence action is necessary for the store operation. A store-without-coherence-action instruction is generated for the store operation, responsive to determining that no cache coherence action is necessary. The store-without-coherence-action instruction specifies that the store operation is to be performed without a cache coherence action, and cache coherence is maintained upon execution of the store-without-coherence-action instruction.

  13. Experience of maintaining laboratory educational website's sustainability.

    Science.gov (United States)

    Dimenstein, Izak B

    2016-01-01

    Laboratory methodology websites are specialized niche websites. The visibility of a niche website transforms it into an authority site on a particular "niche of knowledge." This article presents some ways in which a laboratory methodology website can maintain its sustainability. The optimal composition of the website includes a basic content, a blog, and an ancillary part. This article discusses experimenting with the search engine optimization query results page. Strategic placement of keywords and even phrases, as well as fragmentation of the post's material, can improve the website's visibility to search engines. Hyperlinks open a chain reaction of additional links and draw attention to the previous posts. Publications in printed periodicals are a substantial part of a niche website presence on the Internet. Although this article explores a laboratory website on the basis of our hands-on expertise maintaining "Grossing Technology in Surgical Pathology" (www.grossing-technology.com) website with a high volume of traffic for more than a decade, the recommendations presented here for developing an authority website can be applied to other professional specialized websites. The authority websites visibility and sustainability are preconditions for aggregating them in a specialized educational laboratory portal.

  14. Maintaining ancient organelles: mitochondrial biogenesis and maturation.

    Science.gov (United States)

    Vega, Rick B; Horton, Julie L; Kelly, Daniel P

    2015-05-22

    The ultrastructure of the cardiac myocyte is remarkable for the high density of mitochondria tightly packed between sarcomeres. This structural organization is designed to provide energy in the form of ATP to fuel normal pump function of the heart. A complex system comprised of regulatory factors and energy metabolic machinery, encoded by both mitochondrial and nuclear genomes, is required for the coordinate control of cardiac mitochondrial biogenesis, maturation, and high-capacity function. This process involves the action of a transcriptional regulatory network that builds and maintains the mitochondrial genome and drives the expression of the energy transduction machinery. This finely tuned system is responsive to developmental and physiological cues, as well as changes in fuel substrate availability. Deficiency of components critical for mitochondrial energy production frequently manifests as a cardiomyopathic phenotype, underscoring the requirement to maintain high respiration rates in the heart. Although a precise causative role is not clear, there is increasing evidence that perturbations in this regulatory system occur in the hypertrophied and failing heart. This review summarizes current knowledge and highlights recent advances in our understanding of the transcriptional regulatory factors and signaling networks that serve to regulate mitochondrial biogenesis and function in the mammalian heart. © 2015 American Heart Association, Inc.

  15. Chewing Maintains Hippocampus-Dependent Cognitive Function.

    Science.gov (United States)

    Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

    2015-01-01

    Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research.

  16. Maintaining heterokaryosis in pseudo-homothallic fungi.

    Science.gov (United States)

    Grognet, Pierre; Silar, Philippe

    2015-01-01

    Among all the strategies displayed by fungi to reproduce and propagate, some species have adopted a peculiar behavior called pseudo-homothallism. Pseudo-homothallic fungi are true heterothallics, i.e., they need 2 genetically-compatible partners to mate, but they produce self-fertile mycelium in which the 2 different nuclei carrying the compatible mating types are present. This lifestyle not only enables the fungus to reproduce without finding a compatible partner, but also to cross with any mate it may encounter. However, to be fully functional, pseudo-homothallism requires maintaining heterokaryosis at every stage of the life cycle. We recently showed that neither the structure of the mating-type locus nor hybrid-enhancing effect due to the presence of the 2 mating types accounts for the maintenance of heterokaryosis in the pseudo-homothallic fungus P. anserina. In this addendum, we summarize the mechanisms creating heterokaryosis in P. anserina and 2 other well-known pseudo-homothallic fungi, Neurospora tetrasperma and Agaricus bisporus. We also discuss mechanisms potentially involved in maintaining heterokaryosis in these 3 species.

  17. [Maintaining solidarity: is mutuality the solution?].

    Science.gov (United States)

    Gevers, J K M; Ploem, M C

    2013-01-01

    Solidarity is essentially the willingness to contribute to the community and its demands, which may even involve contributing more than one is expecting to receive. Another principle is mutuality: this refers to a balance between rights and obligations or between mutual obligations. In its advisory document 'The importance of mutuality......solidarity takes work!', The Dutch Council for Public Health and Health Care underlines the importance of ensuring solidarity within the Dutch health care system, e.g. by encouraging patients to take responsibility for their own health, possibly by introducing elements of mutuality. In our contribution, we comment on the Council's advice. Although we fully agree with the overall conclusion that solidarity should be maintained within the system, we do not see how the introduction of increased mutuality will contribute to this goal.

  18. Maintaining human productivity during Mars transit

    Science.gov (United States)

    Statler, Irving C.; Billings, Charles E.

    1989-01-01

    This paper addresses the special nature of the human-machine relationship during a trip to Mars. In particular, the potential for monotony and boredom during a long-duration space voyage and the effect on motivation and productivity can be important considerations to the health and welfare of the crew. For the voyage to Mars, a design may be considered that will purposefully maintain some level of workload for the crew as a preventive measure for the deterioration of productivity that comes with boredom. This paper speculates on these considerations, on the appropriate level of workload for maximum productivity, and on what might be done during the mission to alleviate the problems caused by monotony and boredom.

  19. Heartwarming memories: Nostalgia maintains physiological comfort.

    Science.gov (United States)

    Zhou, Xinyue; Wildschut, Tim; Sedikides, Constantine; Chen, Xiaoxi; Vingerhoets, Ad J J M

    2012-08-01

    Nostalgia, a sentimental longing or wistful affection for the past, is a predominantly positive and social emotion. Recent evidence suggests that nostalgia maintains psychological comfort. Here, we propose, and document in five methodologically diverse studies, a broader homeostatic function for nostalgia that also encompasses the maintenance of physiological comfort. We show that nostalgia--an emotion with a strong connotation of warmth--is triggered by coldness. Participants reported stronger nostalgia on colder (vs. warmer) days and in a cold (vs. neutral or warm) room. Nostalgia, in turn, modulates the interoceptive feeling of temperature. Higher levels of music-evoked nostalgia predicted increased physical warmth, and participants who recalled a nostalgic (vs. ordinary autobiographical) event perceived ambient temperature as higher. Finally, and consistent with the close central nervous system integration of temperature and pain sensations, participants who recalled a nostalgic (vs. ordinary autobiographical) event evinced greater tolerance to noxious cold.

  20. Human factors review of power plant maintainability

    International Nuclear Information System (INIS)

    Seminara, J.L.; Parsons, S.O.; Schmidt, W.J.; Gonzalez, W.R.; Dove, L.E.

    1980-10-01

    Human factors engineering is an interdisciplinary science and technology concerned with shaping the design of machines, facilities, and operational environments to promote safe, efficient, and reliable performance on the part of operators and maintainers of equipment systems. The human factors aspects of five nuclear power plants and four fossil fuel plants were evaluated using such methods as a checklist guided observation system, structured interviews with maintenance personnel, direct observations of maintenance tasks, reviews of procedures, and analyses of maintenance errors or accidents by means of the critical incident technique. The study revealed a wide variety of human factors problem areas, most of which are extensively photodocumented. The study recommends that a more systematic and formal approach be adopted to ensure that future power plants are human engineered to the needs of maintenance personnel

  1. Maintaining and troubleshooting your 3D printer

    CERN Document Server

    Bell, Charles

    2014-01-01

    Maintaining and Troubleshooting Your 3D Printer by Charles Bell is your guide to keeping your 3D printer running through preventive maintenance, repair, and diagnosing and solving problems in 3D printing. If you've bought or built a 3D printer such as a MakerBot only to be confounded by jagged edges, corner lift, top layers that aren't solid, or any of a myriad of other problems that plague 3D printer enthusiasts, then here is the book to help you get past all that and recapture the joy of creative fabrication. The book also includes valuable tips for builders and those who want to modify the

  2. AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

    Science.gov (United States)

    Chen, Peili; Li, Yan Chun; Toback, F Gary

    2015-01-01

    Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD). We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP)-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF)-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI) mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

  3. AMP-18 Targets p21 to Maintain Epithelial Homeostasis.

    Directory of Open Access Journals (Sweden)

    Peili Chen

    Full Text Available Dysregulated homeostasis of epithelial cells resulting in disruption of mucosal barrier function is an important pathogenic mechanism in inflammatory bowel diseases (IBD. We have characterized a novel gastric protein, Antrum Mucosal Protein (AMP-18, that has pleiotropic properties; it is mitogenic, anti-apoptotic and can stimulate formation of tight junctions. A 21-mer synthetic peptide derived from AMP-18 exhibits the same biological functions as the full-length protein and is an effective therapeutic agent in mouse models of IBD. In this study we set out to characterize therapeutic mechanisms and identify molecular targets by which AMP-18 maintains and restores disrupted epithelial homeostasis in cultured intestinal epithelial cells and a mouse model of IBD. Tumor necrosis factor (TNF-α, a pro-inflammatory cytokine known to mediate gastrointestinal (GI mucosal injury in IBD, was used to induce intestinal epithelial cell injury, and study the effects of AMP-18 on apoptosis and the cell cycle. An apoptosis array used to search for targets of AMP-18 in cells exposed to TNF-α identified the cyclin-dependent kinase inhibitor p21 WAF1/CIP1. Treatment with AMP-18 blunted increases in p21 expression and apoptosis, while reversing disturbed cell cycle kinetics induced by TNF-α. AMP-18 appears to act through PI3K/AKT pathways to increase p21 phosphorylation, thereby reducing its nuclear accumulation to overcome the antiproliferative effects of TNF-α. In vitamin D receptor-deficient mice with TNBS-induced IBD, the observed increase in p21 expression in colonic epithelial cells was suppressed by treatment with AMP peptide. The results indicate that AMP-18 can maintain and/or restore the homeostatic balance between proliferation and apoptosis in intestinal epithelial cells to protect and repair mucosal barrier homeostasis and function, suggesting a therapeutic role in IBD.

  4. Balancing selection maintains cryptic colour morphs.

    Science.gov (United States)

    Wellenreuther, Maren

    2017-11-01

    Animals display incredibly diverse colour patterns, a testament to evolution's endless innovation in shaping life. In many species, the interplay between males and females in the pursuit of mates has driven the evolution of a myriad of colour forms, from the flashy peacock tail feathers to the tiniest colour markings in damselflies. In others, colour provides crypsis by allowing to blend into the background and to escape the eyes of predators. While the obvious benefits of this dazzling diversity for reproduction and survival seem straightforward, its maintenance is not. Theory predicts that genetic drift and various forms of selection reduce variation over time, making the persistence of colour variants over generations a puzzle. In this issue of Molecular Ecology, Lindtke et al. () study the cryptic colour morphs of Timema cristinae walking sticks to shed light on the genetic architecture and mechanisms that allow colour polymorphism maintenance over long timescales. By combining genome-wide data with phenotyping information from natural populations, they were able to map the green and melanistic colour to one genomic region with highly reduced effective recombination rate between two main chromosomal variants, consistent with an inversion polymorphism. These two main chromosomal variants showed geographically widespread heterozygote excess, and genomic signatures consistent with long-term balancing selection. A younger chromosomal variant was detected for the third morph, the green-striped colour morphs, in the same genomic regions as the melanistic and the green-unstriped morphs. Together, these results suggest that the genetic architecture of cryptic T. cristinae morphs is caused by nonrecombining genomic blocks that have been maintained over extended time periods by balancing selection making this study one of the few available empirical examples documenting that balancing selection of various forms may play an important role in maintaining adaptive genetic

  5. Maintaining nuclear competence and expertise in Japan

    International Nuclear Information System (INIS)

    Fujii, Y.

    2004-01-01

    The fundamental law of atomic energy, which strictly restricts the application of atomic energy to the peaceful use, was established in 1955 in Japan. Since then, during the past five decades, great efforts were made to develop atomic energy. So far 52 units of light water reactors, 29 BWRs and 23 PWRs, have been built and in operation, 5 units are under construction and 6 units are planed to be built. Total capacity of presently operated NPPs amounts to 45.7 Gwe and the nuclear energy shares 30 % of the total electricity generation in Japan. During the past 10 years, several accidents occur in the nuclear facilities of electric power companies, and JNC ( previously PNC ). In spite of these accidents, including the accident of Kansai Electric Power Co. this year, the important role of nuclear energy to sustain the lives of people in Japan is intact. In the nuclear energy projection, the construction of NPPs continues till 2010. Thereafter reconstructions of NPPs are foreseen in the decade 2030's for the replacement of present NPPs in operation after 60 years services. Attention has been directed to the technology preservation: how competence and expertise of nuclear engineering can be maintained till the next period of replacement construction, in particular, the period between years 2010 and 2030. The present paper reviews the status of nuclear engineering programs in universities in Japan. The nuclear education programs started in graduate schools in 1957 and expanded to undergraduate schools of major national universities. Presently nine universities are providing systematic nuclear education programs in their graduate schools, although the corresponding department have been changed their names from 'nuclear' to more broaden terms of 'quantum', 'energy' and 'system' in several universities. Under the conditions of shrinking nuclear industries, how to maintain the present education system is seriously concerned matter in the universities. The present paper

  6. Maintaining Gamma Spectrometer and its challenges

    International Nuclear Information System (INIS)

    Mazlipah Mohd Ramlan; Ramzah Mohamed; Saipo Bahari Abdul Ratan

    2011-01-01

    This paper discusses the activities of the Group Maintenance of Instrumentation and Automation Center. Maintenance of group activities is to provide maintenance service on equipment at the Malaysian Nuclear Agency. Category of equipment is maintained instrumentation / nuclear electronics, scientific, analytical, security, communications, audio visual and other related. Maintenance services is to support research and development and scientific services at Nuclear Malaysia. Equipment maintenance services including repair service (CM), periodic maintenance (PM), technical testing and calibration of new devices. The objective is to ensure that maintenance activities can be the hope of an equipment, extend the life of the operation of the equipment, reducing 'down time' and reduce maintenance costs. Among the challenges in managing the maintenance of equipment in Nuclear Malaysia is the lack of expertise in specific areas such as nuclear instrumentation, analytical instruments, the problem of the inability of local suppliers to provide after-sales service, lack of spares, maintenance and nothing less emphasis on preventive maintenance schedule is perfect. (author)

  7. Sociable Robots Through Self-Maintained Energy

    Directory of Open Access Journals (Sweden)

    Trung Dung Ngo

    2006-12-01

    Full Text Available Research of autonomous mobile robots has mostly emphasized interaction and coordination that are natually inspired from biological behavior of birds, insects, and fish: flocking, foraging, collecting, and sharing. However, most research has been only focused on autonomous behaviors in order to perform robots like animals, whereas it is lacked of determinant to those behaviours: energy. Approaching to clusted amimal and the higher, collective and sharing food among individuals are major activity to keep society being. This paper issues an approach to sociable robots using self-maintained energy in cooperative mobile robots, which is dominantly inspired from swarm behavior of collecting and sharing food of honey-bee and ant. Autonomous mobile robots are usually equipped with a finite energy, thus they can operate in a finite time. To overcome the finitude, we describe practical deployment of mobile robots that are capable of carrying and exchanging fuel to other robots. Mechanism implementation including modular hardware and control architecture to demonstrate the capabicities of the approach is presented. Subsequently, the battery exchange algorithm basically based on probabilistic modeling of total energy on each robot located in its local vicinity is described. The paper is concluded with challenging works of chain of mobile robots, rescue, repair, and relation of heterogeneous robots.

  8. Sociable Robots through Self-maintained Energy

    Directory of Open Access Journals (Sweden)

    Henrik Schioler

    2008-11-01

    Full Text Available Research of autonomous mobile robots has mostly emphasized interaction and coordination that are natually inspired from biological behavior of birds, insects, and fish: flocking, foraging, collecting, and sharing. However, most research has been only focused on autonomous behaviors in order to perform robots like animals, whereas it is lacked of determinant to those behaviours: energy. Approaching to clusted amimal and the higher, collective and sharing food among individuals are major activity to keep society being. This paper issues an approach to sociable robots using self-maintained energy in cooperative mobile robots, which is dominantly inspired from swarm behavior of collecting and sharing food of honey-bee and ant. Autonomous mobile robots are usually equipped with a finite energy, thus they can operate in a finite time. To overcome the finitude, we describe practical deployment of mobile robots that are capable of carrying and exchanging fuel to other robots. Mechanism implementation including modular hardware and control architecture to demonstrate the capabicities of the approach is presented. Subsequently, the battery exchange algorithm basically based on probabilistic modeling of total energy on each robot located in its local vicinity is described. The paper is concluded with challenging works of chain of mobile robots, rescue, repair, and relation of heterogeneous robots.

  9. Survival pathways under stress

    Indian Academy of Sciences (India)

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

  10. Dual Pathways to Prospective Remembering

    Directory of Open Access Journals (Sweden)

    Mark A Mcdaniel

    2015-07-01

    Full Text Available According to the multiprocess framework (McDaniel & Einstein, 2000, the cognitive system can support prospective memory (PM retrieval through two general pathways. One pathway depends on top-down attentional control processes that maintain activation of the intention and/or monitor the environment for the triggering or target cues that indicate that the intention should be executed. A second pathway depends on (bottom-up spontaneous retrieval processes, processes that are often triggered by a PM target cue; critically spontaneous retrieval is assumed to not require monitoring or active maintenance of the intention. Given demand characteristics associated with experimental settings, however, participants are often inclined to monitor, thereby potentially masking discovery of bottom-up spontaneous retrieval processes. In this article, we discuss parameters of laboratory PM paradigms to discourage monitoring and review recent behavioral evidence from such paradigms that implicate spontaneous retrieval in PM. We then re-examine the neuro-imaging evidence from the lens of the multiprocess framework and suggest some critical modifications to existing neuro-cognitive interpretations of the neuro-imaging results. These modifications illuminate possible directions and refinements for further neuro-imaging investigations of PM.

  11. Dual pathways to prospective remembering

    Science.gov (United States)

    McDaniel, Mark A.; Umanath, Sharda; Einstein, Gilles O.; Waldum, Emily R.

    2015-01-01

    According to the multiprocess framework (McDaniel and Einstein, 2000), the cognitive system can support prospective memory (PM) retrieval through two general pathways. One pathway depends on top–down attentional control processes that maintain activation of the intention and/or monitor the environment for the triggering or target cues that indicate that the intention should be executed. A second pathway depends on (bottom–up) spontaneous retrieval processes, processes that are often triggered by a PM target cue; critically, spontaneous retrieval is assumed not to require monitoring or active maintenance of the intention. Given demand characteristics associated with experimental settings, however, participants are often inclined to monitor, thereby potentially masking discovery of bottom–up spontaneous retrieval processes. In this article, we discuss parameters of laboratory PM paradigms to discourage monitoring and review recent behavioral evidence from such paradigms that implicate spontaneous retrieval in PM. We then re-examine the neuro-imaging evidence from the lens of the multiprocess framework and suggest some critical modifications to existing neuro-cognitive interpretations of the neuro-imaging results. These modifications illuminate possible directions and refinements for further neuro-imaging investigations of PM. PMID:26236213

  12. Maintaining homeostasis by decision-making.

    Directory of Open Access Journals (Sweden)

    Christoph W Korn

    2015-05-01

    Full Text Available Living organisms need to maintain energetic homeostasis. For many species, this implies taking actions with delayed consequences. For example, humans may have to decide between foraging for high-calorie but hard-to-get, and low-calorie but easy-to-get food, under threat of starvation. Homeostatic principles prescribe decisions that maximize the probability of sustaining appropriate energy levels across the entire foraging trajectory. Here, predictions from biological principles contrast with predictions from economic decision-making models based on maximizing the utility of the endpoint outcome of a choice. To empirically arbitrate between the predictions of biological and economic models for individual human decision-making, we devised a virtual foraging task in which players chose repeatedly between two foraging environments, lost energy by the passage of time, and gained energy probabilistically according to the statistics of the environment they chose. Reaching zero energy was framed as starvation. We used the mathematics of random walks to derive endpoint outcome distributions of the choices. This also furnished equivalent lotteries, presented in a purely economic, casino-like frame, in which starvation corresponded to winning nothing. Bayesian model comparison showed that--in both the foraging and the casino frames--participants' choices depended jointly on the probability of starvation and the expected endpoint value of the outcome, but could not be explained by economic models based on combinations of statistical moments or on rank-dependent utility. This implies that under precisely defined constraints biological principles are better suited to explain human decision-making than economic models based on endpoint utility maximization.

  13. Pathways Intern Report

    Science.gov (United States)

    Huggett, Daniel James

    2017-01-01

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

  14. Neurophysiology and itch pathways.

    Science.gov (United States)

    Schmelz, Martin

    2015-01-01

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

  15. Can we safely target the WNT pathway?

    Science.gov (United States)

    Kahn, Michael

    2015-01-01

    WNT–β-catenin signalling is involved in a multitude of developmental processes and the maintenance of adult tissue homeostasis by regulating cell proliferation, differentiation, migration, genetic stability and apoptosis, as well as by maintaining adult stem cells in a pluripotent state. Not surprisingly, aberrant regulation of this pathway is therefore associated with a variety of diseases, including cancer, fibrosis and neurodegeneration. Despite this knowledge, therapeutic agents specifically targeting the WNT pathway have only recently entered clinical trials and none has yet been approved. This Review examines the problems and potential solutions to this vexing situation and attempts to bring them into perspective. PMID:24981364

  16. Community College Pathways: A Descriptive Report of Summative Assessments and Student Learning

    Science.gov (United States)

    Strother, Scott; Sowers, Nicole

    2014-01-01

    Carnegie's Community College Pathways (CCP) offers two pathways, Statway® and Quantway®, that reduce the amount of time required to complete developmental mathematics and earn college-level mathematics credit. The Pathways aim to improve student success in mathematics while maintaining rigorous content, pedagogy, and learning outcomes. It is…

  17. 33 CFR 150.555 - How must cranes be maintained?

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false How must cranes be maintained? 150.555 Section 150.555 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Operations § 150.555 How must cranes be maintained? Cranes must be operated, maintained, and tested in...

  18. Valve maintainability in CANDU-PHW nuclear generating stations

    International Nuclear Information System (INIS)

    Pothier, N.E.; Crago, W.A.

    1977-09-01

    Design, application, layout and administrative factors which affect valve maintainability in CANDU-PHW power reactors are identified and discussed. Some of these are illustrated by examples based on prototype reactor operation experience. Valve maintainability improvements resulting from laboratory development and maintainability analysis, have been incorporated in commercial CANDU-PHW nuclear generating stations. These, also, are discussed and illustrated. (author)

  19. The SUMO Pathway in Mitosis.

    Science.gov (United States)

    Mukhopadhyay, Debaditya; Dasso, Mary

    2017-01-01

    Mitosis is the stage of the cell cycle during which replicated chromosomes must be precisely divided to allow the formation of two daughter cells possessing equal genetic material. Much of the careful spatial and temporal organization of mitosis is maintained through post-translational modifications, such as phosphorylation and ubiquitination, of key cellular proteins. Here, we will review evidence that sumoylation, conjugation to the SUMO family of small ubiquitin-like modifiers, also serves essential regulatory roles during mitosis. We will discuss the basic biology of sumoylation, how the SUMO pathway has been implicated in particular mitotic functions, including chromosome condensation, centromere/kinetochore organization and cytokinesis, and what cellular proteins may be the targets underlying these phenomena.

  20. Central neural pathways for thermoregulation

    Science.gov (United States)

    Morrison, Shaun F.; Nakamura, Kazuhiro

    2010-01-01

    Central neural circuits orchestrate a homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. This review summarizes the functional organization of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for heat loss, the brown adipose tissue, skeletal muscle and heart for thermogenesis and species-dependent mechanisms (sweating, panting and saliva spreading) for evaporative heat loss. These effectors are regulated by parallel but distinct, effector-specific neural pathways that share a common peripheral thermal sensory input. The thermal afferent circuits include cutaneous thermal receptors, spinal dorsal horn neurons and lateral parabrachial nucleus neurons projecting to the preoptic area to influence warm-sensitive, inhibitory output neurons which control thermogenesis-promoting neurons in the dorsomedial hypothalamus that project to premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, that descend to provide the excitation necessary to drive thermogenic thermal effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus neurons controlling cutaneous vasoconstriction. PMID:21196160

  1. Pathways from Poverty.

    Science.gov (United States)

    Baldwin, Barbara, Ed.

    1995-01-01

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

  2. Crystallization Pathways in Biomineralization

    Science.gov (United States)

    Weiner, Steve; Addadi, Lia

    2011-08-01

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

  3. Tongue and Taste Organ Biology and Function: Homeostasis Maintained by Hedgehog Signaling.

    Science.gov (United States)

    Mistretta, Charlotte M; Kumari, Archana

    2017-02-10

    The tongue is an elaborate complex of heterogeneous tissues with taste organs of diverse embryonic origins. The lingual taste organs are papillae, composed of an epithelium that includes specialized taste buds, the basal lamina, and a lamina propria core with matrix molecules, fibroblasts, nerves, and vessels. Because taste organs are dynamic in cell biology and sensory function, homeostasis requires tight regulation in specific compartments or niches. Recently, the Hedgehog (Hh) pathway has emerged as an essential regulator that maintains lingual taste papillae, taste bud and progenitor cell proliferation and differentiation, and neurophysiological function. Activating or suppressing Hh signaling, with genetic models or pharmacological agents used in cancer treatments, disrupts taste papilla and taste bud integrity and can eliminate responses from taste nerves to chemical stimuli but not to touch or temperature. Understanding Hh regulation of taste organ homeostasis contributes knowledge about the basic biology underlying taste disruptions in patients treated with Hh pathway inhibitors.

  4. Involvement of extracellular factors in maintaining self-renewal of neural stem cell by nestin.

    Science.gov (United States)

    Di, Chun Guang; Xiang, Andy Peng; Jia, Lei; Liu, Jun Feng; Lahn, Bruce T; Ma, Bao Feng

    2014-07-09

    Nestin knockout leads to embryonic lethality and self-renewal deficiency in neural stem cells (NSCs). However, how nestin maintains self-renewal remains uncertain. Here, we used the dosage effect of nestin in heterozygous mice (Nes+/-) to study self-renewal of NSCs. With existing extracellular signaling in vivo or in vitro, nestin levels do not affect proliferation ability or apoptosis when compared between Nes+/- and Nes+/+ NSCs. However, self-renewal ability of Nes+/- NSCs is impaired when plated at a low cell density and completely lost at a clonal density. This deficiency in self-renewal at a clonal density is rescued using a medium conditioned by Nes+/+ NSCs. In addition, the Akt signaling pathway is altered at low density and reversed by conditioned medium. Our data show that secreted factors contribute toward maintaining self-renewal of NSCs by nestin, potentially through Akt signaling.

  5. Migration pathways in soils

    International Nuclear Information System (INIS)

    Gronow, J.R.

    1986-01-01

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

  6. Maintainability design and evaluation of mechanical systems based on tribology

    International Nuclear Information System (INIS)

    Wani, M.F.; Gandhi, O.P.

    2002-01-01

    Maintainability of mechanical systems based on tribology is suggested and evaluated in this paper. Tribo-features of mechanical systems, which characterise maintainability are identified and are modelled in terms of tribo-maintainability digraph. The nodes in the digraph represent the tribo-features and edges represent the degree of influence among the features. A matrix, one to one representation of the digraph, is defined to develop system maintainability expression (SPF-t) based on the tribology. It is also useful in comparing the various design alternatives from tribo-maintainability point of view. Maintainability is evaluated from the tribo-maintainability index, obtained from SPF-t (i.e. permanent of the matrix) by substituting the numerical values of the features and their interdependence. A higher value of the index implies better maintainability of the systems. The proposed methodology also guides designers in enhancing the maintainability of a system by appropriately incorporating tribo-features. An example to illustrate the methodology is also presented

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

    Lifescience Database Archive (English)

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

  8. Quadrupolar transfer pathways

    Science.gov (United States)

    Antonijevic, Sasa; Bodenhausen, Geoffrey

    2006-06-01

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

  9. HDR-Pathways

    Data.gov (United States)

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

  10. Updating the Wnt pathways

    Science.gov (United States)

    Yu, Jia; Virshup, David M.

    2014-01-01

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

  11. 33 CFR 118.5 - Penalty for failure to maintain.

    Science.gov (United States)

    2010-07-01

    ... States who fails or refuses to maintain such lights and other signals, or to obey any of the lawful rules... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Penalty for failure to maintain. 118.5 Section 118.5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY...

  12. Maintaining patients' dignity during clinical care: a qualitative interview study.

    Science.gov (United States)

    Lin, Yea-Pyng; Tsai, Yun-Fang

    2011-02-01

    This article is a report of a study undertaken to understand how nurses maintain patients' dignity in clinical practice. Dignity is a core concept in nursing care and maintaining patients' dignity is critical to their recovery. In Western countries, measures to maintain dignity in patients' care include maintaining privacy of the body, providing spatial privacy, giving sufficient time, treating patients as a whole person and allowing patients to have autonomy. However, this is an under-studied topic in Asian countries. For this qualitative descriptive study, data were collected in Taiwan in 2009 using in-depth interviews with a purposive sample of 30 nurses from a teaching hospital in eastern Taiwan. The audiotaped interviews were transcribed verbatim and analysed using content analysis. Nurses' measures to maintain dignity in patient care were captured in five themes: respect, protecting privacy, emotional support, treating all patients alike and maintaining body image. Participants did not mention beneficence, a crucial element achieved through the professional care of nurses that can enhance the recovery of patients. In-service education to help nurses enhance dignity in patient care should emphasize emotional support, maintaining body image and treating all patients alike. Our model for maintaining dignity in patient care could be used to develop a clinical care protocol for nurses to use in clinical practice. © 2010 Blackwell Publishing Ltd.

  13. A Methodology for Integrating Maintainability Using Software Metrics

    OpenAIRE

    Lewis, John A.; Henry, Sallie M.

    1989-01-01

    Maintainability must be integrated into software early in the development process. But for practical use, the techniques used must be as unobtrusive to the existing software development process as possible. This paper defines a methodology for integrating maintainability into large-scale software and describes an experiment which implemented the methodology into a major commercial software development environment.

  14. Evolving Reliability and Maintainability Allocations for NASA Ground Systems

    Science.gov (United States)

    Munoz, Gisela; Toon, T.; Toon, J.; Conner, A.; Adams, T.; Miranda, D.

    2016-01-01

    This paper describes the methodology and value of modifying allocations to reliability and maintainability requirements for the NASA Ground Systems Development and Operations (GSDO) programs subsystems. As systems progressed through their design life cycle and hardware data became available, it became necessary to reexamine the previously derived allocations. This iterative process provided an opportunity for the reliability engineering team to reevaluate allocations as systems moved beyond their conceptual and preliminary design phases. These new allocations are based on updated designs and maintainability characteristics of the components. It was found that trade-offs in reliability and maintainability were essential to ensuring the integrity of the reliability and maintainability analysis. This paper discusses the results of reliability and maintainability reallocations made for the GSDO subsystems as the program nears the end of its design phase.

  15. Maintaining dignity. The perspective of nursing home residents

    DEFF Research Database (Denmark)

    Høy, Bente

    2016-01-01

    body image; feeling recognised and valued as a person of worth; Abilities and opportunities for changing of lifevalues; to exert control; to form and maintain meaningful relationships and to participation in meaningful activity. Conclusion. Although there is no one way to maintain dignity, the themes...... dignity is maintained. Background. Elderly living in nursing homes are vulnerable which appeal to nursing care ethics and emphasise the importance of care for human dignity. There have been several attempts to define dignity as a theoretical concept, but few studies on how dignity is maintained from...... was used to understand the meaning of the narrated text. Findings. The residents’ experiences revealed one main theme and seven sub-themes contributing to maintain dignity. The overall theme was: Coping with vulnerability and the subthemes were: Attention and care for basic needs; preserving a positive...

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

    Science.gov (United States)

    Hale, Rosalind; Strutt, David

    2015-01-01

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

  17. Stress responses during ageing: molecular pathways regulating protein homeostasis.

    Science.gov (United States)

    Kyriakakis, Emmanouil; Princz, Andrea; Tavernarakis, Nektarios

    2015-01-01

    The ageing process is characterized by deterioration of physiological function accompanied by frailty and ageing-associated diseases. The most broadly and well-studied pathways influencing ageing are the insulin/insulin-like growth factor 1 signaling pathway and the dietary restriction pathway. Recent studies in diverse organisms have also delineated emerging pathways, which collectively or independently contribute to ageing. Among them the proteostatic-stress-response networks, inextricably affect normal ageing by maintaining or restoring protein homeostasis to preserve proper cellular and organismal function. In this chapter, we survey the involvement of heat stress and endoplasmic reticulum stress responses in the regulation of longevity, placing emphasis on the cross talk between different response mechanisms and their systemic effects. We further discuss novel insights relevant to the molecular pathways mediating these stress responses that may facilitate the development of innovative interventions targeting age-related pathologies such as diabetes, cancer, cardiovascular and neurodegenerative diseases.

  18. Prefoldin Promotes Proteasomal Degradation of Cytosolic Proteins with Missense Mutations by Maintaining Substrate Solubility.

    Directory of Open Access Journals (Sweden)

    Sophie A Comyn

    2016-07-01

    Full Text Available Misfolded proteins challenge the ability of cells to maintain protein homeostasis and can accumulate into toxic protein aggregates. As a consequence, cells have adopted a number of protein quality control pathways to prevent protein aggregation, promote protein folding, and target terminally misfolded proteins for degradation. In this study, we employed a thermosensitive allele of the yeast Guk1 guanylate kinase as a model misfolded protein to investigate degradative protein quality control pathways. We performed a flow cytometry based screen to identify factors that promote proteasomal degradation of proteins misfolded as the result of missense mutations. In addition to the E3 ubiquitin ligase Ubr1, we identified the prefoldin chaperone subunit Gim3 as an important quality control factor. Whereas the absence of GIM3 did not impair proteasomal function or the ubiquitination of the model substrate, it led to the accumulation of the poorly soluble model substrate in cellular inclusions that was accompanied by delayed degradation. We found that Gim3 interacted with the Guk1 mutant allele and propose that prefoldin promotes the degradation of the unstable model substrate by maintaining the solubility of the misfolded protein. We also demonstrated that in addition to the Guk1 mutant, prefoldin can stabilize other misfolded cytosolic proteins containing missense mutations.

  19. Comparing Effective Treatments for Attention-Maintained and Escape- Maintained Behaviors in Children with Behavior Disorders: Brief Review and Analysis

    OpenAIRE

    Lauren Worcester; T. F. McLaughlin

    2013-01-01

    This literature review compares treatment for attention-maintainedversus escape maintained aberrant behavior in children with behavior disorders. Specifically, studies utilizing time out procedures, differential reinforcement procedures, noncontingent reinforcement, and functional communication training are discussed. It was found that these are effective treatments for attention-maintained behaviors; while escape extinction, positive and negative reinforcement, functional communication trai...

  20. Probabilistic pathway construction.

    Science.gov (United States)

    Yousofshahi, Mona; Lee, Kyongbum; Hassoun, Soha

    2011-07-01

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

  1. Pathway-based analyses.

    Science.gov (United States)

    Kent, Jack W

    2016-02-03

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

  2. Pathways to youth homelessness.

    Science.gov (United States)

    Martijn, Claudine; Sharpe, Louise

    2006-01-01

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

  3. Developing maintainability for fusion power systems. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Zahn, H.S.; Mantz, H.C.; Curtis, C.T.; Buchheit, R.J.; Green, W.M.; Zuckerman, D.S.

    1979-11-01

    The overall purpose of the study is to identify design features of fusion power reactors which contribute to the achievement of high levels of maintainability. Previous phases evaluated several commercial tokamak reactor design concepts. This final phase compares the maintainability of a tandem mirror reactor (TMR) commercial conceptual design with the most maintainable tokamak concept selected from earlier work. A series of maintainability design guidelines and desirable TMR design features are defined. The effects of scheduled and unscheduled maintenance for most of the reactor subsystems are defined. The comparison of the TMR and tokamak reactor maintenance costs and availabilities show that both reactors have similar costs for scheduled maintenance at 19.4 and 20.8 million dollars annually and similar scheduled downtime availability impacts, achieving approximate availabilities of 79% at optimized maintenance intervals and cost of electricity.

  4. Reliability and maintainability data acquisition in equipment development tests

    International Nuclear Information System (INIS)

    Haire, M.J.; Gift, E.H.

    1983-10-01

    The need for collection of reliability, maintainability, and availability data adds a new dimension to the data acquisition requirements of equipment development tests. This report describes the reliability and maintainability data that are considered necessary to ensure that sufficient and high quality data exist for a comprehensive, quantitative evaluation of equipment and system availability. These necessary data are presented as a set of data collection forms. Three data acquisition forms are discussed: an inventory and technical data form, which is filed by the design engineer when the design is finished or the equipment is received; an event report form, which is completed by the senior test operator at each shutdown; and a maintainability report, which is a collaborative effort between senior operators and lead engineers and is completed on restart. In addition, elements of a reliability, maintainability evaluation program are described. Emphasis is placed on the role of data, its storage, and use in such a program

  5. 399 Maintaining Discipline and Orderliness in Secondary Education ...

    African Journals Online (AJOL)

    User

    2010-10-17

    Oct 17, 2010 ... complicated that most teachers find it difficult to maintain and keep their ... gang fighting, drug abuse, unrest, smoking, armed robbery, students/ ... instance, both the principals' and teachers' leadership styles can affect the.

  6. A cryogenic optical feedthrough using polarization maintaining fibers.

    Science.gov (United States)

    Nelson, M J; Collins, C J; Speake, C C

    2016-03-01

    Polarization maintaining optical fibers can be used to transmit linearly polarized light over long distances but their use in cryogenic environments has been limited by their sensitivity to temperature changes and associated mechanical stress. We investigate experimentally how thermal stresses affect the polarization maintaining fibers and model the observations with Jones matrices. We describe the design, construction, and testing of a feedthrough and fiber termination assembly that uses polarization maintaining fiber to transmit light from a 633 nm HeNe laser at room temperature to a homodyne polarization-based interferometer in a cryogenic vacuum. We report on the efficiency of the polarization maintaining properties of the feedthrough assembly. We also report that, at cryogenic temperatures, the interferometer can achieve a sensitivity of 8 × 10(-10) rad/√Hz at 0.05 Hz using this feedthrough.

  7. The Costs and Benefits of Maintaining the Buy American Act

    National Research Council Canada - National Science Library

    Hirschman, Keith

    1998-01-01

    .... The thesis uses accepted economic analysis on the gains from international trade to show that the costs of maintaining such protectionist legislation are potentially high relative to the uncertain...

  8. Developing maintainability for fusion power systems. Final report

    International Nuclear Information System (INIS)

    Zahn, H.S.; Mantz, H.C.; Curtis, C.T.; Buchheit, R.J.; Green, W.M.; Zuckerman, D.S.

    1979-11-01

    The overall purpose of the study is to identify design features of fusion power reactors which contribute to the achievement of high levels of maintainability. Previous phases evaluated several commercial tokamak reactor design concepts. This final phase compares the maintainability of a tandem mirror reactor (TMR) commercial conceptual design with the most maintainable tokamak concept selected from earlier work. A series of maintainability design guidelines and desirable TMR design features are defined. The effects of scheduled and unscheduled maintenance for most of the reactor subsystems are defined. The comparison of the TMR and tokamak reactor maintenance costs and availabilities show that both reactors have similar costs for scheduled maintenance at 19.4 and 20.8 million dollars annually and similar scheduled downtime availability impacts, achieving approximate availabilities of 79% at optimized maintenance intervals and cost of electricity

  9. Na(+) /H(+) exchanger 1 (NHE1) function is necessary for maintaining mammary tissue architecture.

    Science.gov (United States)

    Jenkins, Edmund C; Debnath, Shawon; Varriano, Sophia; Gundry, Stephen; Fata, Jimmie E

    2014-02-01

    The mammary gland is an ideal model to study the link between form and function in normal tissue. Perhaps as interesting as the cues necessary to generate this structure are the signals required to maintain its branched architecture over the lifetime of the organism, since likely these pathways are de-regulated in malignancies. Previously, we have shown that the Na(+) /H(+) exchanger 1 (NHE1), a critical regulator of intracellular pH, was necessary for mammary branching morphogenesis. Here we provide strong evidence that NHE1 function is also necessary for maintaining mammary branched architecture. Inhibition of NHE1 with 5-N-Methy-N-isobutyl amiloride (MIA) on branched structures resulted in a rapid (within 24 hr) and reversible loss of branched architecture that was not accompanied by any overt changes in cell proliferation or cell death. NHE1 inhibition led to a significant acidification of intracellular pH in the branched end buds that preceded a number of events, including altered tissue polarity of myoepithelial cells, loss of NHE1 basal polarity, F-actin rearrangements, and decreased E-cadherin expression. Our results implicate NHE1 function and intracellular pH homeostasis as key factors that maintain mammary tissue architecture, thus, indirectly allowing for mammary function as a milk-providing (form) and -producing (function) gland. Copyright © 2013 Wiley Periodicals, Inc.

  10. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    OpenAIRE

    Kosan, Christian; Godmann, Maren

    2015-01-01

    All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several trans...

  11. Policies built upon pathways

    NARCIS (Netherlands)

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

    2013-01-01

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

  12. Synthetic Metabolic Pathways

    DEFF Research Database (Denmark)

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

  13. Dexter energy transfer pathways.

    Science.gov (United States)

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

    2016-07-19

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

  14. Compliance evaluation of removable space maintainer or space regainer usage

    Directory of Open Access Journals (Sweden)

    Revanti Ramadhani

    2018-01-01

    Full Text Available Premature loss could cause a problem with the tooth arrangement or the dental arch size. A space left by the primary tooth loss could cause migration of the adjacent teeth. As a result, space will be narrowed and undermined the eruption of the permanent teeth. The success of the space maintainer or space regainer usage due to the premature loss marked by space for the replacement of the permanent teeth. The purpose of this research was to evaluate the compliance of children in wearing a space maintainer or space regainer after insertion at Pedodontics Installation of Faculty of Dentistry Universitas Padjadjaran Dental Hospital, Bandung, Indonesia. The research method was descriptive survey technique. The sample consisted of 30 patients selected using the total sampling technique. Data were obtained with a questionnaire and statistically analyzed. The results showed that majority of the children uses the removable space maintainer or the space regainer daily was only about 23,3% overall. Most of the children only use the removable space maintainer or the space regainer for sometimes. The research concluded that the low rate of pedodontic patients compliance at Pedodontics Installation of Faculty of Dentistry Universitas Padjadjaran Dental Hospital in the usage of the removable space maintainer or the space regainer was usually caused by pain or discomfort. This fact was evidence of a low awareness of parents in preventing malocclusion to their children.

  15. STRATEGIES OF MAINTAINING PROFICIENCY BY TEACHERS OF ENGLISH IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Junaidi Mistar, Alfan Zuhairini

    2011-10-01

    Full Text Available The objectives of the present study are four-fold: (1 to identify the types of strategies to maintain proficiency used by teachers of English in Indonesia, (2 to know the intensity of use of the obtained strategy types, (3 to measure the inter-correlation in the use of the obtained strategy types, and (4 to investigate the effect of proficiency level on the use of maintaining strategies. The subjects were 93 teachers applying for S2 degree in 2010/2011 at the postgraduate program of the Islamic University of Malang. They were given two sets of instrument, a Likert-scale questionnaire of English proficiency maintaining strategies and a TOEFL test. Then, a factor analysis identified nine strategy categories, including language focusing, metacognitive and affective developing, reading and writing activating, language resource utilizing, cognitive processing, culture learning, social communicating, text analyzing, and radio listening strategies. These strategy types explained 63.84% of variances of maintaining strategies and they were used at high level of intensity. Moreover, the use of the nine strategy types were found to be inter-correlated with one another. Finally, no significant effect of proficiency level on strategy use was found, indicating that teachers with different level of proficiency reported using the same strategies of maintaining their proficiency.

  16. PathwayAccess: CellDesigner plugins for pathway databases.

    Science.gov (United States)

    Van Hemert, John L; Dickerson, Julie A

    2010-09-15

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

  17. Rwanda Economic Update, May 2013 : Maintaining Momentum with a Special Focus on Rwanda's Pathway Out of Poverty

    OpenAIRE

    World Bank

    2013-01-01

    The Rwanda economic update reports and synthesizes recent economic developments and places them in a medium term and global context. It analyzes the implications of these developments and policies for the outlook of Rwanda's economy. In this way, these reports contribute to the implementation of the Bank's Africa strategy. The economic update reports cover in each edition a special feature...

  18. Challenges of designing fusion reactors for remote maintainability

    International Nuclear Information System (INIS)

    Mason, L.S.

    1981-01-01

    One of the major problems faced by the fusion community is the development of the high level of reliability required to assure that fusion will be a viable commercial power source. Much of the responsibility for solving this problem falls directly on the designer in developing concepts that have a high level of maintainability. The problems are both near-term, in developing maintainability for next generation engineering oriented reactors; and long range, in developing full maintainability for the more commercial concepts with their required high level of on-line time. The near-time challenge will include development of unqiue design concepts to perform inspection, maintenance, replacement, and testing under the stringent conditions imposed by the next generation engineering oriented machines. The long range challenge will focus on basic design concepts that will enable the full mainatability required by commerical fusion

  19. Advanced remotely maintainable force-reflecting servomanipulator concept

    International Nuclear Information System (INIS)

    Kuban, D.P.; Martin, H.L.

    1984-01-01

    A remotely maintainable force-reflecting servomanipulator concept is being developed at the Oak Ridge National Laboratory as part of the Consolidated Fuel Reprocessing Program. This new manipulator addresses requirements of advanced nuclear fuel reprocessing with emphasis on force reflection, remote maintainability, reliability, radiation tolerance, and corrosion resistance. The advanced servomanipulator is uniquely subdivided into remotely replaceable modules which will permit in situ manipulator repair by spare module replacement. Manipulator modularization and increased reliability are accomplished through a force transmission system that uses gears and torque tubes. Digital control algorithms and mechanical precision are used to offset the increased backlash, friction, and inertia resulting from the gear drives. This results in the first remotely maintainable force-reflecting servomanipulator in the world. 10 references, 4 figures, 1 table

  20. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    Science.gov (United States)

    Kosan, Christian; Godmann, Maren

    2016-01-01

    All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC) have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function. PMID:26798358

  1. Microenvironment Dependent Photobiomodulation on Function-Specific Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    Timon Cheng-Yi Liu

    2014-01-01

    Full Text Available Cellular photobiomodulation on a cellular function has been shown to be homeostatic. Its function-specific pathway mechanism would be further discussed in this paper. The signal transduction pathways maintaining a normal function in its function-specific homeostasis (FSH, resisting the activation of many other irrelative signal transduction pathways, are so sparse that it can be supposed that there may be normal function-specific signal transduction pathways (NSPs. A low level laser irradiation or monochromatic light may promote the activation of partially activated NSP and/or its redundant NSP so that it may induce the second-order phase transition of a function from its dysfunctional one far from its FSH to its normal one in a function-specific microenvironment and may also induce the first-order functional phase transition of the normal function from low level to high level.

