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Sample records for chp-pak-pix pathway maintains

  1. The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Ethan V Abel

    Full Text Available Pancreatic cancer stem cells (CSCs represent a small subpopulation of pancreatic cancer cells that have the capacity to initiate and propagate tumor formation. However, the mechanisms by which pancreatic CSCs are maintained are not well understood or characterized.Expression of Notch receptors, ligands, and Notch signaling target genes was quantitated in the CSC and non-CSC populations from 8 primary human pancreatic xenografts. A gamma secretase inhibitor (GSI that inhibits the Notch pathway and a shRNA targeting the Notch target gene Hes1 were used to assess the role of the Notch pathway in CSC population maintenance and pancreatic tumor growth.Notch pathway components were found to be upregulated in pancreatic CSCs. Inhibition of the Notch pathway using either a gamma secretase inhibitor or Hes1 shRNA in pancreatic cancer cells reduced the percentage of CSCs and tumorsphere formation. Conversely, activation of the Notch pathway with an exogenous Notch peptide ligand increased the percentage of CSCs as well as tumorsphere formation. In vivo treatment of orthotopic pancreatic tumors in NOD/SCID mice with GSI blocked tumor growth and reduced the CSC population.The Notch signaling pathway is important in maintaining the pancreatic CSC population and is a potential therapeutic target in pancreatic cancer.

  2. Epigenetic regulator Lid maintains germline stem cells through regulating JAK-STAT signaling pathway activity

    Directory of Open Access Journals (Sweden)

    Lama Tarayrah

    2015-11-01

    Full Text Available Signaling pathways and epigenetic mechanisms have both been shown to play essential roles in regulating stem cell activity. While the role of either mechanism in this regulation is well established in multiple stem cell lineages, how the two mechanisms interact to regulate stem cell activity is not as well understood. Here we report that in the Drosophila testis, an H3K4me3-specific histone demethylase encoded by little imaginal discs (lid maintains germline stem cell (GSC mitotic index and prevents GSC premature differentiation. Lid is required in germ cells for proper expression of the Stat92E transcription factor, the downstream effector of the Janus kinase signal transducer and activator of transcription (JAK-STAT signaling pathway. Our findings support a germ cell autonomous role for the JAK-STAT pathway in maintaining GSCs and place Lid as an upstream regulator of this pathway. Our study provides new insights into the biological functions of a histone demethylase in vivo and sheds light on the interaction between epigenetic mechanisms and signaling pathways in regulating stem cell activities.

  3. Malaria parasites utilize both homologous recombination and alternative end joining pathways to maintain genome integrity.

    Science.gov (United States)

    Kirkman, Laura A; Lawrence, Elizabeth A; Deitsch, Kirk W

    2014-01-01

    Malaria parasites replicate asexually within their mammalian hosts as haploid cells and are subject to DNA damage from the immune response and chemotherapeutic agents that can significantly disrupt genomic integrity. Examination of the annotated genome of the parasite Plasmodium falciparum identified genes encoding core proteins required for the homologous recombination (HR) pathway for repairing DNA double-strand breaks (DSBs), but surprisingly none of the components of the canonical non-homologous end joining (C-NHEJ) pathway were identified. To better understand how malaria parasites repair DSBs and maintain genome integrity, we modified the yeast I-SceI endonuclease system to generate inducible, site-specific DSBs within the parasite's genome. Analysis of repaired genomic DNA showed that parasites possess both a typical HR pathway resulting in gene conversion events as well as an end joining (EJ) pathway for repair of DSBs when no homologous sequence is available. The products of EJ were limited in number and identical products were observed in multiple independent experiments. The repair junctions frequently contained short insertions also found in the surrounding sequences, suggesting the possibility of a templated repair process. We propose that an alternative end-joining pathway rather than C-NHEJ, serves as a primary method for repairing DSBs in malaria parasites.

  4. 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

    . 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...... female development and that the csd gene exclusively processes the heterozygous state. Fem activity is also required to maintain the female determined pathway throughout development, which we show by mosaic structures in fem-repressed intersexuals. We use expression of Fem protein in males to demonstrate...