  2. Maintainability design criteria for packaging of spacecraft replaceable electronic equipment.

    Science.gov (United States)

    Kappler, J. R.; Folsom, A. B.

    1972-01-01

    Maintainability must be designed into long-duration spacecraft and equipment to provide the required high probability of mission success with the least cost and weight. The ability to perform repairs quickly and easily in a space environment can be achieved by imposing specific maintainability design criteria on spacecraft equipment design and installation. A study was funded to investigate and define design criteria for electronic equipment that would permit rapid removal and replacement in a space environment. The results of the study are discussed together with subsequent simulated zero-g demonstration tests of a mockup with new concepts for packaging.

  3. Pathway analysis of IMC

    DEFF Research Database (Denmark)

    Skrypnyuk, Nataliya; Nielson, Flemming; Pilegaard, Henrik

    2009-01-01

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

  4. Aquatic pathway 2

    International Nuclear Information System (INIS)

    1977-01-01

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

  5. Pathways to diversification

    OpenAIRE

    Al Hashemi, Hamed

    2016-01-01

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

  6. The Glymphatic Pathway.

    Science.gov (United States)

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

    2017-01-01

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

  7. Working memory benefits creative insight, musical improvisation, and original ideation through maintained task-focused attention.

    Science.gov (United States)

    De Dreu, Carsten K W; Nijstad, Bernard A; Baas, Matthijs; Wolsink, Inge; Roskes, Marieke

    2012-05-01

    Anecdotes from creative eminences suggest that executive control plays an important role in creativity, but scientific evidence is sparse. Invoking the Dual Pathway to Creativity Model, the authors hypothesize that working memory capacity (WMC) relates to creative performance because it enables persistent, focused, and systematic combining of elements and possibilities (persistence). Study 1 indeed showed that under cognitive load, participants performed worse on a creative insight task. Study 2 revealed positive associations between time-on-task and creativity among individuals high but not low in WMC, even after controlling for general intelligence. Study 3 revealed that across trials, semiprofessional cellists performed increasingly more creative improvisations when they had high rather than low WMC. Study 4 showed that WMC predicts original ideation because it allows persistent (rather than flexible) processing. The authors conclude that WMC benefits creativity because it enables the individual to maintain attention focused on the task and prevents undesirable mind wandering.

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

    Science.gov (United States)

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

    2012-01-01

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

  9. Smoke considerations for using fire in maintaining healthy forest ecosystems

    Science.gov (United States)

    Roger D. Ottmar; Mark D. Schaaf; Ernesto Alvarado

    1996-01-01

    Fire is the single most important ecological disturbance process throughout the interior Pacific Northwest (Mutch and others 1993; Agee 1994). It is also a natural process that helps maintain a diverse ecological landscape. Fire suppression and timber harvesting have drastically altered this process during the past 50 to 90 years. Natural resource specialists generally...

  10. JWIG: Yet Another Framework for Maintainable and Secure Web Applications

    DEFF Research Database (Denmark)

    Møller, Anders; Schwarz, Mathias Romme

    2009-01-01

    Although numerous frameworks for web application programming have been developed in recent years, writing web applications remains a challenging task. Guided by a collection of classical design principles, we propose yet another framework. It is based on a simple but flexible server-oriented arch...... services.The resulting framework provides a novel foundation for developing maintainable and secure web applications....

  11. 44 CFR 321.3 - Maintaining the mobilization base.

    Science.gov (United States)

    2010-10-01

    ... base. 321.3 Section 321.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS MAINTENANCE OF THE MOBILIZATION BASE (DEPARTMENT OF DEFENSE, DEPARTMENT OF ENERGY, MARITIME ADMINISTRATION) § 321.3 Maintaining the mobilization base. (a) Facilities...

  12. Maintaining connections in children's grief narratives in popular film.

    Science.gov (United States)

    Sedney, Mary Anne

    2002-04-01

    Children's grief narratives in popular films were examined for their portrayal of connection-maintaining strategies with the deceased. Comparisons were made between strategies found in actual parentally bereaved children and in child characters in films. Implications of these filmed grief narratives for models of grieving and for practice are discussed.

  13. Maintaining a Cybersecurity Curriculum: Professional Certifications as Valuable Guidance

    Science.gov (United States)

    Knapp, Kenneth J.; Maurer, Christopher; Plachkinova, Miloslava

    2017-01-01

    Much has been published about developing a cybersecurity curriculum for institutes of higher learning (IHL). Now that a growing number of IHLs globally offer such programs, a need exists on how to guide, maintain, and improve the relevancy of existing curricula. Just as cybersecurity professionals must be hone their skills continually to keep with…

  14. Declarative versus imperative process modeling languages : the issue of maintainability

    NARCIS (Netherlands)

    Fahland, D.; Mendling, J.; Reijers, H.A.; Weber, B.; Weidlich, M.; Zugal, S.; Rinderle-Ma, S.; Sadiq, S.; Leymann, F.

    2010-01-01

    The rise of interest in declarative languages for process modeling both justifies and demands empirical investigations into their presumed advantages over more traditional, imperative alternatives. Our concern in this paper is with the ease of maintaining business process models, for example due to

  15. Maintaining public confidence in UK nuclear safety regulation

    International Nuclear Information System (INIS)

    Williams, L.

    2001-01-01

    The key to maintaining stake holder confidence is competence and having the resources necessary to not only carry out regulatory functions effectively, but also to keep the public informed and respond to their questions. This does not come cheap but it is a price well worth paying. (N.C.)

  16. Genetic and somatic effects in animals maintained on tritiated water

    International Nuclear Information System (INIS)

    Carsten, A.L.; Brooks, A.; Commerford, S.L.; Cronkite, E.P.

    1981-01-01

    The possible genetic (dominant lethal mutations (DLM) and cytogenetic changes in the regenerating liver) and somatic (hematopoietic stem cell changes, growth and nonspecific life time shortening) effects in mice maintained on tritiated water (HTO) over two generations was investigated. Results to date are summarized

  17. 4 CFR 200.11 - Maintaining records of disclosure.

    Science.gov (United States)

    2010-01-01

    ... the Freedom of Information Act (5 U.S.C. 552). (b) An accounting of each disclosure shall be retained..., whichever is longer. (c) The Board shall make the accounting of disclosure of a record pertaining to an... 4 Accounts 1 2010-01-01 2010-01-01 false Maintaining records of disclosure. 200.11 Section 200.11...

  18. Maintaining the power balance in an "empty network"

    NARCIS (Netherlands)

    Reza, M.; Dominguez, A.O.; Schavemaker, P.H.; Kling, W.L.

    2006-01-01

    This paper presents the concept of an empty network and shows how the power balance can be maintained in such a system. In this study, an empty network is defined as a power system in which no rotating mass is present; all generators are grid-connected via power electronic interfaces. One generator

  19. Maintaining of the demineralized water quality in storage tanks

    International Nuclear Information System (INIS)

    Hochmueller, K.; Wandelt, E.

    1981-03-01

    Two processes for maintaining the quality of the mineralized water in storage tanks are considered. A slight overpressure of nitrogen can be created above the water, or the air flowing in the tank can be cleaned by passing it through a soda-containing lime filter [fr

  20. Sponsored Grant-maintained Schools: Extending the Franchise?

    Science.gov (United States)

    Walford, Geoffrey

    1997-01-01

    Discusses the introduction and implementation of the 1988 Education Reform Act for England and Wales. Traces the attempts of several existing private schools to become grant maintained (eligible for various forms of government support). Most private and faith-based schools have not been successful in this endeavor. Discusses the reasons for this.…

  1. Maintaining and restoring sustainable ecosystems in southern Nevada [Chapter 7

    Science.gov (United States)

    Jeanne C. Chambers; Burton K. Pendleton; Donald W. Sada; Steven M. Ostoja; Matthew L. Brooks

    2013-01-01

    Managers in southern Nevada are challenged with determining appropriate goals and objectives and developing viable approaches for maintaining and restoring sustainable ecosystems in a time of rapid socio-ecological and environmental change. Sustainable or “healthy” ecosystems supply clean air, water and habitat for a diverse array of plants and animals. As described in...

  2. Impact of Agile Software Development Model on Software Maintainability

    Science.gov (United States)

    Gawali, Ajay R.

    2012-01-01

    Software maintenance and support costs account for up to 60% of the overall software life cycle cost and often burdens tightly budgeted information technology (IT) organizations. Agile software development approach delivers business value early, but implications on software maintainability are still unknown. The purpose of this quantitative study…

  3. The evaluation of kikuyu foggage for maintaining dry ewes

    African Journals Online (AJOL)

    DeVilliersJ

    flow programme to maintain dry ewes during the winter in a system where their lambs were weaned onto .... IVDOM of the combined values of the January and February oesophageal and hand-cut foggage samples and ... The ability of the grazing animal to select material of higher quality than hand-cut samples of the.

  4. 19 CFR 115.12 - Records maintained by Certifying Authority.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Records maintained by Certifying Authority. 115.12 Section 115.12 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CARGO CONTAINER AND ROAD VEHICLE CERTIFICATION PURSUANT TO INTERNATIONAL CUSTOMS...

  5. Oct-4 expression maintained stem cell properties in prostate cancer ...

    African Journals Online (AJOL)

    Erah

    Keywords: Prostate cancer, Cancer stem-like cells, Oct-4, CD133, Multi-drug resistance1 (MDR1). Received: 7 ... mechanisms in maintaining the self-renewal and drug resistant ... (platelet-derived growth factor α receptor). This suggests that ...

  6. Banded vs Bonded Space Maintainers: Finding Better Way Out.

    Science.gov (United States)

    Setia, Vikas; Kumar Pandit, Inder; Srivastava, Nikhil; Gugnani, Neeraj; Gupta, Monika

    2014-05-01

    Of this in vivo study was to evaluate various space maintainers in terms of survival rate, gingival health and presence of caries. A total of 60 extraction sites in the age group of 4 to 9 years were divided into four groups and different space maintainers were placed in them viz (conventional band and loop, prefabricated band with custom made loop, Ribbond, Super splint). Prefabricated bands with custom made loop showed maximum success rates (84.6%), while super splint (33.33%) was found to be least successful. In terms of gingival health, prefabricated band with custom made loop reported minimum cases with poor gingival health (27.2%), while maximum cases with poor gingival health (50%) were reported with Super splint. None of the space maintainers developed caries at the end of 9 months. How to cite this article: Setia v, Pandit IK, Srivastava N, Gugnani N, Gupta M. Banded vs Bonded Space Maintainers: Finding Better Way Out. Int J Clin Pediatr Dent 2014;7(2):97-104.

  7. A Platform for Developing and Maintaining Competences in PBL Supervision

    DEFF Research Database (Denmark)

    Gnaur, Dorina; Huttel, Hans

    2017-01-01

    One of the emerging challenges in academia is that of developing and maintaining teaching qualifications in a setting where teaching staff is often temporary and with diverse backgrounds. At Aalborg University, project-organized problem-based learning is at the heart of all degree programmes...

  8. Maintaining Continuity of Knowledge of Spent Fuel Pools: Tool Survey

    Energy Technology Data Exchange (ETDEWEB)

    Benz, Jacob M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Smartt, Heidi A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Tanner, Jennifer E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); MacDougall, Matthew R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-08-30

    This report examines supplemental tools that can be used in addition to optical surveillance cameras to maintain CoK in low-to-no light conditions, and increase the efficiency and effectiveness of spent fuel CoK, including item counting and ID verification, in challenging conditions.

  9. Contribution of maintainability and maintenance to problems of safety evaluation

    International Nuclear Information System (INIS)

    Adnot, Serge; Meriaux, Pierre.

    1977-10-01

    A method has been developed for defining the contribution of Maintainability and the Maintenance Studies to Safety evaluation problems. The efficiency of this method is shown and results obtained are given for two theoretical examples approximating reality. For repairable systems, the risk defined according to such given safety criterion, becomes a characteristic of the systems in operation [fr

  10. Maintaining excellence in teaching of human anatomy: University of ...

    African Journals Online (AJOL)

    Measures to address these challenges have resulted in wide disparities in curriculum design teaching methods, number and composition of instructors. Inspite of the challenges, the Department of Human Anatomy of the University of Nairobi (UON) maintained excellence of teaching for over 40yrs. This article describes the ...

  11. Characterization of cyanobacterial hydrocarbon composition and distribution of biosynthetic pathways.

    Directory of Open Access Journals (Sweden)

    R Cameron Coates

    Full Text Available Cyanobacteria possess the unique capacity to naturally produce hydrocarbons from fatty acids. Hydrocarbon compositions of thirty-two strains of cyanobacteria were characterized to reveal novel structural features and insights into hydrocarbon biosynthesis in cyanobacteria. This investigation revealed new double bond (2- and 3-heptadecene and methyl group positions (3-, 4- and 5-methylheptadecane for a variety of strains. Additionally, results from this study and literature reports indicate that hydrocarbon production is a universal phenomenon in cyanobacteria. All cyanobacteria possess the capacity to produce hydrocarbons from fatty acids yet not all accomplish this through the same metabolic pathway. One pathway comprises a two-step conversion of fatty acids first to fatty aldehydes and then alkanes that involves a fatty acyl ACP reductase (FAAR and aldehyde deformylating oxygenase (ADO. The second involves a polyketide synthase (PKS pathway that first elongates the acyl chain followed by decarboxylation to produce a terminal alkene (olefin synthase, OLS. Sixty-one strains possessing the FAAR/ADO pathway and twelve strains possessing the OLS pathway were newly identified through bioinformatic analyses. Strains possessing the OLS pathway formed a cohesive phylogenetic clade with the exception of three Moorea strains and Leptolyngbya sp. PCC 6406 which may have acquired the OLS pathway via horizontal gene transfer. Hydrocarbon pathways were identified in one-hundred-forty-two strains of cyanobacteria over a broad phylogenetic range and there were no instances where both the FAAR/ADO and the OLS pathways were found together in the same genome, suggesting an unknown selective pressure maintains one or the other pathway, but not both.

  12. Protein degradation pathways in Parkinson's disease: curse or blessing.

    Science.gov (United States)

    Ebrahimi-Fakhari, Darius; Wahlster, Lara; McLean, Pamela J

    2012-08-01

    Protein misfolding, aggregation and deposition are common disease mechanisms in many neurodegenerative diseases including Parkinson's disease (PD). Accumulation of damaged or abnormally modified proteins may lead to perturbed cellular function and eventually to cell death. Thus, neurons rely on elaborated pathways of protein quality control and removal to maintain intracellular protein homeostasis. Molecular chaperones, the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP) are critical pathways that mediate the refolding or removal of abnormal proteins. The successive failure of these protein degradation pathways, as a cause or consequence of early pathological alterations in vulnerable neurons at risk, may present a key step in the pathological cascade that leads to spreading neurodegeneration. A growing number of studies in disease models and patients have implicated dysfunction of the UPS and ALP in the pathogenesis of Parkinson's disease and related disorders. Deciphering the exact mechanism by which the different proteolytic systems contribute to the elimination of pathogenic proteins, like α-synuclein, is therefore of paramount importance. We herein review the role of protein degradation pathways in Parkinson's disease and elaborate on the different contributions of the UPS and the ALP to the clearance of altered proteins. We examine the interplay between different degradation pathways and provide a model for the role of the UPS and ALP in the evolution and progression of α-synuclein pathology. With regards to exciting recent studies we also discuss the putative potential of using protein degradation pathways as novel therapeutic targets in Parkinson's disease.

  13. Mechanical properties of different types of space maintainers

    Science.gov (United States)

    Beldiman, M.-A.; Mârţu, I.; Leiţoiu, B.; Luchian, I.; Lupescu, O.; Bârcă, E. S.

    2015-11-01

    Currently, inside the oral cavity, the dental space maintainers are subjected to forces exerted on them when performing various functions; therefore, it is important to know how each of these mechanisms behave and respond to forces that are applied directly to them. The mechanical properties of the materials used in dentistry are defined by a set of characteristics representing the behaviour of their particular working conditions and it is qualitatively expressed by a number of parameters.The study aimed to determine the pressing force that can be taken by four 4 types of space maintainers frequently used in practice - fixed and removable, applied on four samples realized with human teeth extracted for orthodontic purposes. Static tests were carried out on a machine type short WDW-5 EC with a maximum force of 5 kN and a loading speed of 5 mm/min by a special testing machine, with an innovative appliance; data recording was automatically performed, using a computer with a special program that present the specific diagrams. Experimental determinations included the following aspects: to determine the maximum force that can be supported by each sample, and to observe the deformations. The values obtained indicate that the best option in terms of behavior under the conditions specified is the removable appliance, and the less functional version is the fixed space maintainer using brackets. According to tests conducted, the fracture strength was found to be more important for fixed space maintainers (band and loop, for example) so, in practice is using more frequent these types of space maintainers.

  14. Dicer maintains the identity and function of proprioceptive sensory neurons.

    Science.gov (United States)

    O'Toole, Sean M; Ferrer, Monica M; Mekonnen, Jennifer; Zhang, Haihan; Shima, Yasuyuki; Ladle, David R; Nelson, Sacha B

    2017-03-01

    Neuronal cell identity is established during development and must be maintained throughout an animal's life (Fishell G, Heintz N. Neuron 80: 602-612, 2013). Transcription factors critical for establishing neuronal identity can be required for maintaining it (Deneris ES, Hobert O. Nat Neurosci 17: 899-907, 2014). Posttranscriptional regulation also plays an important role in neuronal differentiation (Bian S, Sun T. Mol Neurobiol 44: 359-373, 2011), but its role in maintaining cell identity is less established. To better understand how posttranscriptional regulation might contribute to cell identity, we examined the proprioceptive neurons in the dorsal root ganglion (DRG), a highly specialized sensory neuron class, with well-established properties that distinguish them from other neurons in the ganglion. By conditionally ablating Dicer in mice, using parvalbumin (Pvalb)-driven Cre recombinase, we impaired posttranscriptional regulation in the proprioceptive sensory neuron population. Knockout (KO) animals display a progressive form of ataxia at the beginning of the fourth postnatal week that is accompanied by a cell death within the DRG. Before cell loss, expression profiling shows a reduction of proprioceptor specific genes and an increased expression of nonproprioceptive genes normally enriched in other ganglion neurons. Furthermore, although central connections of these neurons are intact, the peripheral connections to the muscle are functionally impaired. Posttranscriptional regulation is therefore necessary to retain the transcriptional identity and support functional specialization of the proprioceptive sensory neurons. NEW & NOTEWORTHY We have demonstrated that selectively impairing Dicer in parvalbumin-positive neurons, which include the proprioceptors, triggers behavioral changes, a lack of muscle connectivity, and a loss of transcriptional identity as observed through RNA sequencing. These results suggest that Dicer and, most likely by extension, micro

  15. Nutrient sensing via mTOR in T cells maintains a tolerogenic microenvironment

    Directory of Open Access Journals (Sweden)

    Duncan eHowie

    2014-08-01

    Full Text Available We have proposed that tolerance can be maintained by the induction, by Treg cells, of a tolerogenic microenvironment within tolerated tissues that inhibits effector cell activity but which supports the generation of further Treg cells by infectious tolerance. Two important components of this tolerogenic microenvironment depend on metabolism and nutrient sensing. The first is due to the up-regulation of multiple enzymes that consume essential amino acids (EAAs, which are sensed in naive T cells primarily via inhibition of the mTOR pathway, which in turn encourages their further differentiation into foxp3+ Treg cells. The second mechanism is the metabolism of extracellular ATP to adenosine by the ectoenzymes CD39 and CD73. These two enzymes are constitutively co-expressed on Treg cells, but can also be induced on a wide variety of cell types by TGFbeta and the adenosine generated can be shown to be a potent inhibitor of T cell proliferation. This review will focus on mechanisms of nutrient sensing in T cells, how these are integrated with TCR and cytokine signals via the mnTOR pathway, and what impact this has on intracellular metabolism and subsequently the control of differentiation into different effector or regulatory T cell subsets.

  16. A computational platform to maintain and migrate manual functional annotations for BioCyc databases.

    Science.gov (United States)

    Walsh, Jesse R; Sen, Taner Z; Dickerson, Julie A

    2014-10-12

    BioCyc databases are an important resource for information on biological pathways and genomic data. Such databases represent the accumulation of biological data, some of which has been manually curated from literature. An essential feature of these databases is the continuing data integration as new knowledge is discovered. As functional annotations are improved, scalable methods are needed for curators to manage annotations without detailed knowledge of the specific design of the BioCyc database. We have developed CycTools, a software tool which allows curators to maintain functional annotations in a model organism database. This tool builds on existing software to improve and simplify annotation data imports of user provided data into BioCyc databases. Additionally, CycTools automatically resolves synonyms and alternate identifiers contained within the database into the appropriate internal identifiers. Automating steps in the manual data entry process can improve curation efforts for major biological databases. The functionality of CycTools is demonstrated by transferring GO term annotations from MaizeCyc to matching proteins in CornCyc, both maize metabolic pathway databases available at MaizeGDB, and by creating strain specific databases for metabolic engineering.

  17. Aquatic pathway 1

    International Nuclear Information System (INIS)

    1976-01-01

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

  18. The Reactome pathway knowledgebase.

    Science.gov (United States)

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

    2014-01-01

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

  19. Cultural pathways through universal development.

    Science.gov (United States)

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

    2003-01-01

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

  20. Care and management of a stoma: maintaining peristomal skin health.

    Science.gov (United States)

    Boyles, Anna; Hunt, Sharon

    2016-09-22

    It is estimated that around one in 500 people in the UK are living with a stoma, with approximately 21 000 operations that result in stoma formation being performed each year ( Colostomy Association, 2016 ). These people face a unique set of challenges in maintaining the integrity of their peristomal skin. This article explores the normal structure and function of skin and how the care and management of a stoma presents challenges for maintaining peristomal skin health. Particular focus is paid to the incidence of skin problems for those living with a stoma, whether it is temporary or permanent, and the factors that contribute to skin breakdown in this population. Wider factors such as the central role of the clinical nurse specialist and the impact of product usage on positive outcomes and health economics are also considered.

  1. Application of Ultrasonic Waves on Maintaining Freshness of Tilapia Fillet

    Directory of Open Access Journals (Sweden)

    Ruddy Suwandi

    2015-06-01

    Full Text Available ish fillet is one of fisheries products that easily deteriorated; hence handling techniques are needed to maintain the freshness. Ultrasonic wave have been widely applied to some of food products for maintaining freshness through microbial inactivation, however the ultrasonic application to fisheries products has not been reported. The purpose of this study was to analyze the effect of ultrasonic wave on fish freshness. The stages of the study were sample preparation, sonication, freshness parameters examination and histology observation. Ultrasonic wave did not affectthe organoleptic value and the TVB, but affected the pH value and the TPC. The sample in which the TPC value was found significantly different, were further observed after 48 and 96 hours storage. The result showed that the TPC value of sonicated sample for 9 minutes was lower to that of without sonication. Histology analysis showed, however, sonication made the structure of muscle fiber less compact and deformation of myomer was found.

  2. Understanding how to maintain compliance in the current regulatory climate

    International Nuclear Information System (INIS)

    Bignell, D.T.; Burns, R.

    1995-01-01

    High level radioactive waste facilities must maintain compliance with all regulatory requirements, even those requirements that have been promulgated after the facility was placed into operation. Facilities must aggressively pursue compliance because environmental laws often impose strict liability for violations; therefore, an honest mistake is no defense. Radioactive waste management is constantly under the public microscope, particularly those facilities that handle high-level radioactive waste. The Savannah River Site has effectively met the challenges of regulatory compliance in its HLRW facilities and plans are being formulated to meet future regulatory requirements as well. Understanding, aggressively achieving, and clearly demonstrating compliance is essential for the continued operations of radioactive waste management facilities. This paper examines how HLRW facilities are impacted by regulatory requirements and how compliance in this difficult area is achieved and maintained

  3. Maintaining students’ Speaking Fluency through Exhibition Examination in Sociolinguistic Studies

    Directory of Open Access Journals (Sweden)

    Khusnul Qhotimah Yuliatuty

    2013-07-01

    Full Text Available Using exhibition for the final project in Sociolinguistic study is really interesting for Universitas Siswa Bangsa Internasional students, especially for 2011 English Department students. Exhibition becomes interesting because this is the new thing to conduct the final project for English Department students’ cohort 2011 at Universitas Siswa Bangsa Internasional. The lecturer divides the students into pairs and each pairs should master one content or topic in Sociolinguistic study.  The students will do the exhibition about the topic that they get in a pairs. The lecturer also gives the students rubric sheet to fill by the visitors. The exhibition will make the students prepare themselves well because they will face many questions about the content which will be delivered by them. Beside, this exhibition also maintains students’ fluency in speaking English because they will explain and answer the questions from visitors with English. This paper tries to focus on how exhibition examination can maintain students’ fluency in speaking English.

  4. The Role of Leptin in Maintaining Plasma Glucose During Starvation.

    Science.gov (United States)

    Perry, Rachel J; Shulman, Gerald I

    2018-03-01

    For 20 years it has been known that concentrations of leptin, a hormone produced by the white adipose tissue (WAT) largely in proportion to body fat, drops precipitously with starvation, particularly in lean humans and animals. The role of leptin to suppress the thyroid and reproductive axes during a prolonged fast has been well defined; however, the impact of leptin on metabolic regulation has been incompletely understood. However emerging evidence suggests that, in starvation, hypoleptinemia increases activity of the hypothalamic-pituitary-adrenal axis, promoting WAT lipolysis, increasing hepatic acetyl-CoA concentrations, and maintaining euglycemia. In addition, leptin may be largely responsible for mediating a shift from a reliance upon glucose metabolism (absorption and glycogenolysis) to fat metabolism (lipolysis increasing gluconeogenesis) which preserves substrates for the brain, heart, and other critical organs. In this way a leptin-mediated glucose-fatty acid cycle appears to maintain glycemia and permit survival in starvation.

  5. Reciprocity and the Tragedies of Maintaining and Providing the Commons.

    Science.gov (United States)

    Gächter, Simon; Kölle, Felix; Quercia, Simone

    2017-09-01

    Social cooperation often requires collectively beneficial but individually costly restraint to maintain a public good1-4, or it needs costly generosity to create one1,5. Status quo effects6 predict that maintaining a public good is easier than providing a new one. Here we show experimentally and with simulations that even under identical incentives, low levels of cooperation (the 'tragedy of the commons'2) are systematically more likely in Maintenance than Provision. Across three series of experiments, we find that strong and weak positive reciprocity, known to be fundamental tendencies underpinning human cooperation7-10, are substantially diminished under Maintenance compared to Provision. As we show in a fourth experiment, the opposite holds for negative reciprocity ('punishment'). Our findings suggest that incentives to avoid the 'tragedy of the commons' need to contend with dilemma-specific reciprocity.

  6. Creating and maintaining chemical artificial life by robotic symbiosis

    DEFF Research Database (Denmark)

    Hanczyc, Martin M.; Parrilla, Juan M.; Nicholson, Arwen

    2015-01-01

    We present a robotic platform based on the open source RepRap 3D printer that can print and maintain chemical artificial life in the form of a dynamic, chemical droplet. The robot uses computer vision, a self-organizing map, and a learning program to automatically categorize the behavior of the d......We present a robotic platform based on the open source RepRap 3D printer that can print and maintain chemical artificial life in the form of a dynamic, chemical droplet. The robot uses computer vision, a self-organizing map, and a learning program to automatically categorize the behavior...... confluence of chemical, artificial intelligence, and robotic approaches to artificial life....

  7. Creating and Maintaining Chemical Artificial Life by Robotic Symbiosis

    DEFF Research Database (Denmark)

    Hanczyc, Martin; Parrilla, Juan M.; Nicholson, Arwen

    2015-01-01

    We present a robotic platform based on the open source RepRap 3D printer that can print and maintain chemical artificial life in the form of a dynamic, chemical droplet. The robot uses computer vision, a self-organizing map, and a learning program to automatically categorize the behavior of the d......We present a robotic platform based on the open source RepRap 3D printer that can print and maintain chemical artificial life in the form of a dynamic, chemical droplet. The robot uses computer vision, a self-organizing map, and a learning program to automatically categorize the behavior...... confluence of chemical, artificial intelligence, and robotic approaches to artificial life....

  8. The importance of university research in maintaining the nuclear option

    International Nuclear Information System (INIS)

    Bruschi, H.J.; Hochreiter, L.E.

    1991-01-01

    The role of the university in maintaining and revitalizing the nuclear option should have four goals. First, it must attract highly skilled students who have an interest in math and science and help foster their interest in nuclear science and engineering. Next, it must present a state-of-the-art educational program that contains meaningful research to maintain these students. The third goal of nuclear engineering departments is to provide the nontechnical student a fair assessment of benefits and risks associated with commercial nuclear power relative to other sources of electricity. Lastly, it must effectively communicate to all students a compelling vision of nuclear power as a vital energy resource that will grow. The most difficult role for the university is to successfully convey a future for those in the nuclear science and engineering program

  9. Maintaining Genome Stability: The Role of Helicases and Deaminases

    Science.gov (United States)

    2008-07-01

    Errors in duplicating DNA can result in genomic instability, leading to various human diseases, such as cancer, immune system disorder, muscle dystrophy ...as cancer, immune system disorder, muscle dystrophy , and neurodegenerations. Thus, maintaining genomic integrity is vital to the normal growth of...31–38. Eberharter, A., R. Ferreira and P. Becker , 2005 Dynamic chro- matin: concerted nucleosome remodelling and acetylation. Biol. Chem. 386: 745

  10. Maintaining Customer Loyalty : Case company: Industrail Securities Ltd (China)

    OpenAIRE

    Zhang, Wenqing

    2010-01-01

    The purpose of this thesis is to investigate how customer relationship management can be applied in maintaining customer loyalty. The study will assist the case company to find the way to develop a long-term relationship with existing customers. The better relationship with customers, the higher customer loyalty will be obtained. The theoretical background of the thesis begins with general view of customer relationship management, which embodies the concept of managing customer relations...

  11. Prefrontal Neuronal Excitability Maintains Cocaine-Associated Memory During Retrieval

    Directory of Open Access Journals (Sweden)

    James M. Otis

    2018-06-01

    Full Text Available Presentation of drug-associated cues provokes craving and drug seeking, and elimination of these associative memories would facilitate recovery from addiction. Emotionally salient memories are maintained during retrieval, as particular pharmacologic or optogenetic perturbations of memory circuits during retrieval, but not after, can induce long-lasting memory impairments. For example, in rats, inhibition of noradrenergic beta-receptors, which control intrinsic neuronal excitability, in the prelimbic medial prefrontal cortex (PL-mPFC can cause long-term memory impairments that prevent subsequent cocaine-induced reinstatement. The physiologic mechanisms that allow noradrenergic signaling to maintain drug-associated memories during retrieval, however, are unclear. Here we combine patch-clamp electrophysiology ex vivo and behavioral neuropharmacology in vivo to evaluate the mechanisms that maintain drug-associated memory during retrieval in rats. Consistent with previous studies, we find that cocaine experience increases the intrinsic excitability of pyramidal neurons in PL-mPFC. In addition, we now find that this intrinsic plasticity positively predicts the retrieval of a cocaine-induced conditioned place preference (CPP memory, suggesting that such plasticity may contribute to drug-associated memory retrieval. In further support of this, we find that pharmacological blockade of a cAMP-dependent signaling cascade, which allows noradrenergic signaling to elevate neuronal excitability, is required for memory maintenance during retrieval. Thus, inhibition of PL-mPFC neuronal excitability during memory retrieval not only leads to long-term deficits in the memory, but this memory deficit provides protection against subsequent cocaine-induced reinstatement. These data reveal that PL-mPFC intrinsic neuronal excitability maintains a cocaine-associated memory during retrieval and suggest a unique mechanism whereby drug-associated memories could be targeted

  12. Incisional abdominal hernia repair with concomitant abdominoplasty: Maintaining umbilical viability

    OpenAIRE

    Robert Phan; Elan Kaplan; Jemma K. Porrett; Yik-Hong Ho; Warren M. Rozen

    2018-01-01

    Introduction: Abdominoplasty and abdominal hernia repair are often carried out in two-stage procedures, and those describing single-stage surgery require careful dissection to preserve often only partial blood supply to the umbilicus to maintain its viability. This paper aims to describe the surgical method of laparoscopic umbilical hernia repair in association with abdominoplasty. Case presentation: A patient presents with an incisional hernia at a previous periumbilical port site of size 14...

  13. Ballast system for maintaining constant pressure in a glove box

    Science.gov (United States)

    Shlichta, Paul J.

    1989-09-01

    A ballast system is disclosed for a glove box including a fixed platform on which is mounted an inflatable bag on top of which resides a cover and a weight. The variable gas volume of the inflatable bag communicates with that of the glove box via a valved tube. The weight and the gas volume are selected to maintain a relatively constant pressure in the glove box despite variations in the glove box volume while avoiding the use of complicated valving apparatus.

  14. Maintaining Limited-Range Connectivity Among Second-Order Agents

    Science.gov (United States)

    2016-07-07

    we consider ad-hoc networks of robotic agents with double integrator dynamics. For such networks, the connectivity maintenance problems are: (i) do...connectivity-maintaining controls in a distributed fashion? The proposed solution is based on three contributions. First, we define and characterize...hoc networks of mobile autonomous agents. This loose ter- minology refers to groups of robotic agents with limited mobility and communica- tion

  15. Columbia River pathway report

    International Nuclear Information System (INIS)

    1991-07-01

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

  16. Mapping Nursing Pathways

    Directory of Open Access Journals (Sweden)

    Melanie Birks

    2015-09-01

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

  17. Improved reliability, maintainability and safety through elastomer upgrading

    International Nuclear Information System (INIS)

    Wensel, R.; Wittich, K.C.

    1995-01-01

    Equipment in nuclear plants has historically contained whatever elastomer each component supplier traditionally used for corresponding non-nuclear service. The resulting proliferation of elastomer compounds, many of which are far from optimal for the service conditions (e.g., pressure, temperature, radiation, etc.), has multiplied the costs to provide station reliability, maintainability and safety. Cost-effective improvements are being achieved in CANDU plants by upgrading and standardizing on a handful of high performing elastomer compounds. These upgraded materials offer significant gains in service life over the materials they replace (often by factors of 2 or more). This rationalization of elastomer compounds also facilitates the EQ process for safety-related equipment. Detailed test data on aging is currently being generated for these specific elastomers, encompassing the conditions and media (air, water, oil) common in CANDU service. Two key elements characterize this testing. First, each result is specific to the compound used in the test, and second, it is specific to the tested failure mode (e.g., compression set, extrusion, fracture, etc.). Having fewer, but more thoroughly tested compounds, avoids the penalty (associated with poorly characterized materials) of having to replace parts prematurely because of conservatism, while maintaining safe, reliable service. This paper provides an overview of this approach covering: the benefits of compound rationalization; and the how and why of establishing relevant failure criteria; appropriate quality assurance to maintain EQ; procurement, storage and handling guidelines; and monitoring and predicting in-service degradation. (author)

  18. Challenges of designing fusion reactors for remote maintainability

    International Nuclear Information System (INIS)

    Masson, L.S.

    1981-01-01

    One of the major problems faced by the fusion community is the development of the high level of reliability required to assure that fusion will be a viable commercial power source. Much of the responsibility for solving this problem falls directly on the designer in developing concepts that have a high level of maintainability for the next generation engineering oriented reactors; and long range, in developing full maintainability for the more complicated commercial concepts with their required high level of on-line time. The near-term challenge will include development of unique design concepts to perform inspection, maintenance, replacement, and testing under the stringent conditions imposed by the next generation engineering oriented machines. The long range challenge will focus on basic design concepts that will enable the full maintainability required by commercial fusion. In addition to the purely technical challenges, the fusion community is also faced with the problem of developing programmatic means to assure that reactor maintenance issues are given proper and timely emphasis as the nuclear phase of fusion is approached

  19. The importance of maintainability in maintenance cost management

    International Nuclear Information System (INIS)

    Allen, R.R.

    1996-01-01

    This paper provides specific examples and results from ongoing projects at Power Plants, and for offshore oil platforms. The paper describes the vital role maintainability has on plant availability. How the application of equipment maintainability principles, if addressed using state of the art computer tools and advanced business processes can bring annual return on investment results as high as 15 to 1. The maintenance process of today and for the future must provide for high plant availability at the lowest possible cost. The high cost of obtaining equipment reliability levels necessary to meet required availability demands has not proved to be sustainable. Therefore new business decision processes that address equipment failures as part of the maintenance process have been developed. Repair costs require that equipment failures be selective and controlled so that a high level of safety and plant availability is assurance. This can only be accomplished by the use of advanced computer tools in the hands of well trained maintenance-engineering specialist. The relationship between Reliability Centered Maintenance (RCM), Condition Directed Planned Maintenance (CDPM), and maintainability is also presented

  20. Genetic and Epigenetic Mechanisms That Maintain Hematopoietic Stem Cell Function

    Directory of Open Access Journals (Sweden)

    Christian Kosan

    2016-01-01

    Full Text Available All hematopoiesis cells develop from multipotent progenitor cells. Hematopoietic stem cells (HSC have the ability to develop into all blood lineages but also maintain their stemness. Different molecular mechanisms have been identified that are crucial for regulating quiescence and self-renewal to maintain the stem cell pool and for inducing proliferation and lineage differentiation. The stem cell niche provides the microenvironment to keep HSC in a quiescent state. Furthermore, several transcription factors and epigenetic modifiers are involved in this process. These create modifications that regulate the cell fate in a more or less reversible and dynamic way and contribute to HSC homeostasis. In addition, HSC respond in a unique way to DNA damage. These mechanisms also contribute to the regulation of HSC function and are essential to ensure viability after DNA damage. How HSC maintain their quiescent stage during the entire life is still matter of ongoing research. Here we will focus on the molecular mechanisms that regulate HSC function.

  1. Establishing and maintaining international collaborative research teams: an autobiographical insight

    Directory of Open Access Journals (Sweden)

    T J Carr

    2013-07-01

    Full Text Available Despite the growing impetus for international collaborative research teams (ICRT, there are relatively few resources available to guide and support researchers through the processes of establishing and maintaining ICRTs. In particular, no articles were found that provided researchers’ firsthand accounts of being a member of such a team. Having access to such personal accounts can help both experienced and novice researchers learn more directly about what to expect, as well as the benefits, challenges, pitfalls, and success strategies for establishing and maintaining ICRTs. The authors used phenomenological autobiographical reflective journaling to capture their experiences as members of ICRTs. In this article we provide an overview of key themes that emerged from the analysis of our reflections as members of ICRTs. These themes include: benefits, challenges, and strategies for success. Our aim is to share our first-hand experiences of what it is like to establish and participate in ICRT. It is not our intention to provide readers with prescriptive guidelines on how to set up and maintain ICRTs. Every ICRT is unique and some of these ideas may or may not apply in every case. Instead, we are describing what worked for us, hoping that others may benefit from our experience. Consequently, we suggest that the focus of ICRT should be on the benefits thereof which promote and encourage interaction between disciplines, transfer of knowledge and techniques and personal and professional development. Keywords: international, collaborative, research, teams, interdisciplinary

  2. Vestibular feedback maintains reaching accuracy during body movement

    Science.gov (United States)

    Reynolds, Raymond F.

    2016-01-01

    Key points Reaching movements can be perturbed by vestibular input, but the function of this response is unclear.Here, we applied galvanic vestibular stimulation concurrently with real body movement while subjects maintained arm position either fixed in space or fixed with respect to their body.During the fixed‐in‐space conditions, galvanic vestibular stimulation caused large changes in arm trajectory consistent with a compensatory response to maintain upper‐limb accuracy in the face of body movement.Galvanic vestibular stimulation responses were absent during the body‐fixed task, demonstrating task dependency in vestibular control of the upper limb.The results suggest that the function of vestibular‐evoked arm movements is to maintain the accuracy of the upper limb during unpredictable body movement, but only when reaching in an earth‐fixed reference frame. Abstract When using our arms to interact with the world, unintended body motion can introduce movement error. A mechanism that could detect and compensate for such motion would be beneficial. Observations of arm movements evoked by vestibular stimulation provide some support for this mechanism. However, the physiological function underlying these artificially evoked movements is unclear from previous research. For such a mechanism to be functional, it should operate only when the arm is being controlled in an earth‐fixed rather than a body‐fixed reference frame. In the latter case, compensation would be unnecessary and even deleterious. To test this hypothesis, subjects were gently rotated in a chair while being asked to maintain their outstretched arm pointing towards either earth‐fixed or body‐fixed memorized targets. Galvanic vestibular stimulation was applied concurrently during rotation to isolate the influence of vestibular input, uncontaminated by inertial factors. During the earth‐fixed task, galvanic vestibular stimulation produced large polarity‐dependent corrections in arm

  3. The photovoltaic pathway

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  4. The einkorn wheat (Triticum monococcum) mutant, maintained vegetative phase, is caused by a deletion in the VRN1 gene

    International Nuclear Information System (INIS)

    Shitsukawa, N.; Ikari, C.; Shimada, S.; Kitagawa, S.; Sakamoto, K.; Saito, H.; Ryuto, H.; Fukunishi, N.; Abe, T.; Takumi, S.; Nasuda, S.; Murai, K.

    2007-01-01

    The einkorn wheat (Triticum monococcum) mutant, maintained vegetative phase (mvp), was induced by nitrogen ion-beam treatment and was identified by its inability to transit from the vegetative to reproductive phase. In our previous study, we showed that WAP1 (wheat APETALA1) is a key gene in the regulatory pathway that controls phase transition from vegetative to reproductive growth in common wheat. WAP1 is an ortholog of the VRN1 gene that is responsible for vernalization insensitivity in einkorn wheat. The mvp mutation resulted from deletion of the VRN1 coding and promoter regions, demonstrating that WAP1/VRN1 is an indispensable gene for phase transition in wheat. Expression analysis of flowering-related genes in mvp plants indicated that wheat GIGANTIA (GI), CONSTANS (CO) and SUPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) genes either act upstream of or in a different pathway to WAP1/VRN1

  5. Summer 2014 Pathways Report

    Science.gov (United States)

    Hand, Zachary

    2014-01-01

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

  6. Exposures from aquatic pathways

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  7. Maintaining system homeostasis: the third law of Newtonian immunology.

    Science.gov (United States)

    Germain, Ronald N

    2012-10-01

    Because of the potent effector mechanisms of the immune system, the potential for self-destructive immune responses is especially high and many negative regulatory modalities exist to prevent excessive tissue damage. This Commentary places such regulatory mechanisms in the larger context of system organization on many scales. The sometimes counterintuitive nature of feedback control is discussed and a case is made for greater attention to quantitative spatiotemporal aspects of regulation, rather than limiting the discussion to the qualitative descriptions of pathways that dominate at present.

  8. Maintaining experiences of nature as a city grows

    Directory of Open Access Journals (Sweden)

    Jessica R. Sushinsky

    2017-09-01

    Full Text Available Experiences of nature contribute to human health and well-being, yet as the world's population continues to concentrate in towns and cities there is mounting concern that these experiences are diminishing. Despite this, little is known about how we can maintain experiences of nature as cities grow. Here, we quantify how people's opportunities to experience nature might change with future urban growth in the city of Brisbane, Australia. We simulated the addition of 84,642 houses under compact and sprawling growth scenarios and modeled changes in people's opportunities to experience nature by estimating changes in backyard size, public green space provision, and bird species richness close to households. We discovered that the form of urban growth could strongly influence people's opportunities to experience nature in a way that is highly nonrandom across the socioeconomic gradient. Under a sprawling pattern of development, with low residential densities and few interstitial green spaces, our models suggest severe declines in access to public green space and bird species richness around people's homes. These declines are predicted to be concentrated in socioeconomically disadvantaged areas of the city. Compact development leads to greater reductions in backyard size, but smaller declines in access to public green space and bird species richness. Our results point to a difficult trade-off; residential infill will maintain larger green spaces and higher overall bird diversity but reduce backyard sizes, impacting people's opportunities to experience nature in a different way. Careful planning is needed to balance the availability of public and private urban green spaces to ensure that the opportunities for people to experience nature are maintained as urbanization continues.

  9. Maintaining Students’ Involvement in a Math Lecture Using Countdown Timers

    Directory of Open Access Journals (Sweden)

    Ann Krizzel A. Aban

    2015-12-01

    Full Text Available Involving students in a lecture is an important but not an easy task that every lecturer must encourage. This task becomes even greater in a math class that is composed of eighty to a hundred sixty students. In 2007, the University of the Philippines Los Baños (UPLB started offering some of its basic math courses in lecture-recitation set-up. This shift and many other factors drove most math instructors of UPLB to widely use presentation software, such as the PowerPoint (PPT, to deliver their lectures. The non-stop use of these softwares, however, seems to have negative effects on the students when it comes to maintaining their involvement in a lecture discussion for they tend to be more passive spectators. On the other hand, adding countdown timers strategically on some parts of the discussion seems to lessen such negative effects. This study determined the effectiveness of using countdown timers in maintaining students’ involvement in a lecture of MATH 27 (Analytic Geometry and Calculus II, a course in UPLB commonly taken by sophomore students. Results show that the effectiveness of countdown timers, as perceived by the students, is independent to students’ genders and degree programs, but is dependent to the colleges where the students belong to. Also, some effects of countdown timers are significantly correlated to various data from students’ profiles. It was concluded in the study that the use of countdown timers is effective in maintaining student’s involvement in MATH 27 lectures and might also be useful in other math lecture classes

  10. Research Trends on Benefits of Implementing Constructability, Operability, and Maintainability

    Directory of Open Access Journals (Sweden)

    Kordestani Ghaleenoe, N.

    2017-07-01

    Full Text Available Despite allocating huge budgets to civil engineering projects, detailed planning, and employing human resources, project managers still face time, cost, and quality constraints. Most of these challenges are due to a lack of integration of different project phases and the limitations of the presence of construction and maintenance contractors in the initial stages of the project. Considering the benefits of applying constructability, operability, and maintainability (COM concepts, many problems caused by lack of coordination, or duplications and weakness in management, and also time and extra costs due to lack of presence of construction and maintenance contractors in the early stages of the project are resolvable. In this regard, various studies have investigated the benefits of applying these concepts; however, there has been no comprehensive analysis of the benefits of COM. As a result of focus on the benefits of implementation of these concepts and evaluating the effect of each of these strategies and benefits, from different perspectives during various time periods, managers can increase project efficiency and productivity, and improve their performance, through using concepts and strategies of their implementation. This research aims to evaluate the trend of studies on the benefits of implementing constructability, operability, and maintainability in the construction industry. For that, the in-depth literature review method is applied. For qualitative analysis of the obtained information, descriptive analysis has been used. Then, the data was coded, and classified using Excel Software for quantitative data analysis. Finally, the charts presented were evaluated according to the classified fields of study. The necessity of performing such a study is significant because of the fact that a large share of a project’s problems, such as lack of plans’ integration and weakness of administrative system, and increasing time and cost, are due to

  11. Managers' duty to maintain good workplace communications skills.

    Science.gov (United States)

    Timmins, Fiona

    2011-06-01

    Communication is a fundamental element of care at every level of nursing practice. It is important, therefore, for nurse managers to create environments that promote and encourage good communication, and help nurses to develop their communication skills formally and informally. This article discusses the effects of communication on the quality of care. It examines nurses' professional duty to maintain good communication skills and how managers can help them do this. It also discusses nurse managers' communication skills in the context of leadership style, conflict resolution and self-awareness. Finally, it considers the notion of shared governance as good practice.

  12. Prepare to protect: Operating and maintaining a tornado safe room.

    Science.gov (United States)

    Herseth, Andrew; Goldsmith-Grinspoon, Jennifer; Scott, Pataya

    2017-06-01

    Operating and maintaining a tornado safe room can be critical to the effective continuity of business operations because a firm's most valuable asset is its people. This paper describes aspects of operations and maintenance (O&M) for existing tornado safe rooms as well as a few planning and design aspects that affect the ultimate operation of a safe room for situations where a safe room is planned, but not yet constructed. The information is based on several Federal Emergency Management Agency safe room publications that provide guidance on emergency management and operations, as well as the design and construction of tornado safe rooms.

  13. JWIG: Yet Another Framework for Maintainable and Secure Web Applications

    DEFF Research Database (Denmark)

    Møller, Anders; Schwarz, Mathias Romme

    2009-01-01

    Although numerous frameworks for web application programming have been developed in recent years, writing web applications remains a challenging task. Guided by a collection of classical design principles, we propose yet another framework. It is based on a simple but flexible server......-oriented architecture that coherently supports general aspects of modern web applications, including dynamic XML construction, session management, data persistence, caching, and authentication, but it also simplifies programming of server-push communication and integration of XHTML-based applications and XML-based web...... services.The resulting framework provides a novel foundation for developing maintainable and secure web applications....

  14. Phase noise cancellation in polarisation-maintaining fibre links

    Science.gov (United States)

    Rauf, B.; Vélez López, M. C.; Thoumany, P.; Pizzocaro, M.; Calonico, D.

    2018-03-01

    The distribution of ultra-narrow linewidth laser radiation is an integral part of many challenging metrological applications. Changes in the optical pathlength induced by environmental disturbances compromise the stability and accuracy of optical fibre networks distributing the laser light and call for active phase noise cancellation. Here we present a laboratory scale optical (at 578 nm) fibre network featuring all polarisation maintaining fibres in a setup with low optical powers available and tracking voltage-controlled oscillators implemented. The stability and accuracy of this system reach performance levels below 1 × 10-19 after 10 000 s of averaging.

  15. Social Pharmacy Research in Copenhagen—Maintaining a Broad Approach

    Directory of Open Access Journals (Sweden)

    Sofia Kälvemark Sporrong

    2016-02-01

    Full Text Available Social Pharmacy (SP is a multidisciplinary field to promote the adequate use of medicine. The field of SP is increasingly important due to a numbers of new trends all posing challenges to society. The SP group at the University of Copenhagen has for several years used a broad approach to SP teaching and research, often illustrated by the four levels: individual, group, organizational, and societal. In this paper the relevance of maintaining a broad approach to SP research is argued for and examples of the importance of such type of research is presented.

  16. Maintaining Traceability in an Evolving Distributed Computing Environment

    Science.gov (United States)

    Collier, I.; Wartel, R.

    2015-12-01

    The management of risk is fundamental to the operation of any distributed computing infrastructure. Identifying the cause of incidents is essential to prevent them from re-occurring. In addition, it is a goal to contain the impact of an incident while keeping services operational. For response to incidents to be acceptable this needs to be commensurate with the scale of the problem. The minimum level of traceability for distributed computing infrastructure usage is to be able to identify the source of all actions (executables, file transfers, pilot jobs, portal jobs, etc.) and the individual who initiated them. In addition, sufficiently fine-grained controls, such as blocking the originating user and monitoring to detect abnormal behaviour, are necessary for keeping services operational. It is essential to be able to understand the cause and to fix any problems before re-enabling access for the user. The aim is to be able to answer the basic questions who, what, where, and when concerning any incident. This requires retaining all relevant information, including timestamps and the digital identity of the user, sufficient to identify, for each service instance, and for every security event including at least the following: connect, authenticate, authorize (including identity changes) and disconnect. In traditional grid infrastructures (WLCG, EGI, OSG etc.) best practices and procedures for gathering and maintaining the information required to maintain traceability are well established. In particular, sites collect and store information required to ensure traceability of events at their sites. With the increased use of virtualisation and private and public clouds for HEP workloads established procedures, which are unable to see 'inside' running virtual machines no longer capture all the information required. Maintaining traceability will at least involve a shift of responsibility from sites to Virtual Organisations (VOs) bringing with it new requirements for their

  17. Experience with managing, operating and maintaining gas turbine powerplants

    International Nuclear Information System (INIS)

    Wadman, B.

    1994-01-01

    Stewart ampersand Stevenson, a major supplier of gas turbine powered cogeneration systems to worldwide markets, established plant management, operations and maintenance capabilities in 1985 in order to provide complete service capability to the customer. As of the fall of 1993, twenty-two individual cogeneration facilities are now being operated and maintained by this company with a total capacity of 1100+ MW. More than 300 plant management and operating personnel are employed in this operation. To date, activities have been concentrated in North and South America. Negotiations are in process in a number of other areas including the Pacific Rim, China, and several Middle East countries. 7 figs

  18. The Fog signaling pathway: Insights into signaling in morphogenesis

    Science.gov (United States)

    Manning, Alyssa J.; Rogers, Stephen L.

    2014-01-01

    Epithelia form the building blocks of many tissue and organ types. Epithelial cells often form a contiguous 2-dimensional sheet that is held together by strong adhesions. The mechanical properties conferred by these adhesions allow the cells to undergo dramatic three-dimensional morphogenetic movements while maintaining cell–cell contacts during embryogenesis and post-embryonic development. The Drosophila Folded gastrulation pathway triggers epithelial cell shape changes that drive gastrulation and tissue folding and is one of the most extensively studied examples of epithelial morphogenesis. This pathway has yielded key insights into the signaling mechanisms and cellular machinery involved in epithelial remodeling. In this review, we discuss principles of morphogenesis and signaling that have been discovered through genetic and cell biological examination of this pathway. We also consider various regulatory mechanisms and the system's relevance to mammalian development. We propose future directions that will continue to broaden our knowledge of morphogenesis across taxa. PMID:25127992

  19. Maintaining Genome Stability in Defiance of Mitotic DNA Damage

    Science.gov (United States)

    Ferrari, Stefano; Gentili, Christian

    2016-01-01

    The implementation of decisions affecting cell viability and proliferation is based on prompt detection of the issue to be addressed, formulation and transmission of a correct set of instructions and fidelity in the execution of orders. While the first and the last are purely mechanical processes relying on the faithful functioning of single proteins or macromolecular complexes (sensors and effectors), information is the real cue, with signal amplitude, duration, and frequency ultimately determining the type of response. The cellular response to DNA damage is no exception to the rule. In this review article we focus on DNA damage responses in G2 and Mitosis. First, we set the stage describing mitosis and the machineries in charge of assembling the apparatus responsible for chromosome alignment and segregation as well as the inputs that control its function (checkpoints). Next, we examine the type of issues that a cell approaching mitosis might face, presenting the impact of post-translational modifications (PTMs) on the correct and timely functioning of pathways correcting errors or damage before chromosome segregation. We conclude this essay with a perspective on the current status of mitotic signaling pathway inhibitors and their potential use in cancer therapy. PMID:27493659

  20. Preserving breastfeeding for the rehospitalized infant: a clinical pathway.

    Science.gov (United States)

    Spatz, Diane L; Goldschmidt, Karen A

    2006-01-01

    The benefits of feeding newborns with human milk are well established. Unfortunately some hospital practices do not support successful breastfeeding; practices such as early hospital discharge after birth, lack of appropriate follow-up primary care providers, and lack of access to breastfeeding support services can contribute to breastfeeding failure, as well as morbidity and mortality in the infant. Infants experiencing breastfeeding difficulties are sometimes admitted to the hospital with diagnoses such as hyperbilirubinemia/jaundice, dehydration/hypernatremia, rule out sepsis, and weight loss/failure to thrive. This article describes a clinical pathway developed with the express purpose of maintaining and enhancing lactation in mother-infant dyads experiencing breastfeeding difficulties. The goal of the pathway is to maintain lactation and breastfeeding while returning the infant to a state of health. A key focus of the pathway is milk transfer, a concept that is missing from much of the research on lactation difficulties. The pathway considers breastfeeding from both a maternal and an infant perspective, with a goal of preserving breastfeeding. It uses technology to support the breastfeeding process and could be useful for all practitioners working with mother-infant dyads experiencing breastfeeding difficulties.

  1. Experience of maintaining laboratory educational website′s sustainability

    Directory of Open Access Journals (Sweden)

    Izak B Dimenstein

    2016-01-01

    Full Text Available Laboratory methodology websites are specialized niche websites. The visibility of a niche website transforms it into an authority site on a particular "niche of knowledge." This article presents some ways in which a laboratory methodology website can maintain its sustainability. The optimal composition of the website includes a basic content, a blog, and an ancillary part. This article discusses experimenting with the search engine optimization query results page. Strategic placement of keywords and even phrases, as well as fragmentation of the post′s material, can improve the website′s visibility to search engines. Hyperlinks open a chain reaction of additional links and draw attention to the previous posts. Publications in printed periodicals are a substantial part of a niche website presence on the Internet. Although this article explores a laboratory website on the basis of our hands-on expertise maintaining "Grossing Technology in Surgical Pathology" (www.grossing-technology.com website with a high volume of traffic for more than a decade, the recommendations presented here for developing an authority website can be applied to other professional specialized websites. The authority websites visibility and sustainability are preconditions for aggregating them in a specialized educational laboratory portal.

  2. Maintaining operational excellence: building capability beyond knowledge transfer

    International Nuclear Information System (INIS)

    Ramjist, S.

    2013-01-01

    This paper describes the issues relating to human resources and maintaining capabilities in an organization. The sustaining elements are: vision and plan for excellence; invest in the plant; invest in human capital; find and fix problems. There is much discussion about knowledge transfer and retention that is mainly focused on technical attributes and proficiency. We are losing more people with the requisite managerial and leadership capability than we can develop and backfill at a Time when our industry is facing increased competition and decreased margins. We are vulnerable because this Increases our dependence on augmented staff for certain key leadership roles. Previous methods for developing people will take too long and does not appeal to current generation. A solution, not the only solution, but the one we have chosen is initial hiring of operators, maintainers and engineers, internal promotion for key roles (FLM, FSOS, Shift Supervisor, Section Manager, ANO) and focus on all three aspects of capability and looking for leadership traits. Look for ambition, drive, initiative and motivation. Identify, separate and stream. Take specific measures to accelerate growth.

  3. Multiple Relationships : Maintaining Professional Identity in Rural Social Work Practice

    Directory of Open Access Journals (Sweden)

    Keith Brownlee

    2015-03-01

    Full Text Available Working in a rural community locates the professional in a wider social network as community members often expect more from their professionals; not only as service providers, but also as engaged members of the community. This can result in the rural social worker being highly visible both personally and professionally and it can also lead to overlapping relationships. These higher expectations can place stress on the worker in terms of maintaining accepted professional roles and a sense of professional identity. This qualitative study explores the first-hand experiences of a cross-section of service providers in more than a dozen communities within northwestern Ontario and northern Manitoba, Canada. The responses of the participants provide some insight into how rural practitioners maintain their professional identity when working within the unique demands of the rural and remote context. Recurring themes from the interviews suggest that these professionals craft their own informal decision-making processes to address intersecting roles, community gossip, and personal isolation, even while, in some cases, practicing in their home community. The findings provide greater understanding of the pressures and realities of working in small remote towns and the challenges of responding to the expectations and realities of relationships including the expectation of working with friends and family members of friends or colleagues: issues that have not been adequately studied in the literature to date.

  4. The human brain maintains contradictory and redundant auditory sensory predictions.

    Directory of Open Access Journals (Sweden)

    Marika Pieszek

    Full Text Available Computational and experimental research has revealed that auditory sensory predictions are derived from regularities of the current environment by using internal generative models. However, so far, what has not been addressed is how the auditory system handles situations giving rise to redundant or even contradictory predictions derived from different sources of information. To this end, we measured error signals in the event-related brain potentials (ERPs in response to violations of auditory predictions. Sounds could be predicted on the basis of overall probability, i.e., one sound was presented frequently and another sound rarely. Furthermore, each sound was predicted by an informative visual cue. Participants' task was to use the cue and to discriminate the two sounds as fast as possible. Violations of the probability based prediction (i.e., a rare sound as well as violations of the visual-auditory prediction (i.e., an incongruent sound elicited error signals in the ERPs (Mismatch Negativity [MMN] and Incongruency Response [IR]. Particular error signals were observed even in case the overall probability and the visual symbol predicted different sounds. That is, the auditory system concurrently maintains and tests contradictory predictions. Moreover, if the same sound was predicted, we observed an additive error signal (scalp potential and primary current density equaling the sum of the specific error signals. Thus, the auditory system maintains and tolerates functionally independently represented redundant and contradictory predictions. We argue that the auditory system exploits all currently active regularities in order to optimally prepare for future events.

  5. The Challenges of Maintaining Nuclear Cultures. US and UK Perspectives

    International Nuclear Information System (INIS)

    Brooks, Linton; McKane, Tom

    2016-01-01

    After the world entered the nuclear age, civilian and military organizations have witnessed the slow emergence of nuclear cultures, defined as the set of values and knowledge, shared among the national security community, about the relative importance of nuclear weapons in the country's defense posture, the distinctive features of nuclear weapons in terms of security, safety and operational requirements, and the workings of deterrence. Nuclear cultures have helped to ensure some level of coherence in policy-making and, most importantly, to maintain safe and effective deterrents. At a national level, however, each nuclear culture is confronted with significant challenges, such as generational change, decreasing levels of understanding or attention among the political and military leadership, insufficient funding or a growing inability to meet manpower requirements in both the nuclear weapons complexes and the armed forces. This paper looks at the United States and United Kingdom's recent efforts to maintain their nuclear culture, and at the key challenges these two countries face while pursuing this aim. (authors)

  6. Maintaining families’ well-being in everyday life

    Directory of Open Access Journals (Sweden)

    Kristina Ziegert

    2011-05-01

    Full Text Available The aim of this paper is to discuss how everyday life changes for the family in the event of chronic illness or disability. It changes physically due to loss of body function and socially due to time and other constraints related to treatment or lack of mobility. Equally important, there is a psychological impact due to the uncertainty of the future. The article will explore how family participation can help to maintain well-being in everyday life. The family should therefore focus on their own needs as much as on the needs of the family members who are ill. In order to maintain well-being in everyday life, it is crucial for the family to create routines and spend time doing things that they enjoy. By doing this, the family will create a rhythm of well-being regardless of the critical family situation. Family members and professional caregivers also need to come together at the beginning and during the illness or disability event to discuss changes that could be made day-to-day for all those involved, thereby making for an easier transition into care giving.

  7. Acoustic waves in M dwarfs: Maintaining a corona

    Science.gov (United States)

    Mullan, D. J.; Cheng, Q. Q.

    1994-01-01

    We use a time-dependent hydrodynamics code to follow the propagation of acoustic waves into the corona of an M dwarf star. An important qualitative difference between M dwarfs and stars such as the Sun is that the acoustic spectrum in M dwarfs is expected to peak at periods close to the acoustic cutoff P(sub A): this allows more effective penetration of waves into the corona. In our code, radiative losses in the photosphere, chromosphere, and corona are computed using Rosseland mean opacities, Mg II kappa and Ly alpha emission, and optically thin emissivities respectively. We find that acoustic heating can maintain a corona with a temperature of order 0.7-1 x 10(exp 6) K and a surface X-ray flux as large as 10(exp 5)ergs/sq cm/s. In a recent survey of X-rays from M dwarfs, some (20%-30%) of the stars lie at or below this limiting X-ray flux: we suggest that such stars may be candidates for acoustically maintained coronae.

  8. How to keep punishment to maintain cooperation: Introducing social vaccine

    Science.gov (United States)

    Yamamoto, Hitoshi; Okada, Isamu

    2016-02-01

    Although there is much support for the punishment system as a sophisticated approach to resolving social dilemmas, more than a few researchers have also pointed out the limitations of such an approach. Second-order free riding is a serious issue facing the punishment system. Various pioneering works have suggested that an anti-social behavior or noise stemming from a mutation may, surprisingly, be helpful for avoiding second-order freeloaders. In this work, we show through mathematical analysis and an agent-based simulation of a model extending the meta-norms game that the coercive introduction of a small number of non-cooperators can maintain a cooperative regime robustly. This paradoxical idea was inspired by the effect of a vaccine, which is a weakened pathogen injected into a human body to create antibodies and ward off infection by that pathogen. Our expectation is that the coercive introduction of a few defectors, i.e., a social vaccine, will help maintain a highly cooperative regime because it will ensure that the punishment system works.

  9. Sister chromosome pairing maintains heterozygosity in parthenogenetic lizards.

    Science.gov (United States)

    Lutes, Aracely A; Neaves, William B; Baumann, Diana P; Wiegraebe, Winfried; Baumann, Peter

    2010-03-11

    Although bisexual reproduction has proven to be highly successful, parthenogenetic all-female populations occur frequently in certain taxa, including the whiptail lizards of the genus Aspidoscelis. Allozyme analysis revealed a high degree of fixed heterozygosity in these parthenogenetic species, supporting the view that they originated from hybridization events between related sexual species. It has remained unclear how the meiotic program is altered to produce diploid eggs while maintaining heterozygosity. Here we show that meiosis commences with twice the number of chromosomes in parthenogenetic versus sexual species, a mechanism that provides the basis for generating gametes with unreduced chromosome content without fundamental deviation from the classic meiotic program. Our observation of synaptonemal complexes and chiasmata demonstrate that a typical meiotic program occurs and that heterozygosity is not maintained by bypassing recombination. Instead, fluorescent in situ hybridization probes that distinguish between homologues reveal that bivalents form between sister chromosomes, the genetically identical products of the first of two premeiotic replication cycles. Sister chromosome pairing provides a mechanism for the maintenance of heterozygosity, which is critical for offsetting the reduced fitness associated with the lack of genetic diversity in parthenogenetic species.

  10. Hamilton's inclusive fitness maintains heritable altruism polymorphism through rb = c.

    Science.gov (United States)

    Wang, Changcao; Lu, Xin

    2018-02-20

    How can altruism evolve or be maintained in a selfish world? Hamilton's rule shows that the former process will occur when rb > c -the benefits to the recipients of an altruistic act b , weighted by the relatedness between the social partners r , exceed the costs to the altruists c -drives altruistic genotypes spreading against nonaltruistic ones. From this rule, we infer that altruistic genotypes will persist in a population by forming a stable heritable polymorphism with nonaltruistic genotypes if rb = c makes inclusive fitness of the two morphs equal. We test this prediction using the data of 12 years of study on a cooperatively breeding bird, the Tibetan ground tit Pseudopodoces humilis , where helping is performed by males only and kin-directed. Individual variation in ever acting as a helper was heritable ( h 2 = 0.47), and the resultant altruism polymorphism remained stable as indicated by low-level annual fluctuation of the percentage of helpers among all adult males (24-28%). Helpers' indirect fitness gains from increased lifetime reproductive success of related breeders statistically fully compensated for their lifetime direct fitness losses, suggesting that rb = c holds. While our work provides a fundamental support for Hamilton's idea, it highlights the equivalent inclusive fitness returns to altruists and nonaltruists mediated by rb = c as a theoretically and realistically important mechanism to maintain social polymorphism.

  11. Local neutral networks help maintain inaccurately replicating ribozymes.

    Science.gov (United States)

    Szilágyi, András; Kun, Ádám; Szathmáry, Eörs

    2014-01-01

    The error threshold of replication limits the selectively maintainable genome size against recurrent deleterious mutations for most fitness landscapes. In the context of RNA replication a distinction between the genotypic and the phenotypic error threshold has been made; where the latter concerns the maintenance of secondary structure rather than sequence. RNA secondary structure is treated as a proxy for function. The phenotypic error threshold allows higher per digit mutation rates than its genotypic counterpart, and is known to increase with the frequency of neutral mutations in sequence space. Here we show that the degree of neutrality, i.e. the frequency of nearest-neighbour (one-step) neutral mutants is a remarkably accurate proxy for the overall frequency of such mutants in an experimentally verifiable formula for the phenotypic error threshold; this we achieve by the full numerical solution for the concentration of all sequences in mutation-selection balance up to length 16. We reinforce our previous result that currently known ribozymes could be selectively maintained by the accuracy known from the best available polymerase ribozymes. Furthermore, we show that in silico stabilizing selection can increase the mutational robustness of ribozymes due to the fact that they were produced by artificial directional selection in the first place. Our finding offers a better understanding of the error threshold and provides further insight into the plausibility of an ancient RNA world.

  12. Maintaining operational excellence: building capability beyond knowledge transfer

    Energy Technology Data Exchange (ETDEWEB)

    Ramjist, S. [Ontario Power Generation, Darlington Nuclear Generating Station, Bowmanville, Ontario (Canada)

    2013-07-01

    This paper describes the issues relating to human resources and maintaining capabilities in an organization. The sustaining elements are: vision and plan for excellence; invest in the plant; invest in human capital; find and fix problems. There is much discussion about knowledge transfer and retention that is mainly focused on technical attributes and proficiency. We are losing more people with the requisite managerial and leadership capability than we can develop and backfill at a Time when our industry is facing increased competition and decreased margins. We are vulnerable because this Increases our dependence on augmented staff for certain key leadership roles. Previous methods for developing people will take too long and does not appeal to current generation. A solution, not the only solution, but the one we have chosen is initial hiring of operators, maintainers and engineers, internal promotion for key roles (FLM, FSOS, Shift Supervisor, Section Manager, ANO) and focus on all three aspects of capability and looking for leadership traits. Look for ambition, drive, initiative and motivation. Identify, separate and stream. Take specific measures to accelerate growth.

  13. Maintaining Sibling Relationships for Children in Foster and Adoptive Placements.

    Science.gov (United States)

    James, Sigrid; Monn, Amy R; Palinkas, Lawrence A; Leslie, Laurel K

    2008-01-01

    To better understand the nature of sibling relationships among children in foster or adoptive placement and the challenges and processes involved in maintaining these relationships, we conducted an exploratory analysis of data collected from semi-structured interviews with caregivers of 14 foster and adopted children in San Diego County. We identified three patterns of placement histories and living situations which appeared to impact the degree of contact maintained with siblings: (1) children who had never lived together and were not currently placed together; (2) children who at some point lived with or were placed together with their siblings, but were now separated from them; and (3) children who had lived with their siblings all their life and were placed together with at least some of their siblings at the time of the interview. Children's current living situations and placement histories, caregivers' experiences and perceptions of feasibility and desirability of sibling contact, and the sibling relationship itself are primary determinants in the development and maintenance of contact between siblings. Implications for child welfare policy and practice are discussed.

  14. Pathways to man

    International Nuclear Information System (INIS)

    Harley, J.H.

    1980-01-01

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

  15. Guide to Operating and Maintaining EnergySmart Schools

    Energy Technology Data Exchange (ETDEWEB)

    None

    2010-01-01

    Through a commitment to high performance, school districts are discovering that smart energy choices can create lasting benefits for students, communities, and the environment. For example, an energy efficient school district with 4,000 students can save as much as $160,000 a year in energy costs. Over 10 years, those savings can reach $1.6 million, translating into the ability to hire more teachers, purchase more textbooks and computers, or invest in additional high performance facilities. Beyond these bottomline benefits, schools can better foster student health, decrease absenteeism, and serve as centers of community life. The U.S. Department of Energy's EnergySmart Schools Program promotes a 30 percent improvement in existing school energy use. It also encourages the building of new schools that exceed code (ASHRAE 90.11999) by 50 percent or more. The program provides resources like this Guide to Operating and Maintaining EnergySmart Schools to assist school decisionmakers in planning, financing, operating, and maintaining energy efficient, high performance schools. It also offers education and training for building industry professionals. Operations and maintenance refer to all scheduled and unscheduled actions for preventing equipment failure or decline with the goal of increasing efficiency, reliability, and safety. A preventative maintenance program is the organized and planned performance of maintenance activities in order to prevent system or production problems or failures from occurring. In contrast, deferred maintenance or reactive maintenance (also called diagnostic or corrective maintenance) is conducted to address an existing problem. This guide is a primary resource for developing and implementing a districtor schoolwide operations and maintenance (O&M) program that focuses on energy efficiency. The EnergySmart Schools Solutions companion CD contains additional supporting information for design, renovation, and retrofit projects. The objective

  16. Discriminant analysis of maintaining a vertical position in the water

    Directory of Open Access Journals (Sweden)

    Bratuša Zoran

    2015-01-01

    Full Text Available Water polo is the only sports game that takes place in the water. During the outplay, a vertical body position with the two basic mechanisms of the leg work - a breaststroke leg kick and an eggbeater leg kick, prevails. Starting from the significance of a vertical position during the game play, the methods of assessing physical preparedness of the athletes of all the categories also include the evaluation of maintaining a vertical position and consequently the load of the leg muscles. The measurements are performed during the maintenance of a vertical position (swimming in place through one of the specified mechanisms of leg work, i.e. a vertical position technique. The aim of this paper was to determine the application of different mechanisms of the leg kicks in maintaining a vertical position with young water polo players in relation to their position. The study included 29 selected junior water polo players (age_15.8 ± 0.8 years; BH_185.2 ± 5.3cm and BW_81.7 ± 7.7kg. The measurements were performed during the tests of swimming in place at the maximum intensity lasting 10 seconds, by the breaststroke and eggbeater leg kicks. The isometric tensiometry tests were used for the measurements. The results were analysed by the application of descriptive statistics, and the kinetic selection characteristic was defined by the application of discriminant analysis. Higher average values were achieved with the breaststroke leg kick technique Fmax, ImpF and RFD (avgFmaxLEGGBK =157.46±19.93N; avgImpF_LEGGBK =45.43±10.64Ns; avgRFD_LEGGBK=337.85±80.73N/s; avgFmaxLBKICK=227.18±49.17N; avgImpF_LBKICK=55.99±14.59Ns; avgRFD_LBKICK=545.47±159.15N/s. After discriminant analysis, the results have shown that the eggbeater leg kick is a selection technique, whereas the force - Fmax is a kinetic selection variable. Based on the obtained results and the analyses performed it may be concluded that a training factor dominant for maintaining a vertical position by

  17. Novel metabolic pathways in Archaea.

    Science.gov (United States)

    Sato, Takaaki; Atomi, Haruyuki

    2011-06-01

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

  18. Evolution of the TOR Pathway.

    NARCIS (Netherlands)

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

    2011-01-01

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

  19. Sox11 is required to maintain proper levels of Hedgehog signaling during vertebrate ocular morphogenesis.

    Directory of Open Access Journals (Sweden)

    Lakshmi Pillai-Kastoori

    2014-07-01

    Full Text Available Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders.

  20. Microbiota-stimulated immune mechanisms to maintain gut homeostasis.

    Science.gov (United States)

    Chung, Hachung; Kasper, Dennis Lee

    2010-08-01

    In recent years there has been an explosion of interest to identify microbial inhabitants of human and understand their beneficial role in health. In the gut, a symbiotic host-microbial interaction has coevolved as bacteria make essential contributions to human metabolism and bacteria in turn benefits from the nutrient-rich niche in the intestine. To maintain host-microbe coexistence, the host must protect itself against microbial invasion, injury, and overreactions to foreign food antigens, and gut microbes need protection against competing microbes and the host immune system. Perturbation of this homeostatic coexistence has been strongly associated with human disease. This review discusses how gut bacteria regulate host innate and adaptive immunity, with emphasis on how this regulation contributes to host-microbe homeostasis in the gut. Copyright 2010 Elsevier Ltd. All rights reserved.

  1. Reliability And Maintainability Issues for the Next Linear Collider

    International Nuclear Information System (INIS)

    Wilson, Zane J.; Gold, Saul L.; Koontz, Ron F.; Lavine, Ted L.

    2011-01-01

    Large accelerators for high energy physics research traditionally have been designed using informal best design, engineering, and management practices to achieve acceptable levels of operational availability. However, the Next Linear Collider(NLC) project presents a particular challenge for operational availability due to the unprecedented size and complexity of the accelerator systems required to achieve the physics goals of high center-of-mass energy and high luminosity. Formal reliability and maintainability analysis, design, and implementation will be required to achieve acceptable operational availability for the high energy physics research program. This paper introduces some of the basic concepts of reliability analysis and applies them to the 2.6-cm microwave power system of the two 10-km-long, 250-GeV linacs that are currently proposed for the NLC design.

  2. Maintaining consistency between planning hierarchies: Techniques and applications

    Science.gov (United States)

    Zoch, David R.

    1987-01-01

    In many planning and scheduling environments, it is desirable to be able to view and manipulate plans at different levels of abstraction, allowing the users the option of viewing and manipulating either a very detailed representation of the plan or a high-level more abstract version of the plan. Generating a detailed plan from a more abstract plan requires domain-specific planning/scheduling knowledge; the reverse process of generating a high-level plan from a detailed plan Reverse Plan Maintenance, or RPM) requires having the system remember the actions it took based on its domain-specific knowledge and its reasons for taking those actions. This reverse plan maintenance process is described as implemented in a specific planning and scheduling tool, The Mission Operations Planning Assistant (MOPA), as well as the applications of RPM to other planning and scheduling problems; emphasizing the knowledge that is needed to maintain the correspondence between the different hierarchical planning levels.

  3. Method for rudder roll stabilization control by maintaining ship speed

    Directory of Open Access Journals (Sweden)

    LIU Zhiquan

    2017-01-01

    Full Text Available A ship navigating on the surface of the water may experience greater resistance, adversely affect-ing its speed and leading to energy loss. The added resistance of surface ships in both still water and waves are investigated, and the computation method of total speed loss is presented. An autopilot system is intro-duced to constrain the speed loss, and course keeping and rudder roll stabilization sliding mode control laws are proposed according to a compact control strategy. The two working conditions of "heading" and "heading plus anti-roll" are discussed, including roll stabilization, heading error, speed maintenance and rudder abrasion. The results show that the speed can be effectively maintained using this method, and from a commercial point of view, the fin-rudder roll stabilization control is not recommended for vessels equipped with both fins and rudders.

  4. Study on eliminating fire dampers to maintain process confinement

    International Nuclear Information System (INIS)

    Walling, R.C.; Patel, J.B.; Strunk, A.J.

    1991-01-01

    The DOE General Design Criteria for the Defense Waste Processing Facility (DWPF) at the Westinghouse Savannah River Site (WSRS) requires the NFPA National Fire Codes to be incorporated into the design and simultaneously maintain process confinement integrity to prevent the release of radioactivity. Although the NFPA Standard for the Installation of Air Conditioning and Ventilation Systems, NFPA 90, requires fire dampers (FD) in HVAC duct penetrations of two hour rated fire barriers, closure of fire dampers at DWPF may compromise the integrity of the process confinement system. This leads to the need for an overall risk assessment to determine the value of 39 fire dampers that are identified later in the study as capable of a confinement system upset

  5. NiTi bonded space regainer/maintainer

    Directory of Open Access Journals (Sweden)

    Negi K

    2010-06-01

    Full Text Available Early orthodontic interventions are often initiated in the developing dentition to promote favorable developmental changes. Interceptive orthodontic can eliminate or reduce the severity of a developing malocclusion, the complexity of orthodontic treatment, overall treatment time and cost. Premature loss of deciduous tooth or teeth can often destroy the integrity of normal occlusion. There are many space regaining and maintaining devices mentioned in literature. In this article, I present a simple space regaining method by a piece of nickel titanium (NiTi wire bonded between the teeth in active loop form, and the unique shape memory property of NiTi wire will upright or move the teeth and the lost space can be regained easily.

  6. Maintaining bone health in prostate cancer throughout the disease continuum.

    Science.gov (United States)

    Saad, Fred; Eastham, James

    2010-06-01

    Prostate cancer (PC) is the most prevalent malignancy in men, with 604,506 new cases diagnosed yearly worldwide. Maintaining bone health is important during all stages of PC, including patients who experience bone loss from androgen-deprivation therapy and patients who develop bone metastases. Patients with bone metastases often experience severe bone pain and are at increased risk for potentially debilitating skeletal-related events. Bisphosphonates are a well-established treatment option for patients with bone metastases from solid tumors and bone lesions from multiple myeloma. Zoledronic acid (ZOL) is the only bisphosphonate (BP) that has been extensively studied in patients with castration-recurrent PC and is indicated for treating patients with bone metastases from PC in conjunction with standard antineoplastic therapy. This review will examine the breadth of evidence supporting a role for ZOL and emerging therapies in managing patients with PC throughout the disease continuum. 2010 Elsevier Inc. All rights reserved.

  7. Hepatobiliary scanning in cardiac transplant patients maintained on cyclosporine

    International Nuclear Information System (INIS)

    Dhekne, R.D.; Long, S.E.; Moore, W.H.; Frazier, O.H.

    1987-01-01

    Many patients receiving cyclosporine (CSA) develop hepatic dysfunction or pancreatitis. The authors reviewed 106 records of cardiac transplant patients maintained on CSA. Eleven patients underwent 16 hepatobiliary scans (HBSs) for abdominal pain and/or abnormal liver function. Of 16 HBSs, ten demonstrated normal gallbladder visualization. Follow-up in all cases confirmed scan findings. Five patients had no gallbladder visualization; confirmation of acute cholecystitis was obtained by surgery in two and by autopsy in three. One patient had previous cholecystectomy. The authors found HPS useful for evaluating acute cholecystitis in patients receiving CSA with or without associated drug-related pancreatitis and hepatic insufficiency and suggest that HBS can assist in the selection of patients for CSA dose adjustment

  8. Gamma radiation combined with cinnamon oil to maintain fish quality

    Science.gov (United States)

    Lyu, Fei; Zhang, Jing; Wei, Qianqian; Gao, Fei; Ding, Yuting; Liu, Shulai

    2017-12-01

    Effects of gamma radiation combined with cinnamon oil on quality of Northern Snakehead fish fillets were observed during storage at 4 °C. Fish fillets were treated with 1-5 kGy gamma radiation, 0.05-0.5% cinnamon oil or the combination of radiation and cinnamon oil. The antimicrobial activity increased with radiation dose and cinnamon oil concentration. During storage, the combination of 1 kGy radiation and 0.5% cinnamon oil displayed better inhibiting activities on aerobic plate counts, total volatile basic nitrogen, thiobarbituric acid reaction substances than 1 kGy radiation or 0.5% cinnamon oil used alone. Moreover, the combination could arrive at the similar inhibiting activities of cinnamon oil with higher concentration of 0.5% or radiation with higher dose of 5 kGy. Thus, the combination could decrease the radiation dose and cinnamon oil concentration without decreasing the effect of them on maintaining fish quality.

  9. Human factors review of power plant maintainability. Final report

    International Nuclear Information System (INIS)

    Seminara, J.L.; Parsons, S.O.

    1981-02-01

    Human factors engineering is an interdisciplinary science and technology concerned with shaping the design of machines, facilities, and operational environments to promote safe, efficient, and reliable performance on the part of operators and maintainers of equipment systems. The human factors aspects of five nuclear power plants and four fossil fuel plants were evaluated using such methods as a check list guided observation system, structured interviews with maintenance personnel, direct observation of maintenance tasks, reviews of procedures, and analyses of maintenance errors or accidents by means of the critical incident technique. The study revealed a wide variety of human factors problem areas, most of which are extensively photodocumented. The study recommends that a more systematic and formal approach to ensure that future power plants are human engineered to the needs of maintenance personnel

  10. Sociable mobile robots through self-maintained energy

    DEFF Research Database (Denmark)

    Ngo, Trung Dung; Schiøler, Henrik

    2006-01-01

    society, collecting and sharing are experimentally recognized as the highest property. This paper issues an approach to sociable robots using self-maintained energy in robot society, which is naturally inspired from swarm behavior of honey-bee and ant. Typically, autonomous mobile robots are usually......Research of sociable robots has emphasized interaction and coordination of mobile robots with inspiration from natural behavior of birds, insects, and fish: flocking, foraging, collecting, sharing and so forth. However, the animal behaviors are looking for food towards survival. In an animal...... equipped with a finite energy, thus they can operate in a finite time. To overcome the limitation, we describe practical deployment of a group of mobile robot with the possibility of carrying and exchanging fuel, e.g. battery to other robots. Early implementation that includes modular hardware and control...

  11. The role of lactobacilli and probiotics in maintaining vaginal health.

    Science.gov (United States)

    Borges, Sandra; Silva, Joana; Teixeira, Paula

    2014-03-01

    The vaginal microbiota of healthy women consists typically of a diversity of anaerobic and aerobic microorganisms. Lactobacilli are the most prevalent and often numerically dominant microorganisms and are relevant as a barrier to infection. The capacity of lactobacilli to adhere and compete for adhesion sites in the vaginal epithelium and the capacity to produce antimicrobial compounds (hydrogen peroxide, lactic acid, bacteriocin-like substances), are important in the impairment of colonization by pathogens. This review summarizes the role of lactic acid bacteria in preventing illness of the host, including bacterial vaginosis, yeast vaginitis, urinary tract infection and sexually transmitted diseases. The administration of probiotics that colonize the vaginal tract can be important in maintaining a normal urogenital health and also to prevent or treat infections.

  12. Optimal design of a maintainable cold-standby system

    Energy Technology Data Exchange (ETDEWEB)

    Yu Haiyang [Universite de technologie de Troyes, ISTIT, Rue Marie Curie, BP 2060, 10010 TROYES (France)]. E-mail: Haiyang.YU@utt.fr; Yalaoui, Farouk [Universite de technologie de Troyes, ISTIT, Rue Marie Curie, BP 2060, 10010 TROYES (France); Chatelet, Eric [Universite de technologie de Troyes, ISTIT, Rue Marie Curie, BP 2060, 10010 TROYES (France); Chu Chengbin [Universite de technologie de Troyes, ISTIT, Rue Marie Curie, BP 2060, 10010 TROYES (France); Management School, Hefei University of Technology, Hefei (China)

    2007-01-15

    This paper considers a framework to optimally design a maintainable cold-standby system. Not only the maintenance policy is to be determined, but also the reliability character of the components will be taken into account. Hence, the mean time to failure of the components and the policy time of good-as-new maintenances are proposed as decision variables. Following probability analyses, the system cost rate and the system availability are formulated as the optimization object and the constraint, respectively. Then, this optimization problem is directly resolved by recognizing its underlying properties. Moreover, the resolving procedure is found to be independent of the failure distributions of the components and the forms of the system cost, which is illustrated through a numerical example. As a conclusion, an exact method is successfully established to minimize the cost rate of a cold-standby system with the given maintenance facility.

  13. Optimal design of a maintainable cold-standby system

    International Nuclear Information System (INIS)

    Yu Haiyang; Yalaoui, Farouk; Chatelet, Eric; Chu Chengbin

    2007-01-01

    This paper considers a framework to optimally design a maintainable cold-standby system. Not only the maintenance policy is to be determined, but also the reliability character of the components will be taken into account. Hence, the mean time to failure of the components and the policy time of good-as-new maintenances are proposed as decision variables. Following probability analyses, the system cost rate and the system availability are formulated as the optimization object and the constraint, respectively. Then, this optimization problem is directly resolved by recognizing its underlying properties. Moreover, the resolving procedure is found to be independent of the failure distributions of the components and the forms of the system cost, which is illustrated through a numerical example. As a conclusion, an exact method is successfully established to minimize the cost rate of a cold-standby system with the given maintenance facility

  14. The effects of irradiation on Babesia maintained in vitro

    International Nuclear Information System (INIS)

    Irvin, A.D.; Young, E.R.; Adams, P.J.V.

    1979-01-01

    Blood infected with Babesia rodhaini, B major or B divergens was irradiated to different absorbed doses between 0 and 120 krad, and then maintained in vitro in the presence of 3 H hypoxanthine for 24 h. The effects of irradiation were measured by the ability of the parasites to incorporate 3 H hypoxanthine and, in the case of B rodhaini, by the ability of the parasite to infect mice. B major and B divergens were slightly more radioresistant than B rodhaini, but all showed a progressive fall in ability to incorporate 3 H hypoxanthine with increasing does of irradiation when there was increased uptake of 3 H hypoxanthine. In the case of B rodhaini there was close correlation between the ability of the parasites to incorporate 3 H hypoxanthine and their infectivity for mice. Both types of activity were abolished at doses of 40 krad and above. (author)

  15. Rewarding peer reviewers: maintaining the integrity of science communication.

    Science.gov (United States)

    Gasparyan, Armen Yuri; Gerasimov, Alexey N; Voronov, Alexander A; Kitas, George D

    2015-04-01

    This article overviews currently available options for rewarding peer reviewers. Rewards and incentives may help maintain the quality and integrity of scholarly publications. Publishers around the world implemented a variety of financial and nonfinancial mechanisms for incentivizing their best reviewers. None of these is proved effective on its own. A strategy of combined rewards and credits for the reviewers1 creative contributions seems a workable solution. Opening access to reviews and assigning publication credits to the best reviews is one of the latest achievements of digitization. Reviews, posted on academic networking platforms, such as Publons, add to the transparency of the whole system of peer review. Reviewer credits, properly counted and displayed on individual digital profiles, help distinguish the best contributors, invite them to review and offer responsible editorial posts.

  16. Lipoprotein Lipase Maintains Microglial Innate Immunity in Obesity

    Directory of Open Access Journals (Sweden)

    Yuanqing Gao

    2017-09-01

    Full Text Available Consumption of a hypercaloric diet upregulates microglial innate immune reactivity along with a higher expression of lipoprotein lipase (Lpl within the reactive microglia in the mouse brain. Here, we show that knockdown of the Lpl gene specifically in microglia resulted in deficient microglial uptake of lipid, mitochondrial fuel utilization shifting to glutamine, and significantly decreased immune reactivity. Mice with knockdown of the Lpl gene in microglia gained more body weight than control mice on a high-carbohydrate high-fat (HCHF diet. In these mice, microglial reactivity was significantly decreased in the mediobasal hypothalamus, accompanied by downregulation of phagocytic capacity and increased mitochondrial dysmorphologies. Furthermore, HCHF-diet-induced POMC neuronal loss was accelerated. These results show that LPL-governed microglial immunometabolism is essential to maintain microglial function upon exposure to an HCHF diet. In a hypercaloric environment, lack of such an adaptive immunometabolic response has detrimental effects on CNS regulation of energy metabolism.

  17. Methods of achieving and maintaining an appropriate caesarean section rate.

    LENUS (Irish Health Repository)

    Robson, Michael

    2013-04-01

    Caesarean section rates continue to increase worldwide. The appropriate caesarean section rate remains a topic of debate among women and professionals. Evidence-based medicine has not provided an answer and depends on interpretation of the literature. Overall caesarean section rates are unhelpful, and caesarean section rates should not be judged in isolation from other outcomes and epidemiological characteristics. Better understanding of caesarean section rates, their consequences and their benefits will improve care, and enable learning between delivery units nationally and internationally. To achieve and maintain an appropriate caesarean section rate requires a Multidisciplinary Quality Assurance Programme in each delivery unit, recognising caesarean section rates as one of many factors that determine quality. Women will always choose the type of delivery that seems safest to them and their babies. Professionals need to monitor the quality of their practice continuously in a standardised way to ensure that women can make the right choice.

  18. Optimal fit of chairside-fabricated distal shoe space maintainer.

    Science.gov (United States)

    Nouri, M R; Kennedy, D B

    2013-10-01

    Premature loss of a primary second molar may lead to space loss in the dental arch. This space loss tends to be more severe in unfavourable malocclusions. The distal shoe space maintainer (DSSM) may be beneficial in controlling the path of eruption of an unerupted permanent first molar from the primary into the early mixed dentition. This article describes the technique for achieving optimal fit of a chairside-fabricated band and DSSM in a single visit by contouring the distal shoe blade, and by extending it to the mesial surface of the permanent first molar. Upon the eruption of the permanent first molar DSSM may be modified to a reverse band-and-loop, or replaced by a lingual holding arch.

  19. Hindbrain ghrelin receptor signaling is sufficient to maintain fasting glucose.

    Directory of Open Access Journals (Sweden)

    Michael M Scott

    Full Text Available The neuronal coordination of metabolic homeostasis requires the integration of hormonal signals with multiple interrelated central neuronal circuits to produce appropriate levels of food intake, energy expenditure and fuel availability. Ghrelin, a peripherally produced peptide hormone, circulates at high concentrations during nutrient scarcity. Ghrelin promotes food intake, an action lost in ghrelin receptor null mice and also helps maintain fasting blood glucose levels, ensuring an adequate supply of nutrients to the central nervous system. To better understand mechanisms of ghrelin action, we have examined the roles of ghrelin receptor (GHSR expression in the mouse hindbrain. Notably, selective hindbrain ghrelin receptor expression was not sufficient to restore ghrelin-stimulated food intake. In contrast, the lowered fasting blood glucose levels observed in ghrelin receptor-deficient mice were returned to wild-type levels by selective re-expression of the ghrelin receptor in the hindbrain. Our results demonstrate the distributed nature of the neurons mediating ghrelin action.

  20. Ecuador to withdraw from OPEC; group to maintain present flow

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that the Organization of Petroleum Exporting Countries, which has agreed to maintain its present combined production of 24.2 million b/d of oil in the fourth quarter, will soon see the first pullout of a member. The 13 member group will shrink to 12, probably in November, when Ecuador withdraws. Ecuador President Sixto Duran Ballen issued notice of the pullout Sept. 17, a little more than 1 month after he took office. Ecuador, strapped for cash, wants to save OPEC membership dues reported to be $2-3 million/year. It plans to remain an associate member, although it wasn't immediately clear what that means. No other countries are regarded as associate members

  1. KeyPathwayMinerWeb

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  2. Variability of Plyometric and Ballistic Exercise Technique Maintains Jump Performance.