  5. Maintaining postreproductive health: A care pathway from the European Menopause and Andropause Society (EMAS).

    Science.gov (United States)

    Armeni, Eleni; Lambrinoudaki, Irene; Ceausu, Iuliana; Depypere, Herman; Mueck, Alfred; Pérez-López, Faustino R; Schouw, Yvonne T van der; Senturk, Levent M; Simoncini, Tommaso; Stevenson, John C; Stute, Petra; Rees, Margaret

    2016-07-01

    This position statement from the European Menopause and Andropause Society (EMAS) provides a care pathway for the maintenance of women's health during and after the menopause. It is designed for use by all those involved in women's health. It covers assessment, screening for diseases in later life, treatment and follow-up. Strategies need to be optimised to maintain postreproductive health, in part because of increased longevity. They encompass optimising diet and lifestyle, menopausal hormone therapy and non-estrogen-based treatment options for climacteric symptoms and skeletal conservation, personalised to individual needs.

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

    Science.gov (United States)

    Gempe, Tanja; Hasselmann, Martin; Schiøtt, Morten; Hause, Gerd; Otte, Marianne; Beye, Martin

    2009-10-01

    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 female development and that the csd gene exclusively processes the heterozygous state. Fem activity is also required to maintain the female determined pathway throughout development, which we show by mosaic structures in fem-repressed intersexuals. We use expression of Fem protein in males to demonstrate that the female maintenance mechanism is controlled by a positive feedback splicing loop in which Fem proteins mediate their own synthesis by directing female fem mRNA splicing. The csd gene is only necessary to induce this positive feedback loop in early embryogenesis by directing splicing of fem mRNAs. Finally, fem also controls the splicing of Am-doublesex transcripts encoding conserved male- and female-specific transcription factors involved in sexual differentiation. Our findings reveal how the sex determination process is realized in honeybees differing from Drosophila melanogaster.

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

    Directory of Open Access Journals (Sweden)

    Tanja Gempe

    2009-10-01

    Full Text Available 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 female development and that the csd gene exclusively processes the heterozygous state. Fem activity is also required to maintain the female determined pathway throughout development, which we show by mosaic structures in fem-repressed intersexuals. We use expression of Fem protein in males to demonstrate that the female maintenance mechanism is controlled by a positive feedback splicing loop in which Fem proteins mediate their own synthesis by directing female fem mRNA splicing. The csd gene is only necessary to induce this positive feedback loop in early embryogenesis by directing splicing of fem mRNAs. Finally, fem also controls the splicing of Am-doublesex transcripts encoding conserved male- and female-specific transcription factors involved in sexual differentiation. Our findings reveal how the sex determination process is realized in honeybees differing from Drosophila melanogaster.

  8. Combinatory action of VEGFR2 and MAP kinase pathways maintains endothelial-cell integrity

    Institute of Scientific and Technical Information of China (English)

    Hanbing Zhong; Danyang Wang; Nan Wang; Yesenia Rios; Haigen Huang; Song Li; Xinrong Wu; Shuo Lin

    2011-01-01

    Blood vessels normally maintain stereotyped lumen diameters and their stable structures are crucial for vascular function. However, very little is known about the molecular mechanisms controlling the maintenance of vessel diameters and the integrity of endothelial cells. We investigated this issue in zebrafish embryos by a chemical genetics approach. Small molecule libraries were screened using live Tg(kdrl:GRCFP)zn1 transgenic embryos in which endothelial cells are specifically labeled with GFP. By analyzing the effects of compounds on the morphology and function of embryonic blood vessels after lumen formation, PP1, a putative Src kinase inhibitor, was identified as capable of specifically reducing vascular lumen size by interrupting endothelial-cell integrity. The inhibitory effect is not due to Src or general VEGF signaling inhibition because another Src inhibitor and Src morpholino as well as several VEGFR inhibitors failed to produce a similar phenotype. After profiling a panel of 22 representative mammalian kinases and surveying published data, we selected a few possible new candidates. Combinational analysis of these candidate kinase inhibitors established that PP1 induced endothelial collapse by inhibiting both the VEGFR2 and MAP kinase pathways. More importantly, combinatory use of two clinically approved drugs Dasatinib and Sunitinib produced the same phenotype. This is the first study to elucidate the pathways controlling maintenance of endothelial integrity using a chemical genetics approach, indicating that endothelial integrity is controlled by the combined action of the VEGFR2 and MAP kinase pathways. Our results also suggest the possible side effect of the combination of two anticancer drugs on the circulatory system.