    Science.gov (United States)

    Chandler, Phillip T; Greig, Matthew; Comfort, Paul; McMahon, John J

    2018-06-01

    Chandler, PT, Greig, M, Comfort, P, and McMahon, JJ. Variability of plyometric and ballistic exercise technique maintains jump performance. J Strength Cond Res 32(6): 1571-1582, 2018-The aim of this study was to investigate changes in vertical jump technique over the course of a training session. Twelve plyometric and ballistic exercise-trained male athletes (age = 23.4 ± 4.6 years, body mass = 78.7 ± 18.8 kg, height = 177.1 ± 9.0 cm) performed 3 sets of 10 repetitions of drop jump (DJ), rebound jump (RJ) and squat jump (SJ). Each exercise was analyzed from touchdown to peak joint flexion and peak joint flexion to take-off. Squat jump was analyzed from peak joint flexion to take-off only. Jump height, flexion and extension time and range of motion, and instantaneous angles of the ankle, knee, and hip joints were measured. Separate 1-way repeated analyses of variance compared vertical jump technique across exercise sets and repetitions. Exercise set analysis found that SJ had lower results than DJ and RJ for the angle at peak joint flexion for the hip, knee, and ankle joints and take-off angle of the hip joint. Exercise repetition analysis found that the ankle joint had variable differences for the angle at take-off, flexion, and extension time for RJ. The knee joint had variable differences for flexion time for DJ and angle at take-off and touchdown for RJ. There was no difference in jump height. Variation in measured parameters across repetitions highlights variable technique across plyometric and ballistic exercises. This did not affect jump performance, but likely maintained jump performance by overcoming constraints (e.g., level of rate coding).

  3. Human sclera maintains common characteristics with cartilage throughout evolution.

    Directory of Open Access Journals (Sweden)

    Yuko Seko

    Full Text Available BACKGROUND: The sclera maintains and protects the eye ball, which receives visual inputs. Although the sclera does not contribute significantly to visual perception, scleral diseases such as refractory scleritis, scleral perforation and pathological myopia are considered incurable or difficult to cure. The aim of this study is to identify characteristics of the human sclera as one of the connective tissues derived from the neural crest and mesoderm. METHODOLOGY/PRINCIPAL FINDINGS: We have demonstrated microarray data of cultured human infant scleral cells. Hierarchical clustering was performed to group scleral cells and other mesenchymal cells into subcategories. Hierarchical clustering analysis showed similarity between scleral cells and auricular cartilage-derived cells. Cultured micromasses of scleral cells exposed to TGF-betas and BMP2 produced an abundant matrix. The expression of cartilage-associated genes, such as Indian hedge hog, type X collagen, and MMP13, was up-regulated within 3 weeks in vitro. These results suggest that human 'sclera'-derived cells can be considered chondrocytes when cultured ex vivo. CONCLUSIONS/SIGNIFICANCE: Our present study shows a chondrogenic potential of human sclera. Interestingly, the sclera of certain vertebrates, such as birds and fish, is composed of hyaline cartilage. Although the human sclera is not a cartilaginous tissue, the human sclera maintains chondrogenic potential throughout evolution. In addition, our findings directly explain an enigma that the sclera and the joint cartilage are common targets of inflammatory cells in rheumatic arthritis. The present global gene expression database will contribute to the clarification of the pathogenesis of developmental diseases such as high myopia.

  4. Interferometric sensor based on the polarization-maintaining fibers

    Science.gov (United States)

    Cubik, Jakub; Kepak, Stanislav; Doricak, Jan; Vašinek, Vladimir; Liner, Andrej; Papes, Martin

    2012-01-01

    The interferometers composed of optical fibers are due to its high sensitivity capable of to measure various influences affecting the fiber. These influences may be bending or different sorts of fiber deformations, vibration, temperature, etc. In this case the vibration is the measured quantity, which is evaluated by analyzing the interference fringes representing changes in the fiber. Was used a Mach-Zehnder interferometer composed of the polarization maintaining elements. The polarization maintaining elements were used because of high sensitivity to polarization state inside the interferometer. The light was splitted into the two optical paths, where the first one is the reference fiber and it is separated from the actual phenomenon, and the second one is measuring fiber, which is directly exposed to vibration transmission from the underlying surface. The light source was narrowband DFB laser serating at a wavelength of 1550nm and as a detector an InGaAs PIN photodiode were used in this measurement. The electrical signal from the photodiode was amplified and fed into the measuring card. On the incoming signal the FFT was applied, which performs the transformation into the frequency domain and the results were further evaluated by software. We were evaluating the characteristic frequencies and their amplitude ratios. The frequency responses are unique for a given phenomenon, thus it is possible to identify recurring events by the characteristic frequencies and their amplitude ratios. The frequency range was limited by the properties of the used speaker, by the frequency characteristics of the filter in the amplifier and used resonant element. For the experiment evaluation the repeated impact of the various spherical objects on the surface board was performed and measured. The stability of amplitude and frequency and also the frequency range was verified in this measurement.

  5. Neural stem cells achieve and maintain pluripotency without feeder cells.

    Directory of Open Access Journals (Sweden)

    Hyun Woo Choi

    Full Text Available BACKGROUND: Differentiated cells can be reprogrammed into pluripotency by transduction of four defined transcription factors. Induced pluripotent stem cells (iPS cells are expected to be useful for regenerative medicine as well as basic research. Recently, the report showed that mouse embryonic fibroblasts (MEF cells are not essential for reprogramming. However, in using fibroblasts as donor cells for reprogramming, individual fibroblasts that had failed to reprogram could function as feeder cells. METHODOLOGY/PRINCIPAL FINDING: Here, we show that adult mouse neural stem cells (NSCs, which are not functional feeder cells, can be reprogrammed into iPS cells using defined four factors (Oct4, Sox2, Klf4, and c-Myc under feeder-free conditions. The iPS cells, generated from NSCs expressing the Oct4-GFP reporter gene, could proliferate for more than two months (passage 20. Generated and maintained without feeder cells, these iPS cells expressed pluripotency markers (Oct4 and Nanog, the promoter regions of Oct4 and Nanog were hypomethylated, could differentiated into to all three germ layers in vitro, and formed a germline chimera. These data indicate that NSCs can achieve and maintain pluripotency under feeder-free conditions. CONCLUSION/SIGNIFICANCE: This study suggested that factors secreted by feeder cells are not essential in the initial/early stages of reprogramming and for pluripotency maintenance. This technology might be useful for a human system, as a feeder-free reprogramming system may help generate iPS cells of a clinical grade for tissue or organ regeneration.

  6. Cost-effective solutions to maintaining smart grid reliability

    Science.gov (United States)

    Qin, Qiu

    As the aging power systems are increasingly working closer to the capacity and thermal limits, maintaining an sufficient reliability has been of great concern to the government agency, utility companies and users. This dissertation focuses on improving the reliability of transmission and distribution systems. Based on the wide area measurements, multiple model algorithms are developed to diagnose transmission line three-phase short to ground faults in the presence of protection misoperations. The multiple model algorithms utilize the electric network dynamics to provide prompt and reliable diagnosis outcomes. Computational complexity of the diagnosis algorithm is reduced by using a two-step heuristic. The multiple model algorithm is incorporated into a hybrid simulation framework, which consist of both continuous state simulation and discrete event simulation, to study the operation of transmission systems. With hybrid simulation, line switching strategy for enhancing the tolerance to protection misoperations is studied based on the concept of security index, which involves the faulted mode probability and stability coverage. Local measurements are used to track the generator state and faulty mode probabilities are calculated in the multiple model algorithms. FACTS devices are considered as controllers for the transmission system. The placement of FACTS devices into power systems is investigated with a criterion of maintaining a prescribed level of control reconfigurability. Control reconfigurability measures the small signal combined controllability and observability of a power system with an additional requirement on fault tolerance. For the distribution systems, a hierarchical framework, including a high level recloser allocation scheme and a low level recloser placement scheme, is presented. The impacts of recloser placement on the reliability indices is analyzed. Evaluation of reliability indices in the placement process is carried out via discrete event

  7. Pathways Intern Report

    Science.gov (United States)

    Bell, Evan A.

    2015-01-01

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

  8. pathways in myogenesis

    Directory of Open Access Journals (Sweden)

    Marta Milewska

    2014-05-01

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

  9. Recommended techniques for effective maintainability. A continuous improvement initiative of the NASA Reliability and Maintainability Steering Committee

    Science.gov (United States)

    1994-01-01

    This manual presents a series of recommended techniques that can increase overall operational effectiveness of both flight and ground based NASA systems. It provides a set of tools that minimizes risk associated with: (1) restoring failed functions (both ground and flight based); (2) conducting complex and highly visible maintenance operations; and (3) sustaining a technical capability to support the NASA mission using aging equipment or facilities. It considers (1) program management - key elements of an effective maintainability effort; (2) design and development - techniques that have benefited previous programs; (3) analysis and test - quantitative and qualitative analysis processes and testing techniques; and (4) operations and operational design techniques that address NASA field experience. This document is a valuable resource for continuous improvement ideas in executing the systems development process in accordance with the NASA 'better, faster, smaller, and cheaper' goal without compromising safety.

  10. Non-Smad signaling pathways.

    Science.gov (United States)

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

    2012-01-01

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

  11. Protein design for pathway engineering.

    Science.gov (United States)

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

    2014-02-01

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

  12. Advanced digital technology - improving nuclear power plant performance through maintainability

    International Nuclear Information System (INIS)

    Ford, J.L.; Senechal, R.R.; Altenhein, G.D.; Harvey, R.P.

    1998-01-01

    In today's energy sector there is ever increasing pressure on utilities to operate power plants at high capacity factors. To ensure nuclear power is competitive into the next century, it is imperative that strategic design improvements be made to enhance the performance of nuclear power plants. There are a number of factors that affect a nuclear power plant's performance; lifetime maintenance is one of the major contributors. The maturing of digital technology has afforded ABB the opportunity to make significant design improvements in the area of maintainability. In keeping with ABB's evolutionary advanced nuclear plant design approach, digital technology has systematically been incorporated into the control and protection systems of the most recent Korean nuclear units in operation and under construction. One example of this was the multi-functional design team approach that was utilized for the development of ABB's Digital Plant Protection System (DPPS). The design team consisted of engineers, maintenance technicians, procurement specialists and manufacturing personnel in order to provide a complete perspective on all facets of the design. The governing design goals of increased reliability and safety, simplicity of design, use of off-the-shelf products and reduced need for periodic surveillance testing were met with the selection of proven ABB-Advant Programmable Logic Controllers (PLCs) as the heart of the DPPS. The application of digital PLC technology allows operation for extended periods without requiring routine maintenance or re-calibration. A well documented commercial dedication program approved by the United States Nuclear Regulatory Commission (US NRC) as part of the System 80+ TM Advanced Light Water Reactor Design Certification Program, allowed the use of off-the shelf products in the design of the safety protection system. In addition, a number of mechanical and electrical improvements were made which support maintainability. The result is a DPPS

  13. How to maintain nuclear competence and knowledge management in Europe

    International Nuclear Information System (INIS)

    Comsa, Olivia; Meglea, Claudia; Paraschiva, M. V.; Banutoiu, Maria; Popescu, C.

    2002-01-01

    possible measures envisaged at European level should especially support those candidate countries that are using nuclear power. All states must have their own access to the appropriate nuclear education and research programmes. This support is important for the whole European nuclear community to ensure the continued safe operation and decommissioning of nuclear plants in the future. Another aspect to be taken fully into consideration is the fact that assuring nuclear education and training and maintaining nuclear competence necessitates the existence of a significant infrastructure. This costly infrastructure has lasted several decades but over the past few years has undergone many changes in response to the needs of a changing nuclear sector. An appropriate infrastructure, which meets future needs, has to be maintained, but this has to be in a sustainable way and with the necessary means. Steps need to be taken to proactively define what are an appropriate infrastructure and the possible measures, which can be used to ensure its continued support. (authors)

  14. Professionals with hearing loss: maintaining that competitive edge.

    Science.gov (United States)

    Tye-Murray, Nancy; Spry, Jacqueline L; Mauzé, Elizabeth

    2009-08-01

    The goals of this investigation were to gauge how hearing loss affects the self-perceived job performance and psycho-emotional status of professionals in the workforce and to develop a profile of their aural rehabilitation needs. Forty-eight participants who had at least a high school education and who hold salaried positions participated in one of seven focus groups. Participants first answered questions about a hypothetical executive who had hearing loss and considered how she might react to various communication issues. They then addressed questions about their own work-related predicaments. The sessions were audiovideo recorded and later transcribed for analysis. Unlike workers who have occupational hearing loss, the professionals in this investigation seem not to experience an inordinate degree of stigmatization in their workplaces, although most believe that hearing loss has negatively affected their job performance. Some of the participants believe that they have lost their "competitive edge," and some believe that they have been denied promotions because of hearing loss. However, most report that they have overcome their hearing-related difficulties by various means, and many have developed a determination and stamina to remain active in the workforce. The majority of the participants seemed to be unfamiliar with the Americans with Disability Act, Public Law 101-336. The overriding theme to emerge is that professionals desire to maintain their competency to perform their jobs and will do what they have to do to "get the job done." The situations of professionals who have hearing loss can be modeled, with a central theme of maintaining job competency or a competitive edge. It is hypothesized that five factors affect professionals' abilities to continue their optimal work performance in the face of hearing loss: (a) self-concept and sense of internal locus of control, (b) use of hearing assistive technology, (c) supervisor's and co-workers' perceptions and

  15. The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity

    Science.gov (United States)

    Li, Yuan; Chen, Baohui; Zou, Wei; Wang, Xin; Wu, Yanwei; Zhao, Dongfeng; Sun, Yanan; Liu, Yubing

    2016-01-01

    Lysosomes degrade macromolecules and recycle metabolites as well as being involved in diverse processes that regulate cellular homeostasis. The lysosome is limited by a single phospholipid bilayer that forms a barrier to separate the potent luminal hydrolases from other cellular constituents, thus protecting the latter from unwanted degradation. The mechanisms that maintain lysosomal membrane integrity remain unknown. Here, we identified SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, as a key regulator of lysosome integrity, motility, and dynamics. Loss of scav-3 caused rupture of lysosome membranes and significantly shortened lifespan. Both of these phenotypes were suppressed by reinforced expression of LMP-1 or LMP-2, the C. elegans LAMPs, indicating that longevity requires maintenance of lysosome integrity. Remarkably, reduction in insulin/insulin-like growth factor 1 (IGF-1) signaling suppressed lysosomal damage and extended the lifespan in scav-3(lf) animals in a DAF-16–dependent manner. Our data reveal that SCAV-3 is essential for preserving lysosomal membrane stability and that modulation of lysosome integrity by the insulin/IGF-1 signaling pathway affects longevity. PMID:27810910

  16. Solar Energy Grid Integration Systems (SEGIS): adding functionality while maintaining reliability and economics

    Science.gov (United States)

    Bower, Ward

    2011-09-01

    An overview of the activities and progress made during the US DOE Solar Energy Grid Integration Systems (SEGIS) solicitation, while maintaining reliability and economics is provided. The SEGIS R&D opened pathways for interconnecting PV systems to intelligent utility grids and micro-grids of the future. In addition to new capabilities are "value added" features. The new hardware designs resulted in smaller, less material-intensive products that are being viewed by utilities as enabling dispatchable generation and not just unpredictable negative loads. The technical solutions enable "advanced integrated system" concepts and "smart grid" processes to move forward in a faster and focused manner. The advanced integrated inverters/controllers can now incorporate energy management functionality, intelligent electrical grid support features and a multiplicity of communication technologies. Portals for energy flow and two-way communications have been implemented. SEGIS hardware was developed for the utility grid of today, which was designed for one-way power flow, for intermediate grid scenarios, AND for the grid of tomorrow, which will seamlessly accommodate managed two-way power flows as required by large-scale deployment of solar and other distributed generation. The SEGIS hardware and control developed for today meets existing standards and codes AND provides for future connections to a "smart grid" mode that enables utility control and optimized performance.

  17. Canonical Wnt signaling maintains the quiescent stage of hepatic stellate cells

    International Nuclear Information System (INIS)

    Kordes, Claus; Sawitza, Iris; Haeussinger, Dieter

    2008-01-01

    It is well known that hepatic stellate cells (HSC) develop into cells, which are thought to contribute to liver fibrogenesis. Recent data suggest that HSC are progenitor cells with the capacity to differentiate into cells of endothelial and hepatocyte lineages. The present study shows that β-catenin-dependent canonical Wnt signaling is active in freshly isolated HSC of rats. Mimicking of the canonical Wnt pathway in cultured HSC by TWS119, an inhibitor of the glycogen synthase kinase 3β, led to reduced β-catenin phosphorylation, induced nuclear translocation of β-catenin, elevated glutamine synthetase production, impeded synthesis of α-smooth muscle actin and Wnt5a, but promoted the expression of glial fibrillary acidic protein, Wnt10b, and paired-like homeodomain transcription factor 2c. In addition, canonical Wnt signaling lowered DNA synthesis and hindered HSC from entering the cell cycle. The findings demonstrate that β-catenin-dependent Wnt signaling maintains the quiescent state of HSC and, similar to stem and progenitor cells, influences their developmental fate

  18. Focal adhesion kinase maintains, but not increases the adhesion of dental pulp cells.

    Science.gov (United States)

    Qian, Yuyan; Shao, Meiying; Zou, Wenlin; Wang, Linyan; Cheng, Ran; Hu, Tao

    2017-04-01

    Focal adhesion kinase (FAK) functions as a key enzyme in the integrin-mediated adhesion-signalling pathway. Here, we aimed to investigate the effects of FAK on adhesion of human dental pulp (HDP) cells. We transfected lentiviral vectors to silence or overexpress FAK in HDP cells ex vivo. Early cell adhesion, cell survival and focal contacts (FCs)-related proteins (FAK and paxillin) were examined. By using immunofluorescence, the formation of FCs and cytoskeleton was detected, respectively. We found that both adhesion and survival of HDP cells were suppressed by FAK inhibition. However, FAK overexpression slightly inhibited cell adhesion and exhibited no change in cell survival compared with the control. A thick rim of cytoskeleton accumulated and smaller dot-shaped FCs appeared in FAK knockdown cells. Phosphorylation of paxillin (p-paxillin) was inhibited in FAK knockdown cells, verifying that the adhesion was inhibited. Less cytoskeleton and elongated FCs were observed in FAK-overexpressed cells. However, p-paxillin had no significant difference compared with the control. In conclusion, the data suggest that FAK maintains cell adhesion, survival and cytoskeleton formation, but excessive FAK has no positive effects on these aspects.

  19. Do multiple herbivores maintain chemical diversity of Scots pine monoterpenes?

    Science.gov (United States)

    Iason, Glenn R.; O'Reilly-Wapstra, Julianne M.; Brewer, Mark J.; Summers, Ron W.; Moore, Ben D.

    2011-01-01

    A central issue in our understanding of the evolution of the diversity of plant secondary metabolites (PSMs) is whether or not compounds are functional, conferring an advantage to the plant, or non-functional. We examine the hypothesis that the diversity of monoterpene PSMs within a plant species (Scots pine Pinus sylvestris) may be explained by different compounds acting as defences against high-impact herbivores operating at different life stages. We also hypothesize that pairwise coevolution, with uncorrelated interactions, is more likely to result in greater PSM diversity, than diffuse coevolution. We tested whether up to 13 different monoterpenes in Scots pine were inhibitory to herbivory by slugs (Arion ater), bank voles (Clethrionomys glareolus), red deer (Cervus elaphus) and capercaillie (Tetrao urogallus), each of which attack trees at a different life stage. Plants containing more α-pinene were avoided by both slugs and capercaillie, which may act as reinforcing selective agents for this dominant defensive compound. Herbivory by red deer and capercaillie were, respectively, weakly negatively associated with δ3-carene, and strongly negatively correlated with the minor compound β-ocimene. Three of the four herbivores are probably contributory selective agents on some of the terpenes, and thus maintain some, but by no means all, of the phytochemical diversity in the species. The correlated defensive function of α-pinene against slugs and capercaillie is consistent with diffuse coevolutionary processes. PMID:21444308

  20. Maintaining replication origins in the face of genomic change.

    Science.gov (United States)

    Di Rienzi, Sara C; Lindstrom, Kimberly C; Mann, Tobias; Noble, William S; Raghuraman, M K; Brewer, Bonita J

    2012-10-01

    Origins of replication present a paradox to evolutionary biologists. As a collection, they are absolutely essential genomic features, but individually are highly redundant and nonessential. It is therefore difficult to predict to what extent and in what regard origins are conserved over evolutionary time. Here, through a comparative genomic analysis of replication origins and chromosomal replication patterns in the budding yeasts Saccharomyces cerevisiae and Lachancea waltii, we assess to what extent replication origins survived genomic change produced from 150 million years of evolution. We find that L. waltii origins exhibit a core consensus sequence and nucleosome occupancy pattern highly similar to those of S. cerevisiae origins. We further observe that the overall progression of chromosomal replication is similar between L. waltii and S. cerevisiae. Nevertheless, few origins show evidence of being conserved in location between the two species. Among the conserved origins are those surrounding centromeres and adjacent to histone genes, suggesting that proximity to an origin may be important for their regulation. We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved.

  1. Nutritional support to maintain proper immune status during intense training.

    Science.gov (United States)

    Gleeson, Michael

    2013-01-01

    Prolonged exercise and heavy training are associated with depressed immune function which can increase the risk of picking up minor infections. To maintain robust immunity, athletes should eat a well-balanced diet sufficient to meet their energy, carbohydrate, protein, and micronutrient requirements. Dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction and an adequate intake of iron, zinc, and vitamins A, D, E, B6 and B12 is particularly important in the maintenance of immune function. Consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears to limit the degree of exercise-induced immune depression. Similar effects can be seen with daily ingestion of high-dose antioxidant vitamin supplements, though concerns have been expressed that excessive antioxidant intake may impair exercise training adaptations. It is safe to say with reasonable confidence that individual amino acids, colostrum, Echinacea, and zinc are unlikely to boost immunity or reduce infection risk in athletes. The ingestion of carbohydrate during exercise and daily consumption of probiotic and plant polyphenol (e.g. quercetin)-containing supplements or foodstuffs (e.g. non-alcoholic beer) currently offer the best chance of success. This approach is likely to be most effective for individuals who are particularly prone to illness. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  2. Evolution of design concepts for remotely maintainable equipment racks

    International Nuclear Information System (INIS)

    Peishel, F.L.; Mouring, R.W.; Schrock, S.L.

    1986-01-01

    Equipment racks have been used to support process equipment in radioactive facilities for many years. Improvements in the design of these racks have evolved relatively slowly primarily as a result of limitations in the capabilities of maintenance equipment; that is, tasks could only be approached from above using bridge cranes with viewing primarily through periscopes. In recent years, however, technological advances have been made by the Consolidated Fuel Reprocessing Program (CFRP) at Oak Ridge National Laboratory (ORNL) in bridge-mounted servomanipulators with onboard auxiliary hoists and television viewing systems. These advances permit full cell coverage by the manipulator arms which, in turn, allow maintenance tasks to be approached horizontally as well as from above. Maintainable equipment items can be stacked vertically on a rack because total overhead access is less important and maintenance tasks that would not have been attempted in the past can now be performed. These advances permit greater flexibility in the design and cell layout of the racks and lead to concepts that could significantly increase the availability of a facility. The evolution of rack design and a description of the alternative concepts based on present maintenance systems capabilities are presented in this paper. 13 refs., 11 figs

  3. Diminishing self-disclosure to maintain security in partners' care.

    Science.gov (United States)

    Lemay, Edward P; Melville, Michael C

    2014-01-01

    Six studies demonstrate that perceivers' desire to bond with targets motivates perceivers to misconstrue their own self-disclosure in ways that maintain perceivers' security in targets' care and commitment. Perceivers who strongly valued relationships with targets reported high levels of global self-disclosure, consistent with many findings suggesting salutary effects of disclosure. However, these same perceivers reported low self-disclosure of needs and desires in hypothetical (Study 1) and actual (Study 2) situations characterized by targets' unresponsive behavior. Similarly, in daily report (Study 3) and behavioral observation (Study 4) studies, perceivers who valued relationships with targets perceived high levels of self-disclosure when targets were responsive, but they perceived low self-disclosure when targets were unresponsive, and these perceptions seemed partly illusory. In turn, these perceptions of low self-disclosure in situations characterized by partners' unresponsive behavior predicted decreased perceptions of diagnosticity of targets' behavior (Studies 1-3) and buffered the negative affective and interpersonal effects of unresponsive behavior (Study 4). Experimental manipulations (Studies 5 and 6) demonstrated the motivational nature of perceived self-disclosure. Collectively, the results suggest that a desire to bond with targets motivates perceivers to downplay the diagnosticity of targets' unresponsive behavior through diminishing their self-disclosure, in turn preserving perceivers' trust in targets' care and commitment.

  4. Customer retention: maintaining the competitive edge in the retail market

    Energy Technology Data Exchange (ETDEWEB)

    Wright, T. [CitiPower Ltd., Melbourne, VIC (Australia)

    1997-09-01

    The current market environment in the electricity industry is one of changing regulations with many of the rules being developed. There is a great deal of customer confusion and uncertainty with some customers unaware of their contestable status and many are insecure about mixing retail and distribution supplies. This paper discusses customer retention and maintaining the competitive edge in the retail market. It draws on some conclusions from a survey released by the Australian Chamber of Manufacturers entitled `Customer feedback on Victoria`s competitive electricity market`. An overview is presented of the retail market in Australia which is one of very strong price-based competition, with as yet little differentiation. A process is described for retaining customers which involves asking the customer what he/she wants in a language which they understand. The best way to determine customer needs is through a combination of internal and external sources. Enhancing customer loyalty and differentiating and marketing the product are also discussed. As the market matures, customer retention and satisfaction will be based on value added services at a reasonable cost. (author). 6 figs.

  5. Maintaining the Link to The Floodplain: Scour Dynamics in Crevasses

    Science.gov (United States)

    Esposito, C. R.; Liang, M.; Yuill, B. T.; Meselhe, E. A.

    2017-12-01

    In river deltas, crevasses are the primary geomorphic feature that traverse the levee, connecting the river to its floodplain and facilitating the transfer of water, sediment, and chemical constituents from the trunk channel. Despite their fundamental position linking river and floodplain, the factors that are important to crevasse evolution are not well understood, and their enumeration is the subject of active research across multiple earth surface process subfields. Crevasses are often associated with a zone of intense scour proximal to the trunk channel. Surprisingly little is known about the morphological dynamics in this zone, but there is evidence from studies of river avulsion that scour zone evolution plays an important role in determining crevasse sustainability. Here we use Delft3D to simulate the development of managed crevasse splays - river diversions - for the purpose of landscape management in the Mississippi River Delta. Our model runs vary the erodibility of the substrate in the receiving basin and the extent and location of erosion protection along the conveyance channel. We find that substrate erodibility in the basin plays a critical role in determining the long-term performance of sediment diversions. Crevasses that create large scours tend to maintain their performance over several decades, but those that only create small scours are subject to rapidly declining performance as the scour pit fills in with coarse sediments. Finally, we compare the evolution of our modeled scour zone to the West Bay Sediment Diversion, where regular bathymetric surveys have documented the evolution of the scour zone since 2004.

  6. Maintaining leak tightness capability of Caorso BWR containment

    International Nuclear Information System (INIS)

    Barsanti, P.; Di Palo, L.; Grimaldi, G.

    1988-01-01

    In 1987 the local leak rate test (LLRT) results of the primary containment were revised, with the following main goals: to highlight recurring problems, leading to lack of leak tightness of the primary containment; to individuate the pertinent degradation mechanisms; to assess the corrective actions already implemented and to plan further improvements, if necessary; and to optimize the preventive maintenance program on the containment, particularly the inspection frequency. All LLRTs in the past operating period, both before (as found) and after (as left) maintenance were analyzed, in terms of leakage rate and equivalent area of leak, for each penetration. Corrective actions already implemented included replacement of some valves with better quality type one, passivation of the carbon steel pipes and improvement of the pertinent surveillance procedures. Long term corrective actions, now under consideration, will include the following: more extensive passivation of pipes, carrying humid air, so that oxidation could be drastically reduced; better chemistry control in fluid systems; extensive replacement of the butterfly valves presently used; implementation of the LLRT practice, such to quantitatively measure the leakage rate, also in presence of large leak; and reduction of the time interval between periodical tests, on the basis of the results of the previous ones. Following these guidelines, future overall leakage tests would be performed in as found condition, aimed to verify the effectiveness of the entire maintenance and testing program of the primary containment and of its capability to maintain leak tightness during the time between two subsequent tests

  7. Strategies to maintain health in the Third World.

    Science.gov (United States)

    Korte, R; Rehle, T; Merkle, A

    1991-12-01

    International cooperation with Third World countries aims at reducing the high morbidity and mortality of the population to a tolerable level. The main health problems are caused by poverty. Thus, the range of diseases in tropical countries can be explained more readily by the socio-economic situation than solely by the climate. Health services, in Africa in particular, have had to reduce drastically their budgets in the last ten years and now have only approximately 1/1000th of the funds usually available in industrialised countries. High population growth reduces the resources available per head, increases infection potential and worsens living conditions. Control strategies must take account of these circumstances in order to achieve the required sustained effect within the framework of primary health care. The example of the control of several infectious diseases, such as schistosomiasis, pneumonia, malaria and AIDS, is used to show that control programmes can be effective but, in the current conditions, can hardly be maintained without outside support. In the future, diseases caused by environmental problems and new life styles as a result of industrialization, urbanization and slum growth will move dramatically into the foreground.

  8. Lactobacillus casei combats acid stress by maintaining cell membrane functionality.

    Science.gov (United States)

    Wu, Chongde; Zhang, Juan; Wang, Miao; Du, Guocheng; Chen, Jian

    2012-07-01

    Lactobacillus casei strains have traditionally been recognized as probiotics and frequently used as adjunct culture in fermented dairy products where lactic acid stress is a frequently encountered environmental condition. We have investigated the effect of lactic acid stress on the cell membrane of L. casei Zhang [wild type (WT)] and its acid-resistant mutant Lbz-2. Both strains were grown under glucose-limiting conditions in chemostats; following challenge by low pH, the cell membrane stress responses were investigated. In response to acid stress, cell membrane fluidity decreased and its fatty acid composition changed to reduce the damage caused by lactic acid. Compared with the WT, the acid-resistant mutant exhibited numerous survival advantages, such as higher membrane fluidity, higher proportions of unsaturated fatty acids, and higher mean chain length. In addition, cell integrity analysis showed that the mutant maintained a more intact cellular structure and lower membrane permeability after environmental acidification. These results indicate that alteration in membrane fluidity, fatty acid distribution, and cell integrity are common mechanisms utilized by L. casei to withstand severe acidification and to reduce the deleterious effect of lactic acid on the cell membrane. This detailed comparison of cell membrane responses between the WT and mutant add to our knowledge of the acid stress adaptation and thus enable new strategies to be developed aimed at improving the industrial performance of this species under acid stress.

  9. Refractive index retrieving of polarization maintaining optical fibers

    Science.gov (United States)

    Ramadan, W. A.; Wahba, H. H.; Shams El-Din, M. A.; Abd El-Sadek, I. G.

    2018-01-01

    In this paper, the cross-section images, of two different types of polarization maintaining (PM) optical fibers, are employed to estimate the optical phase variation due to transverse optical rays passing through these optical fibers. An adaptive algorithm is proposed to recognize the different areas constituting the PM optical fibers cross-sections. These areas are scanned by a transverse beam to calculate the optical paths for given values of refractive indices. Consequently, the optical phases across the PM optical fibers could be recovered. PM optical fiber is immersed in a matching fluid and set in the object arm of Mach-Zehnder interferometer. The produced interferograms are analyzed to extract the optical phases caused by the PM optical fibers. The estimated optical phases could be optimized to be in good coincidence with experimentally extracted ones. This has been achieved through changing of the PM optical fibers refractive indices to retrieve the correct values. The correct refractive indices values are confirmed by getting the best fit between the estimated and the extracted optical phases. The presented approach is a promising one because it provides a quite direct and accurate information about refractive index, birefringence and beat length of PM optical fibers comparing with different techniques handle the same task.

  10. GABA-independent GABAA Receptor Openings Maintain Tonic Currents

    Science.gov (United States)

    Wlodarczyk, Agnieszka I.; Sylantyev, Sergiy; Herd, Murray B.; Kersanté, Flavie; Lambert, Jeremy J.; Rusakov, Dmitri A.; Linthorst, Astrid C.E.; Semyanov, Alexey; Belelli, Delia; Pavlov, Ivan; Walker, Matthew C.

    2013-01-01

    Activation of GABAA receptors (GABAARs) produces two forms of inhibition: ‘phasic’ inhibition generated by the rapid, transient activation of synaptic GABAARs by presynaptic GABA release, and tonic inhibition generated by the persistent activation of peri- or extrasynaptic GABAARs which can detect extracellular GABA. Such tonic GABAAR-mediated currents are particularly evident in dentate granule cells in which they play a major role in regulating cell excitability. Here we show that in rat dentate granule cells in ex-vivo hippocampal slices, tonic currents are predominantly generated by GABA-independent GABAA receptor openings. This tonic GABAAR conductance is resistant to the competitive GABAAR antagonist SR95531, which at high concentrations acts as a partial agonist, but can be blocked by an open channel blocker picrotoxin. When slices are perfused with 200 nM GABA, a concentration that is comparable to cerebrospinal fluid concentrations but is twice that measured by us in the hippocampus in vivo using zero-net-flux microdialysis, negligible GABA is detected by dentate granule cells. Spontaneously opening GABAARs, therefore, maintain dentate granule cell tonic currents in the face of low extracellular GABA concentrations. PMID:23447601

  11. Creatine maintains intestinal homeostasis and protects against colitis.

    Science.gov (United States)

    Turer, Emre; McAlpine, William; Wang, Kuan-Wen; Lu, Tianshi; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Wang, Tao; Zhan, Xiaowei; Bu, Chun-Hui; Murray, Anne R; Beutler, Bruce

    2017-02-14

    Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N -ethyl- N -nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted ( Gatm c/c ) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatm c/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatm c/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury.

  12. Maintaining relationships with your patients by maximizing your online presence.

    Science.gov (United States)

    Donnelly, John; Kaaihue, Maarit

    2011-01-01

    Medical practices that take full advantage of today's online consumer-driven culture will leave other practices in their wake. With today's modern consumers looking to the Internet more and more for finding medical solutions for their family, it is imperative that your practice uses all of the tools available for creating and maintaining its online presence. We all know that having a functional Web site these days is a necessity for practically any business in any industry; however, taking your online presence further by using a few techniques can set up your practice for great success. Your online marketing should help your practice with managing patient relationships at all levels. To best reach this goal, continually analyzing data and updating your online marketing approach will help further drive leads and conversions. Using a few search engine optimization techniques as well as optimal design and marketing methods will allow you to more easily find prospective patients, build trust and credibility with your current patients, and manage your reputation.

  13. Microbiological testing of devices used in maintaining peripheral venous catheters

    Directory of Open Access Journals (Sweden)

    Fernanda de Paula Rossini

    Full Text Available ABSTRACT Objective: to evaluate the use of peripheral venous catheters based on microbiological analysis of devices (dressing and three-way stopcocks and thus contribute to the prevention and infection control. Methods: this was a prospective study of microbiological analysis of 30 three-way stopcocks (external surfaces and lumens and 30 dressing used in maintaining the peripheral venous catheters of hospitalized adult patients. Results: all external surfaces, 40% of lumens, and 86.7% of dressing presented bacterial growth. The main species isolated in the lumen were 50% coagulase-negative Staphylococcus, 14.3% Staphylococcus aureus, and 14.3% Pseudomonas aeruginosa. Fifty nine percent of multidrug-resistant bacteria were isolated of the three-way stopcocks, 42% of the lumens, and 44% of the dressing with a predominance of coagulase-negative Staphylococcus resistant to methicillin. Besides, 18% gram-negative bacteria with resistance to carbapenems were identified from multidrug-resistant bacteria on the external surfaces of the three-way stopcocks. Conclusion: it is important to emphasize the isolation of coagulase-negative Staphylococcus and gram-negative bacteria resistant to methicillin and carbapenems in samples of devices, respectively, which reinforces the importance of nursing care in the maintenance of the biologically safe environment as well as prevention and infection control practices.

  14. Maintaining US Space Weather Capabilities after DMSP: Research to Operations

    Science.gov (United States)

    Machuzak, J. S.; Gentile, L. C.; Burke, W. J.; Holeman, E. G.; Ober, D. M.; Wilson, G. R.

    2012-12-01

    The first Defense Meteorological Satellite Program (DMSP) spacecraft was launched in 1972; the last is scheduled to fly in 2020. Presently, there is no replacement for the space-weather monitoring sensors that now fly on DMSP. The present suite has provided comprehensive, long-term records that constitute a critical component of the US space weather corporate memory. Evolving operational needs and research accomplishments justify continued collection of space environmental data. Examples include measurements to: (1) Monitor the Dst index in real time as a driver of next-generation satellite drag models; (2) Quantify electromagnetic energy fluxes from deep space to the ionosphere/ thermosphere that heat neutrals, drive disturbance-dynamo winds and degrade precise orbit determinations; (3) Determine strengths of stormtime electric fields at high and low latitudes that lead to severe blackouts and spacecraft anomalies; (4) Specify variability of plasma density irregularities, equatorial plasma bubbles, and the Appleton anomaly to improve reliability of communication, navigation and surveillance links; (5) Characterize energetic particle fluxes responsible for auroral clutter and radar degradation; (6) Map regions of L-Band scintillation for robust GPS applications; and (7) Update the World Magnetic Field Model needed to maintain guidance system superiority. These examples illustrate the utility of continued space environment awareness. Comprehensive assessments of both operational requirements and research advances are needed to make informed selections of sensors and spacecraft that support future capabilities. A proposed sensor set and satellite constellation to provide the needed measurement capabilities will be presented.

  15. Interaction of historical and nonhistorical disturbances maintains native plant communities.

    Science.gov (United States)

    Davies, K W; Svejcar, T J; Bates, J D

    2009-09-01

    Historical disturbance regimes are often considered a critical element in maintaining native plant communities. However, the response of plant communities to disturbance may be fundamentally altered as a consequence of invasive plants, climate change, or prior disturbances. The appropriateness of historical disturbance patterns under modern conditions and the interactions among disturbances are issues that ecologists must address to protect and restore native plant communities. We evaluated the response of Artemisia tridentata ssp. wyomingensis (Beetle & A. Young) S.L. Welsh plant communities to their historical disturbance regime compared to other disturbance regimes. The historical disturbance regime of these plant communities was periodic fires with minimal grazing by large herbivores. We also investigated the influence of prior disturbance (grazing) on the response of these communities to subsequent disturbance (burning). Treatments were: (1) ungrazed (livestock grazing excluded since 1936) and unburned, (2) grazed and unburned, (3) ungrazed and burned (burned in 1993), and (4) grazed and burned. The ungrazed-burned treatment emulated the historical disturbance regime. Vegetation cover, density, and biomass production were measured the 12th, 13th, and 14th year post-burning. Prior to burning the presence of Bromus tectorum L., an exotic annual grass, was minimal (resilience to more severe disturbances. Modern deviations from historical conditions can alter ecosystem response to disturbances, thus restoring the historical disturbance regime may not be an appropriate strategy for all ecosystems.

  16. Dangerous Animals Capture and Maintain Attention in Humans

    Directory of Open Access Journals (Sweden)

    Jessica L. Yorzinski

    2014-07-01

    Full Text Available Predation is a major source of natural selection on primates and may have shaped attentional processes that allow primates to rapidly detect dangerous animals. Because ancestral humans were subjected to predation, a process that continues at very low frequencies, we examined the visual processes by which men and women detect dangerous animals (snakes and lions. We recorded the eye movements of participants as they detected images of a dangerous animal (target among arrays of nondangerous animals (distractors as well as detected images of a nondangerous animal (target among arrays of dangerous animals (distractors. We found that participants were quicker to locate targets when the targets were dangerous animals compared with nondangerous animals, even when spatial frequency and luminance were controlled. The participants were slower to locate nondangerous targets because they spent more time looking at dangerous distractors, a process known as delayed disengagement, and looked at a larger number of dangerous distractors. These results indicate that dangerous animals capture and maintain attention in humans, suggesting that historical predation has shaped some facets of visual orienting and its underlying neural architecture in modern humans.

  17. Dangerous animals capture and maintain attention in humans.

    Science.gov (United States)

    Yorzinski, Jessica L; Penkunas, Michael J; Platt, Michael L; Coss, Richard G

    2014-05-28

    Predation is a major source of natural selection on primates and may have shaped attentional processes that allow primates to rapidly detect dangerous animals. Because ancestral humans were subjected to predation, a process that continues at very low frequencies, we examined the visual processes by which men and women detect dangerous animals (snakes and lions). We recorded the eye movements of participants as they detected images of a dangerous animal (target) among arrays of nondangerous animals (distractors) as well as detected images of a nondangerous animal (target) among arrays of dangerous animals (distractors). We found that participants were quicker to locate targets when the targets were dangerous animals compared with nondangerous animals, even when spatial frequency and luminance were controlled. The participants were slower to locate nondangerous targets because they spent more time looking at dangerous distractors, a process known as delayed disengagement, and looked at a larger number of dangerous distractors. These results indicate that dangerous animals capture and maintain attention in humans, suggesting that historical predation has shaped some facets of visual orienting and its underlying neural architecture in modern humans.

  18. Lifelong bilingualism maintains neural efficiency for cognitive control in aging.

    Science.gov (United States)

    Gold, Brian T; Kim, Chobok; Johnson, Nathan F; Kryscio, Richard J; Smith, Charles D

    2013-01-09

    Recent behavioral data have shown that lifelong bilingualism can maintain youthful cognitive control abilities in aging. Here, we provide the first direct evidence of a neural basis for the bilingual cognitive control boost in aging. Two experiments were conducted, using a perceptual task-switching paradigm, including a total of 110 participants. In Experiment 1, older adult bilinguals showed better perceptual switching performance than their monolingual peers. In Experiment 2, younger and older adult monolinguals and bilinguals completed the same perceptual task-switching experiment while functional magnetic resonance imaging (fMRI) was performed. Typical age-related performance reductions and fMRI activation increases were observed. However, like younger adults, bilingual older adults outperformed their monolingual peers while displaying decreased activation in left lateral frontal cortex and cingulate cortex. Critically, this attenuation of age-related over-recruitment associated with bilingualism was directly correlated with better task-switching performance. In addition, the lower blood oxygenation level-dependent response in frontal regions accounted for 82% of the variance in the bilingual task-switching reaction time advantage. These results suggest that lifelong bilingualism offsets age-related declines in the neural efficiency for cognitive control processes.

  19. Pathway Design, Engineering, and Optimization.

    Science.gov (United States)

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

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

  20. Pathways of Unconventional Protein Secretion

    NARCIS (Netherlands)

    Rabouille, Catherine

    2017-01-01

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

  1. Pathways of Unconventional Protein Secretion

    NARCIS (Netherlands)

    Rabouille, Catherine

    2016-01-01

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

  2. Junction detection and pathway selection

    Science.gov (United States)

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

    1992-02-01

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

  3. Effective sharing of health records, maintaining privacy: a practical schema.

    Science.gov (United States)

    Neame, Roderick

    2013-01-01

    A principal goal of computerisation of medical records is to join up care services for patients, so that their records can follow them wherever they go and thereby reduce delays, duplications, risks and errors, and costs. Healthcare records are increasingly being stored electronically, which has created the necessary conditions for them to be readily sharable. However simply driving the implementation of electronic medical records is not sufficient, as recent developments have demonstrated (1): there remain significant obstacles. The three main obstacles relate to (a) record accessibility (knowing where event records are and being able to access them), (b) maintaining privacy (ensuring that only those authorised by the patient can access and extract meaning from the records) and (c) assuring the functionality of the shared information (ensuring that the records can be shared non-proprietorially across platforms without loss of meaning, and that their authenticity and trustworthiness are demonstrable). These constitute a set of issues that need new thinking, since existing systems are struggling to deliver them. The solution to this puzzle lies in three main parts. Clearly there is only one environment suited to such widespread sharing, which is the World Wide Web, so this is the communications basis. Part one requires that a sharable synoptic record is created for each care event and stored in standard web-format and in readily accessible locations, on 'the web' or in 'the cloud'. To maintain privacy these publicly-accessible records must be suitably protected either stripped of identifiers (names, addresses, dates, places etc.) and/or encrypted: either way the record must be tagged with a tag that means nothing to anyone, but serves to identify and authenticate a specific record when retrieved. For ease of retrieval patients must hold an index of care events, records and web locations (plus any associated information for each such as encryption keys, context etc

  4. Academic Advising and Maintaining Major: Is There a Relation?

    Directory of Open Access Journals (Sweden)

    Maram S. Jaradat

    2017-12-01

    Full Text Available The purpose of this study is to investigate the effect of academic advising on changing or maintaining majors in university degrees. It is also a goal of the study to determine which semester students change their majors and whether advising contributes to that change. Through this correlational study, the researchers explored students’ perceptions about the academic advising they received and the relationship of its absence on students’ major change. The participants were 1725 undergraduate students from all year levels. The survey used to collect the data for this study is: the Influences on Choice of Major survey. Based on the findings, it was found that university advisors have a very poor effect on students’ decisions to select their majors as 45.6% of the 1725 participants indicated no influence of advising in their survey answers. Whereas career advancement opportunities, students’ interests, and job opportunities indicate a strong effect on their majors’ selections, as they score the highest means of 3.76, 3.73, and 3.64, respectively. In addition, findings show that students are most likely changing their majors in their second year, and specifically in the second semester. Second year major change scored 36.9% in the second semester and 30.9% in the first semester. More importantly, results indicate that there is a positive significant correlation between college advisors and major change in the second year (p = 0.000. It is to researchers’ understanding based on the findings that when students receive enough academic advising in the first year of study, and this advising continues steadily into the next year, the probability of students changing their majors decreases greatly.

  5. Management of wound infection after lumbar arthrodesis maintaining the instrumentation

    Directory of Open Access Journals (Sweden)

    Asdrubal Falavigna

    2015-06-01

    Full Text Available OBJECTIVE: To determinate whether a surgical protocol with immediate extensive debridement, closed irrigation system and antibiotic therapy would be effective to achieve healing of deep wound infection without removing the instrumentation.METHODS: Prospective cohort study with 19 patients presenting degenerative spinal stenosis or degenerative spondylolisthesis, who developed infection after posterior lumbar arthrodesis. The diagnosis was confirmed by a microbial culture from subfascial lumbar fluid and/or blood. Patients were treated with a protocol of wound exploration, extensive flushing and debridement, placement of a closed irrigation system that was maintained for five days and intravenous antibiotics. The instrumentation system was not removed.RESULTS: Mean age was 59.31 (±13.17 years old and most patients were female (94.7%; 18/19. The mean period for the identification of the infection was 2 weeks and 57.9% underwent a single wound exploration. White blood count, erythrocyte sedimentation rate and C-reactive protein showed a significant decrease post-treatment when compared to pre-treatment values. A significant reduction of erythrocyte sedimentation rate and C-reactive protein was also observed at the final evaluation. No laboratory test was useful to predict the need for more than one debridement.CONCLUSION: Patients with wound infection after instrumentation can be treated without removal of the instrumentation through wound exploration, extensive flushing, debridement of necrotic tissue, closed irrigation system during 5 days and proper antibiotic therapy. The blood tests were not useful to predict surgical re-interventions.

  6. Intraglomerular inhibition maintains mitral cell response contrast across input frequencies.

    Science.gov (United States)

    Shao, Zuoyi; Puche, Adam C; Shipley, Michael T

    2013-11-01

    Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON) synapses onto mitral/tufted cells (MTCs) and external tufted cells (ETCs); ETCs provide additional feed-forward excitation to MTCs. Both are strongly regulated by intraglomerular inhibition that can last up to 1 s and, when blocked, dramatically increases ON-evoked MC spiking. Intraglomerular inhibition thus limits the magnitude and duration of MC spike responses to sensory input. In vivo, sensory input is repetitive, dictated by sniffing rates from 1 to 8 Hz, potentially summing intraglomerular inhibition. To investigate this, we recorded MTC responses to 1- to 8-Hz ON stimulation in slices. Inhibitory postsynaptic current area (charge) following each ON stimulation was unchanged from 1 to 5 Hz and modestly paired-pulse attenuated at 8 Hz, suggesting there is no summation and only limited decrement at the highest input frequencies. Next, we investigated frequency independence of intraglomerular inhibition on MC spiking. MCs respond to single ON shocks with an initial spike burst followed by reduced spiking decaying to baseline. Upon repetitive ON stimulation peak spiking is identical across input frequencies but the ratio of peak-to-minimum rate before the stimulus (max-min) diminishes from 30:1 at 1 Hz to 15:1 at 8 Hz. When intraglomerular inhibition is selectively blocked, peak spike rate is unchanged but trough spiking increases markedly decreasing max-min firing ratios from 30:1 at 1 Hz to 2:1 at 8 Hz. Together, these results suggest intraglomerular inhibition is relatively frequency independent and can "sharpen" MC responses to input across the range of frequencies. This suggests that glomerular circuits can maintain "contrast" in MC encoding during sniff-sampled inputs.

  7. Maintaining Sentiment Polarity in Translation of User-Generated Content

    Directory of Open Access Journals (Sweden)

    Lohar Pintu

    2017-06-01

    Full Text Available The advent of social media has shaken the very foundations of how we share information, with Twitter, Facebook, and Linkedin among many well-known social networking platforms that facilitate information generation and distribution. However, the maximum 140-character restriction in Twitter encourages users to (sometimes deliberately write somewhat informally in most cases. As a result, machine translation (MT of user-generated content (UGC becomes much more difficult for such noisy texts. In addition to translation quality being affected, this phenomenon may also negatively impact sentiment preservation in the translation process. That is, a sentence with positive sentiment in the source language may be translated into a sentence with negative or neutral sentiment in the target language. In this paper, we analyse both sentiment preservation and MT quality per se in the context of UGC, focusing especially on whether sentiment classification helps improve sentiment preservation in MT of UGC. We build four different experimental setups for tweet translation (i using a single MT model trained on the whole Twitter parallel corpus, (ii using multiple MT models based on sentiment classification, (iii using MT models including additional out-of-domain data, and (iv adding MT models based on the phrase-table fill-up method to accompany the sentiment translation models with an aim of improving MT quality and at the same time maintaining sentiment polarity preservation. Our empirical evaluation shows that despite a slight deterioration in MT quality, our system significantly outperforms the Baseline MT system (without using sentiment classification in terms of sentiment preservation. We also demonstrate that using an MT engine that conveys a sentiment different from that of the UGC can even worsen both the translation quality and sentiment preservation.

  8. How to Maintain Computerized Procedure System in the same Version

    International Nuclear Information System (INIS)

    Jung, Yeon Sub

    2016-01-01

    CPS(Computerized Procedure System) has been introduced in advanced nuclear power plant worldwide. Korean CPS complies with this trend. It has been applied to Shinkori3,4 and all their successors including BNPP1,2,3,4. CPS is designed by KHNP CRI, and developed by Westinghouse or Doosan. Initial design has been improved by reflecting operator experience, human factor V and V, and advanced engineering method. Design improvement makes CPS differ from plant to plant. For example CPS in Shinhanul cannot interpret CP(Computerized Procedure) of ShinKori3, 4. Different CPS makes it difficult to utilize CP and train operators. Therefore it is important to keep CPS in single version. Note that typical text editors in the office are kept in single version. On the other hand, plant monitoring systems in main control room are actually different. Because CPS is positioned between text editor and monitoring system, goal to maintain CPS in single version is not an easy task. From Shinkori3,4, lots of improvements are achieved in CPS. This improvement surely makes operation easy and will not introduce human errors. Side effect of improvement is that PXS and CPS ES may not be compatible among nuclear power plants. So the side effect should be avoided by minimizing change of XML. Initial XML had been developed for Shinkori3,4. The XML has been modified slightly for Shinhanul1,2. PXS and CPS ES are being developed for the same version for all nuclear power plants of APR1400

  9. Genetic and somatic effects in animals maintained on tritiated water

    International Nuclear Information System (INIS)

    Carsten, A.L.; Commerford, S.L.; Cronkite, E.P.; Brooks, A.

    1982-01-01

    Somatic and genetic effects of the continuous ingestion of tritiated water (HTO) at concentrations of 0.3, 1.0 and 3.0 μCi/ml were investigated in mice of the Hale-Stoner-Brookhaven strain. At these levels, there was no measurable somatic effect. Although genetic effects as measured by dominant lethal mutation (DLM) assay indicated a significant effect (P>0.01) on the number of viable embryos and early deaths in the 3.0 μCi/ml HTO group and on the number of viable embryos in the 1.0 μCi/ml HTO group, no genetic effects were significantly noted in the 0.3 μCi/ml HTO group. Liver cytogenetic studies showed a significant increase in the number of abnormal cells in the 3.0 μCi/ml HTO group. A reduction in bone marrow stem cells, without an attendant reduction in total marrow cellularity, was noted in the 3.0 and 1.0 μCi/ml HTO groups. There was no significant difference in any of the DLM parameters between animals maintained on 3.0 μCi/ml of HTO and animals exposed to the equivalent 137 Cs gamma dose (22 hours/day exposure). Consideration of the relative amounts and biological half lives of tritium present in the nucleus as water, DNA and histone suggests that after transient exposure to tritiated water, nearly all significant radiation damage can be attributed to tritium present in the nucleus as water. These data suggest that hazards from tritium attendant with normal reactor operation should not at this time be considered as a deterrent to the further development of fission and/or fusion reactor technology. (Namekawa, K.)

  10. Maintaining staff competence-a NPP operator viewpoint

    International Nuclear Information System (INIS)

    Patrakka, E.

    2000-01-01

    For a nuclear power plant operator, it is crucial to guarantee the safe and economic operation of the power plant as well as to look after the general acceptability of nuclear power. As to human resources management, this requires continuous maintenance and enhancement of the performance of the individuals and organisation. To this end, several development projects have recently been implemented by Teollisuuden Voima Oy (TVO) at the Olkiluoto nuclear power plant, which consists of twin 840 MWe BWR units that commenced their operation in 1978 and 1980. Systematic initial and continuing training programmes are needed to maintain the technical and managerial skills and know-how at a high level. The present stabile state of nuclear power, i.e. operation of ageing plants with personnel ageing as well, requires a variety of actions to reinforce the training efforts. At Olkiluoto NPP, we have carried out an extensive modernization programme that allowed the personnel to strengthen their knowledge and supplement it with the most recent results of development. We have also closely monitored the NPP development projects of the vendors, which has added to the preservation of know-how and understanding of advanced nuclear power technology. We have close contacts to the research institutes and universities, and have performed R and D activities to limited extent. In addition to the projects mentioned above, a co-ordinated development programme, 'TVO 2002', was initiated last year. The main objective of this programme is to ensure the functional preconditions and the competitiveness of the company in a changing environment. The management and operational procedures will be developed in such a way that the goals set for year 2002 will be achieved. The programme is organised as ten projects, which cover a variety of development subjects. One of the focal areas includes projects that can be characterised with the words 'Survey of competencies' and 'Preservation of know

  11. Activin pathway enhances colorectal cancer stem cell self-renew and tumor progression.

    Science.gov (United States)

    Liu, Rui; Wang, Jun-Hua; Xu, Chengxiong; Sun, Bo; Kang, Sa-Ouk

    2016-10-28

    Activin belongs to transforming growth factor (TGF)-β super family of growth and differentiation factors and activin pathway participated in broad range of cell process. Studies elaborated activin pathway maintain pluripotency in human stem cells and suggest that the function of activin/nodal signaling in self-renew would be conserved across embryonic and adult stem cells. In this study, we tried to determine the effect of activin signaling pathway in regulation of cancer stem cells as a potential target for cancer therapy in clinical trials. A population of colorectal cancer cells was selected by the treatment of activin A. This population of cell possessed stem cell character with sphere formation ability. We demonstrated activin pathway enhanced the colorectal cancer stem cells self-renew and contribute to colorectal cancer progression in vivo. Targeting activin pathway potentially provide effective strategy for colorectal cancer therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Computed tomographic characteristics of collateral venous pathways in dogs with caudal vena cava obstruction.

    Science.gov (United States)

    Specchi, Swan; d'Anjou, Marc-André; Carmel, Eric Norman; Bertolini, Giovanna

    2014-01-01

    Collateral venous pathways develop in dogs with obstruction or increased blood flow resistance at any level of the caudal vena cava in order to maintain venous drainage to the right atrium. The purpose of this retrospective study was to describe the sites, causes of obstruction, and configurations of venous collateral pathways for a group of dogs with caudal vena cava obstruction. Computed tomography databases from two veterinary hospitals were searched for dogs with a diagnosis of caudal vena cava obstruction and multidetector row computed tomographic angiographic (CTA) scans that included the entire caudal vena cava. Images for each included dog were retrieved and collateral venous pathways were characterized using image postprocessing and a classification system previously reported for humans. A total of nine dogs met inclusion criteria and four major collateral venous pathways were identified: deep (n = 2), portal (n = 2), intermediate (n = 7), and superficial (n = 5). More than one collateral venous pathway was present in 5 dogs. An alternative pathway consisting of renal subcapsular collateral veins, arising mainly from the caudal pole of both kidneys, was found in three dogs. In conclusion, findings indicated that collateral venous pathway patterns similar to those described in humans are also present in dogs with caudal vena cava obstruction. These collateral pathways need to be distinguished from other vascular anomalies in dogs. Postprocessing of multidetector-row CTA images allowed delineation of the course of these complicated venous pathways and may be a helpful adjunct for treatment planning in future cases. © 2014 American College of Veterinary Radiology.

  13. Should we maintain baby hatches in our society?

    Directory of Open Access Journals (Sweden)

    Asai Atsushi

    2013-02-01

    Full Text Available Abstract Background A baby hatch called the “Stork’s Cradle” has been in place at Jikei Hospital in Kumamoto City, Japan, since May 10, 2007. Babyklappes were first established in Germany in 2000, and there are currently more than 90 locations. Attitudes regarding baby hatches are divided in Japan and neither opinions for nor against baby hatches have thus far been overwhelming. To consider the appropriateness of baby hatches, we present and examine the validity of each major objection to establishing baby hatches. Discussion There are various objections to baby hatches as follows: It violates a child’s right to know the identity of his or her biological parents by allowing anonymous birth; it neglects fulfillment of the biological parents’ basic obligation to raise their child and its very availability induces abandonment of infants; some people abuse it for very selfish reasons; it cannot save babies’ lives; the rights of one parent can be ignored if the other surrenders a child without his or her consent; it puts a baby in medical jeopardy; and it has no clear legal basis. The authors would argue that there are many plausible refutations for each objection mainly based on priority of child’s right to life, pregnant women’s vulnerability and necessity of anonymity, social responsibility to protect and raise children, differences between dropping a child off at a baby hatch and child neglect, limited function of social childcare center, inevitability of abuse by a minority of people, necessary distinction between outcomes that occur only because baby hatches exist and those that occur regardless of their existence, important local direct and upmost measures for women in trouble, and difference between ambiguous legality and illegality. Summary We argue that a certain number of baby hatches should continue to be established as a last resort, in a form that can maintain anonymity if the parent dropping the child off so desires. It

  14. Reducing costs while maintaining quality in endovascular neurosurgical procedures.

    Science.gov (United States)

    Kashlan, Osama N; Wilson, Thomas J; Chaudhary, Neeraj; Gemmete, Joseph J; Stetler, William R; Dunnick, N Reed; Thompson, B Gregory; Pandey, Aditya S

    2014-11-01

    extrapolation over a 1-year period, the 3 policy changes decreased costs by an estimated $323,561.34. Simple cost-saving policies can lead to substantial reductions in costs of neurointerventional procedures while maintaining high levels of quality and growth of services.

  15. Components for Maintaining and Publishing Earth Science Vocabularies

    Science.gov (United States)

    Cox, S. J. D.; Yu, J.

    2014-12-01

    Shared vocabularies are an important aid to geoscience data interoperability. Many organizations maintain useful vocabularies, with Geologic Surveys having a particularly long history of vocabulary and lexicon development. However, the mode of publication is heterogeneous, ranging from PDFs and HTML web pages, spreadsheets and CSV, through various user-interfaces and APIs. Update and maintenance ranges from tightly-governed and externally opaque, through various community processes, all the way to crowd-sourcing ('folksonomies'). A general expectation, however, is for greater harmonization and vocabulary re-use. In order to be successful this requires (a) standardized content formalization and APIs (b) transparent content maintenance and versioning. We have been trialling a combination of software dealing with registration, search and linking. SKOS is designed for formalizing multi-lingual, hierarchical vocabularies, and has been widely adopted in earth and environmental sciences. SKOS is an RDF vocabulary, for which SPARQL is the standard low-level API. However, for interoperability between SKOS vocabulary sources, a SKOS-based API (i.e. based on the SKOS predicates prefLabel, broader, narrower, etc) is required. We have developed SISSvoc for this purpose, and used it to deploy a number of vocabularies on behalf of the IUGS, ICS, NERC, OGC, the Australian Government, and CSIRO projects. SISSvoc Search provides simple search UI on top of one or more SISSvoc sources. Content maintenance is composed of many elements, including content-formalization, definition-update, and mappings to related vocabularies. Typically there is a degree of expert judgement required. In order to provide confidence in users, two requirements are paramount: (i) once published, a URI that denotes a vocabulary item must remain dereferenceable; (ii) the history and status of the content denoted by a URI must be available. These requirements match the standard 'registration' paradigm which is

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

    Science.gov (United States)

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

    2018-03-01

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

  17. The return of metabolism: biochemistry and physiology of the pentose phosphate pathway

    NARCIS (Netherlands)

    Stincone, A.; Prigione, A.; Cramer, T.; Wamelink, M.M.C.; Campbell, K.; Cheung, E.; Olin-Sandoval, V.; Gruning, N.M.; Kruger, A.; Alam, M.T.; Keller, M.A.; Breitenbach, M.; Brindle, K.M.; Rabinowitz, J.D.; Ralser, M.

    2015-01-01

    The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares

  18. Can Cultural Behavior Have a Negative Impact on the Development of Visual Integration Pathways?

    Science.gov (United States)

    Pretorius, E.; Naude, H.; van Vuuren, C. J.

    2002-01-01

    Contends that cultural practices such as carrying the baby on the mother's back for prolonged periods can impact negatively on development of visual integration during the sensorimotor stage pathways by preventing adequate or enough crawling. Maintains that crawling is essential for cross- modality integration and that higher mental functions may…

  19. Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues.

    Science.gov (United States)

    Cifola, Ingrid; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A

    2011-06-13

    Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

  20. Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues

    International Nuclear Information System (INIS)

    Cifola, Ingrid; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A

    2011-01-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

  1. Nitric oxide maintains cell survival of Trichomonas vaginalis upon iron depletion.

    Science.gov (United States)

    Cheng, Wei-Hung; Huang, Kuo-Yang; Huang, Po-Jung; Hsu, Jo-Hsuan; Fang, Yi-Kai; Chiu, Cheng-Hsun; Tang, Petrus

    2015-07-25

    Iron plays a pivotal role in the pathogenesis of Trichomonas vaginalis, the causative agent of highly prevalent human trichomoniasis. T. vaginalis resides in the vaginal region, where the iron concentration is constantly changing. Hence, T. vaginalis must adapt to variations in iron availability to establish and maintain an infection. The free radical signaling molecules reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been proven to participate in iron deficiency in eukaryotes. However, little is known about the roles of these molecules in iron-deficient T. vaginalis. T. vaginalis cultured in iron-rich and -deficient conditions were collected for all experiments in this study. Next generation RNA sequencing was conducted to investigate the impact of iron on transcriptome of T. vaginalis. The cell viabilities were monitored after the trophozoites treated with the inhibitors of nitric oxide (NO) synthase (L-NG-monomethyl arginine, L-NMMA) and proteasome (MG132). Hydrogenosomal membrane potential was measured using JC-1 staining. We demonstrated that NO rather than ROS accumulates in iron-deficient T. vaginalis. The level of NO was blocked by MG132 and L-NMMA, indicating that NO production is through a proteasome and arginine dependent pathway. We found that the inhibition of proteasome activity shortened the survival of iron-deficient cells compared with untreated iron-deficient cells. Surprisingly, the addition of arginine restored both NO level and the survival of proteasome-inhibited cells, suggesting that proteasome-derived NO is crucial for cell survival under iron-limited conditions. Additionally, NO maintains the hydrogenosomal membrane potential, a determinant for cell survival, emphasizing the cytoprotective effect of NO on iron-deficient T. vaginalis. Collectively, we determined that NO produced by the proteasome prolonged the survival of iron-deficient T. vaginalis via maintenance of the hydrogenosomal functions. The findings in this

  2. Alternative pathways for angiotensin II generation in the cardiovascular system

    Directory of Open Access Journals (Sweden)

    C. Becari

    2011-09-01

    Full Text Available The classical renin-angiotensin system (RAS consists of enzymes and peptides that regulate blood pressure and electrolyte and fluid homeostasis. Angiotensin II (Ang II is one of the most important and extensively studied components of the RAS. The beneficial effects of angiotensin converting enzyme (ACE inhibitors in the treatment of hypertension and heart failure, among other diseases, are well known. However, it has been reported that patients chronically treated with effective doses of these inhibitors do not show suppression of Ang II formation, suggesting the involvement of pathways alternative to ACE in the generation of Ang II. Moreover, the finding that the concentration of Ang II is preserved in the kidney, heart and lungs of mice with an ACE deletion indicates the important role of alternative pathways under basal conditions to maintain the levels of Ang II. Our group has characterized the serine protease elastase-2 as an alternative pathway for Ang II generation from Ang I in rats. A role for elastase-2 in the cardiovascular system was suggested by studies performed in heart and conductance and resistance vessels of normotensive and spontaneously hypertensive rats. This mini-review will highlight the pharmacological aspects of the RAS, emphasizing the role of elastase-2, an alternative pathway for Ang II generation.

  3. New Pathways for Alimentary Mucositis

    Directory of Open Access Journals (Sweden)

    Joanne M. Bowen

    2008-01-01

    Full Text Available Alimentary mucositis is a major dose-limiting toxicity associated with anticancer treatment. It is responsible for reducing patient quality of life and represents a significant economic burden in oncology. The pathobiology of alimentary mucositis is extremely complex, and an increased understanding of mechanisms and pathway interactions is required to rationally design improved therapies. This review describes the latest advances in defining mechanisms of alimentary mucositis pathobiology in the context of pathway activation. It focuses particularly on the recent genome-wide analyses of regimen-related mucosal injury and the identification of specific regulatory pathways implicated in mucositis development. This review also discusses the currently known alimentary mucositis risk factors and the development of novel treatments. Suggestions for future research directions have been raised.

  4. Targeting Wnt Pathways in Disease

    Science.gov (United States)

    Zimmerman, Zachary F.; Moon, Randall T.

    2012-01-01

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

  5. Aberrant Signaling Pathways in Glioma

    International Nuclear Information System (INIS)

    Nakada, Mitsutoshi; Kita, Daisuke; Watanabe, Takuya; Hayashi, Yutaka; Teng, Lei; Pyko, Ilya V.; Hamada, Jun-Ichiro

    2011-01-01

    Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12–15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. This is mainly due to highly deregulated signaling pathways in the tumor. Studies of these signaling pathways have greatly increased our understanding of the biology and clinical behavior of GBM. An integrated view of signal transduction will provide a more useful approach in designing novel therapies for this devastating disease. In this review, we summarize the current understanding of GBM signaling pathways with a focus on potential molecular targets for anti-signaling molecular therapies

  6. Personal branding: building your pathway to professional success.

    Science.gov (United States)

    Philbrick, Jodi L; Cleveland, Ana D

    2015-01-01

    Personal branding is an introspective process by which you define yourself professionally, and it can serve as your pathway to professional success. There are six steps to building your personal brand: (1) taking an introspective look, (2) understanding the brand that may already exist, (3) developing your personal brand mantra, (4) crafting your physical footprint, (5) creating your digital footprint, and (6) communicating your message. Your personal brand is a promise of value and performance, and it is necessary to meet the expectations of your audience. Effective brand management is a key component to maintaining a positive brand reputation.

  7. Targeting the GPI biosynthetic pathway.

    Science.gov (United States)

    Yadav, Usha; Khan, Mohd Ashraf

    2018-02-27

    The GPI (Glycosylphosphatidylinositol) biosynthetic pathway is a multistep conserved pathway in eukaryotes that culminates in the generation of GPI glycolipid which in turn anchors many proteins (GPI-APs) to the cell surface. In spite of the overall conservation of the pathway, there still exist subtle differences in the GPI pathway of mammals and other eukaryotes which holds a great promise so far as the development of drugs/inhibitors against specific targets in the GPI pathway of pathogens is concerned. Many of the GPI structures and their anchored proteins in pathogenic protozoans and fungi act as pathogenicity factors. Notable examples include GPI-anchored variant surface glycoprotein (VSG) in Trypanosoma brucei, GPI-anchored merozoite surface protein 1 (MSP1) and MSP2 in Plasmodium falciparum, protein-free GPI related molecules like lipophosphoglycans (LPGs) and glycoinositolphospholipids (GIPLs) in Leishmania spp., GPI-anchored Gal/GalNAc lectin and proteophosphoglycans in Entamoeba histolytica or the GPI-anchored mannoproteins in pathogenic fungi like Candida albicans. Research in this active area has already yielded encouraging results in Trypanosoma brucei by the development of parasite-specific inhibitors of GlcNCONH 2 -β-PI, GlcNCONH 2 -(2-O-octyl)-PI and salicylic hydroxamic acid (SHAM) targeting trypanosomal GlcNAc-PI de-N-acetylase as well as the development of antifungal inhibitors like BIQ/E1210/gepinacin/G365/G884 and YW3548/M743/M720 targeting the GPI specific fungal inositol acyltransferase (Gwt1) and the phosphoethanolamine transferase-I (Mcd4), respectively. These confirm the fact that the GPI pathway continues to be the focus of researchers, given its implications for the betterment of human life.

  8. Increased Body Weight Reduces Voluntary Movement to Maintain Energy Expenditure of Rats Exposed to Increases in Gravity

    Science.gov (United States)

    Wade, C. E.; Moran, M. M.; Stein, T. P.; Sin, Sidney (Technical Monitor)

    2001-01-01

    With the increase in obesity related diseases there is heightened interest in mechanisms regulating body weight. To assess the influence of increases in body weight on energy expenditure and intake in rats we employed variable levels of gravity. Our approach afforded the means to measure interactions of energy expenditure and intake in response to increases in body weight (body mass x gravity level). We found a dose relationship between rapid elevation of body weight and reduction of voluntary movement, such that the energy requirements for activity are unchanged, and total energy expenditure and intake maintained. Reduction of movement appears to be a response to increased body weight, rather than a contributing factor, suggesting a new regulatory pathway.

  9. ′Metal to resin′: A comparative evaluation of conventional band and loop space maintainer with the fiber reinforced composite resin space maintainer in children

    Directory of Open Access Journals (Sweden)

    A Garg

    2014-01-01

    Full Text Available Aims: To compare the clinical efficacy of two space maintainers namely, conventional band and loop and Fiber Reinforced Composite Resin (FRCR space maintainers . Subjects and Methods: Thirty healthy children, aged 5 to 8 years were selected having at least two deciduous molars in different quadrants indicated for extraction or lost previously. FRCR space maintainer was placed in one quadrant and in the other quadrant band and loop space maintainer was cemented. All the patients were recalled at 1 st , 3 rd , and 6 th months for evaluation of both types of space maintainer. Patient acceptability, time taken, and clinical efficacy was recorded. Statistical analysis used: The observations thus obtained were subjected to statistical analysis using Chi- square test and Mann-Whitney U test. Results: Patient acceptability was greater in Group I (FRCR in comparison to Group II (band and loop space maintainer. The time taken by Group I was significantly lower as compared to that of Group II. In Group I, debonding of enamel, composite was the most common complication leading to failure followed by debonding of fiber composite. In Group II, cement loss was the most common complication leading to failure followed by slippage of band and fracture of loop. The success rates of Groups I and Group II weares 63.3% and 36.7%, respectively. Conclusion: The study concluded that FRCRFiber Reinforced Composite Resin (Ribbond space maintainers can be considered as viable alternative to the conventional band and loop space maintainers.

  10. Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers.

    Science.gov (United States)

    Cleary, Allison S; Leonard, Travis L; Gestl, Shelley A; Gunther, Edward J

    2014-04-03

    Cancer genome sequencing studies indicate that a single breast cancer typically harbours multiple genetically distinct subclones. As carcinogenesis involves a breakdown in the cell-cell cooperation that normally maintains epithelial tissue architecture, individual subclones within a malignant microenvironment are commonly depicted as self-interested competitors. Alternatively, breast cancer subclones might interact cooperatively to gain a selective growth advantage in some cases. Although interclonal cooperation has been shown to drive tumorigenesis in fruitfly models, definitive evidence for functional cooperation between epithelial tumour cell subclones in mammals is lacking. Here we use mouse models of breast cancer to show that interclonal cooperation can be essential for tumour maintenance. Aberrant expression of the secreted signalling molecule Wnt1 generates mixed-lineage mammary tumours composed of basal and luminal tumour cell subtypes, which purportedly derive from a bipotent malignant progenitor cell residing atop a tumour cell hierarchy. Using somatic Hras mutations as clonal markers, we show that some Wnt tumours indeed conform to a hierarchical configuration, but that others unexpectedly harbour genetically distinct basal Hras mutant and luminal Hras wild-type subclones. Both subclones are required for efficient tumour propagation, which strictly depends on luminally produced Wnt1. When biclonal tumours were challenged with Wnt withdrawal to simulate targeted therapy, analysis of tumour regression and relapse revealed that basal subclones recruit heterologous Wnt-producing cells to restore tumour growth. Alternatively, in the absence of a substitute Wnt source, the original subclones often evolve to rescue Wnt pathway activation and drive relapse, either by restoring cooperation or by switching to a defector strategy. Uncovering similar modes of interclonal cooperation in human cancers may inform efforts aimed at eradicating tumour cell communities.

  11. 3D hepatic cultures simultaneously maintain primary hepatocyte and liver sinusoidal endothelial cell phenotypes.

    Directory of Open Access Journals (Sweden)

    Yeonhee Kim

    Full Text Available Developing in vitro engineered hepatic tissues that exhibit stable phenotype is a major challenge in the field of hepatic tissue engineering. However, the rapid dedifferentiation of hepatic parenchymal (hepatocytes and non-parenchymal (liver sinusoidal endothelial, LSEC cell types when removed from their natural environment in vivo remains a major obstacle. The primary goal of this study was to demonstrate that hepatic cells cultured in layered architectures could preserve or potentially enhance liver-specific behavior of both cell types. Primary rat hepatocytes and rat LSECs (rLSECs were cultured in a layered three-dimensional (3D configuration. The cell layers were separated by a chitosan-hyaluronic acid polyelectrolyte multilayer (PEM, which served to mimic the Space of Disse. Hepatocytes and rLSECs exhibited several key phenotypic characteristics over a twelve day culture period. Immunostaining for the sinusoidal endothelial 1 antibody (SE-1 demonstrated that rLSECs cultured in the 3D hepatic model maintained this unique feature over twelve days. In contrast, rLSECs cultured in monolayers lost their phenotype within three days. The unique stratified structure of the 3D culture resulted in enhanced heterotypic cell-cell interactions, which led to improvements in hepatocyte functions. Albumin production increased three to six fold in the rLSEC-PEM-Hepatocyte cultures. Only rLSEC-PEM-Hepatocyte cultures exhibited increasing CYP1A1/2 and CYP3A activity. Well-defined bile canaliculi were observed only in the rLSEC-PEM-Hepatocyte cultures. Together, these data suggest that rLSEC-PEM-Hepatocyte cultures are highly suitable models to monitor the transformation of toxins in the liver and their transport out of this organ. In summary, these results indicate that the layered rLSEC-PEM-hepatocyte model, which recapitulates key features of hepatic sinusoids, is a potentially powerful medium for obtaining comprehensive knowledge on liver metabolism

  12. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis: LAMP-2 deficient mice develop pancreatitis.

    Science.gov (United States)

    Mareninova, Olga A; Sendler, Matthias; Malla, Sudarshan Ravi; Yakubov, Iskandar; French, Samuel W; Tokhtaeva, Elmira; Vagin, Olga; Oorschot, Viola; Lüllmann-Rauch, Renate; Blanz, Judith; Dawson, David; Klumperman, Judith; Lerch, Markus M; Mayerle, Julia; Gukovsky, Ilya; Gukovskaya, Anna S

    2015-11-01

    The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated membrane proteins (LAMPs) in pancreatitis. We analyzed changes in LAMPs in experimental models and human pancreatitis, and the underlying mechanisms: LAMP de-glycosylation and degradation. LAMP cleavage by cathepsin B (CatB) was analyzed by mass spectrometry. We used mice deficient in LAMP-2 to assess its role in pancreatitis. Pancreatic levels of LAMP-1 and LAMP-2 greatly decrease across various pancreatitis models and in human disease. Pancreatitis does not trigger LAMPs' bulk de-glycosylation, but induces their degradation via CatB-mediated cleavage of LAMP molecule close to the boundary between luminal and transmembrane domains. LAMP-2 null mice spontaneously develop pancreatitis that begins with acinar cell vacuolization due to impaired autophagic flux, and progresses to severe pancreas damage characterized by trypsinogen activation, macrophage-driven inflammation, and acinar cell death. LAMP-2 deficiency causes a decrease in pancreatic digestive enzymes content, stimulates the basal and inhibits CCK-induced amylase secretion by acinar cells. The effects of LAMP-2 knockout and acute cerulein pancreatitis overlap, which corroborates the pathogenic role of LAMP decrease in experimental pancreatitis models. The results indicate a critical role for LAMPs, particularly LAMP-2, in maintaining pancreatic acinar cell homeostasis, and provide evidence that defective lysosomal function, resulting in impaired autophagy, leads to pancreatitis. Mice with LAMP-2 deficiency present a novel genetic model of human pancreatitis caused by lysosomal/autophagic dysfunction.

  13. AP1 transcription factors are required to maintain the peripheral taste system.

    Science.gov (United States)

    Shandilya, Jayasha; Gao, Yankun; Nayak, Tapan K; Roberts, Stefan G E; Medler, Kathryn F

    2016-10-27

    The sense of taste is used by organisms to achieve the optimal nutritional requirement and avoid potentially toxic compounds. In the oral cavity, taste receptor cells are grouped together in taste buds that are present in specialized taste papillae in the tongue. Taste receptor cells are the cells that detect chemicals in potential food items and transmit that information to gustatory nerves that convey the taste information to the brain. As taste cells are in contact with the external environment, they can be damaged and are routinely replaced throughout an organism's lifetime to maintain functionality. However, this taste cell turnover loses efficiency over time resulting in a reduction in taste ability. Currently, very little is known about the mechanisms that regulate the renewal and maintenance of taste cells. We therefore performed RNA-sequencing analysis on isolated taste cells from 2 and 6-month-old mice to determine how alterations in the taste cell-transcriptome regulate taste cell maintenance and function in adults. We found that the activator protein-1 (AP1) transcription factors (c-Fos, Fosb and c-Jun) and genes associated with this pathway were significantly downregulated in taste cells by 6 months and further declined at 12 months. We generated conditional c-Fos-knockout mice to target K14-expressing cells, including differentiating taste cells. c-Fos deletion caused a severe perturbation in taste bud structure and resulted in a significant reduction in the taste bud size. c-Fos deletion also affected taste cell turnover as evident by a decrease in proliferative marker, and upregulation of the apoptotic marker cleaved-PARP. Thus, AP1 factors are important regulators of adult taste cell renewal and their downregulation negatively impacts taste maintenance.

  14. DNA double-strand break response in stem cells: mechanisms to maintain genomic integrity.

    Science.gov (United States)

    Nagaria, Pratik; Robert, Carine; Rassool, Feyruz V

    2013-02-01

    Embryonic stem cells (ESCs) represent the point of origin of all cells in a given organism and must protect their genomes from both endogenous and exogenous genotoxic stress. DNA double-strand breaks (DSBs) are one of the most lethal forms of damage, and failure to adequately repair DSBs would not only compromise the ability of SCs to self-renew and differentiate, but will also lead to genomic instability and disease. Herein, we describe the mechanisms by which ESCs respond to DSB-inducing agents such as reactive oxygen species (ROS) and ionizing radiation, compared to somatic cells. We will also discuss whether the DSB response is fully reprogrammed in induced pluripotent stem cells (iPSCs) and the role of the DNA damage response (DDR) in the reprogramming of these cells. ESCs have distinct mechanisms to protect themselves against DSBs and oxidative stress compared to somatic cells. The response to damage and stress is crucial for the maintenance of self-renewal and differentiation capacity in SCs. iPSCs appear to reprogram some of the responses to genotoxic stress. However, it remains to be determined if iPSCs also retain some DDR characteristics of the somatic cells of origin. The mechanisms regulating the genomic integrity in ESCs and iPSCs are critical for its safe use in regenerative medicine and may shed light on the pathways and factors that maintain genomic stability, preventing diseases such as cancer. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Determination of maintainability for Dacia 1304, 1,9 D utility vehicle

    Science.gov (United States)

    Budiul Berghian, A.; Vasiu, T.; Birtok Baneasa, C.

    2018-01-01

    The study analyses the ability to be maintained or rehabilitation of Dacia 1304, 1,9D utility vehicle. The paper comprises the determination of its maintainability using the Weibull++8 specialized software.

  16. Measures geared to maintain the competence of operating personnel at Grohnde nuclear power plant

    International Nuclear Information System (INIS)

    Bohr, H.

    1986-01-01

    Organizational structure of the German power plant 'Gemeinschaftskernkraftwerk Grohnde GmbH'. The plant characteristics of the tasks and duties and definition of competence. Measures to maintain competence. The experience by the realization of training programs to maintain competence. (orig.)

  17. Combined Non-Self-Maintained Discharge in Air for Generating of Chemically Active Particles

    National Research Council Canada - National Science Library

    Ardelyan, N. V; Bychkov, V. L; Gordeev, O. A; Klimov, A. I

    2003-01-01

    Development of plasma technologies for problems of external and internal gas dynamics is impossible without the detailed studies of different discharge types both self maintained and non-self maintained improvement...

  18. Microbiological testing of devices used in maintaining peripheral venous catheters.

    Science.gov (United States)

    Rossini, Fernanda de Paula; Andrade, Denise de; Santos, Lissandra Chaves de Sousa; Ferreira, Adriano Menis; Tieppo, Caroline; Watanabe, Evandro

    2017-05-15

    to evaluate the use of peripheral venous catheters based on microbiological analysis of devices (dressing and three-way stopcocks) and thus contribute to the prevention and infection control. this was a prospective study of microbiological analysis of 30 three-way stopcocks (external surfaces and lumens) and 30 dressing used in maintaining the peripheral venous catheters of hospitalized adult patients. all external surfaces, 40% of lumens, and 86.7% of dressing presented bacterial growth. The main species isolated in the lumen were 50% coagulase-negative Staphylococcus, 14.3% Staphylococcus aureus, and 14.3% Pseudomonas aeruginosa. Fifty nine percent of multidrug-resistant bacteria were isolated of the three-way stopcocks, 42% of the lumens, and 44% of the dressing with a predominance of coagulase-negative Staphylococcus resistant to methicillin. Besides, 18% gram-negative bacteria with resistance to carbapenems were identified from multidrug-resistant bacteria on the external surfaces of the three-way stopcocks. it is important to emphasize the isolation of coagulase-negative Staphylococcus and gram-negative bacteria resistant to methicillin and carbapenems in samples of devices, respectively, which reinforces the importance of nursing care in the maintenance of the biologically safe environment as well as prevention and infection control practices. avaliar o uso de cateteres venosos periféricos com base em análises microbiológicas de dispositivos (curativos e torneiras de três vias - T3Vs) e assim contribuir para a prevenção e controle de infecção. estudo prospectivo de análise microbiológica de 30 T3Vs (superfícies externas e lúmens) e 30 curativos utilizados na manutenção dos cateteres venosos periféricos de pacientes adultos hospitalizados. todas as superfícies externas, 40% dos lúmens e 86,7% dos curativos apresentaram crescimento bacteriano. As principais espécies isoladas no lúmen foram 50% Staphylococcus coagulase-negativa, 14

  19. Sensing coral reef connectivity pathways from space

    KAUST Repository

    Raitsos, Dionysios E.; Brewin, Robert J. W.; Zhan, Peng; Dreano, Denis; Pradhan, Yaswant; Nanninga, Gerrit B.; Hoteit, Ibrahim

    2017-01-01

    Coral reefs rely on inter-habitat connectivity to maintain gene flow, biodiversity and ecosystem resilience. Coral reef communities of the Red Sea exhibit remarkable genetic homogeneity across most of the Arabian Peninsula coastline, with a genetic break towards the southern part of the basin. While previous studies have attributed these patterns to environmental heterogeneity, we hypothesize that they may also emerge as a result of dynamic circulation flow; yet, such linkages remain undemonstrated. Here, we integrate satellite-derived biophysical observations, particle dispersion model simulations, genetic population data and ship-borne in situ profiles to assess reef connectivity in the Red Sea. We simulated long-term (>20 yrs.) connectivity patterns driven by remotely-sensed sea surface height and evaluated results against estimates of genetic distance among populations of anemonefish, Amphiprion bicinctus, along the eastern Red Sea coastline. Predicted connectivity was remarkably consistent with genetic population data, demonstrating that circulation features (eddies, surface currents) formulate physical pathways for gene flow. The southern basin has lower physical connectivity than elsewhere, agreeing with known genetic structure of coral reef organisms. The central Red Sea provides key source regions, meriting conservation priority. Our analysis demonstrates a cost-effective tool to estimate biophysical connectivity remotely, supporting coastal management in data-limited regions.

  20. Epigenetic Pathways of Oncogenic Viruses: Therapeutic Promises.

    Science.gov (United States)

    El-Araby, Amr M; Fouad, Abdelrahman A; Hanbal, Amr M; Abdelwahab, Sara M; Qassem, Omar M; El-Araby, Moustafa E

    2016-02-01

    Cancerous transformation comprises different events that are both genetic and epigenetic. The ultimate goal for such events is to maintain cell survival and proliferation. This transformation occurs as a consequence of different features such as environmental and genetic factors, as well as some types of infection. Many viral infections are considered to be causative agents of a number of different malignancies. To convert normal cells into cancerous cells, oncogenic viruses must function at the epigenetic level to communicate with their host cells. Oncogenic viruses encode certain epigenetic factors that lead to the immortality and proliferation of infected cells. The epigenetic effectors produced by oncogenic viruses constitute appealing targets to prevent and treat malignant diseases caused by these viruses. In this review, we highlight the importance of epigenetic reprogramming for virus-induced oncogenesis, with special emphasis on viral epigenetic oncoproteins as therapeutic targets. The discovery of molecular components that target epigenetic pathways, especially viral factors, is also discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Sensing coral reef connectivity pathways from space

    KAUST Repository

    Raitsos, Dionysios E.

    2017-08-18

    Coral reefs rely on inter-habitat connectivity to maintain gene flow, biodiversity and ecosystem resilience. Coral reef communities of the Red Sea exhibit remarkable genetic homogeneity across most of the Arabian Peninsula coastline, with a genetic break towards the southern part of the basin. While previous studies have attributed these patterns to environmental heterogeneity, we hypothesize that they may also emerge as a result of dynamic circulation flow; yet, such linkages remain undemonstrated. Here, we integrate satellite-derived biophysical observations, particle dispersion model simulations, genetic population data and ship-borne in situ profiles to assess reef connectivity in the Red Sea. We simulated long-term (>20 yrs.) connectivity patterns driven by remotely-sensed sea surface height and evaluated results against estimates of genetic distance among populations of anemonefish, Amphiprion bicinctus, along the eastern Red Sea coastline. Predicted connectivity was remarkably consistent with genetic population data, demonstrating that circulation features (eddies, surface currents) formulate physical pathways for gene flow. The southern basin has lower physical connectivity than elsewhere, agreeing with known genetic structure of coral reef organisms. The central Red Sea provides key source regions, meriting conservation priority. Our analysis demonstrates a cost-effective tool to estimate biophysical connectivity remotely, supporting coastal management in data-limited regions.

  2. Programming of stress pathways: A transgenerational perspective.

    Science.gov (United States)

    Constantinof, Andrea; Moisiadis, Vasilis G; Matthews, Stephen G

    2016-06-01

    The embryo and fetus are highly responsive to the gestational environment. Glucocorticoids (GC) represent an important class of developmental cues and are crucial for normal brain development. Levels of GC in the fetal circulation are tightly regulated. They are maintained at low levels during pregnancy, and increase rapidly at the end of gestation. This surge in GC is critical for maturation of the organs, specifically the lungs, brain and kidney. There are extensive changes in brain epigenetic profiles that accompany the GC surge, suggesting that GC may drive regulation of gene transcription through altered epigenetic pathways. The epigenetic profiles produced by the GC surge can be prematurely induced as a result of maternal or fetal stress, as well as through exposure to synthetic glucocorticoids (sGC). This is highly clinically relevant as 10% of pregnant women are at risk for preterm labour and receive treatment with sGC to promote lung development in the fetus. Fetal overexposure to GC (including sGC) has been shown to cause lasting changes in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis leading to altered stress responses, and mood and anxiety disorders in humans and animals. In animal models, GC exposure is associated with transcriptomic and epigenomic changes that influence behaviour, HPA function and growth. Importantly, programming by GC results in sex-specific effects that can be inherited over multiple generations via paternal and maternal transmission. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. C. elegans GATA factors EGL-18 and ELT-6 function downstream of Wnt signaling to maintain the progenitor fate during larval asymmetric divisions of the seam cells.

    Science.gov (United States)

    Gorrepati, Lakshmi; Thompson, Kenneth W; Eisenmann, David M

    2013-05-01

    The C. elegans seam cells are lateral epithelial cells arrayed in a single line from anterior to posterior that divide in an asymmetric, stem cell-like manner during larval development. These asymmetric divisions are regulated by Wnt signaling; in most divisions, the posterior daughter in which the Wnt pathway is activated maintains the progenitor seam fate, while the anterior daughter in which the Wnt pathway is not activated adopts a differentiated hypodermal fate. Using mRNA tagging and microarray analysis, we identified the functionally redundant GATA factor genes egl-18 and elt-6 as Wnt pathway targets in the larval seam cells. EGL-18 and ELT-6 have previously been shown to be required for initial seam cell specification in the embryo. We show that in larval seam cell asymmetric divisions, EGL-18 is expressed strongly in the posterior seam-fated daughter. egl-18 and elt-6 are necessary for larval seam cell specification, and for hypodermal to seam cell fate transformations induced by ectopic Wnt pathway overactivation. The TCF homolog POP-1 binds a site in the egl-18 promoter in vitro, and this site is necessary for robust seam cell expression in vivo. Finally, larval overexpression of EGL-18 is sufficient to drive expression of a seam marker in other hypodermal cells in wild-type animals, and in anterior hypodermal-fated daughters in a Wnt pathway-sensitized background. These data suggest that two GATA factors that are required for seam cell specification in the embryo independently of Wnt signaling are reused downstream of Wnt signaling to maintain the progenitor fate during stem cell-like divisions in larval development.

  4. Maintaining a Distinction Between Possible and Impossible Topics of Conversation in the Outpatient Respiratory Medical Clinic

    DEFF Research Database (Denmark)

    Birgitte Skov Jensen, Lone; Larsen, Kristian; Konradsen, Hanne

    2016-01-01

    by maintaining a distinction between possible and impossible topics to counseling. Three subcategories explaining the effort that maintain the impossible and possible topics separated were identified: (a) an effort to maintain the diseased lungs as the main task in counseling, (b) navigating interactions...

  5. Maintaining adequate nutrient supply - Principles, decision-support tools, and best management practices [Chapter 6

    Science.gov (United States)

    Robert B. Harrison; Douglas A. Maguire; Deborah Page-Dumroese

    2011-01-01

    Maintaining adequate nutrient supply to maintain or enhance tree vigor and forest growth requires conservation of topsoil and soil organic matter. Sometimes nutrient amendments are also required to supplement inherent nutrient-pool limitations or replenish nutrients removed in harvested material. The goal is to maintain the productive potential of the soil and, when...

  6. Career Technical Education Pathways Initiative

    Science.gov (United States)

    California Community Colleges, Chancellor's Office, 2013

    2013-01-01

    California's education system--the largest in the United States--is an essential resource for ensuring strong economic growth in the state. The Career Technical Education Pathways Initiative (referred to as the Initiative in this report), which became law in 2005, brings together community colleges, K-12 school districts, employers, organized…

  7. Pentose pathway in human liver

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  8. Diverse Pathways in Children's Learning.