  9. The Notch Pathway Is Important in Maintaining the Cancer Stem Cell Population in Pancreatic Cancer

    OpenAIRE

    Abel, Ethan V.; Kim, Edward J.; Jingjiang Wu; Mark Hynes; Filip Bednar; Erica Proctor; Lidong Wang; Dziubinski, Michele L; Simeone, Diane M.

    2014-01-01

    Background Pancreatic cancer stem cells (CSCs) represent a small subpopulation of pancreatic cancer cells that have the capacity to initiate and propagate tumor formation. However, the mechanisms by which pancreatic CSCs are maintained are not well understood or characterized. Methods Expression of Notch receptors, ligands, and Notch signaling target genes was quantitated in the CSC and non-CSC populations from 8 primary human pancreatic xenografts. A gamma secretase inhibitor (GSI) that inhi...

  10. Malaria parasites utilize both homologous recombination and alternative end joining pathways to maintain genome integrity

    OpenAIRE

    2013-01-01

    Malaria parasites replicate asexually within their mammalian hosts as haploid cells and are subject to DNA damage from the immune response and chemotherapeutic agents that can significantly disrupt genomic integrity. Examination of the annotated genome of the parasite Plasmodium falciparum identified genes encoding core proteins required for the homologous recombination (HR) pathway for repairing DNA double-strand breaks (DSBs), but surprisingly none of the components of the canonical non-hom...

  11. 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.

  12. Current advances in DNA repair: regulation of enzymes and pathways involved in maintaining genomic stability.

    Science.gov (United States)

    Neher, Tracy M; Turchi, John J

    2011-06-15

    Novel discoveries in the DNA repair field have lead to continuous and rapid advancement of our understanding of not only DNA repair but also DNA replication and recombination. Research in the field transcends numerous areas of biology, biochemistry, physiology, and medicine, making significant connections across these broad areas of study. From early studies conducted in bacterial systems to current analyses in eukaryotic systems and human disease, the innovative research into the mechanisms of repair machines and the consequences of ineffective DNA repair has impacted a wide scientific community. This Forum contains a select mix of primary research articles in addition to a number of timely reviews covering a subset of DNA repair pathways where recent advances and novel discoveries are improving our understanding of DNA repair, its regulation, and implications to human disease.

  13. Sun leaves up-regulate the photorespiratory pathway to maintain a high rate of CO2 assimilation in tobacco.

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    Huang, Wei; Zhang, Shi-Bao; Hu, Hong

    2014-01-01

    The greater rate of CO2 assimilation (A n) in sun-grown tobacco leaves leads to lower intercellular and chloroplast CO2 concentrations and, thus, a higher rate of oxygenation of ribulose-1,5-bisphosphate (RuBP) than in shade-grown leaves. Impairment of the photorespiratory pathway suppresses photosynthetic CO2 assimilation. Here, we hypothesized that sun leaves can up-regulate photorespiratory pathway to enhance the A n in tobacco. To test this hypothesis, we examined the responses of photosynthetic electron flow (J T) and CO2 assimilation to incident light intensity and intercellular CO2 concentration (C i) in leaves of 'k326' tobacco plants grown at 95% sunlight (sun plants) or 28% sunlight (shade plants). The sun leaves had higher photosynthetic capacity and electron flow devoted to RuBP carboxylation (J C) than the shade leaves. When exposed to high light, the higher Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase) content and lower C i in the sun leaves led to greater electron flow devoted to RuBP oxygenation (J O). The J O/J C ratio was significantly higher in the sun leaves than in the shade leaves under strong illumination. As estimated from CO2-response curves, the maximum J O was linearly correlated with the estimated Rubisco content. Based on light-response curves, the light-saturated J O was linearly correlated with light-saturated J T and light-saturated photosynthesis. These findings indicate that enhancement of the photorespiratory pathway is an important strategy by which sun plants maintain a high A n.

  14. HMGB1-induced autophagy: a new pathway to maintain Treg function during chronic hepatitis B virus infection.

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    Cheng, Li-Sha; Li, Jing; Liu, Yun; Wang, Fu-Ping; Wang, Si-Qi; She, Wei-Min; Wu, Sheng-di; Qi, Xiao-Long; Zhou, Yong-Ping; Jiang, Wei