    Science.gov (United States)

    Lambert, Beverley

    1996-01-01

    Used a Partially Ordered Scaling of Items method to analyze block construction play in a replication of Innes and King-Shaw's 1985 study. Found several developmental pathways for block play, illustrating the web-like nature of conceptual development. Results suggest a contextual developmental approach to better acknowledge individual diversity in…

  9. Critical nodes in signalling pathways

    DEFF Research Database (Denmark)

    Taniguchi, Cullen M; Emanuelli, Brice; Kahn, C Ronald

    2006-01-01

    Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role...... using insulin signalling as a model system....

  10. The oxylipin pathway in Arabidopsis.

    Science.gov (United States)

    Creelman, Robert A; Mulpuri, Rao

    2002-01-01

    Oxylipins are acyclic or cyclic oxidation products derived from the catabolism of fatty acids which regulate many defense and developmental pathways in plants. The dramatic increase in the volume of publications and reviews on these compounds since 1997 documents the increasing interest in this compound and its role in plants. Research on this topic has solidified our understanding of the chemistry and biosynthetic pathways for oxylipin production. However, more information is still needed on how free fatty acids are produced and the role of beta-oxidation in the biosynthetic pathway for oxylipins. It is also becoming apparent that oxylipin content and composition changes during growth and development and during pathogen or insect attack. Oxylipins such as jasmonic acid (JA) or 12-oxo-phytodienoic acid modulate the expression of numerous genes and influence specific aspects of plant growth, development and responses to abiotic and biotic stresses. Although oxylipins are believed to act alone, several examples were presented to illustrate that JA-induced responses are modulated by the type and the nature of crosstalk with other signaling molecules such as ethylene and salicylic acid. How oxylipins cause changes in gene expression and instigate a physiological response is becoming understood with the isolation of mutations in both positive and negative regulators in the jasmonate signaling pathway and the use of cDNA microarrays.

  11. Two-Electron Transfer Pathways.

    Science.gov (United States)

    Lin, Jiaxing; Balamurugan, D; Zhang, Peng; Skourtis, Spiros S; Beratan, David N

    2015-06-18

    The frontiers of electron-transfer chemistry demand that we develop theoretical frameworks to describe the delivery of multiple electrons, atoms, and ions in molecular systems. When electrons move over long distances through high barriers, where the probability for thermal population of oxidized or reduced bridge-localized states is very small, the electrons will tunnel from the donor (D) to acceptor (A), facilitated by bridge-mediated superexchange interactions. If the stable donor and acceptor redox states on D and A differ by two electrons, it is possible that the electrons will propagate coherently from D to A. While structure-function relations for single-electron superexchange in molecules are well established, strategies to manipulate the coherent flow of multiple electrons are largely unknown. In contrast to one-electron superexchange, two-electron superexchange involves both one- and two-electron virtual intermediate states, the number of virtual intermediates increases very rapidly with system size, and multiple classes of pathways interfere with one another. In the study described here, we developed simple superexchange models for two-electron transfer. We explored how the bridge structure and energetics influence multielectron superexchange, and we compared two-electron superexchange interactions to single-electron superexchange. Multielectron superexchange introduces interference between singly and doubly oxidized (or reduced) bridge virtual states, so that even simple linear donor-bridge-acceptor systems have pathway topologies that resemble those seen for one-electron superexchange through bridges with multiple parallel pathways. The simple model systems studied here exhibit a richness that is amenable to experimental exploration by manipulating the multiple pathways, pathway crosstalk, and changes in the number of donor and acceptor species. The features that emerge from these studies may assist in developing new strategies to deliver multiple

  12. FANCD2 Maintains Fork Stability in BRCA1/2-Deficient Tumors and Promotes Alternative End-Joining DNA Repair

    Directory of Open Access Journals (Sweden)

    Zeina Kais

    2016-06-01

    Full Text Available BRCA1/2 proteins function in homologous recombination (HR-mediated DNA repair and cooperate with Fanconi anemia (FA proteins to maintain genomic integrity through replication fork stabilization. Loss of BRCA1/2 proteins results in DNA repair deficiency and replicative stress, leading to genomic instability and enhanced sensitivity to DNA-damaging agents. Recent studies have shown that BRCA1/2-deficient tumors upregulate Polθ-mediated alternative end-joining (alt-EJ repair as a survival mechanism. Whether other mechanisms maintain genomic integrity upon loss of BRCA1/2 proteins is currently unknown. Here we show that BRCA1/2-deficient tumors also upregulate FANCD2 activity. FANCD2 is required for fork protection and fork restart in BRCA1/2-deficient tumors. Moreover, FANCD2 promotes Polθ recruitment at sites of damage and alt-EJ repair. Finally, loss of FANCD2 in BRCA1/2-deficient tumors enhances cell death. These results reveal a synthetic lethal relationship between FANCD2 and BRCA1/2, and they identify FANCD2 as a central player orchestrating DNA repair pathway choice at the replication fork.

  13. Using Vector Projection Method to evaluate maintainability of mechanical system in design review

    International Nuclear Information System (INIS)

    Chen Lu; Cai Jianguo

    2003-01-01

    Maintainability of a mechanical system is one of the system design parameters that has a great impact in terms of ease of maintenance. In this article, based on the definition of the terms of maintenance and maintainability, an important tool of Design for Maintenance is developed as a way to improve maintainability through design. A set of standard and organized guidelines is provided and maintainability factors in terms of physical design, logistics support and ergonomics are identified. As a specific application of design review, a methodology so called Vector Projection Method is developed to evaluate the maintainability of the mechanical system. Lastly, an example is discussed

  14. Weakened Intracellular Zn2+-Buffering in the Aged Dentate Gyrus and Its Involvement in Erasure of Maintained LTP.

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna; Murakami, Taku; Nakada, Hiroyuki; Minamino, Tatsuya; Koike, Yuta

    2018-05-01

    Memory is lost by the increased influx of extracellular Zn 2+ into neurons. It is possible that intracellular Zn 2+ dynamics is modified even at non-zincergic medial perforant pathway-dentate granule cell synapses along with aging and that vulnerability to the modification is linked to age-related cognitive decline. To examine these possibilities, vulnerability of long-term potentiation (LTP) maintenance, which underlies memory retention, to modification of synaptic Zn 2+ dynamics was compared between young and aged rats. The influx of extracellular Zn 2+ into dentate granule cells was increased in aged rats after injection of high K + into the dentate gyrus, but not in young rats. This increase impaired maintained LTP in aged rats. However, the impairment was rescued by co-injection of CaEDTA, an extracellular Zn 2+ chelator, or CNQX, an AMPA receptor antagonist, which suppressed the Zn 2+ influx. Maintained LTP was also impaired in aged rats after injection of ZnAF-2DA into the dentate gyrus that chelates intracellular Zn 2+ , but not in young rats. Interestingly, the capacity of chelating intracellular Zn 2+ with intracellular ZnAF-2 was almost lost in the aged dentate gyrus 2 h after injection of ZnAF-2DA into the dentate gyrus, suggesting that intracellular Zn 2+ -buffering is weakened in the aged dentate gyrus, compared to the young dentate gyrus. In the dentate gyrus of aged rats, maintained LTP is more vulnerable to modification of intracellular Zn 2+ dynamics than in young rats, probably due to weakened intracellular Zn 2+ -buffering.

  15. CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Hieu T Nim

    Full Text Available The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP, an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1 relevant to cardiac literature, and (2 differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10 are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research.

  16. CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts.

    Science.gov (United States)

    Nim, Hieu T; Furtado, Milena B; Costa, Mauro W; Kitano, Hiroaki; Rosenthal, Nadia A; Boyd, Sarah E

    2015-01-01

    The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP), an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1) relevant to cardiac literature, and (2) differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10) are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research.

  17. A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

    Science.gov (United States)

    Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

    2017-09-01

    The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

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

    Directory of Open Access Journals (Sweden)

    Wufeng Fan

    2017-01-01

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

  19. The lectin pathway of complement

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  20. Alternative pathways to antimatter containment

    International Nuclear Information System (INIS)

    Rejcek, J.M.; Browder, M.K.; Fry, J.L.; Koymen, A.; Weiss, A.H.

    2003-01-01

    Antimatter containment is a gateway technology for future advancements in many areas. Immediate applications in propulsion, medicine, and instrumentation have already been envisioned and many others are yet to be considered. Key to this technological advance is identifying one or more pathways to achieve safe reliable containment of antimatter in sufficient quantities to be useful on an engineering and industrial scale. The goal of this paper is to review current approaches and discuss possible alternative pathways to antimatter containment. Specifically, this paper will address the possibility of designing a solid-state containment system that will safely hold antimatter in quantities dense enough to be of any engineering utility. A discussion of the current research, the needed engineering requirements, and a survey of current research is presented

  1. Molecular pathways towards psychiatric disorders

    International Nuclear Information System (INIS)

    Chela-Flores, J.

    1987-07-01

    The observed fibrillar-neuronal organization of the cerebral cortex suggests that in the aetiology of certain psychiatric disorders the genomic response of the neuron to the challenge presented by stress or insults at various stages of development, is to set off a programmed chain of molecular events (or ''pathways''), as demonstrated in previous genetic studies. The understanding of these pathways is important in order to enhance our ability to influence these illnesses, and are hypothesized to be initiated by a nucleolar mechanism for inducing abnormal synthesis of the nerve growth factor (NGF). The hypothesis is used to approach tentatively the still open question regarding the pathogenesis of mental retardation (MR) and senile dementia (SD). (author). 25 refs

  2. Reliability and Maintainability Analysis for the Amine Swingbed Carbon Dioxide Removal System

    Science.gov (United States)

    Dunbar, Tyler

    2016-01-01

    I have performed a reliability & maintainability analysis for the Amine Swingbed payload system. The Amine Swingbed is a carbon dioxide removal technology that has gone through 2,400 hours of International Space Station on-orbit use between 2013 and 2016. While the Amine Swingbed is currently an experimental payload system, the Amine Swingbed may be converted to system hardware. If the Amine Swingbed becomes system hardware, it will supplement the Carbon Dioxide Removal Assembly (CDRA) as the primary CO2 removal technology on the International Space Station. NASA is also considering using the Amine Swingbed as the primary carbon dioxide removal technology for future extravehicular mobility units and for the Orion, which will be used for the Asteroid Redirect and Journey to Mars missions. The qualitative component of the reliability and maintainability analysis is a Failure Modes and Effects Analysis (FMEA). In the FMEA, I have investigated how individual components in the Amine Swingbed may fail, and what the worst case scenario is should a failure occur. The significant failure effects are the loss of ability to remove carbon dioxide, the formation of ammonia due to chemical degradation of the amine, and loss of atmosphere because the Amine Swingbed uses the vacuum of space to regenerate the Amine Swingbed. In the quantitative component of the reliability and maintainability analysis, I have assumed a constant failure rate for both electronic and nonelectronic parts. Using this data, I have created a Poisson distribution to predict the failure rate of the Amine Swingbed as a whole. I have determined a mean time to failure for the Amine Swingbed to be approximately 1,400 hours. The observed mean time to failure for the system is between 600 and 1,200 hours. This range includes initial testing of the Amine Swingbed, as well as software faults that are understood to be non-critical. If many of the commercial parts were switched to military-grade parts, the expected

  3. Vanillin biosynthetic pathways in plants.

    Science.gov (United States)

    Kundu, Anish

    2017-06-01

    The present review compiles the up-to-date knowledge on vanillin biosynthesis in plant systems to focus principally on the enzymatic reactions of in planta vanillin biosynthetic pathway and to find out its impact and prospect in future research in this field. Vanillin, a very popular flavouring compound, is widely used throughout the world. The principal natural resource of vanillin is the cured vanilla pods. Due to the high demand of vanillin as a flavouring agent, it is necessary to explore its biosynthetic enzymes and genes, so that improvement in its commercial production can be achieved through metabolic engineering. In spite of significant advancement in elucidating vanillin biosynthetic pathway in the last two decades, no conclusive demonstration had been reported yet for plant system. Several biosynthetic enzymes have been worked upon but divergences in published reports, particularly in characterizing the crucial biochemical steps of vanillin biosynthesis, such as side-chain shortening, methylation, and glucoside formation and have created a space for discussion. Recently, published reviews on vanillin biosynthesis have focused mainly on the biotechnological approaches and bioconversion in microbial systems. This review, however, aims to compile in brief the overall vanillin biosynthetic route and present a comparative as well as comprehensive description of enzymes involved in the pathway in Vanilla planifolia and other plants. Special emphasis has been given on the key enzymatic biochemical reactions that have been investigated extensively. Finally, the present standpoint and future prospects have been highlighted.

  4. Transuranic element pathways to man

    International Nuclear Information System (INIS)

    Bennett, B.G.

    1976-01-01

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

  5. Imbalanced Kynurenine Pathway in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Magdalena E. Kegel

    2014-01-01

    Full Text Available Several studies suggest a role for kynurenic acid (KYNA in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN. Here we investigate the levels of QUIN in cerebrospinal fluid (CSF of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22 and those of controls (n = 26 were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36. CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls ( P = 0.027. In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

  6. A practical method for the maintainability assessment in industrial devices using indicators and specific attributes

    International Nuclear Information System (INIS)

    Moreu De Leon, Pedro; González-Prida Díaz, Vicente; Barberá Martínez, Luis; Crespo Márquez, Adolfo

    2012-01-01

    The objective of this paper is to describe a procedure to obtain maintainability indicators for industrial devices. This analysis can be helpful, among other cases, to compare systems, to achieve a better design regarding maintainability requirements, to improve this maintainability under specific industrial environment and to foresee maintainability problems due to eventual changes in a device operation conditions. This maintainability assessment can be carried out at any stage of the industrial asset life cycle. With this purpose, this work first introduces the notion of maintainability and the implementation of assessment indicators, including some important requirements to perform that. Then, a brief literature review is presented, including the definition of the main concepts, which are later used in the paper. After studying the maintenance levels and the maintainability attributes, both terms are linked, leading all this analysis to the assessment of the maintainability indicators. It follows a discussion about the information obtained through the maintainability assessment process and its computation into several maintainability indicators. The paper includes a case study, which implements the defined assessment into a practical scenario. Finally, the work concludes summarizing the more significant aspects and suggesting future researches.

  7. Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

    Science.gov (United States)

    Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

    2017-06-01

    Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017

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

    Directory of Open Access Journals (Sweden)

    Q. Wang

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

  9. Method for determining heterologous biosynthesis pathways

    KAUST Repository

    Gao, Xin; Kuwahara, Hiroyuki; Alazmi, Meshari Saud; Cui, Xuefeng

    2017-01-01

    suitable pathways for the endogenous metabolism of a host organism because the efficacy of heterologous biosynthesis is affected by competing endogenous pathways. The present invention is called MRE (Metabolic Route Explorer), and it was conceived

  10. Primary Metabolic Pathways and Metabolic Flux Analysis

    DEFF Research Database (Denmark)

    Villadsen, John

    2015-01-01

    his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...... the reader who is primarily trained in the engineering sciences with atleast a preliminary introduction to biochemistry and also shows how carbon is drained off the catabolic pathways to provide precursors for cell mass building and sometimes for important industrial products. The primary pathways...... to be examined in the following are: glycolysis, primarily by the EMP pathway, but other glycolytic pathways is also mentioned; fermentative pathways in which the redox generated in the glycolytic reactions are consumed; reactions in the tricarboxylic acid (TCA) cycle, which produce biomass precursors and redox...

  11. KRE5 Suppression Induces Cell Wall Stress and Alternative ER Stress Response Required for Maintaining Cell Wall Integrity in Candida glabrata

    Science.gov (United States)

    Sasaki, Masato; Ito, Fumie; Aoyama, Toshio; Sato-Okamoto, Michiyo; Takahashi-Nakaguchi, Azusa; Chibana, Hiroji; Shibata, Nobuyuki

    2016-01-01

    The maintenance of cell wall integrity in fungi is required for normal cell growth, division, hyphae formation, and antifungal tolerance. We observed that endoplasmic reticulum stress regulated cell wall integrity in Candida glabrata, which possesses uniquely evolved mechanisms for unfolded protein response mechanisms. Tetracycline-mediated suppression of KRE5, which encodes a predicted UDP-glucose:glycoprotein glucosyltransferase localized in the endoplasmic reticulum, significantly increased cell wall chitin content and decreased cell wall β-1,6-glucan content. KRE5 repression induced endoplasmic reticulum stress-related gene expression and MAP kinase pathway activation, including Slt2p and Hog1p phosphorylation, through the cell wall integrity signaling pathway. Moreover, the calcineurin pathway negatively regulated cell wall integrity, but not the reduction of β-1,6-glucan content. These results indicate that KRE5 is required for maintaining both endoplasmic reticulum homeostasis and cell wall integrity, and that the calcineurin pathway acts as a regulator of chitin-glucan balance in the cell wall and as an alternative mediator of endoplasmic reticulum stress in C. glabrata. PMID:27548283

  12. CD137 pathway: immunology and diseases

    National Research Council Canada - National Science Library

    Chen, Lieping

    2006-01-01

    ... may work in either interconnected or linear fashion. Therefore, the combined understanding of each pathway, their interactions with other pathways, and the functional consequence, is a cornerstone for our interpretation of pathological basis of diseases and future treatments. It is important to stay abreast on the pace of progress, which I refer to as periodic summary of incremental and breakthrough discoveries in each pathway by the experts and the leader in the field. The CD137 Pathway: Immu...

  13. Cancer Therapy Targeting the HER2-PI3K Pathway: Potential Impact on the Heart

    Directory of Open Access Journals (Sweden)

    Giannoula Lakka Klement

    2012-06-01

    Full Text Available The HER2-PI3K pathway is the one of the most mutated pathways in cancer. Several drugs targeting the major kinases of this pathway have been approved by the Food and Drug Administration and many are being tested in clinical trials for the treatment of various cancers. However, the HER2-PI3K pathway is also pivotal for maintaining the physiological function of the heart, especially in the presence of cardiac stress. Clinical studies have shown that in patients treated with doxorubicin concurrently with Trastuzumab, a monoclonal antibody that blocks the HER2 receptor, the New York Heart Association class III/IV heart failure was significantly increased compared to those who were treated with doxorubicin alone (16 vs. 3%. Studies in transgenic mice have also shown that other key kinases of this pathway, such as PI3Kα, PDK1, Akt and mTOR, are important for protecting the heart from ischemia-reperfusion and aortic stenosis induced cardiac dysfunction. Studies, however, have also shown that inhibition of PI3Kγ improve cardiac function of a failing heart. In addition, results from transgenic mouse models are not always consistent with the outcome of the pharmacological inhibition of this pathway. Here, we will review these findings and discuss how we can address the cardiac side-effects caused by inhibition of this important pathway in both cancer and cardiac biology.

  14. Arabidopsis chlorophyll biosynthesis: an essential balance between the methylerythritol phosphate and tetrapyrrole pathways.

    Science.gov (United States)

    Kim, Se; Schlicke, Hagen; Van Ree, Kalie; Karvonen, Kristine; Subramaniam, Anant; Richter, Andreas; Grimm, Bernhard; Braam, Janet

    2013-12-01

    Chlorophyll, essential for photosynthesis, is composed of a chlorin ring and a geranylgeranyl diphosphate (GGPP)-derived isoprenoid, which are generated by the tetrapyrrole and methylerythritol phosphate (MEP) biosynthesis pathways, respectively. Although a functional MEP pathway is essential for plant viability, the underlying basis of the requirement has been unclear. We hypothesized that MEP pathway inhibition is lethal because a reduction in GGPP availability results in a stoichiometric imbalance in tetrapyrrolic chlorophyll precursors, which can cause deadly photooxidative stress. Consistent with this hypothesis, lethality of MEP pathway inhibition in Arabidopsis thaliana by fosmidomycin (FSM) is light dependent, and toxicity of MEP pathway inhibition is reduced by genetic and chemical impairment of the tetrapyrrole pathway. In addition, FSM treatment causes a transient accumulation of chlorophyllide and transcripts associated with singlet oxygen-induced stress. Furthermore, exogenous provision of the phytol molecule reduces FSM toxicity when the phytol can be modified for chlorophyll incorporation. These data provide an explanation for FSM toxicity and thereby provide enhanced understanding of the mechanisms of FSM resistance. This insight into MEP pathway inhibition consequences underlines the risk plants undertake to synthesize chlorophyll and suggests the existence of regulation, possibly involving chloroplast-to-nucleus retrograde signaling, that may monitor and maintain balance of chlorophyll precursor synthesis.

  15. Understanding the Contribution of Zinc Transporters in the Function of the Early Secretory Pathway.

    Science.gov (United States)

    Kambe, Taiho; Matsunaga, Mayu; Takeda, Taka-Aki

    2017-10-19

    More than one-third of newly synthesized proteins are targeted to the early secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi apparatus, and other intermediate compartments. The early secretory pathway plays a key role in controlling the folding, assembly, maturation, modification, trafficking, and degradation of such proteins. A considerable proportion of the secretome requires zinc as an essential factor for its structural and catalytic functions, and recent findings reveal that zinc plays a pivotal role in the function of the early secretory pathway. Hence, a disruption of zinc homeostasis and metabolism involving the early secretory pathway will lead to pathway dysregulation, resulting in various defects, including an exacerbation of homeostatic ER stress. The accumulated evidence indicates that specific members of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs), which operate in the early secretory pathway, play indispensable roles in maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this review, the biological functions of these transporters are discussed, focusing on recent aspects of their roles. In particular, we discuss in depth how specific ZNT transporters are employed in the activation of zinc-requiring ectoenzymes. The means by which early secretory pathway functions are controlled by zinc, mediated by specific ZNT and ZIP transporters, are also subjects of this review.

  16. Internal medicine board certification and career pathways in Japan.

    Science.gov (United States)

    Koike, Soichi; Matsumoto, Masatoshi; Ide, Hiroo; Kawaguchi, Hideaki; Shimpo, Masahisa; Yasunaga, Hideo

    2017-05-08

    Establishing and managing a board certification system is a common concern for many countries. In Japan, the board certification system is under revision. The purpose of this study was to describe present status of internal medicine specialist board certification, to identify factors associated with maintenance of board certification and to investigate changes in area of practice when physicians move from hospital to clinic practice. We analyzed 2010 and 2012 data from the Survey of Physicians, Dentists and Pharmacists. We conducted logistic regression analysis to identify factors associated with the maintenance of board certification between 2010 and 2012. We also analyzed data on career transition from hospitals to clinics for hospital physicians with board certification. It was common for physicians seeking board certification to do so in their early career. The odds of maintaining board certification were lower in women and those working in locations other than academic hospitals, and higher in physicians with subspecialty practice areas. Among hospital physicians with board certification who moved to clinics between 2010 and 2012, 95.8% remained in internal medicine or its subspecialty areas and 87.7% maintained board certification but changed their practice from a subspecialty area to more general internal medicine. Revisions of the internal medicine board certification system must consider different physician career pathways including mid-career moves while maintaining certification quality. This will help to secure an adequate number and distribution of specialists. To meet the increasing demand for generalist physicians, it is important to design programs to train specialists in general practice.

  17. Atg12 Maintains Skeletal Integrity by Modulating Pro-Osteoclastogenic Signals and Chondrocyte Differentiation

    Science.gov (United States)

    Tahimic, Candice; Bahl, Disha; Shirazi-Fard, Yasaman; Marsh, Timothy; Schreurs, Anne-Sofie; Rael, Victoria E.; Glikbarg, Chloe; Debnath, Jayantha; Globus, Ruth K.

    2016-01-01

    Weightlessness and radiation, two unique elements of space, profoundly decreases bone mass. This bone loss is attributed to increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Our long-term goal is to identify signaling pathways that may be targeted to mitigate bone loss in scenarios of space exploration, radiotherapy and accidental radiation exposure. We have previously shown that exposure of MLO-Y4 osteocyte-like cells to simulated space radiation (56Fe) increased the expression of the pro-osteoclastogenic gene rankl and decreased protein levels of LC3B-II, a key player in autophagy. In this current study, we aimed to further elucidate the role of autophagy in maintaining structural integrity of the skeleton. We hypothesize that loss of autophagy in bone leads to an imbalance in pro-osteoclastogenic and pro-osteogenic signals, resulting in net bone loss. To test our hypothesis we performed global postnatal deletion of Atg12 using tamoxifeninducible Cre recombinase under the control of the CAG promoter. Six-week-old CAGCreERT2/ FloxAtg12 animals were treated daily with Tamoxifen or Vehicle (Control, oil only) for five days and euthanasia performed two weeks after the onset of treatment. Percent change in body weights (prior to treatment and at euthanasia) was not significantly different between treatment groups within the same gender. Compared to Vehicle (Control) groups, Tamoxifen (Atg12 iKO) groups showed decreased LC3B-I to II conversion and increased p62 protein levels, consistent with loss of autophagy. Quantitative PCR revealed increased expression of proosteoclastogenic cytokines mcp1 and rankl in bone and marrow respectively in male iKOs compared to male controls. Expression levels of these genes were not significantly altered in the Atg12 iKO females compared to females controls. Microcomputed tomography of tibiae revealed decreased cortical bone volume, cortical

  18. Different Roles of Direct and Indirect Frontoparietal Pathways for Individual Working Memory Capacity.

    Science.gov (United States)

    Ekman, Matthias; Fiebach, Christian J; Melzer, Corina; Tittgemeyer, Marc; Derrfuss, Jan

    2016-03-09

    The ability to temporarily store and manipulate information in working memory is a hallmark of human intelligence and differs considerably across individuals, but the structural brain correlates underlying these differences in working memory capacity (WMC) are only poorly understood. In two separate studies, diffusion MRI data and WMC scores were collected for 70 and 109 healthy individuals. Using a combination of probabilistic tractography and network analysis of the white matter tracts, we examined whether structural brain network properties were predictive of individual WMC. Converging evidence from both studies showed that lateral prefrontal cortex and posterior parietal cortex of high-capacity individuals are more densely connected compared with low-capacity individuals. Importantly, our network approach was further able to dissociate putative functional roles associated with two different pathways connecting frontal and parietal regions: a corticocortical pathway and a subcortical pathway. In Study 1, where participants were required to maintain and update working memory items, the connectivity of the direct and indirect pathway was predictive of WMC. In contrast, in Study 2, where participants were required to maintain working memory items without updating, only the connectivity of the direct pathway was predictive of individual WMC. Our results suggest an important dissociation in the circuitry connecting frontal and parietal regions, where direct frontoparietal connections might support storage and maintenance, whereas subcortically mediated connections support the flexible updating of working memory content. Copyright © 2016 the authors 0270-6474/16/362894-10$15.00/0.

  19. Certification Criteria for Linked Learning Pathways

    Science.gov (United States)

    ConnectEd: The California Center for College and Career, 2010

    2010-01-01

    Pathways offer a promising strategy for transforming high schools and improving student outcomes. However, to achieve these desired results, pathways must be of high quality. To guide sites in planning and implementing such pathways, a design team of experts developed the criteria outlined in this document. Sites can choose to go through a…

  20. A long slanted transseptal accessory pathway

    Directory of Open Access Journals (Sweden)

    Hui-Min Wang

    2011-05-01

    Full Text Available A 63-year-old male with Wolff-Parkinson-White syndrome was admitted for ablation of accessory pathway. Intracardiac electrogram revealed a left-side accessory pathway during tachycardia, which was successfully ablated from the right posterior tricuspid annulus because of a long slanted transseptal accessory pathway (2.2 cm.

  1. Maintaining evolvability

    Indian Academy of Sciences (India)

    2008-12-23

    % of the variance would have passed the stringent tests for inclusion in the ... genetic complication (e.g. a balanced lethal system) or in- compatibility of .... have important evolutionary roles (genes of large effect; du- plications ...

  2. A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways

    Science.gov (United States)

    Han, Junwei; Li, Chunquan; Yang, Haixiu; Xu, Yanjun; Zhang, Chunlong; Ma, Jiquan; Shi, Xinrui; Liu, Wei; Shang, Desi; Yao, Qianlan; Zhang, Yunpeng; Su, Fei; Feng, Li; Li, Xia

    2015-01-01

    Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI). PMID:25551156

  3. Merging building maintainability and sustainability assessment: A multicriteria decision making approach

    Science.gov (United States)

    Asmone, A. S.; Chew, M. Y. L.

    2018-02-01

    Accurately predicting maintainability has been a challenge due to the complex nature of buildings, yet it is an important research area with a rising necessity. This paper explores the use of multicriteria decision making approach for merging maintainability and sustainability elements into building grading systems to attain long-term sustainability in the building industry. The paper conducts a systematic literature review on multicriteria decision analysis approach and builds on the existing knowledge of maintainability to achieve this. A conceptual framework is developed to bridge the gap between building operations and maintenance with green facilities management by forecasting green maintainability at the design stage.

  4. IntPath--an integrated pathway gene relationship database for model organisms and important pathogens.

    Science.gov (United States)

    Zhou, Hufeng; Jin, Jingjing; Zhang, Haojun; Yi, Bo; Wozniak, Michal; Wong, Limsoon

    2012-01-01

    Pathway data are important for understanding the relationship between genes, proteins and many other molecules in living organisms. Pathway gene relationships are crucial information for guidance, prediction, reference and assessment in biochemistry, computational biology, and medicine. Many well-established databases--e.g., KEGG, WikiPathways, and BioCyc--are dedicated to collecting pathway data for public access. However, the effectiveness of these databases is hindered by issues such as incompatible data formats, inconsistent molecular representations, inconsistent molecular relationship representations, inconsistent referrals to pathway names, and incomprehensive data from different databases. In this paper, we overcome these issues through extraction, normalization and integration of pathway data from several major public databases (KEGG, WikiPathways, BioCyc, etc). We build a database that not only hosts our integrated pathway gene relationship data for public access but also maintains the necessary updates in the long run. This public repository is named IntPath (Integrated Pathway gene relationship database for model organisms and important pathogens). Four organisms--S. cerevisiae, M. tuberculosis H37Rv, H. Sapiens and M. musculus--are included in this version (V2.0) of IntPath. IntPath uses the "full unification" approach to ensure no deletion and no introduced noise in this process. Therefore, IntPath contains much richer pathway-gene and pathway-gene pair relationships and much larger number of non-redundant genes and gene pairs than any of the single-source databases. The gene relationships of each gene (measured by average node degree) per pathway are significantly richer. The gene relationships in each pathway (measured by average number of gene pairs per pathway) are also considerably richer in the integrated pathways. Moderate manual curation are involved to get rid of errors and noises from source data (e.g., the gene ID errors in WikiPathways and

  5. Apoptotic engulfment pathway and schizophrenia.

    LENUS (Irish Health Repository)

    Chen, Xiangning

    2009-01-01

    BACKGROUND: Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease. METHODOLOGY\\/PRINCIPAL FINDINGS: Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively). We sought replication in independent samples for this marker and found highly significant association (p = 0.0003) in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075) interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022) and a 3-marker interaction (rs246896 * rs4522565 * rs3858075) amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120). Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples. CONCLUSIONS\\/SIGNIFICANCE: From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease.

  6. Nutrition pathways in consequence modeling

    International Nuclear Information System (INIS)

    Tveten, U.

    1982-01-01

    During 1979-1980 calculations of risk from waste transportation by truck (fire following collision) and fire in temporary storage for waste were performed. A modified version of the consequence model of WASH-1400 (CRAC) was used. Two exposure pathways dominated the results: external exposure from material on the ground and exposure via nutrition. Many of the parameters entering into the nutrition calculations will depend upon local conditions, like soil composition, crop yield, etc. It was decided to collect detailed comments upon the CRAC nutritions model and parameter values from radioecologists in the four Nordic countries. Four alternate sets of parameter values were derived from these comments, and new risk calculations were performed

  7. Thermodynamics of metabolic pathways for penicillin production: Analysis of thermodynamic feasibility and free energy changes during fed-batch cultivation

    DEFF Research Database (Denmark)

    Pissarra, P.D.; Nielsen, Jens Bredal

    1997-01-01

    This paper describes the thermodynamic analysis of pathways related to penicillin production in Penicillium chrysogenum. First a thermodynamic feasibility analysis is performed of the L-lysine pathway of which one of the precursors for penicillin biosynthesis (alpha-aminoadipic acid......) is an intermediate. It is found that the L-lysine pathway in P. chrysogenum is thermodynamically feasible and that the calculated standard Gibbs free energy values of the two enzymes controlling the pathway flux indicate that they operate far from equilibrium. It is therefore proposed that the regulation of alpha......-aminoadipate reductase by lysine is important to maintain a high concentration of alpha-aminoadipate in order to direct the carbon flux to penicillin production. Secondly the changes in Gibbs free energy in the penicillin biosynthetic pathway during fed-batch cultivation were studied. The analysis showed that all...

  8. The mevalonate pathway in neurons: It's not just about cholesterol.

    Science.gov (United States)

    Moutinho, Miguel; Nunes, Maria João; Rodrigues, Elsa

    2017-11-01

    Cholesterol homeostasis greatly impacts neuronal function due to the essential role of this sterol in the brain. The mevalonate (MVA) pathway leads to the synthesis of cholesterol, but also supplies cells with many other intermediary molecules crucial for neuronal function. Compelling evidence point to a model in which neurons shutdown cholesterol synthesis, and rely on a shuttle derived from astrocytes to meet their cholesterol needs. Nevertheless, several reports suggest that neurons maintain the MVA pathway active, even with sustained cholesterol supply by astrocytes. Hence, in this review we focus not on cholesterol production, but rather on the role of the MVA pathway in the synthesis of particular intermediaries, namely isoprenoids, and on their role on neuronal function. Isoprenoids act as anchors for membrane association, after being covalently bound to proteins, such as most of the small guanosine triphosphate-binding proteins, which are critical to neuronal cell function. Based on literature, on our own results, and on the analysis of public transcriptomics databases, we raise the idea that in neurons there is a shift of the MVA pathway towards the non-sterol branch, responsible for isoprenoid synthesis, in detriment to post-squalene branch, and that this is ultimately essential for synaptic activity. Nevertheless new tools that facilitate imaging and the biochemical characterization and quantification of the prenylome in neurons and astrocytes are needed to understand the regulation of isoprenoid production and protein prenylation in the brain, and to analyze its differences on diverse physiological or pathological conditions, such as aging and neurodegenerative states. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Magnocellular pathway for rotation invariant Neocognitron.

    Science.gov (United States)

    Ting, C H

    1993-03-01

    In the mammalian visual system, magnocellular pathway and parvocellular pathway cooperatively process visual information in parallel. The magnocellular pathway is more global and less particular about the details while the parvocellular pathway recognizes objects based on the local features. In many aspects, Neocognitron may be regarded as the artificial analogue of the parvocellular pathway. It is interesting then to model the magnocellular pathway. In order to achieve "rotation invariance" for Neocognitron, we propose a neural network model after the magnocellular pathway and expand its roles to include surmising the orientation of the input pattern prior to recognition. With the incorporation of the magnocellular pathway, a basic shift in the original paradigm has taken place. A pattern is now said to be recognized when and only when one of the winners of the magnocellular pathway is validified by the parvocellular pathway. We have implemented the magnocellular pathway coupled with Neocognitron parallel on transputers; our simulation programme is now able to recognize numerals in arbitrary orientation.

  10. Identifying pathways affected by cancer mutations.

    Science.gov (United States)

    Iengar, Prathima

    2017-12-16

    Mutations in 15 cancers, sourced from the COSMIC Whole Genomes database, and 297 human pathways, arranged into pathway groups based on the processes they orchestrate, and sourced from the KEGG pathway database, have together been used to identify pathways affected by cancer mutations. Genes studied in ≥15, and mutated in ≥10 samples of a cancer have been considered recurrently mutated, and pathways with recurrently mutated genes have been considered affected in the cancer. Novel doughnut plots have been presented which enable visualization of the extent to which pathways and genes, in each pathway group, are targeted, in each cancer. The 'organismal systems' pathway group (including organism-level pathways; e.g., nervous system) is the most targeted, more than even the well-recognized signal transduction, cell-cycle and apoptosis, and DNA repair pathway groups. The important, yet poorly-recognized, role played by the group merits attention. Pathways affected in ≥7 cancers yielded insights into processes affected. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Combustion kinetics and reaction pathways

    Energy Technology Data Exchange (ETDEWEB)

    Klemm, R.B.; Sutherland, J.W. [Brookhaven National Laboratory, Upton, NY (United States)

    1993-12-01

    This project is focused on the fundamental chemistry of combustion. The overall objectives are to determine rate constants for elementary reactions and to elucidate the pathways of multichannel reactions. A multitechnique approach that features three independent experiments provides unique capabilities in performing reliable kinetic measurements over an exceptionally wide range in temperature, 300 to 2500 K. Recent kinetic work has focused on experimental studies and theoretical calculations of the methane dissociation system (CH{sub 4} + Ar {yields} CH{sub 3} + H + Ar and H + CH{sub 4} {yields} CH{sub 3} + H{sub 2}). Additionally, a discharge flow-photoionization mass spectrometer (DF-PIMS) experiment is used to determine branching fractions for multichannel reactions and to measure ionization thresholds of free radicals. Thus, these photoionization experiments generate data that are relevant to both reaction pathways studies (reaction dynamics) and fundamental thermochemical research. Two distinct advantages of performing PIMS with high intensity, tunable vacuum ultraviolet light at the National Synchrotron Light Source are high detection sensitivity and exceptional selectivity in monitoring radical species.

  12. 31 CFR 1.30 - Application to system of records maintained by Government contractors.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Application to system of records maintained by Government contractors. 1.30 Section 1.30 Money and Finance: Treasury Office of the Secretary of the Treasury DISCLOSURE OF RECORDS Privacy Act § 1.30 Application to system of records maintained...

  13. 33 CFR 150.705 - What are the requirements for maintaining and inspecting aids to navigation?

    Science.gov (United States)

    2010-07-01

    ... maintaining and inspecting aids to navigation? 150.705 Section 150.705 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS DEEPWATER PORTS: OPERATIONS Aids to Navigation § 150.705 What are the requirements for maintaining and inspecting aids to navigation? (a) All...

  14. 9 CFR 147.26 - Procedures for establishing isolation and maintaining sanitation and good management practices...

    Science.gov (United States)

    2010-01-01

    ... and maintaining sanitation and good management practices for the control of Salmonella and Mycoplasma... Sanitation Procedures § 147.26 Procedures for establishing isolation and maintaining sanitation and good management practices for the control of Salmonella and Mycoplasma infections. (a) The following procedures...

  15. Nuclear power generating station operability assurance reliability, availability, and maintainability application for maintenance management

    International Nuclear Information System (INIS)

    Cleveland, J.W.; Regenie, T.R.; Wilson, R.J.

    1985-01-01

    Environmental qualification and equipment warrantee insurance stipulations should be supplemented with a reliable maintainability program structured to identify and control fast failing subcomponents within critical equipment. Anticipation of equipment subcomponent failures can control unnecessary plant off-line occurrences. Incorporation of reliability, availability, and maintainability considerations into plant maintenance policies on power generation and safety related items have positive cost benefit advantages

  16. 7 CFR 4290.600 - General requirement for RBIC to maintain and preserve records.

    Science.gov (United States)

    2010-01-01

    ...) All your accounting and other financial records; (2) All minutes of meetings of directors.... (a) Maintaining your accounting records. You must establish and maintain your accounting records.... You must keep the following records at your principal place of business or, in the case of paragraph...

  17. 46 CFR 11.713 - Requirements for maintaining current knowledge of waters to be navigated.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Requirements for maintaining current knowledge of waters to be navigated. 11.713 Section 11.713 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY MERCHANT MARINE OFFICERS AND SEAMEN REQUIREMENTS FOR OFFICER ENDORSEMENTS Professional Requirements for Pilots § 11.713 Requirements for maintaining curren...

  18. Management of neonatal abstinence syndrome in neonates born to opioid maintained women.

    Science.gov (United States)

    Ebner, Nina; Rohrmeister, Klaudia; Winklbaur, Bernadette; Baewert, Andjela; Jagsch, Reinhold; Peternell, Alexandra; Thau, Kenneth; Fischer, Gabriele

    2007-03-16

    Neonates born to opioid-maintained mothers are at risk of developing neonatal abstinence syndrome (NAS), which often requires pharmacological treatment. This study examined the effect of opioid maintenance treatment on the incidence and timing of NAS, and compared two different NAS treatments (phenobarbital versus morphine hydrochloride). Fifty-three neonates born to opioid-maintained mothers were included in this study. The mothers received methadone (n=22), slow-release oral morphine (n=17) or buprenorphine (n=14) throughout pregnancy. Irrespective of maintenance treatment, all neonates showed APGAR scores comparable to infants of non-opioid dependent mothers. No difference was found between the three maintenance groups regarding neonatal weight, length or head circumference. Sixty percent (n=32) of neonates required treatment for NAS [68% in the methadone-maintained group (n=15), 82% in the morphine-maintained group (n=14), and 21% in the buprenorphine-maintained group (n=3)]. The mean duration from birth to requirement of NAS treatment was 33 h for the morphine-maintained group, 34 h for the buprenorphine-maintained group and 58 h for the methadone-maintained group. In neonates requiring NAS treatment, those receiving morphine required a significantly shorter mean duration of treatment (9.9 days) versus those treated with phenobarbital (17.7 days). Results suggest that morphine hydrochloride is preferable for neonates suffering NAS due to opioid withdrawal.

  19. 36 CFR 1236.26 - What actions must agencies take to maintain electronic information systems?

    Science.gov (United States)

    2010-07-01

    ... take to maintain electronic information systems? 1236.26 Section 1236.26 Parks, Forests, and Public... electronic information systems? (a) Agencies must maintain inventories of electronic information systems and... electronic information systems that is adequate to: (1) Specify all technical characteristics necessary for...

  20. Responses of the insulin signaling pathways in the brown adipose tissue of rats following cold exposure.

    Science.gov (United States)

    Wang, Xiaofei; Wahl, Richard

    2014-01-01

    The insulin signaling pathway is critical for the control of blood glucose levels. Brown adipose tissue (BAT) has also been implicated as important in glucose homeostasis. The effect of short-term cold exposure on this pathway in BAT has not been explored. We evaluated the effect of 4 hours of cold exposure on the insulin pathway in the BAT of rats. Whole genomic microarray chips were used to examine the transcripts of the pathway in BAT of rats exposed to 4°C and 22°C for 4 hours. The 4 most significantly altered pathways following 4 hours of cold exposure were the insulin signaling pathway, protein kinase A, PI3K/AKT and ERK/MAPK signaling. The insulin signaling pathway was the most affected. In the documented 142 genes of the insulin pathway, 42 transcripts (29.6%) responded significantly to this cold exposure with the least false discovery rate (Benjamini-Hochberg Multiple Testing: -log10 (p-value)  = 7.18). Twenty-seven genes (64%) were up-regulated, including the insulin receptor (Insr), insulin substrates 1 and 2 (Irs1 and Irs2). Fifteen transcripts (36%) were down-regulated. Multiple transcripts of the primary target and secondary effector targets for the insulin signaling were also up-regulated, including those for carbohydrate metabolism. Using western blotting, we demonstrated that the cold induced higher Irs2, Irs1, and Akt-p protein levels in the BAT than in the BAT of controls maintained at room temperature, and higher Akt-p protein level in the muscle. this study demonstrated that 4 hours of cold exposure stimulated the insulin signaling pathway in the BAT and muscle of overnight fasted rats. This raises the possibility that acute cold stimulation may have potential to improve glucose clearance and insulin sensitivity.

  1. BRIT1/MCPH1 is essential for mitotic and meiotic recombination DNA repair and maintaining genomic stability in mice.

    Directory of Open Access Journals (Sweden)

    Yulong Liang

    2010-01-01

    Full Text Available BRIT1 protein (also known as MCPH1 contains 3 BRCT domains which are conserved in BRCA1, BRCA2, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. BRIT1 mutations or aberrant expression are found in primary microcephaly patients as well as in cancer patients. Recent in vitro studies suggest that BRIT1/MCPH1 functions as a novel key regulator in the DNA damage response pathways. To investigate its physiological role and dissect the underlying mechanisms, we generated BRIT1(-/- mice and identified its essential roles in mitotic and meiotic recombination DNA repair and in maintaining genomic stability. Both BRIT1(-/- mice and mouse embryonic fibroblasts (MEFs were hypersensitive to gamma-irradiation. BRIT1(-/- MEFs and T lymphocytes exhibited severe chromatid breaks and reduced RAD51 foci formation after irradiation. Notably, BRIT1(-/- mice were infertile and meiotic homologous recombination was impaired. BRIT1-deficient spermatocytes exhibited a failure of chromosomal synapsis, and meiosis was arrested at late zygotene of prophase I accompanied by apoptosis. In mutant spermatocytes, DNA double-strand breaks (DSBs were formed, but localization of RAD51 or BRCA2 to meiotic chromosomes was severely impaired. In addition, we found that BRIT1 could bind to RAD51/BRCA2 complexes and that, in the absence of BRIT1, recruitment of RAD51 and BRCA2 to chromatin was reduced while their protein levels were not altered, indicating that BRIT1 is involved in mediating recruitment of RAD51/BRCA2 to the damage site. Collectively, our BRIT1-null mouse model demonstrates that BRIT1 is essential for maintaining genomic stability in vivo to protect the hosts from both programmed and irradiation-induced DNA damages, and its depletion causes a failure in both mitotic and meiotic recombination DNA repair via impairing RAD51/BRCA2's function and as a result leads to infertility and genomic instability in mice.

  2. Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Hedi ePeterson

    2013-10-01

    Full Text Available Pluripotency in human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs is regulated by three transcription factors - OCT3/4, SOX2 and NANOG. To fully exploit the therapeutic potential of these cells it is essential to have a good mechanistic understanding of the maintenance of self-renewal and pluripotency. In this study, we demonstrate a powerful systems biology approach in which we first expand literature-based network encompassing the core regulators of pluripotency by assessing the behaviour of genes targeted by perturbation experiments. We focused our attention on highly regulated genes encoding cell surface and secreted proteins as these can be more easily manipulated by the use of inhibitors or recombinant proteins. Qualitative modeling based on combining boolean networks and in silico perturbation experiments were employed to identify novel pluripotency-regulating genes. We validated Interleukin-11 (IL-11 and demonstrate that this cytokine is a novel pluripotency-associated factor capable of supporting self-renewal in the absence of exogenously added bFGF in culture. To date, the various protocols for hESCs maintenance require supplementation with bFGF to activate the Activin/Nodal branch of the TGFβ signaling pathway. Additional evidence supporting our findings is that IL-11 belongs to the same protein family as LIF, which is known to be necessary for maintaining pluripotency in mouse but not in human ESCs. These cytokines operate through the same gp130 receptor which interacts with Janus kinases. Our finding might explain why mESCs are in a more naïve cell state compared to hESCs and how to convert primed hESCs back to the naïve state. Taken together, our integrative modeling approach has identified novel genes as putative candidates to be incorporated into the expansion of the current gene regulatory network responsible for inducing and maintaining pluripotency.

  3. IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils.

    Science.gov (United States)

    Esnault, Stephane; Kelly, Elizabeth A B; Shen, Zhong-Jian; Johansson, Mats W; Malter, James S; Jarjour, Nizar N

    2015-09-15

    IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a result of the functional redundancy of these three cytokines on eosinophils and the loss of IL-5R on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these three cytokines signal through a common β-chain receptor but yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce the production of proteins, such as semaphorin-7A, without affecting mRNA levels suggests a unique influence of IL-3 on translation. The purpose of this study was to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared with IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF, or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein S6 (RPS6) and the upstream kinase 90-kDa ribosomal S6 kinase (p90S6K). Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared with circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations identify IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. Copyright © 2015 by The American Association of Immunologists, Inc.

  4. IL-3 maintains activation of the P90S6K/RPS6 pathway and increases translation in human eosinophils1

    Science.gov (United States)

    Esnault, Stephane; Kelly, Elizabeth A.B.; Shen, Zhong-Jian; Johansson, Mats W.; Malter, James S.; Jarjour, Nizar N.

    2015-01-01

    IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines IL-5, IL-3, and GM-CSF are typically present in atopic diseases including allergic asthma. Due to the functional redundancy of these 3 cytokines on eosinophils and the loss of IL-5 receptor on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these 3 cytokines signal through a common β-chain receptor, and yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce production of proteins such as semaphorin-7A without affecting mRNA level suggests a unique influence by IL-3 on translation. The purpose of this study is to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared to IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein (RP) S6 and the upstream kinase, p90S6K. Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared to circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations place IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. PMID:26276876

  5. Mesenchymal Stem Cells Isolated From Human Gliomas Increase Proliferation and Maintain Stemness of Glioma Stem Cells Through the IL-6/gp130/STAT3 Pathway.

    Science.gov (United States)

    Hossain, Anwar; Gumin, Joy; Gao, Feng; Figueroa, Javier; Shinojima, Naoki; Takezaki, Tatsuya; Priebe, Waldemar; Villarreal, Diana; Kang, Seok-Gu; Joyce, Celine; Sulman, Erik; Wang, Qianghu; Marini, Frank C; Andreeff, Michael; Colman, Howard; Lang, Frederick F

    2015-08-01

    Although mesenchymal stem cells (MSCs) have been implicated as stromal components of several cancers, their ultimate contribution to tumorigenesis and their potential to drive cancer stem cells, particularly in the unique microenvironment of human brain tumors, remain largely undefined. Consequently, using established criteria, we isolated glioma-associated-human MSCs (GA-hMSCs) from fresh human glioma surgical specimens for the first time. We show that these GA-hMSCs are nontumorigenic stromal cells that are phenotypically similar to prototypical bone marrow-MSCs. Low-passage genomic sequencing analyses comparing GA-hMSCs with matched tumor-initiating glioma stem cells (GSCs) suggest that most GA-hMSCs (60%) are normal cells recruited to the tumor (group 1 GA-hMSCs), although, rarely (10%), GA-hMSCs may differentiate directly from GSCs (group 2 GA-hMSCs) or display genetic patterns intermediate between these groups (group 3 GA-hMSCs). Importantly, GA-hMSCs increase proliferation and self-renewal of GSCs in vitro and enhance GSC tumorigenicity and mesenchymal features in vivo, confirming their functional significance within the GSC niche. These effects are mediated by GA-hMSC-secreted interleukin-6, which activates STAT3 in GSCs. Our results establish GA-hMSCs as a potentially new stromal component of gliomas that drives the aggressiveness of GSCs, and point to GA-hMSCs as a novel therapeutic target within gliomas. © 2015 AlphaMed Press.

  6. HPV: Molecular pathways and targets.

    Science.gov (United States)

    Gupta, Shilpi; Kumar, Prabhat; Das, Bhudev C

    2018-04-05

    Infection of high-risk human papillomaviruses (HPVs) is a prerequisite for the development of cervical carcinoma. HPV infections are also implicated in the development of other types of carcinomas. Chronic or persistent infection of HPV is essential but HPV alone is inadequate, additional endogenous or exogenous cues are needed along with HPV to induce cervical carcinogenesis. The strategies that high-risk HPVs have developed in differentiating epithelial cells to reach a DNA-synthesis competent state leading to tumorigenic transformation are basically due to overexpression of the E6 and E7 oncoproteins and the activation of diverse cellular regulatory or signaling pathways that are targeted by them. Moreover, the Wnt/β-catenin/Notch and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways are deregulated in various cancers, and have also been implicated in HPV-induced cancers. These are basically related to the "cancer hallmarks," and include sustaining proliferative signals, the evasion of growth suppression and immune destruction, replicative immortality, inflammation, invasion, metastasis and angiogenesis, as well as genome instability, resisting cell death, and deregulation of cellular energetics. These information could eventually aid in identifying or developing new diagnostic, prognostic biomarkers, and may contribute to design more effective targeted therapeutics and treatment strategies. Although surgery, chemotherapy and radiotherapy can cure more than 90% of women with early stage cervical cancer, the recurrent and metastatic disease remains a major cause of cancer mortality. Numerous efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent years, research on treatment strategies has proposed several options, including the role of HPV E5, E6, and E7 oncogenes, which are retained and overexpressed in most of the cervical cancers and whose respective oncoproteins are critical to the induction

  7. The C. elegans embryonic fate specification factor EGL-18 (GATA) is reutilized downstream of Wnt signaling to maintain a population of larval progenitor cells.

    Science.gov (United States)

    Gorrepati, Lakshmi; Eisenmann, David M

    2015-01-01

    In metazoans, stem cells in developing and adult tissues can divide asymmetrically to give rise to a daughter that differentiates and a daughter that retains the progenitor fate. Although the short-lived nematode C. elegans does not possess adult somatic stem cells, the lateral hypodermal seam cells behave in a similar manner: they divide once per larval stage to generate an anterior daughter that adopts a non-dividing differentiated fate and a posterior daughter that retains the seam fate and the ability to divide further. Wnt signaling pathway is known to regulate the asymmetry of these divisions and maintain the progenitor cell fate in one daughter, but how activation of the Wnt pathway accomplished this was unknown. We describe here our recent work that identified the GATA transcription factor EGL-18 as a downstream target of Wnt signaling necessary for maintenance of a progenitor population of larval seam cells. EGL-18 was previously shown to act in the initial specification of the seam cells in the embryo. Thus the acquisition of a Wnt-responsive cis-regulatory module allows an embryonic fate specification factor to be reutilized later in life downstream of a different regulator (Wnt signaling) to maintain a progenitor cell population. These results support the use of seam cell development in C. elegans as a simple model system for studying stem and progenitor cell biology.

  8. Rising utilization of inpatient pediatric asthma pathways.

    Science.gov (United States)

    Kaiser, Sunitha V; Rodean, Jonathan; Bekmezian, Arpi; Hall, Matt; Shah, Samir S; Mahant, Sanjay; Parikh, Kavita; Morse, Rustin; Puls, Henry; Cabana, Michael D

    2018-02-01

    Clinical pathways are detailed care plans that operationalize evidence-based guidelines into an accessible format for health providers. Their goal is to link evidence to practice to optimize patient outcomes and delivery efficiency. It is unknown to what extent inpatient pediatric asthma pathways are being utilized nationally. (1) Describe inpatient pediatric asthma pathway design and implementation across a large hospital network. (2) Compare characteristics of hospitals with and without pathways. We conducted a descriptive, cross-sectional, survey study of hospitals in the Pediatric Research in Inpatient Settings Network (75% children's hospitals, 25% community hospitals). Our survey determined if each hospital used a pathway and pathway characteristics (e.g. pathway elements, implementation methods). Hospitals with and without pathways were compared using Chi-square tests (categorical variables) and Student's t-tests (continuous variables). Surveys were distributed to 3-5 potential participants from each hospital and 302 (74%) participants responded, representing 86% (106/123) of surveyed hospitals. From 2005-2015, the proportion of hospitals utilizing inpatient asthma pathways increased from 27% to 86%. We found variation in pathway elements, implementation strategies, electronic medical record integration, and compliance monitoring across hospitals. Hospitals with pathways had larger inpatient pediatric programs [mean 12.1 versus 6.1 full-time equivalents, p = 0.04] and were more commonly free-standing children's hospitals (52% versus 23%, p = 0.05). From 2005-2015, there was a dramatic rise in implementation of inpatient pediatric asthma pathways. We found variation in many aspects of pathway design and implementation. Future studies should determine optimal implementation strategies to better support hospital-level efforts in improving pediatric asthma care and outcomes.

  9. Post-Communist Welfare Pathways

    DEFF Research Database (Denmark)

    Cerami, Alfio; Vanhuysse, Pieter

    . The authors' impressive analysis of causal factors, including political elites' strategic use of social policy, makes the book an original and important contribution to the comparative welfare state literature.'- Professor Linda J. Cook, Brown University“ 'This edited volume is extraordinarily good...... factors such as micro-causal mechanisms, ideas, discourses, path departures, power politics, and elite strategies. This book includes contributions from leading international Experts such as Claus Offe, Robert Kaufman, Stefan Haggard, Tomasz Inglot, and Mitchell Orenstein, to examine welfare in specific...... countries and across social policy domains. By providing a broad overview based on a theoretical foundation and drawing on recent empirical evidence, Post-Communist Welfare Pathways offers a comprehensive, state-of-the-art account of the progress that has been made since 1989, and the main challenges...

  10. Biosynthetic Pathways of Ergot Alkaloids

    Directory of Open Access Journals (Sweden)

    Nina Gerhards

    2014-12-01

    Full Text Available Ergot alkaloids are nitrogen-containing natural products belonging to indole alkaloids. The best known producers are fungi of the phylum Ascomycota, e.g., Claviceps, Epichloë, Penicillium and Aspergillus species. According to their structures, ergot alkaloids can be divided into three groups: clavines, lysergic acid amides and peptides (ergopeptines. All of them share the first biosynthetic steps, which lead to the formation of the tetracyclic ergoline ring system (except the simplest, tricyclic compound: chanoclavine. Different modifications on the ergoline ring by specific enzymes result in an abundance of bioactive natural products, which are used as pharmaceutical drugs or precursors thereof. From the 1950s through to recent years, most of the biosynthetic pathways have been elucidated. Gene clusters from several ergot alkaloid producers have been identified by genome mining and the functions of many of those genes have been demonstrated by knock-out experiments or biochemical investigations of the overproduced enzymes.

  11. Changing Arctic Ocean freshwater pathways.

    Science.gov (United States)

    Morison, James; Kwok, Ron; Peralta-Ferriz, Cecilia; Alkire, Matt; Rigor, Ignatius; Andersen, Roger; Steele, Mike

    2012-01-04

    Freshening in the Canada basin of the Arctic Ocean began in the 1990s and continued to at least the end of 2008. By then, the Arctic Ocean might have gained four times as much fresh water as comprised the Great Salinity Anomaly of the 1970s, raising the spectre of slowing global ocean circulation. Freshening has been attributed to increased sea ice melting and contributions from runoff, but a leading explanation has been a strengthening of the Beaufort High--a characteristic peak in sea level atmospheric pressure--which tends to accelerate an anticyclonic (clockwise) wind pattern causing convergence of fresh surface water. Limited observations have made this explanation difficult to verify, and observations of increasing freshwater content under a weakened Beaufort High suggest that other factors must be affecting freshwater content. Here we use observations to show that during a time of record reductions in ice extent from 2005 to 2008, the dominant freshwater content changes were an increase in the Canada basin balanced by a decrease in the Eurasian basin. Observations are drawn from satellite data (sea surface height and ocean-bottom pressure) and in situ data. The freshwater changes were due to a cyclonic (anticlockwise) shift in the ocean pathway of Eurasian runoff forced by strengthening of the west-to-east Northern Hemisphere atmospheric circulation characterized by an increased Arctic Oscillation index. Our results confirm that runoff is an important influence on the Arctic Ocean and establish that the spatial and temporal manifestations of the runoff pathways are modulated by the Arctic Oscillation, rather than the strength of the wind-driven Beaufort Gyre circulation.

  12. Seeking kinetic pathways relevant to the structural evolution of metal nanoparticles

    International Nuclear Information System (INIS)

    Haldar, Paramita; Chatterjee, Abhijit

    2015-01-01

    Understanding the kinetic pathways that cause metal nanoparticles to structurally evolve over time is essential for predicting their shape and size distributions and catalytic properties. Consequently, we need detailed kinetic models that can provide such information. Most kinetic Monte Carlo models used for metal systems contain a fixed catalogue of atomic moves; the catalogue is largely constructed based on our physical understanding of the material. In some situations, it is possible that an incorrect picture of the overall dynamics is obtained when kinetic pathways that are relevant to the dynamics are missing from the catalogue. Hence, a computational framework that can systematically determine the relevant pathways is required. This work intends to fulfil this requirement. Examples involving an Ag nanoparticle are studied to illustrate how molecular dynamics (MD) calculations can be employed to find the relevant pathways in a system. Since pathways that are unlikely to be selected at short timescales can become relevant at longer times, the accuracy of the catalogue is maintained by continually seeking these pathways using MD. We discuss various aspects of our approach, namely, defining the relevance of atomic moves to the dynamics and determining when additional MD is required to ensure the desired accuracy, as well as physical insights into the Ag nanoparticle. (paper)

  13. Lower growth temperature increases alternative pathway capacity and alternative oxidase protein in tobacco.

    Science.gov (United States)

    Vanlerberghe, G C; McIntosh, L

    1992-09-01

    Suspension cells of NT1 tobacco (Nicotiana tabacum L. cv bright yellow) have been used to study the effect of growth temperature on the CN-resistant, salicylhydroxamic acid-sensitive alternative pathway of respiration. Mitochondria isolated from cells maintained at 30 degrees C had a low capacity to oxidize succinate via the alternative pathway, whereas mitochondria isolated from cells 24 h after transfer to 18 degrees C displayed, on average, a 5-fold increase in this capacity (from 7 to 32 nanoatoms oxygen per milligram protein per minute). This represented an increase in alternative pathway capacity from 18 to 45% of the total capacity of electron transport. This increased capacity was lost upon transfer of cells back to 30 degrees C. A monoclonal antibody to the terminal oxidase of the alternative pathway (the alternative oxidase) from Sauromatum guttatum (T.E. Elthon, R.L. Nickels, L. McIntosh [1989] Plant Physiology 89: 1311-1317) recognized a 35-kilodalton mitochondrial protein in tobacco. There was an excellent correlation between the capacity of the alternative path in isolated tobacco mitochondria and the levels of this 35-kilodalton alternative oxidase protein. Cycloheximide could inhibit both the increased level of the 35-kilodalton alternative oxidase protein and the increased alternative pathway capacity normally seen upon transfer to 18 degrees C. We conclude that transfer of tobacco cells to the lower temperature increases the capacity of the alternative pathway due, at least in part, to de novo synthesis of the 35-kilodalton alternative oxidase protein.

  14. Multi-voxel decoding and the topography of maintained information during visual working memory

    Directory of Open Access Journals (Sweden)

    Sue-Hyun eLee

    2016-02-01

    Full Text Available The ability to maintain representations in the absence of external sensory stimulation, such as in working memory, is critical for guiding human behavior. Human functional brain imaging studies suggest that visual working memory can recruit a network of brain regions from visual to parietal to prefrontal cortex. In this review, we focus on the maintenance of representations during visual working memory and discuss factors determining the topography of those representations. In particular, we review recent studies employing multi-voxel pattern analysis that demonstrate decoding of the maintained content in visual cortex, providing support for a ‘sensory recruitment’ model of visual working memory. However, there is some evidence that maintained content can also be decoded in areas outside of visual cortex, including parietal and frontal cortex. We suggest that the ability to maintain representations during working memory is a general property of cortex, not restricted to specific areas, and argue that it is important to consider the nature of the information that must be maintained. Such information-content is critically determined by the task and the recruitment of specific regions during visual working memory will be both task- and stimulus-dependent. Thus, the common finding of maintained information in visual, but not parietal or prefrontal, cortex may be more of a reflection of the need to maintain specific types of visual information and not of a privileged role of visual cortex in maintenance.

  15. Multi-Voxel Decoding and the Topography of Maintained Information During Visual Working Memory.

    Science.gov (United States)

    Lee, Sue-Hyun; Baker, Chris I

    2016-01-01

    The ability to maintain representations in the absence of external sensory stimulation, such as in working memory, is critical for guiding human behavior. Human functional brain imaging studies suggest that visual working memory can recruit a network of brain regions from visual to parietal to prefrontal cortex. In this review, we focus on the maintenance of representations during visual working memory and discuss factors determining the topography of those representations. In particular, we review recent studies employing multi-voxel pattern analysis (MVPA) that demonstrate decoding of the maintained content in visual cortex, providing support for a "sensory recruitment" model of visual working memory. However, there is some evidence that maintained content can also be decoded in areas outside of visual cortex, including parietal and frontal cortex. We suggest that the ability to maintain representations during working memory is a general property of cortex, not restricted to specific areas, and argue that it is important to consider the nature of the information that must be maintained. Such information-content is critically determined by the task and the recruitment of specific regions during visual working memory will be both task- and stimulus-dependent. Thus, the common finding of maintained information in visual, but not parietal or prefrontal, cortex may be more of a reflection of the need to maintain specific types of visual information and not of a privileged role of visual cortex in maintenance.

  16. Multi-Voxel Decoding and the Topography of Maintained Information During Visual Working Memory

    Science.gov (United States)

    Lee, Sue-Hyun; Baker, Chris I.

    2016-01-01

    The ability to maintain representations in the absence of external sensory stimulation, such as in working memory, is critical for guiding human behavior. Human functional brain imaging studies suggest that visual working memory can recruit a network of brain regions from visual to parietal to prefrontal cortex. In this review, we focus on the maintenance of representations during visual working memory and discuss factors determining the topography of those representations. In particular, we review recent studies employing multi-voxel pattern analysis (MVPA) that demonstrate decoding of the maintained content in visual cortex, providing support for a “sensory recruitment” model of visual working memory. However, there is some evidence that maintained content can also be decoded in areas outside of visual cortex, including parietal and frontal cortex. We suggest that the ability to maintain representations during working memory is a general property of cortex, not restricted to specific areas, and argue that it is important to consider the nature of the information that must be maintained. Such information-content is critically determined by the task and the recruitment of specific regions during visual working memory will be both task- and stimulus-dependent. Thus, the common finding of maintained information in visual, but not parietal or prefrontal, cortex may be more of a reflection of the need to maintain specific types of visual information and not of a privileged role of visual cortex in maintenance. PMID:26912997

  17. [Factors influencing the sense of unintegration of thoughts in maintaining anger].

    Science.gov (United States)

    Endo, Hiroko; Yukawa, Shintaro

    2013-12-01

    Endo and Yukawa (2012) investigated the process of maintaining anger and demonstrated that a sense of unintegration of thoughts maintained anger by promoting recurrent thinking and avoidance behavior. Our present study examined how personality characteristics and situational factors affected the process of maintaining anger. Undergraduates (N=713) wrote about an anger episode, and completed questionnaires assessing their sense of unintegration of thoughts, recurrent thinking, avoidance behaviors, and maintaining anger. The questionnaires also assessed personality characteristics such as difficulty in identifying feelings, and situational factors such as the need for maintaining relationships, anger arousability, and meaning-making for the anger episode. The results of covariance structure analysis indicated that difficulties in identifying feelings and anger arousability contributed to maintaining anger by increasing the sense of unintegration of thoughts just after the episode. However, the need for maintaining relationships directly reduced the sense of unintegration of thoughts just after the episode, and indirectly decreased the present sense of unintegration of thoughts by meaning-making. Moreover, although recurrent thinking promoted the current sense of unintegration of thoughts, it also provided meaning.

  18. Stochasticity in the yeast mating pathway

    International Nuclear Information System (INIS)

    Hong-Li, Wang; Zheng-Ping, Fu; Xin-Hang, Xu; Qi, Ouyang

    2009-01-01

    We report stochastic simulations of the yeast mating signal transduction pathway. The effects of intrinsic and external noise, the influence of cell-to-cell difference in the pathway capacity, and noise propagation in the pathway have been examined. The stochastic temporal behaviour of the pathway is found to be robust to the influence of inherent fluctuations, and intrinsic noise propagates in the pathway in a uniform pattern when the yeasts are treated with pheromones of different stimulus strengths and of varied fluctuations. In agreement with recent experimental findings, extrinsic noise is found to play a more prominent role than intrinsic noise in the variability of proteins. The occurrence frequency for the reactions in the pathway are also examined and a more compact network is obtained by dropping most of the reactions of least occurrence

  19. Degenerative Pathways of Lumbar Motion Segments

    DEFF Research Database (Denmark)

    Jensen, Rikke K.; Kjaer, Per; Jensen, Tue S.

    2016-01-01

    pathways of degeneration based on scientific knowledge of disco-vertebral degeneration, and (iii) compare these clusters and degenerative pathways between samples. METHODS: We performed a secondary cross-sectional analysis on two dissimilar MRI samples collected in a hospital department: (1) data from...... pathways of degeneration. RESULTS: Six clusters of MRI findings were identified in each of the two samples. The content of the clusters in the two samples displayed some differences but had the same overall pattern of MRI findings. Although the hypothetical degenerative pathways identified in the two...... samples were not identical, the overall pattern of increasing degeneration within the pathways was the same. CONCLUSIONS: It was expected that different clusters could emerge from different samples, however, when organised into hypothetical pathways of degeneration, the overall pattern of increasing...

  20. Cooperativity of the SUMO and Ubiquitin Pathways in Genome Stability

    Directory of Open Access Journals (Sweden)

    Minghua Nie

    2016-02-01

    Full Text Available Covalent attachment of ubiquitin (Ub or SUMO to DNA repair proteins plays critical roles in maintaining genome stability. These structurally related polypeptides can be viewed as distinct road signs, with each being read by specific protein interaction motifs. Therefore, via their interactions with selective readers in the proteome, ubiquitin and SUMO can elicit distinct cellular responses, such as directing DNA lesions into different repair pathways. On the other hand, through the action of the SUMO-targeted ubiquitin ligase (STUbL family proteins, ubiquitin and SUMO can cooperate in the form of a hybrid signal. These mixed SUMO-ubiquitin chains recruit “effector” proteins such as the AAA+ ATPase Cdc48/p97-Ufd1-Npl4 complex that contain both ubiquitin and SUMO interaction motifs. This review will summarize recent key findings on collaborative and distinct roles that ubiquitin and SUMO play in orchestrating DNA damage responses.

  1. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation

    DEFF Research Database (Denmark)

    Dzamko, Nicolas; Schertzer, Jonathan D.; Ryall, James G.

    2008-01-01

    The activation of AMP-activated protein kinase (AMPK) and phosphorylation/inhibition of acetyl-CoA carboxylase 2 (ACC2) is believed to be the principal pathway regulating fatty acid oxidation. However, during exercise AMPK activity and ACC Ser-221 phosphorylation does not always correlate...... with rates of fatty acid oxidation. To address this issue we have investigated the requirement for skeletal muscle AMPK in controlling aminoimidazole-4-carboxymide-1-beta-d-ribofuranoside (AICAR) and contraction-stimulated fatty acid oxidation utilizing transgenic mice expressing a muscle-specific kinase...... dead (KD) AMPK alpha2. In wild-type (WT) mice, AICAR and contraction increased AMPK alpha2 and alpha1 activities, the phosphorylation of ACC2 and rates of fatty acid oxidation while tending to reduce malonyl-CoA levels. Despite no activation of AMPK in KD mice, ACC2 phosphorylation was maintained...

  2. Developing maintainability for tokamak fusion power systems. Phase II report. Volume II: study results

    International Nuclear Information System (INIS)

    Fuller, G.M.; Zahn, H.S.; Mantz, H.C.; Kaletta, G.R.; Waganer, L.M.; Carosella, L.A.; Conlee, J.L.

    1978-11-01

    In this second phase the impact of unscheduled maintenance, several vacuum wall arrangements, and maintenance of other reactor interfacing subsystems and maintenance equipment are added to the evaluation of the maintainability of the fusion power reactor concepts. Four concepts are normalized to common performance parameters and evaluated for their capability to achieve availability and cost of electricity goals considering both scheduled and unscheduled maintenance. The results of this evaluation are used to generate a series of maintainability design guidelines and to select the more desirable features and design options which are used to configure a preliminary reactor concept having improved maintainability

  3. Troubleshooting and Maintaining Your PC All-in-One Desk Reference For Dummies

    CERN Document Server

    Gookin, Dan

    2009-01-01

    Maintaining a PC is important, and troubleshooting a PC can be a challenge. Dan Gookin is great at explaining how to handle common PC problems, and he's provided a complete, plain-English manual in Troubleshooting & Maintaining Your PC All-in-One For Dummies. Liberally laced with Dan's famous humor and clear instructions, Troubleshooting & Maintaining Your PC All-in-One For Dummies is divided into six minibooks covering hardware, software, laptops, Internet, networking, and maintenance. Each one gives you some background on what causes common problems, to help you understand what's wrong as we

  4. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis : LAMP-2 deficient mice develop pancreatitis

    NARCIS (Netherlands)

    Mareninova, Olga A; Sendler, Matthias; Malla, Sudarshan Ravi; Yakubov, Iskandar; French, Samuel W; Tokhtaeva, Elmira; Vagin, Olga; Oorschot, Viola; Lüllmann-Rauch, Renate; Blanz, Judith; Dawson, David; Klumperman, Judith; Lerch, Markus M; Mayerle, Julia; Gukovsky, Ilya; Gukovskaya, Anna S

    2015-01-01

    BACKGROUND & AIMS: The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated

  5. The effects and mechanisms of SLC34A2 on maintaining stem cell-like phenotypes in CD147+ breast cancer stem cells.

    Science.gov (United States)

    Lv, Yonggang; Wang, Ting; Fan, Jing; Zhang, Zhenzhen; Zhang, Juliang; Xu, Cheng; Li, Yongping; Zhao, Ge; He, Chenyang; Meng, Huimin; Yang, Hua; Wang, Zhen; Liu, Jiayun; Chen, Jianghao; Wang, Ling

    2017-04-01

    The cancer stem cell (CSC) hypothesis has gained significant recognition in describing tumorigenesis. Identification of the factors critical to development of breast cancer stem cells (BCSCs) may provide insight into the improvement of effective therapies against breast cancer. In this study, we aim to investigate the biological function of SLC34A2 in affecting the stem cell-like phenotypes in BCSCs and its underlying mechanisms. We demonstrated that CD147 + cells from breast cancer tissue samples and cell lines possessed BCSC-like features, including the ability of self-renewal in vitro, differentiation, and tumorigenic potential in vivo. Flow cytometry analysis showed the presence of a variable fraction of CD147 + cells in 9 of 10 tumor samples. Significantly, SLC34A2 expression in CD147 + BCSCs was enhanced compared with that in differentiated adherent progeny of CD147 + BCSCs and adherently cultured cell line cells. In breast cancer patient cohorts, SLC34A2 expression was found increased in 9 of 10 tumor samples. By using lentiviral-based approach, si-SLC34A2-transduced CD147 + BCSCs showed decreased ability of sphere formation, cell viability in vitro, and tumorigenicity in vivo, which suggested the essential role of SLC34A2 in CD147 + BCSCs. Furthermore, PI3K/AKT pathway and SOX2 were found necessary to maintain the stemness of CD147 + BCSCs by using LY294002 or lentiviral-si-SOX2. Finally, we indicated that SLC34A2 could regulate SOX2 to maintain the stem cell-like features in CD147 + BCSCs through PI3K/AKT pathway. Therefore, our report identifies a novel role of SLC34A2 in BCSCs' state regulation and establishes a rationale for targeting the SLC34A2/PI3K/AKT/SOX2 signaling pathway for breast cancer therapy.

  6. Stem cell maintenance by manipulating signaling pathways: past, current and future

    Science.gov (United States)

    Chen, Xi; Ye, Shoudong; Ying, Qi-Long

    2015-01-01

    Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and are retainedin various adult tissues and organs. While pluripotent stem cell lines have been established from several species, including mouse, rat, and human, it is still challenging to establish stable multipotent stem cell lines from embryonic or adult tissues. Based on current knowledge, we anticipate that by manipulating extrinsic and intrinsic signaling pathways, most if not all types of stem cells can be maintained in a long-term culture. In this article, we summarize current culture conditions established for the long-term maintenance of authentic pluripotent and multipotent stem cells and the signaling pathways involved. We also discuss the general principles of stem cell maintenance and propose several strategies on the establishment of novel stem cell lines through manipulation of signaling pathways. [BMB Reports 2015; 48(12): 668-676] PMID:26497581

  7. Targeting Apoptosis Signaling Pathways for Anticancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Fulda, Simone, E-mail: simone.fulda@kgu.de [Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt (Germany)

    2011-08-29

    Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

  8. Targeting Apoptosis Signaling Pathways for Anticancer Therapy

    International Nuclear Information System (INIS)

    Fulda, Simone

    2011-01-01

    Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

  9. Method for determining heterologous biosynthesis pathways

    KAUST Repository

    Gao, Xin

    2017-08-10

    The present invention relates to a method and system for dynamically analyzing, determining, predicting and displaying ranked suitable heterologous biosynthesis pathways for a specified host. The present invention addresses the problem of finding suitable pathways for the endogenous metabolism of a host organism because the efficacy of heterologous biosynthesis is affected by competing endogenous pathways. The present invention is called MRE (Metabolic Route Explorer), and it was conceived and developed to systematically and dynamically search for, determine, analyze, and display promising heterologous pathways while considering competing endogenous reactions in a given host organism.

  10. An optimization model for metabolic pathways.

    Science.gov (United States)

    Planes, F J; Beasley, J E

    2009-10-15

    Different mathematical methods have emerged in the post-genomic era to determine metabolic pathways. These methods can be divided into stoichiometric methods and path finding methods. In this paper we detail a novel optimization model, based upon integer linear programming, to determine metabolic pathways. Our model links reaction stoichiometry with path finding in a single approach. We test the ability of our model to determine 40 annotated Escherichia coli metabolic pathways. We show that our model is able to determine 36 of these 40 pathways in a computationally effective manner.

  11. Improving the hydrogen production capacity of Rhodobacter capsulatus by genetically modifying redox balancing pathways

    Energy Technology Data Exchange (ETDEWEB)

    Oeztuerk, Yavuz [TUEBITAK Research Institute for Genetic Engineering and Biotechnology, Gebze Kocaeli (Turkey); Goekce, Abdulmecit [Istanbul Technical Univ. (Turkey). Dept. of Molecular Biology and Genetics; Guergan, Muazzez; Yuecel, Meral [Middle East Technical Univ., Ankara (Turkey). Dept. of Biology

    2010-07-01

    In Rhodobacter capsulatus, balancing the oxidation-reduction potential (redox-balance) is maintained via a number of inter-dependent regulatory mechanisms that enable these organisms to accommodate divergent growth modes. In order to maintain redox homeostasis, this bacterium possesses regulatory mechanisms functioning as electron sinks affecting the oxidation-reduction state of the ubiquinone pool. Under the photoheterotrophic growth conditions with reduced carbon sources, the excess reducing equivalents are primarily consumed via the reduction of CO{sub 2} through the Calvin-Benson-Bassham (CBB) pathway or by the reduction of protons into hydrogen with the use of dinitrogenase enzyme system. In this study, our aim was to develop strategies to funnel the excess reducing equivalents to nitrogenase-dependent hydrogen production by blocking the carbon-fixation pathway. To realize this purpose, CO{sub 2} fixation was blocked by inactivating the Phosphoribulokinase (PRK) of CBB pathway in wild type (MT1131), uptake-hydrogenase (YO3) and cyt cbb{sub 3} oxidase deficient (YO4) strains. The hydrogen production capacity of newly generated strains deficient in the Calvin-Benson-Bassham pathway were analyzed and compared with wild type strains. The results indicated that, the hydrogen production efficiency and capacity of R. capsulatus was further improved by directing the excess reducing equivalents to dinitrogenase-dependent hydrogen production. (orig.)

  12. Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1

    Science.gov (United States)

    Ye, Shoudong; Li, Ping; Tong, Chang; Ying, Qi-Long

    2013-01-01

    Mouse embryonic stem cell (mESC) self-renewal can be maintained by activation of the leukaemia inhibitory factor (LIF)/signal transducer and activator of transcription 3 (Stat3) signalling pathway or dual inhibition (2i) of glycogen synthase kinase 3 (Gsk3) and mitogen-activated protein kinase kinase (MEK). Several downstream targets of the pathways involved have been identified that when individually overexpressed can partially support self-renewal. However, none of these targets is shared among the involved pathways. Here, we show that the CP2 family transcription factor Tfcp2l1 is a common target in LIF/Stat3- and 2i-mediated self-renewal, and forced expression of Tfcp2l1 can recapitulate the self-renewal-promoting effect of LIF or either of the 2i components. In addition, Tfcp2l1 can reprogram post-implantation epiblast stem cells to naïve pluripotent ESCs. Tfcp2l1 upregulates Nanog expression and promotes self-renewal in a Nanog-dependent manner. We conclude that Tfcp2l1 is at the intersection of LIF- and 2i-mediated self-renewal pathways and plays a critical role in maintaining ESC identity. Our study provides an expanded understanding of the current model of ground-state pluripotency. PMID:23942238

  13. Synergy between methylerythritol phosphate pathway and mevalonate pathway for isoprene production in Escherichia coli.

    Science.gov (United States)

    Yang, Chen; Gao, Xiang; Jiang, Yu; Sun, Bingbing; Gao, Fang; Yang, Sheng

    2016-09-01

    Isoprene, a key building block of synthetic rubber, is currently produced entirely from petrochemical sources. In this work, we engineered both the methylerythritol phosphate (MEP) pathway and the mevalonate (MVA) pathway for isoprene production in E. coli. The synergy between the MEP pathway and the MVA pathway was demonstrated by the production experiment, in which overexpression of both pathways improved the isoprene yield about 20-fold and 3-fold, respectively, compared to overexpression of the MEP pathway or the MVA pathway alone. The (13)C metabolic flux analysis revealed that simultaneous utilization of the two pathways resulted in a 4.8-fold increase in the MEP pathway flux and a 1.5-fold increase in the MVA pathway flux. The synergy of the dual pathway was further verified by quantifying intracellular flux responses of the MEP pathway and the MVA pathway to fosmidomycin treatment and mevalonate supplementation. Our results strongly suggest that coupling of the complementary reducing equivalent demand and ATP requirement plays an important role in the synergy of the dual pathway. Fed-batch cultivation of the engineered strain overexpressing the dual pathway resulted in production of 24.0g/L isoprene with a yield of 0.267g/g of glucose. The synergy of the MEP pathway and the MVA pathway also successfully increased the lycopene productivity in E. coli, which demonstrates that it can be used to improve the production of a broad range of terpenoids in microorganisms. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  14. Identification of altered pathways in breast cancer based on individualized pathway aberrance score.

    Science.gov (United States)

    Shi, Sheng-Hong; Zhang, Wei; Jiang, Jing; Sun, Long

    2017-08-01

    The objective of the present study was to identify altered pathways in breast cancer based on the individualized pathway aberrance score (iPAS) method combined with the normal reference (nRef). There were 4 steps to identify altered pathways using the iPAS method: Data preprocessing conducted by the robust multi-array average (RMA) algorithm; gene-level statistics based on average Z ; pathway-level statistics according to iPAS; and a significance test dependent on 1 sample Wilcoxon test. The altered pathways were validated by calculating the changed percentage of each pathway in tumor samples and comparing them with pathways from differentially expressed genes (DEGs). A total of 688 altered pathways with Ppathways were involved in the total 688 altered pathways, which may validate the present results. In addition, there were 324 DEGs and 155 common genes between DEGs and pathway genes. DEGs and common genes were enriched in the same 9 significant terms, which also were members of altered pathways. The iPAS method was suitable for identifying altered pathways in breast cancer. Altered pathways (such as KIF and PLK mediated events) were important for understanding breast cancer mechanisms and for the future application of customized therapeutic decisions.

  15. Dopamine system: Manager of neural pathways

    Directory of Open Access Journals (Sweden)

    Simon eHong

    2013-12-01

    Full Text Available There are a growing number of roles that midbrain dopamine (DA neurons assume, such as, reward, aversion, alerting and vigor. Here I propose a theory that may be able to explain why the suggested functions of DA came about. It has been suggested that largely parallel cortico-basal ganglia-thalamo-cortico loops exist to control different aspects of behavior. I propose that (1 the midbrain DA system is organized in a similar manner, with different groups of DA neurons corresponding to these parallel neural pathways (NPs. The DA system can be viewed as the manager of these parallel NPs in that it recruits and activates only the task-relevant NPs when they are needed. It is likely that the functions of those NPs that have been consistently activated by the corresponding DA groups are facilitated. I also propose that (2 there are two levels of DA roles: the How and What roles. The How role is encoded in tonic and phasic DA neuron firing patterns and gives a directive to its target NP: how vigorously its function needs to be carried out. The tonic DA firing is to maintain a certain level of DA in the target NPs to support their expected behavioral and mental functions; it is only when a sudden unexpected boost or suppression of activity is required by the relevant target NP that DA neurons in the corresponding NP act in a phasic manner. The What role is the implementational aspect of the role of DA in the target NP, such as binding to D1 receptors to boost working memory. This What aspect of DA explains why DA seems to assume different functions depending on the region of the brain in which it is involved. In terms of the role of the lateral habenula (LHb, the LHb is expected to suppress maladaptive behaviors and mental processes by controlling the DA system. The demand-based smart management by the DA system may have given animals an edge in evolution with adaptive behaviors and a better survival rate in resource-scarce situations.

  16. The Effects of Aging on the Costs of Operating and Maintaining Military Equipment

    National Research Council Canada - National Science Library

    Kiley, Gregory

    2001-01-01

    .... According to one interpretation, decisions in the 199Os to reduce purchases of new equipment left the military with aging fleets of ships, aircraft, and armored vehicles that are increasingly expensive to maintain...

  17. Cash Accountability in DOD Imprest Funds Maintained by the Office of the Inspector General, DOD

    National Research Council Canada - National Science Library

    Rau, Russell

    1995-01-01

    We are providing this report for your information and use. The audit was made at your request to examine the imprest funds maintained within the Office of the Inspector General, DoD, Arlington, Virginia...

  18. Teacher collaborative curriculum design in technical vocational colleges: a strategy for maintaining curriculum consistency?

    NARCIS (Netherlands)

    Albashiry, N.M.; Voogt, J.M.; Pieters, J.M.

    2015-01-01

    The Technical Vocational Education and Training (TVET) curriculum requires continuous renewal and constant involvement of stakeholders in the redesign process. Due to a lack of curriculum design expertise, TVET institutions in developing contexts encounter challenges maintaining and advancing the

  19. 34 CFR 377.30 - What information must a grantee maintain and provide to the Secretary?

    Science.gov (United States)

    2010-07-01

    ... DEMONSTRATION PROJECTS TO INCREASE CLIENT CHOICE PROGRAM What Post-Award Conditions Must Be Met by a Grantee... maintain the records that the Secretary requires to conduct an evaluation of projects funded under this...

  20. New strategies for maintaining post-seismic operations of lifeline corridors.

    Science.gov (United States)

    2014-10-01

    This project furthered the development of three strategies that could positively impact maintaining post-seismic operations of lifeline corridors. In Year 1, most of the focus : was on the development of the three individual strategies. In Year 2, a ...

  1. Maintainability analysis considering time-dependent and time-independent covariates

    International Nuclear Information System (INIS)

    Barabadi, Abbas; Barabady, Javad; Markeset, Tore

    2011-01-01

    Traditional parametric methods for assessing maintainability most often only consider time to repair (TTR) as a single explanatory variable. However, to predict availability more precisely for high availability systems, a better model is needed to quantify the effect of operational environment on maintainability. The proportional repair model (PRM), which is developed based on proportional hazard model (PHM), may be used to analyze maintainability in the present of covariates. In the PRM, the effect of covariates is considered to be time independent. However this assumption may not be valid for some situations. The aim of this paper is to develop the Cox regression model and its extension in the presence of time-dependent covariates for determining maintainability. A simple case study is used to demonstrate how the model can be applied in a real case.

  2. Testosterone replacement maintains smooth muscle content in the corpus cavernosum of orchiectomized rats

    Directory of Open Access Journals (Sweden)

    Graziele Halmenschlager

    2017-10-01

    Conclusion: Normal testosterone levels maintain CC smooth muscle content and do not influence elastic fibers, collagen content and apoptotic index. Further studies should be performed in order to investigate the mechanisms by which androgen mediates its effects on CC structure.

  3. JNK signaling maintains the mesenchymal properties of multi-drug resistant human epidermoid carcinoma KB cells through snail and twist1

    International Nuclear Information System (INIS)

    Zhan, Xia; Feng, Xiaobing; Kong, Ying; Chen, Yi; Tan, Wenfu

    2013-01-01

    In addition to possess cross drug resistance characteristic, emerging evidences have shown that multiple-drug resistance (MDR) cancer cells exhibit aberrant metastatic capacity when compared to parental cells. In this study, we explored the contribution of c-Jun N-terminal kinases (JNK) signaling to the mesenchymal phenotypes and the aberrant motile capacity of MDR cells utilizing a well characterized MDR cell line KB/VCR, which is established from KB human epidermoid carcinoma cells by vincristine (VCR), and its parental cell line KB. Taking advantage of experimental strategies including pharmacological tool and gene knockdown, we showed here that interference with JNK signaling pathway by targeting JNK1/2 or c-Jun reversed the mesenchymal properties of KB/VCR cells to epithelial phenotypes and suppressed the motile capacity of KB/VCR cells, such as migration and invasion. These observations support a critical role of JNK signaling in maintaining the mesenchymal properties of KB/VCR cells. Furthermore, we observed that JNK signaling may control the expression of both snail and twist1 in KB/VCR cells, indicating that both snail and twist1 are involved in controlling the mesenchymal characteristics of KB/VCR cells by JNK signaling. JNK signaling is required for maintaining the mesenchymal phenotype of KB/VCR cells; and JNK signaling may maintain the mesenchymal characteristics of KB/VCR cells potentially through snail and twist1

  4. JNK signaling maintains the mesenchymal properties of multi-drug resistant human epidermoid carcinoma KB cells through snail and twist1.

    Science.gov (United States)

    Zhan, Xia; Feng, Xiaobing; Kong, Ying; Chen, Yi; Tan, Wenfu

    2013-04-04

    In addition to possess cross drug resistance characteristic, emerging evidences have shown that multiple-drug resistance (MDR) cancer cells exhibit aberrant metastatic capacity when compared to parental cells. In this study, we explored the contribution of c-Jun N-terminal kinases (JNK) signaling to the mesenchymal phenotypes and the aberrant motile capacity of MDR cells utilizing a well characterized MDR cell line KB/VCR, which is established from KB human epidermoid carcinoma cells by vincristine (VCR), and its parental cell line KB. Taking advantage of experimental strategies including pharmacological tool and gene knockdown, we showed here that interference with JNK signaling pathway by targeting JNK1/2 or c-Jun reversed the mesenchymal properties of KB/VCR cells to epithelial phenotypes and suppressed the motile capacity of KB/VCR cells, such as migration and invasion. These observations support a critical role of JNK signaling in maintaining the mesenchymal properties of KB/VCR cells. Furthermore, we observed that JNK signaling may control the expression of both snail and twist1 in KB/VCR cells, indicating that both snail and twist1 are involved in controlling the mesenchymal characteristics of KB/VCR cells by JNK signaling. JNK signaling is required for maintaining the mesenchymal phenotype of KB/VCR cells; and JNK signaling may maintain the mesenchymal characteristics of KB/VCR cells potentially through snail and twist1.

  5. The return of metabolism: biochemistry and physiology of the pentose phosphate pathway

    Science.gov (United States)

    Stincone, Anna; Prigione, Alessandro; Cramer, Thorsten; Wamelink, Mirjam M. C.; Campbell, Kate; Cheung, Eric; Olin-Sandoval, Viridiana; Grüning, Nana-Maria; Krüger, Antje; Alam, Mohammad Tauqeer; Keller, Markus A.; Breitenbach, Michael; Brindle, Kevin M.; Rabinowitz, Joshua D.; Ralser, Markus

    2015-01-01

    The pentose phosphate pathway (PPP) is a fundamental component of cellular metabolism. The PPP is important to maintain carbon homoeostasis, to provide precursors for nucleotide and amino acid biosynthesis, to provide reducing molecules for anabolism, and to defeat oxidative stress. The PPP shares reactions with the Entner–Doudoroff pathway and Calvin cycle and divides into an oxidative and non-oxidative branch. The oxidative branch is highly active in most eukaryotes and converts glucose 6-phosphate into carbon dioxide, ribulose 5-phosphate and NADPH. The latter function is critical to maintain redox balance under stress situations, when cells proliferate rapidly, in ageing, and for the ‘Warburg effect’ of cancer cells. The non-oxidative branch instead is virtually ubiquitous, and metabolizes the glycolytic intermediates fructose 6-phosphate and glyceraldehyde 3-phosphate as well as sedoheptulose sugars, yielding ribose 5-phosphate for the synthesis of nucleic acids and sugar phosphate precursors for the synthesis of amino acids. Whereas the oxidative PPP is considered unidirectional, the non-oxidative branch can supply glycolysis with intermediates derived from ribose 5-phosphate and vice versa, depending on the biochemical demand. These functions require dynamic regulation of the PPP pathway that is achieved through hierarchical interactions between transcriptome, proteome and metabolome. Consequently, the biochemistry and regulation of this pathway, while still unresolved in many cases, are archetypal for the dynamics of the metabolic network of the cell. In this comprehensive article we review seminal work that led to the discovery and description of the pathway that date back now for 80 years, and address recent results about genetic and metabolic mechanisms that regulate its activity. These biochemical principles are discussed in the context of PPP deficiencies causing metabolic disease and the role of this pathway in biotechnology, bacterial and

  6. Computing Pathways for Urban Decarbonization.

    Science.gov (United States)

    Cremades, R.; Sommer, P.