    2017-03-01

    High-mobility group box-1 (HMGB1) protein, as one of the well-known damage-associated molecular pattern molecules (DAMPs), is enriched in chronic hepatitis B virus (HBV) infection and has a context-dependent role in autophagy, a highly conserved self-digestive process in response to environmental stress. Recent mouse studies indicate that autophagy is highly active in regulatory T (Treg)-cells. In the present study, we evaluated spontaneous and induced autophagy of peripheral Treg cells from 98 patients with chronic hepatitis B (CHB), by measuring levels of lipidated form of microtubule-associated light chain 3 (LC3-II, marker for closed autophagosomes) and observing autophagic vacuoles (AV) with transmission electron microscope. No significant difference was found in spontaneous autophagy of either Treg or CD4(+) naive cells when comparing CHB patients with healthy subjects, apart from CHB-Treg showed significantly higher autophagic activity after activation by anti-CD3-CD28 beads. Besides, incubation of CHB-Treg cells with CHB-serum greatly maintained their autophagic behaviour, which could be significantly diminished by blocking HMGB1 with the neutralizing antibody. Further, we characterized time- and dose-dependent effects by recombinant HMGB1 protein on autophagy of CHB-Treg cells. We also documented a significant up-regulation of HMGB1 and its receptors [toll-like receptor (TLR4), receptor for advanced glycation end-product (RAGE)] in both peripheral and intra-hepatic microenvironments of CHB patients. Moreover, the RAGE-extracellular regulated protein kinases (ERK) axis and rapamycin-sensitive components of mammalian target of rapamycin (mTOR) pathways were demonstrated in vitro to be involved in HMGB1-induced autophagy of Treg cells. Additionally, HMGB1-induced autophagy could maintain cell survival and functional stability of CHB-Treg cells. Our findings could open new perspectives in developing therapeutic strategies to activate specific anti

  15. ALDH maintains the stemness of lung adenoma stem cells by suppressing the Notch/CDK2/CCNE pathway.

    Directory of Open Access Journals (Sweden)

    Zhongjun Li

    Full Text Available To evaluate the expression of ALDH1A1 in lung adenoma stem cells (LASCs and maintenance of their stemness through the Notch pathway.LASCs (A549s were isolated from lung adenoma cells (A549 and identified by their coexpression of CD133 and CD326 and their capacity formulti-directional differentiation. Expression of ALDH1A1 in A549 and A549s cells were evaluated by Real-time PCR. Effects of ALDH1A1 upregulation in A549 cells and its downregulation in A549s cells on the clonogenicity and cell cycle were assessed by colony-forming unit assay. Moreover, the effects of ALDH1A1 on the Notch pathway, and thus on the cell cycle, were studied.A549s cells were successfully isolated and identified.ALDH1A1expression was significantly higher in A549s than in A549 cells. Clonogenicity was significantly decreased in A549s cells treated with ALDH1A1 siRNA. Duration of the G1 stage of the cell cycle increased after ALDH1A1 was overexpressed, or decreased with ALDH1A1 siRNA. ALDH1A1, Notch1, -2, and -3, CDK2, and CCNE1 expression levels were higher in A549s cells than in A549 cells. Expression of Notch1, -2, and -3, CDK2, and CCNE1 was significantly decreased by upregulation of ALDH1A1 in A549 cells, but increased by its interruption in A549s cells. When Notch3 or CDK2 expression was downregulated, the expression levels of ALDH1A1, Notch1, -2, and -3, CDK2, and CCNE1 were reduced in all cell types.ALDH1A1 expression improved clonogenicity and inhibited the cell cycle, maintaining the stemness of the A549s cells; this may involve suppression of the Notch/CDK2/Cyclin pathway.

  16. n-Butylidenephthalide (BP) maintains stem cell pluripotency by activating Jak2/Stat3 pathway and increases the efficiency of iPS cells generation.

    Science.gov (United States)

    Liu, Shih-Ping; Harn, Horng-Jyh; Chien, Ying-Jiun; Chang, Cheng-Hsuan; Hsu, Chien-Yu; Fu, Ru-Huei; Huang, Yu-Chuen; Chen, Shih-Yin; Shyu, Woei-Cherng; Lin, Shinn-Zong