    2016-12-01

    Urban areas emit roughly three quarters of global carbon emissions. Cities are crucial elements for a decarbonized society. Urban expansion and related transportation needs lead to increased energy use, and to carbon-intensive lock-ins that create barriers for climate change mitigation globally. The authors present the Integrated Urban Complexity (IUC) model, based on self-organizing Cellular Automata (CA), and use it to produce a new kind of spatially explicit Transformation Pathways for Urban Decarbonization (TPUD). IUC is based on statistical evidence relating the energy needed for transportation with the spatial distribution of population, specifically IUC incorporates variables from complexity science related to urban form, like the slope of the rank-size rule or spatial entropy, which brings IUC a step beyond existing models. The CA starts its evolution with real-world urban land use and population distribution data from the Global Human Settlement Layer. Thus, the IUC model runs over existing urban settlements, transforming the spatial distribution of population so the energy consumption for transportation is minimized. The statistical evidence that governs the evolution of the CA departs from the database of the International Association of Public Transport. A selected case is presented using Stuttgart (Germany) as an example. The results show how IUC varies urban density in those places where it improves the performance of crucial parameters related to urban form, producing a TPUD that shows where the spatial distribution of population should be modified with a degree of detail of 250 meters of cell size. The TPUD shows how the urban complex system evolves over time to minimize energy consumption for transportation. The resulting dynamics or urban decarbonization show decreased energy per capita, although total energy increases for increasing population. The results provide innovative insights: by checking current urban planning against a TPUD, urban

  7. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  8. Space Maintenance with an Innovative ?Tube and Loop? Space Maintainer (Nikhil Appliance)

    OpenAIRE

    Srivastava, Nikhil; Grover, Jyotika; Panthri, Prerna

    2016-01-01

    ABSTRACT Despite the best efforts in prevention, premature loss of primary teeth continues to be a common problem in pediatric dentistry, resulting in disruption of arch integrity and adversely affecting the proper alignment of permanent successors. Space maintainers (SMs) are special appliances used for maintaining space created due to premature loss of primary teeth. Band and loop SM is mostly indicated for the premature loss of single primary molar, but this appliance has a number of limit...

  9. PTM Along Track Algorithm to Maintain Spacing During Same Direction Pair-Wise Trajectory Management Operations

    Science.gov (United States)

    Carreno, Victor A.

    2015-01-01

    Pair-wise Trajectory Management (PTM) is a cockpit based delegated responsibility separation standard. When an air traffic service provider gives a PTM clearance to an aircraft and the flight crew accepts the clearance, the flight crew will maintain spacing and separation from a designated aircraft. A PTM along track algorithm will receive state information from the designated aircraft and from the own ship to produce speed guidance for the flight crew to maintain spacing and separation

  10. Maintaining and Researching Port Safety: A Case Study of the Port of Kaohsiung

    OpenAIRE

    Tseng, Po-Hsing.; Pilcher, Nick.

    2017-01-01

    Maintaining port safety in full conformity with IMO standards is a requisite for every port and country. To do this, understanding the challenges and human factors involved is key. To date, much research has shed valuable light on these factors and considered how to address them. One aspect that is often noted is that both maintaining port safety and researching port safety presents numerous challenges. This paper considers both these aspects in the context of a case study of port safety in K...

  11. Banded versus Single-sided bonded space maintainers: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Sudhir Mittal

    2018-01-01

    Full Text Available Background: The present study is conducted to evaluate and compare the clinical performance of conventional band and loop space maintainer and fiber reinforced composite resin (FRCR space maintainers. Materials and Methods: A total of 45 extraction sites in the age group of 6–9 years having premature loss of primary molars or indicated for extraction were selected for the study. The patients were randomly divided into three groups as Group I, in which conventional band and loop space maintainer was given, Group II and Group III (FRCR, in which FRCR (everStick CandB and impregnated glass fibers (Interlig space maintainers were given, respectively. Patients were recalled at 3, 6, and 12-month interval for evaluation of all the three types of space maintainer. Results: Overall success rate of Group I was 86.7%, for Group II was 80%, and for Group III was 73.3% at the end of the study. Patient acceptability was significantly higher in Group II and Group III (FRCR as compared to Group I (Conventional band and loop. In Group I, cement loss and fracture of loop, whereas in Group II and Group III, debonding at enamel composite was the most common failure followed by debonding at fiber composite and fiber fracture. FRCR space maintainers were found to be cost-effective as compared to Group I. More linear changes and angular changes were recorded in Group I as compared to Group II and Group III but difference was not significant (P > 0.05. Conclusion: Only single (buccal surface application of FRCR space maintainers showed almost equal clinical efficacy compared to conventional band and loop space maintainer with significantly better patient acceptability, less cost, and time taken.

  12. Hanford site guide for preparing and maintaining generator group pollution prevention program documentation

    International Nuclear Information System (INIS)

    1995-12-01

    This manual provides the necessary guidance to contractor generator groups for developing and maintaining documentation of their pollution prevention (P2) program activities. Preparation of program documentation will demonstrate compliance with contractor and U.S. Department of Energy (DOE) requirements, as well as state and federal regulations. Contractor waste generator groups are no longer required to prepare and update facility waste minimization plans. Developing and maintaining program documentation replace this requirement

  13. An economic perspective on software licenses--open source, maintainers and user-developers

    DEFF Research Database (Denmark)

    Edwards, Kasper

    2005-01-01

    This paper presents a model for understanding behaviour of agents using and/or contributing to open source software. The model illustrates behaviour of agents under three licenses regimes: 1) The GPL, The BSD and 3) The Microsoft EULA. The latter license is not an open source license...... licenses induce different incentives and dynamics for maintainer and user-developer and the paper explains, from an economic standpoint, the mechanisms that ensure programs are developed and maintained under the three license regimes....

  14. DNMT1 Maintains Progenitor Function in Self-Renewing Somatic Tissue

    OpenAIRE

    Sen, George L.; Reuter, Jason A.; Webster, Daniel E.; Zhu, Lilly; Khavari, Paul A.

    2010-01-01

    Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation1,2. DNA methylation3,4,5 provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1)6,7 maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintena...

  15. A Polarization Maintaining Filter based on a Liquid-Crystal-Photonic-Bandgap-Fiber

    DEFF Research Database (Denmark)

    Scolari, Lara; Olausson, Christina Bjarnal Thulin; Turchinovich, Dmitry

    2008-01-01

    A polarization maintaining filter based on a liquid-crystal-photonic-bandgap-fiber is demonstrated. Its polarization extinction ratio is 14 dB at 1550 nm. Its tunability is 150 nm.......A polarization maintaining filter based on a liquid-crystal-photonic-bandgap-fiber is demonstrated. Its polarization extinction ratio is 14 dB at 1550 nm. Its tunability is 150 nm....

  16. Assessment of Geant4 Maintainability with respect to software engineering references

    Science.gov (United States)

    Ronchieri, Elisabetta; Grazia Pia, Maria; Canaparo, Marco

    2017-10-01

    Over time computer scientists have been provided metrics to measure software maintainability. In existing literature, a large number of references can be found about this topic; nevertheless, a lack of quantitative assessment of maintainability metrics has been observed. In this paper, we summarize the challenges of adopting code measurements in the context of physics software system. In this pilot study, we have used Geant4 - a twenty-year-old software system - to conduct this research and set the grounds for further discussion.

  17. Machine learning methods for metabolic pathway prediction

    Directory of Open Access Journals (Sweden)

    Karp Peter D

    2010-01-01

    Full Text Available Abstract Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations.

  18. Machine learning methods for metabolic pathway prediction

    Science.gov (United States)

    2010-01-01

    Background A key challenge in systems biology is the reconstruction of an organism's metabolic network from its genome sequence. One strategy for addressing this problem is to predict which metabolic pathways, from a reference database of known pathways, are present in the organism, based on the annotated genome of the organism. Results To quantitatively validate methods for pathway prediction, we developed a large "gold standard" dataset of 5,610 pathway instances known to be present or absent in curated metabolic pathway databases for six organisms. We defined a collection of 123 pathway features, whose information content we evaluated with respect to the gold standard. Feature data were used as input to an extensive collection of machine learning (ML) methods, including naïve Bayes, decision trees, and logistic regression, together with feature selection and ensemble methods. We compared the ML methods to the previous PathoLogic algorithm for pathway prediction using the gold standard dataset. We found that ML-based prediction methods can match the performance of the PathoLogic algorithm. PathoLogic achieved an accuracy of 91% and an F-measure of 0.786. The ML-based prediction methods achieved accuracy as high as 91.2% and F-measure as high as 0.787. The ML-based methods output a probability for each predicted pathway, whereas PathoLogic does not, which provides more information to the user and facilitates filtering of predicted pathways. Conclusions ML methods for pathway prediction perform as well as existing methods, and have qualitative advantages in terms of extensibility, tunability, and explainability. More advanced prediction methods and/or more sophisticated input features may improve the performance of ML methods. However, pathway prediction performance appears to be limited largely by the ability to correctly match enzymes to the reactions they catalyze based on genome annotations. PMID:20064214

  19. Decoding resistant hypertension signalling pathways.

    Science.gov (United States)

    Parreira, Ricardo Cambraia; Lacerda, Leandro Heleno Guimarães; Vasconcellos, Rebecca; Lima, Swiany Silveira; Santos, Anderson Kenedy; Fontana, Vanessa; Sandrim, Valéria Cristina; Resende, Rodrigo Ribeiro

    2017-12-01

    Resistant hypertension (RH) is a clinical condition in which the hypertensive patient has become resistant to drug therapy and is often associated with increased cardiovascular morbidity and mortality. Several signalling pathways have been studied and related to the development and progression of RH: modulation of sympathetic activity by leptin and aldosterone, primary aldosteronism, arterial stiffness, endothelial dysfunction and variations in the renin-angiotensin-aldosterone system (RAAS). miRNAs comprise a family of small non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level. miRNAs are involved in the development of both cardiovascular damage and hypertension. Little is known of the molecular mechanisms that lead to development and progression of this condition. This review aims to cover the potential roles of miRNAs in the mechanisms associated with the development and consequences of RH, and explore the current state of the art of diagnostic and therapeutic tools based on miRNA approaches. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  20. Autophagic pathways and metabolic stress.

    Science.gov (United States)

    Kaushik, S; Singh, R; Cuervo, A M

    2010-10-01

    Autophagy is an essential intracellular process that mediates degradation of intracellular proteins and organelles in lysosomes. Autophagy was initially identified for its role as alternative source of energy when nutrients are scarce but, in recent years, a previously unknown role for this degradative pathway in the cellular response to stress has gained considerable attention. In this review, we focus on the novel findings linking autophagic function with metabolic stress resulting either from proteins or lipids. Proper autophagic activity is required in the cellular defense against proteotoxicity arising in the cytosol and also in the endoplasmic reticulum, where a vast amount of proteins are synthesized and folded. In addition, autophagy contributes to mobilization of intracellular lipid stores and may be central to lipid metabolism in certain cellular conditions. In this review, we focus on the interrelation between autophagy and different types of metabolic stress, specifically the stress resulting from the presence of misbehaving proteins within the cytosol or in the endoplasmic reticulum and the stress following a lipogenic challenge. We also comment on the consequences that chronic exposure to these metabolic stressors could have on autophagic function and on how this effect may underlie the basis of some common metabolic disorders. © 2010 Blackwell Publishing Ltd.

  1. Comparative expression pathway analysis of human and canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Marconato Laura

    2009-03-01

    Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

  2. Metabolic pathways for the whole community.

    Science.gov (United States)

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

    2014-07-22

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

  3. Calcium influx pathways in rat pancreatic ducts

    DEFF Research Database (Denmark)

    Hug, M J; Pahl, C; Novak, I

    1996-01-01

    A number of agonists increase intracellular Ca2+ activity, [Ca2+]i, in pancreatic ducts, but the influx/efflux pathways and intracellular Ca2+ stores in this epithelium are unknown. The aim of the present study was to characterise the Ca2+ influx pathways, especially their pH sensitivity, in nati...

  4. Pathways to Success for Michigan's Opportunity Youth

    Science.gov (United States)

    American Youth Policy Forum, 2015

    2015-01-01

    Each young person must navigate his/her own pathway into and through postsecondary education and the workforce to long-term success personalized to his/her own unique needs and desires. The pathway to long-term success is often articulated as a straight road through K-12 education into postsecondary education (either academic or technical…

  5. Implementing Guided Pathways: Tips and Tools

    Science.gov (United States)

    Bailey, Thomas; Jaggars, Shanna Smith; Jenkins, Davis

    2015-01-01

    A growing number of community colleges and four-year universities are seeking to improve student outcomes by redesigning academic programs and student support services following the guided pathways approach. These institutions are mapping out highly structured, educationally coherent program pathways for students to follow by starting with the end…

  6. The evolution of plant virus transmission pathways

    Science.gov (United States)

    Frédéric M. Hamelin; Linda J.S. Allen; Holly R. Prendeville; M. Reza Hajimorad; Michael J. Jeger

    2016-01-01

    The evolution of plant virus transmission pathways is studied through transmission via seed, pollen, oravector. We address the questions: under what circumstances does vector transmission make pollen transmission redundant? Can evolution lead to the coexistence of multiple virus transmission pathways? We restrict the analysis to an annual plant population in which...

  7. Women's Work Pathways Across the Life Course.

    Science.gov (United States)

    Damaske, Sarah; Frech, Adrianne

    2016-04-01

    Despite numerous changes in women's employment in the latter half of the twentieth century, women's employment continues to be uneven and stalled. Drawing from data on women's weekly work hours in the National Longitudinal Survey of Youth (NLSY79), we identify significant inequality in women's labor force experiences across adulthood. We find two pathways of stable full-time work for women, three pathways of part-time employment, and a pathway of unpaid labor. A majority of women follow one of the two full-time work pathways, while fewer than 10% follow a pathway of unpaid labor. Our findings provide evidence of the lasting influence of work-family conflict and early socioeconomic advantages and disadvantages on women's work pathways. Indeed, race, poverty, educational attainment, and early family characteristics significantly shaped women's work careers. Work-family opportunities and constraints also were related to women's work hours, as were a woman's gendered beliefs and expectations. We conclude that women's employment pathways are a product of both their resources and changing social environment as well as individual agency. Significantly, we point to social stratification, gender ideologies, and work-family constraints, all working in concert, as key explanations for how women are "tracked" onto work pathways from an early age.

  8. Investigating multiple dysregulated pathways in rheumatoid arthritis ...

    Indian Academy of Sciences (India)

    Xian-Dong Song

    2018-03-09

    Mar 9, 2018 ... 5Department of Kidney Internal Medicine, Hongqi Hospital of ... on the gene expression profile, pathway data, and PPI information. ... controls. These 10 dysregulated pathways might be potential ... a significant burden on the healthcare systems (Yamada ... The risk of adverse effects and expensive treat-.

  9. Investigating dysregulated pathways in cardiomyopathy from ...

    Indian Academy of Sciences (India)

    牛牛

    5 Department of Kidney Internal Medicine, Hongqi Hospital of Mudanjiang ... based on gene expression profile, pathway data, and PPI information. ... control samples was observed in the pathway of epigenetic regulation of gene ... significant burden on the health care systems (Yamada et al., 2016). ..... 2015 The effects.

  10. DMPD: Regulation of mitochondrial antiviral signaling pathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18549796 Regulation of mitochondrial antiviral signaling pathways. Moore CB, Ting J...P. Immunity. 2008 Jun;28(6):735-9. (.png) (.svg) (.html) (.csml) Show Regulation of mitochondrial antiviral ...signaling pathways. PubmedID 18549796 Title Regulation of mitochondrial antiviral signaling pathways. Author

  11. DMPD: Parallel pathways of virus recognition. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16713969 Parallel pathways of virus recognition. Tenoever BR, Maniatis T. Immunity.... 2006 May;24(5):510-2. (.png) (.svg) (.html) (.csml) Show Parallel pathways of virus recognition. PubmedID 1...6713969 Title Parallel pathways of virus recognition. Authors Tenoever BR, Maniatis T. Publication Immunity.

  12. DMPD: All is not Toll: new pathways in DNA recognition. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16446382 All is not Toll: new pathways in DNA recognition. Wagner H, Bauer S. J Exp... Med. 2006 Feb 20;203(2):265-8. Epub 2006 Jan 30. (.png) (.svg) (.html) (.csml) Show All is not Toll: new pathways in DNA recognition.... PubmedID 16446382 Title All is not Toll: new pathways in DNA recognition. Authors

  13. Dysregulated Pathway Identification of Alzheimer's Disease Based on Internal Correlation Analysis of Genes and Pathways.

    Science.gov (United States)

    Kong, Wei; Mou, Xiaoyang; Di, Benteng; Deng, Jin; Zhong, Ruxing; Wang, Shuaiqun

    2017-11-20

    Dysregulated pathway identification is an important task which can gain insight into the underlying biological processes of disease. Current pathway-identification methods focus on a set of co-expression genes and single pathways and ignore the correlation between genes and pathways. The method proposed in this study, takes into account the internal correlations not only between genes but also pathways to identifying dysregulated pathways related to Alzheimer's disease (AD), the most common form of dementia. In order to find the significantly differential genes for AD, mutual information (MI) is used to measure interdependencies between genes other than expression valves. Then, by integrating the topology information from KEGG, the significant pathways involved in the feature genes are identified. Next, the distance correlation (DC) is applied to measure the pairwise pathway crosstalks since DC has the advantage of detecting nonlinear correlations when compared to Pearson correlation. Finally, the pathway pairs with significantly different correlations between normal and AD samples are known as dysregulated pathways. The molecular biology analysis demonstrated that many dysregulated pathways related to AD pathogenesis have been discovered successfully by the internal correlation detection. Furthermore, the insights of the dysregulated pathways in the development and deterioration of AD will help to find new effective target genes and provide important theoretical guidance for drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. DMPD: Signal integration between IFNgamma and TLR signalling pathways in macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16920490 Signal integration between IFNgamma and TLR signalling pathways in macroph...tml) (.csml) Show Signal integration between IFNgamma and TLR signalling pathways in macrophages. PubmedID 16920490 Title Signal inte...gration between IFNgamma and TLR signalling pathways in

  15. DMPD: Signaling pathways activated by microorganisms. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17303405 Signaling pathways activated by microorganisms. Takeuchi O, Akira S. Curr ...Opin Cell Biol. 2007 Apr;19(2):185-91. Epub 2007 Feb 15. (.png) (.svg) (.html) (.csml) Show Signaling pathways activated by microorg...anisms. PubmedID 17303405 Title Signaling pathways activated by microorganisms. Auth

  16. Pathway enrichment analysis approach based on topological structure and updated annotation of pathway.

    Science.gov (United States)

    Yang, Qian; Wang, Shuyuan; Dai, Enyu; Zhou, Shunheng; Liu, Dianming; Liu, Haizhou; Meng, Qianqian; Jiang, Bin; Jiang, Wei

    2017-08-16

    Pathway enrichment analysis has been widely used to identify cancer risk pathways, and contributes to elucidating the mechanism of tumorigenesis. However, most of the existing approaches use the outdated pathway information and neglect the complex gene interactions in pathway. Here, we first reviewed the existing widely used pathway enrichment analysis approaches briefly, and then, we proposed a novel topology-based pathway enrichment analysis (TPEA) method, which integrated topological properties and global upstream/downstream positions of genes in pathways. We compared TPEA with four widely used pathway enrichment analysis tools, including database for annotation, visualization and integrated discovery (DAVID), gene set enrichment analysis (GSEA), centrality-based pathway enrichment (CePa) and signaling pathway impact analysis (SPIA), through analyzing six gene expression profiles of three tumor types (colorectal cancer, thyroid cancer and endometrial cancer). As a result, we identified several well-known cancer risk pathways that could not be obtained by the existing tools, and the results of TPEA were more stable than that of the other tools in analyzing different data sets of the same cancer. Ultimately, we developed an R package to implement TPEA, which could online update KEGG pathway information and is available at the Comprehensive R Archive Network (CRAN): https://cran.r-project.org/web/packages/TPEA/. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Robust de novo pathway enrichment with KeyPathwayMiner 5

    DEFF Research Database (Denmark)

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

    2016-01-01

    Identifying functional modules or novel active pathways, recently termed de novo pathway enrichment, is a computational systems biology challenge that has gained much attention during the last decade. Given a large biological interaction network, KeyPathwayMiner extracts connected subnetworks tha...

  18. Modularized Smad-regulated TGFβ signaling pathway.

    Science.gov (United States)

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

    2012-12-01

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

  19. Wood ethanol and synthetic natural gas pathways

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-11-30

    This report provided details of updates to the wood ethanol pathway recently added to the GHGenius model, an analytical tool used to analyze emissions from conventional and alternative fuel combustion processes. The pathway contains data developed by the United States Department of Energy. A number of co-products were added to the wood and agricultural residue pathways, including furfural, xylitol, lignin, and glycerol. New chemical inputs included nitrogen gas, ammonia, enzymes and yeast. Biological ethanol pathways were reviewed, and separate inputs for wood, agricultural residues, corn ethanol, and wheat ethanol were added. The model was updated to reflect current research conducted on the gasification of wood and the upgrading of the gas to produce pipeline quality natural gas. New process developments in producing pipeline quality gas from coal were also added. The ability to model enzyme consumption was added to all ethanol pathways. 25 refs., 41 tabs., 8 figs.

  20. Wood ethanol and synthetic natural gas pathways

    International Nuclear Information System (INIS)

    2006-01-01

    This report provided details of updates to the wood ethanol pathway recently added to the GHGenius model, an analytical tool used to analyze emissions from conventional and alternative fuel combustion processes. The pathway contains data developed by the United States Department of Energy. A number of co-products were added to the wood and agricultural residue pathways, including furfural, xylitol, lignin, and glycerol. New chemical inputs included nitrogen gas, ammonia, enzymes and yeast. Biological ethanol pathways were reviewed, and separate inputs for wood, agricultural residues, corn ethanol, and wheat ethanol were added. The model was updated to reflect current research conducted on the gasification of wood and the upgrading of the gas to produce pipeline quality natural gas. New process developments in producing pipeline quality gas from coal were also added. The ability to model enzyme consumption was added to all ethanol pathways. 25 refs., 41 tabs., 8 figs

  1. Guidelines on the use of space maintainers following premature loss of primary teeth.

    Science.gov (United States)

    Brothwell, D J

    1997-11-01

    To formulate evidence-based guidelines on the appropriate use of space maintaining appliances to prevent or reduce the severity of malocclusion in the permanent dentition following the premature loss of primary teeth. Placement of lingual arch, palatal arch, band-loop, crown-loop, and intra-alveolar space maintainers. Reduced prevalence or severity of space loss in the primary or mixed dentition, reduced prevalence or severity of malocclusion in the permanent dentition measured as significant changes in: crowding, ectopic eruption, impacted teeth, Angle's class II or III occlusion, crossbite, deep overbite, deep overjet, or midline shift. Articles published from 1966 to 1996, located though Medline searches. Only clinical trials, cohort studies, case-control studies, or large case series were considered. Relevant clinical findings were evaluated and categorized using evidence-based methods and values established by the Canadian Task Force on the Periodic Health Examination. A recommendation was developed for the use of space maintainers. The potential benefits of using space maintaining appliances include reduced prevalence or severity of: crowding, ectopic eruption, tooth impaction, crossbite, excessive overbite and overjet, and poor molar relationship. Other advantages include the potential for considerable cost savings by reducing the need for future orthodontic treatment. The potential disadvantages of using space maintaining appliances include soft tissue impingement, interference with eruption of adjacent teeth, pain, plaque accumulation, caries, and broken, dislodged or lost appliances. There is poor evidence to recommend for or against the use of space maintainers to prevent or reduce the severity of malocclusion in the permanent dentition (see Table 1, Recommendation C) Decisions regarding the use of space maintainers must therefore be guided by factors other than scientific evidence.

  2. Kynurenine Pathway Metabolism is Involved in the Maintenance of the Intracellular NAD Concentration in Human Primary Astrocytes

    Directory of Open Access Journals (Sweden)

    Ross Grant

    2010-01-01

    Full Text Available Efficient synthesis of NAD + is critical to maintaining cell viability in all organs of the body. However, little is known of the pathway(s by which cells of the central nervous system produce NAD + . The aim of this study was to investigate the relationship, between tryptophan degradation via the kynurenine pathway (KP and de novo NAD + synthesis in human astrocytes, a major cell type within the brain. In this study we observed that inhibition of single enzymes of the KP resulted in significant decreases in NAD + levels in astroglial cells after a 24 hr period. We also observed that astrocytes cultured in media deficient in tryptophan, nicotinic acid and nicotinamide resulted in a 50% decrease in NAD + levels after 24 hrs. This decrease in NAD + was partially restored by supplementation of the culture media with either tryptophan or kynurenine, or nicotinic acid or with supply of the salvage pathway precursor nicotinamide.

  3. Kynurenine Pathway Metabolism is Involved in the Maintenance of the Intracellular NAD+ Concentration in Human Primary Astrocytes

    Science.gov (United States)

    Grant, Ross; Nguyen, Susan; Guillemin, Gilles

    2010-01-01

    Efficient synthesis of NAD+ is critical to maintaining cell viability in all organs of the body. However, little is known of the pathway(s) by which cells of the central nervous system produce NAD+. The aim of this study was to investigate the relationship, between tryptophan degradation via the kynurenine pathway (KP) and de novo NAD+ synthesis in human astrocytes, a major cell type within the brain. In this study we observed that inhibition of single enzymes of the KP resulted in significant decreases in NAD+ levels in astroglial cells after a 24 hr period. We also observed that astrocytes cultured in media deficient in tryptophan, nicotinic acid and nicotinamide resulted in a 50% decrease in NAD+ levels after 24 hrs. This decrease in NAD+ was partially restored by supplementation of the culture media with either tryptophan or kynurenine, or nicotinic acid or with supply of the salvage pathway precursor nicotinamide. PMID:22084595

  4. Nonoverlapping roles of PD-1 and FoxP3 in maintaining immune tolerance in a novel autoimmune pancreatitis mouse model.

    Science.gov (United States)

    Zhang, Baihao; Chikuma, Shunsuke; Hori, Shohei; Fagarasan, Sidonia; Honjo, Tasuku

    2016-07-26

    PD-1 (programmed-death 1), an immune-inhibitory receptor required for immune self-tolerance whose deficiency causes autoimmunity with variable severity and tissue specificity depending on other genetic factors, is expressed on activated T cells, including the transcription factor FoxP3(+) Treg cells known to play critical roles in maintaining immune tolerance. However, whether PD-1 expression by the Treg cells is required for their immune regulatory function, especially in autoimmune settings, is still unclear. We found that mice with partial FoxP3 insufficiency developed early-onset lympho-proliferation and lethal autoimmune pancreatitis only when PD-1 is absent. The autoimmune phenotype was rescued by the transfer of FoxP3-sufficient T cells, regardless of whether they were derived from WT or PD-1-deficient mice, indicating that Treg cells dominantly protect against development of spontaneous autoimmunity without intrinsic expression of PD-1. The absence of PD-1 combined with partial FoxP3 insufficiency, however, led to generation of ex-FoxP3 T cells with proinflammatory properties and expansion of effector/memory T cells that contributed to the autoimmune destruction of target tissues. Altogether, the results suggest that PD-1 and FoxP3 work collaboratively in maintaining immune tolerance mostly through nonoverlapping pathways. Thus, PD-1 is modulating the activation threshold and maintaining the balance between regulatory and effector T cells, whereas FoxP3 is sufficient for dominant regulation through maintaining the integrity of the Treg function. We suggest that genetic or environmental factors that even moderately affect the expression of both PD-1 and FoxP3 can cause life-threatening autoimmune diseases by disrupting the T-cell homeostasis.

  5. Native Geoscience: Pathways to Knowledge

    Science.gov (United States)

    Bolman, J. R.; Seielstad, G.

    2006-12-01

    We are living in a definite time of change. Distinct changes are being experienced in our most sacred and natural environments. This is especially true on Native lands. Native people have lived for millennia in distinct and unique ways. The knowledge of balancing the needs of people with the needs of our natural environments is paramount in all tribal societies. This inherent accumulated knowledge has become the foundation on which to build a "blended" contemporary understanding of western science. The Dakota's and Northern California have embraced the critical need of understanding successful tribal strategies to engage educational systems (K-12 and higher education), to bring to prominence the professional development opportunities forged through working with tribal peoples and ensure the continued growth of Native earth and environmental scientists The presentation will highlight: 1) past and present philosophies on building and maintaining Native/Tribal students in earth and environmental sciences; 2) successful educational programs/activities in PreK-Ph.D. systems; 3) current Native leadership development in earth and environmental sciences; and 4) forward thinking for creating proaction collaborations addressing sustainable environmental, educational and social infrastructures for all people. Humboldt State University (HSU) and the University of North Dakota's Northern Great Plains Center for People and the Environment and the Upper Midwest Aerospace Consortium (UMAC) have been recognized nationally for their partnerships with Native communities. Unique collaborations are emerging "bridging" Native people across geographic areas in developing educational/research experiences which integrate the distinctive earth/environmental knowledge of tribal people. The presentation will highlight currently funded projects and initiatives as well as success stories of emerging Native earth system students and scientists.

  6. Meal consumption is ineffective at maintaining or correcting water balance in a desert lizard, Heloderma suspectum.

    Science.gov (United States)

    Wright, Christian D; Jackson, Marin L; DeNardo, Dale F

    2013-04-15

    Many xeric organisms maintain water balance by relying on dietary and metabolic water rather than free water, even when free water may be available. For such organisms, hydric state may influence foraging decisions, since meal consumption is meeting both energy and water demands. To understand foraging decisions it is vital to understand the role of dietary water in maintaining water balance. We investigated whether meal consumption was sufficient to maintain water balance in captive Gila monsters (Heloderma suspectum) at varying levels of dehydration. Gila monsters could not maintain water balance over long time scales through meal consumption alone. Animals fed a single meal took no longer to dehydrate than controls when both groups were deprived of free water. Additionally, meal consumption imparts an acute short-term hydric cost regardless of hydration state. Meal consumption typically resulted in a significant elevation in osmolality at 6 h post-feeding, and plasma osmolality never fell below pre-feeding levels despite high water content (~70%) of meals. These results failed to support our hypothesis that dietary water is valuable to Gila monsters during seasonal drought. When considered in conjunction with previous research, these results demonstrate that Gila monsters, unlike many xeric species, are heavily reliant on seasonal rainfall and the resulting free-standing water to maintain water balance.

  7. The Experience of Young Women Living in a Prostitution Area in Maintaining Their Reproductive Health.

    Science.gov (United States)

    Dovis, Vonyca; Setyowati; Kurniawati, Wiwit

    Young women face a difficult situation when they live in a prostitution area or red light district. A phenomenological approach was applied to explore the experiences in maintaining reproductive health of 10 young women living in the prostitution area in Lampung, one of the provinces in Sumatra. Thematic content analysis found 7 themes including: (1) The participants' perception of prostitution as a place of naughty women and free sexual activity that can transmit STDs and influence adolescent psychology; (2) The ways the participants kept their reproductive organs healthy were through maintaining friendships, maintaining personal hygiene, avoiding free sexual activity, eating healthy food, and having routine medical checkups; (3) Information support was gained from family, health workers, media, and teachers; (4) Emotional support from family and friends; (5) Barriers to maintaining good health were inaccessible health facilities and an underfunded health service; (6) The needs of the participants were reproductive health services and clean environment; (7) The participants hoped for health education and intensive health services with friendly nurses. The results of this research illustrate that there is a need for socializing intensive ways to maintain reproductive health, especially in a risky environment.

  8. Initiating and maintaining recreational walking: a longitudinal study on the influence of neighborhood green space.

    Science.gov (United States)

    Sugiyama, Takemi; Giles-Corti, Billie; Summers, Jacqui; du Toit, Lorinne; Leslie, Eva; Owen, Neville

    2013-09-01

    This study examined prospective relationships of green space attributes with adults initiating or maintaining recreational walking. Postal surveys were completed by 1036 adults living in Adelaide, Australia, at baseline (two time points in 2003-04) and follow-up (2007-08). Initiating or maintaining recreational walking was determined using self-reported walking frequency. Green space attributes examined were perceived presence, quality, proximity, and the objectively measured area (total and largest) and number of green spaces within a 1.6 km buffer drawn from the center of each study neighborhood. Multilevel regression analyses examined the odds of initiating or maintaining walking separately for each green space attribute. At baseline, participants were categorized into non-regular (n = 395), regular (n = 286), and irregular walkers (n = 313). Among non-regular walkers, 30% had initiated walking, while 70% of regular walkers had maintained walking at follow-up. No green space attributes were associated with initiating walking. However, positive perceptions of the presence of and proximity to green spaces and the total and largest areas of green space were significantly associated with a higher likelihood of walking maintenance over four years. Neighborhood green spaces may not assist adults to initiate walking, but their presence and proximity may facilitate them to maintain recreational walking over time. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Transcriptomic analysis of genes in the nitrogen recycling pathway of meat-type chickens divergently selected for feed efficiency.

    Science.gov (United States)

    Aggrey, S E; Lee, J; Karnuah, A B; Rekaya, R

    2014-04-01

    The understanding of the dynamics of ammonia detoxification and excretion in uricotelic species is lagging behind ureotelic species. The relative expression of genes involved in nitrogen recycling and feed efficiency in chickens is unknown. The objective of this study was to investigate the transcriptomics differences in key genes in the nitrogen (N) metabolism and purine biosynthesis pathway in a chicken population divergently selected for low (LRFI) or high (HRFI) residual feed intake at days 35 and 42 using duodenum, liver, pectoralis major (P. major) and kidney. There was a significant positive correlation between RFI and fecal N. The purine salvage pathway was activated in the LRFI compared with HRFI at days 42. The birds in the LRFI population attained greater feed efficiency by having lower FI, increasing their protein retention and producing adequate glutamine to maintain growth compared with the HRFI line. To maintain growth, excess N is deaminated mostly to generate purine nucleotides. Generating purine nucleotides primarily from the purine biosynthesis pathway is energetically costly, and to preserve energy, they preferentially generate nucleotides from the purine salvage pathway. The LRFI birds need to generate sufficient nucleotides to maintain growth despite reduced FI that then results in reduced fecal N. © 2013 Stichting International Foundation for Animal Genetics.

  10. WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research.

    Science.gov (United States)

    Slenter, Denise N; Kutmon, Martina; Hanspers, Kristina; Riutta, Anders; Windsor, Jacob; Nunes, Nuno; Mélius, Jonathan; Cirillo, Elisa; Coort, Susan L; Digles, Daniela; Ehrhart, Friederike; Giesbertz, Pieter; Kalafati, Marianthi; Martens, Marvin; Miller, Ryan; Nishida, Kozo; Rieswijk, Linda; Waagmeester, Andra; Eijssen, Lars M T; Evelo, Chris T; Pico, Alexander R; Willighagen, Egon L

    2018-01-04

    WikiPathways (wikipathways.org) captures the collective knowledge represented in biological pathways. By providing a database in a curated, machine readable way, omics data analysis and visualization is enabled. WikiPathways and other pathway databases are used to analyze experimental data by research groups in many fields. Due to the open and collaborative nature of the WikiPathways platform, our content keeps growing and is getting more accurate, making WikiPathways a reliable and rich pathway database. Previously, however, the focus was primarily on genes and proteins, leaving many metabolites with only limited annotation. Recent curation efforts focused on improving the annotation of metabolism and metabolic pathways by associating unmapped metabolites with database identifiers and providing more detailed interaction knowledge. Here, we report the outcomes of the continued growth and curation efforts, such as a doubling of the number of annotated metabolite nodes in WikiPathways. Furthermore, we introduce an OpenAPI documentation of our web services and the FAIR (Findable, Accessible, Interoperable and Reusable) annotation of resources to increase the interoperability of the knowledge encoded in these pathways and experimental omics data. New search options, monthly downloads, more links to metabolite databases, and new portals make pathway knowledge more effortlessly accessible to individual researchers and research communities. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. PANDA: pathway and annotation explorer for visualizing and interpreting gene-centric data.

    Science.gov (United States)

    Hart, Steven N; Moore, Raymond M; Zimmermann, Michael T; Oliver, Gavin R; Egan, Jan B; Bryce, Alan H; Kocher, Jean-Pierre A

    2015-01-01

    Objective. Bringing together genomics, transcriptomics, proteomics, and other -omics technologies is an important step towards developing highly personalized medicine. However, instrumentation has advances far beyond expectations and now we are able to generate data faster than it can be interpreted. Materials and Methods. We have developed PANDA (Pathway AND Annotation) Explorer, a visualization tool that integrates gene-level annotation in the context of biological pathways to help interpret complex data from disparate sources. PANDA is a web-based application that displays data in the context of well-studied pathways like KEGG, BioCarta, and PharmGKB. PANDA represents data/annotations as icons in the graph while maintaining the other data elements (i.e., other columns for the table of annotations). Custom pathways from underrepresented diseases can be imported when existing data sources are inadequate. PANDA also allows sharing annotations among collaborators. Results. In our first use case, we show how easy it is to view supplemental data from a manuscript in the context of a user's own data. Another use-case is provided describing how PANDA was leveraged to design a treatment strategy from the somatic variants found in the tumor of a patient with metastatic sarcomatoid renal cell carcinoma. Conclusion. PANDA facilitates the interpretation of gene-centric annotations by visually integrating this information with context of biological pathways. The application can be downloaded or used directly from our website: http://bioinformaticstools.mayo.edu/research/panda-viewer/.

  12. Pathway and Molecular Mechanisms for Malachite Green Biodegradation in Exiguobacterium sp. MG2

    Science.gov (United States)

    Wang, Ji’ai; Gao, Feng; Liu, Zhongzhong; Qiao, Min; Niu, Xuemei; Zhang, Ke-Qin; Huang, Xiaowei

    2012-01-01

    Malachite green (MG), N-methylated diaminotriphenylmethane, is one of the most common dyes in textile industry and has also been used as an effective antifungal agent. However, due to its negative impact on the environment and carcinogenic effects to mammalian cells, there is a significant interest in developing microbial agents to degrade this type of recalcitrant molecules. Here, an Exiguobacterium sp. MG2 was isolated from a river in Yunnan Province of China as one of the best malachite green degraders. This strain had a high decolorization capability even at the concentration of 2500 mg/l and maintained its stable activity within the pH range from 5.0 to 9.0. High-pressure liquid chromatography, liquid chromatography-mass spectrometry and gas chromatography–mass spectrometry were employed to detect the catabolic pathway of MG. Six intermediate products were identified and a potential biodegradation pathway was proposed. This pathway involves a series of reactions of N-demethylation, reduction, benzene ring-removal, and oxidation, which eventually converted N-methylated diaminotriphenylmethane into N, N-dimethylaniline that is the key precursor to MG. Furthermore, our molecular biology experiments suggested that both triphenylmethane reductase gene tmr and cytochrome P450 participated in MG degradation, consistent with their roles in the proposed pathway. Collectively, our investigation is the first report on a biodegradation pathway of triphenylmethane dye MG in bacteria. PMID:23251629

  13. Crosstalk between the Tor and Gcn2 pathways in response to different stresses.

    Science.gov (United States)

    Rødland, Gro Elise; Tvegård, Tonje; Boye, Erik; Grallert, Beáta

    2014-01-01

    Regulating growth and the cell cycle in response to environmental fluctuations is important for all organisms in order to maintain viability. Two major pathways for translational regulation are found in higher eukaryotes: the Tor signaling pathway and those operating through the eIF2α kinases. Studies from several organisms indicate that the two pathways are interlinked, in that Tor complex 1 (TORC1) negatively regulates the Gcn2 kinase. Furthermore, inactivation of TORC1 may be required for activation of Gcn2 in response to stress. Here, we use the model organism Schizosaccharomyces pombe to investigate this crosstalk further. We find that the relationship is more complex than previously thought. First, in response to UV irradiation and oxidative stress, Gcn2 is fully activated in the presence of TORC1 signaling. Second, during amino-acid starvation, activation of Gcn2 is dependent on Tor2 activity, and Gcn2 is required for timely inactivation of the Tor pathway. Our data show that the crosstalk between the two pathways varies with the actual stress applied.

  14. Wound care clinical pathway: a conceptual model.

    Science.gov (United States)

    Barr, J E; Cuzzell, J

    1996-08-01

    A clinical pathway is a written sequence of clinical processes or events that guides a patient with a defined problem toward an expected outcome. Clinical pathways are tools to assist with the cost-effective management of clinical outcomes related to specific problems or disease processes. The primary obstacles to developing clinical pathways for wound care are the chronic natures of some wounds and the many variables that can delay healing. The pathway introduced in this article was modeled upon the three phases of tissue repair: inflammatory, proliferative, and maturation. This physiology-based model allows clinicians to identify and monitor outcomes based on observable and measurable clinical parameters. The pathway design, which also includes educational and behavioral outcomes, allows the clinician to individualize the expected timeframe for outcome achievement based on individual patient criteria and expert judgement. Integral to the pathway are the "4P's" which help standardize the clinical processes by wound type: Protocols, Policies, Procedures, and Patient education tools. Four categories into which variances are categorized based on the cause of the deviation from the norm are patient, process/system, practitioner, and planning/discharge. Additional research is warranted to support the value of this clinical pathway in the clinical arena.

  15. Predicting pathway cross-talks in ankylosing spondylitis through investigating the interactions among pathways.

    Science.gov (United States)

    Gu, Xiang; Liu, Cong-Jian; Wei, Jian-Jie

    2017-11-13

    Given that the pathogenesis of ankylosing spondylitis (AS) remains unclear, the aim of this study was to detect the potentially functional pathway cross-talk in AS to further reveal the pathogenesis of this disease. Using microarray profile of AS and biological pathways as study objects, Monte Carlo cross-validation method was used to identify the significant pathway cross-talks. In the process of Monte Carlo cross-validation, all steps were iterated 50 times. For each run, detection of differentially expressed genes (DEGs) between two groups was conducted. The extraction of the potential disrupted pathways enriched by DEGs was then implemented. Subsequently, we established a discriminating score (DS) for each pathway pair according to the distribution of gene expression levels. After that, we utilized random forest (RF) classification model to screen out the top 10 paired pathways with the highest area under the curve (AUCs), which was computed using 10-fold cross-validation approach. After 50 bootstrap, the best pairs of pathways were identified. According to their AUC values, the pair of pathways, antigen presentation pathway and fMLP signaling in neutrophils, achieved the best AUC value of 1.000, which indicated that this pathway cross-talk could distinguish AS patients from normal subjects. Moreover, the paired pathways of SAPK/JNK signaling and mitochondrial dysfunction were involved in 5 bootstraps. Two paired pathways (antigen presentation pathway and fMLP signaling in neutrophil, as well as SAPK/JNK signaling and mitochondrial dysfunction) can accurately distinguish AS and control samples. These paired pathways may be helpful to identify patients with AS for early intervention.

  16. Sustained levels of FGF2 maintain undifferentiated stem cell cultures with biweekly feeding.

    Directory of Open Access Journals (Sweden)

    Steven Lotz

    Full Text Available An essential aspect of stem cell culture is the successful maintenance of the undifferentiated state. Many types of stem cells are FGF2 dependent, and pluripotent stem cells are maintained by replacing FGF2-containing media daily, while tissue-specific stem cells are typically fed every 3rd day. Frequent feeding, however, results in significant variation in growth factor levels due to FGF2 instability, which limits effective maintenance due to spontaneous differentiation. We report that stabilization of FGF2 levels using controlled release PLGA microspheres improves expression of stem cell markers, increases stem cell numbers and decreases spontaneous differentiation. The controlled release FGF2 additive reduces the frequency of media changes needed to maintain stem cell cultures, so that human embryonic stem cells and induced pluripotent stem cells can be maintained successfully with biweekly feedings.

  17. Recommendations to the NRC on human engineering guidelines for nuclear power plant maintainability

    Energy Technology Data Exchange (ETDEWEB)

    Badalamente, R.V.; Fecht, B.A.; Blahnik, D.E.; Eklund, J.D.; Hartley, C.S.

    1986-03-01

    This document contains human engineering guidelines which can enhance the maintainability of nuclear power plants. The guidelines have been derived from general human engineering design principles, criteria, and data. The guidelines may be applied to existing plants as well as to plants under construction. They apply to nuclear power plant systems, equipment and facilities, as well as to maintenance tools and equipment. The guidelines are grouped into seven categories: accessibility and workspace, physical environment, loads and forces, maintenance facilities, maintenance tools and equipment, operating equipment design, and information needs. Each chapter of the document details specific maintainability problems encountered at nuclear power plants, the safety impact of these problems, and the specific maintainability design guidelines whose application can serve to avoid these problems in new or existing plants.

  18. An assessment of maintainability of elevator system to improve facilities management knowledge-base

    Science.gov (United States)

    Siti, N. A.; Asmone, A. S.; Chew, M. Y. L.

    2018-02-01

    Elevator system is a highly specialized machinery that requires technicians that have a wider array of knowledge in maintaining the system to be safe and reliable. While attaining reliable data of elevator malfunction become challenges, this study has filled the gap by gathering the management-maintenance issues and operational defects of elevator system. Forty-three types of operation defects were found and the consequence defects and their possible causes of occurrences were discussed. To respond to the prime challenges of maintaining elevator system provided by the industry players’ perspective, a theoretical framework is established as a recommendation to improve knowledge base of defects in elevator system which comprises good practices, and solutions to rectify each defects found. Hence, this research paper has theoretically improved the knowledge base of maintainability of elevator system and provide meaningful guidelines in practical senses to the industry professionals.

  19. Maintaining a Distinction Between Possible and Impossible Topics of Conversation in the Outpatient Respiratory Medical Clinic.

    Science.gov (United States)

    Jensen, Lone Birgitte Skov; Larsen, Kristian; Konradsen, Hanne

    2016-01-01

    The aim of this study is to generate a grounded theory explaining patterns of behavior among health care professionals (HCPs) during interactions with patients in outpatient respiratory medical clinics. The findings suggest that the HCPs managed contradictory expectations to the interaction by maintaining a distinction between possible and impossible topics to counseling. Three subcategories explaining the effort that maintain the impossible and possible topics separated were identified: (a) an effort to maintain the diseased lungs as the main task in counseling, (b) navigating interactions to avoid strong emotions of suffering in patients to reveal, (c) avoiding the appearance of the non-alterable life circumstances of the patients. The HCPs' attitudes toward what patients could be offered generated a distance and a difficulty during counseling and created further suffering in the patients but likewise a discomfort and frustration among the HCPs.

  20. What older adults find useful for maintaining healthy eating and exercise habits.

    Science.gov (United States)

    Greaney, Mary L; Lees, Faith D; Greene, Geoffrey W; Clark, Phillip G

    2004-01-01

    Four focus groups were conducted with a total of 29 adults 60 years of age and older enrolled in the SENIOR Project, a health promotion intervention study designed to increase fruit and vegetable consumption and exercise among community-dwelling older adults. The focus groups explored the motivations of older adults to eat five or more servings of fruits and vegetables and/or exercise and the strategies used to adopt or maintain these behaviors. Participants stated that maintaining health, remaining independent, and fearing illness provided the motivation needed to adhere to these behaviors. The strategies or the behavioral processes used to adopt or maintain these behaviors included counterconditioning, helping relationships, stimulus control, and self-liberation.