    2012-01-01

    In 2006, induced pluripotent stem (iPS) cells were generated from somatic cells by introducing Oct4, Sox2, c-Myc and Klf4. The original process was inefficient; maintaining the pluripotency of embryonic stem (ES) and iPS cell cultures required an expensive reagent-leukemia induced factor (LIF). Our goal is to find a pure compound that not only maintains ES and iPS cell pluripotency, but also increases iPS cell generation efficiency. From 15 candidate compounds we determined that 10 µg/ml n-Butylidenephthalide (BP), an Angelica sinensis extract, triggers the up-regulation of Oct4 and Sox2 gene expression levels in MEF cells. We used ES and iPS cells treated with different concentrations of BP to test its usefulness for maintaining stem cell pluripotency. Results indicate higher expression levels of several stem cell markers in BP-treated ES and iPS cells compared to controls that did not contain LIF, including alkaline phosphatase, SSEA1, and Nanog. Embryoid body formation and differentiation results confirm that BP containing medium culture was capable of maintaining ES cell pluripotency after six time passage. Microarray analysis data identified PPAR, ECM, and Jak-Stat signaling as the top three deregulated pathways. We subsequently determined that phosphorylated Jak2 and phosphorylated Stat3 protein levels increased following BP treatment and suppressed with the Jak2 inhibitor, AG490. The gene expression levels of cytokines associated with the Jak2-Stat3 pathway were also up-regulated. Last, we used pou5f1-GFP MEF cells to test iPS generation efficiency following BP treatment. Our data demonstrate the ability of BP to maintain stem cell pluripotency via the Jak2-Stat3 pathway by inducing cytokine expression levels, at the same time improving iPS generation efficiency.

  17. Intrinsic and extrinsic mechanisms contribute to maintain the JAK/STAT pathway aberrantly activated in T-type large granular lymphocyte leukemia.

    Science.gov (United States)

    Teramo, Antonella; Gattazzo, Cristina; Passeri, Francesca; Lico, Albana; Tasca, Giulia; Cabrelle, Anna; Martini, Veronica; Frezzato, Federica; Trimarco, Valentina; Ave, Elisa; Boscaro, Elisa; Piazza, Francesco; Facco, Monica; Trentin, Livio; Semenzato, Gianpietro; Zambello, Renato

    2013-05-09

    The JAK/STAT pathway is altered in T-cell large granular lymphocytic leukemia. In all patients, leukemic LGLs display upregulation of phosphorylated STAT3 (P-STAT3) that activates expression of many antiapoptotic genes. To investigate the mechanisms maintaining STAT3 aberrantly phosphorylated using transcriptional protein and functional assays, we analyzed interleukin (IL)-6 and suppressor of cytokine signaling-3 (SOCS3), 2 key factors of the JAK/STAT pathway that induce and inhibit STAT3 activation, respectively. We showed that IL-6 was highly expressed and released by the patients' peripheral blood LGL-depleted population, accounting for a trans-signaling process. By neutralizing IL-6 or its specific receptor with specific antibodies, a significant reduction of P-STAT3 levels and, consequently, LGL survival was demonstrated. In addition, we found that SOCS3 was down-modulated in LGL and unresponsive to IL-6 stimulation. By treating neoplastic LGLs with a demethylating agent, IL-6-mediated SOCS3 expression was restored with consequent P-STAT3 and myeloid cell leukemia-1 down-modulation. Methylation in the SOCS3 promoter was not detectable, suggesting that an epigenetic inhibition mechanism occurs at a different site. Our data indicate that loss of the inhibitor SOCS3 cooperates with IL-6 to maintain JAK/STAT pathway activation, thus contributing to leukemic LGL survival, and suggest a role of demethylating agents in the treatment of this disorder.

  18. Dopamine D1 Receptor-Mediated Transmission Maintains Information Flow Through the Cortico-Striato-Entopeduncular Direct Pathway to Release Movements.

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    Chiken, Satomi; Sato, Asako; Ohta, Chikara; Kurokawa, Makoto; Arai, Satoshi; Maeshima, Jun; Sunayama-Morita, Tomoko; Sasaoka, Toshikuni; Nambu, Atsushi

    2015-12-01

    In the basal ganglia (BG), dopamine plays a pivotal role in motor control, and dopamine deficiency results in severe motor dysfunctions as seen in Parkinson's disease. According to the well-accepted model of the BG, dopamine activates striatal direct pathway neurons that directly project to the output nuclei of the BG through D1 receptors (D1Rs), whereas dopamine inhibits striatal indirect pathway neurons that project to the external pallidum (GPe) through D2 receptors. To clarify the exact role of dopaminergic transmission via D1Rs in vivo, we developed novel D1R knockdown mice in which D1Rs can be conditionally and reversibly regulated. Suppression of D1R expression by doxycycline treatment decreased spontaneous motor activity and impaired motor ability in the mice. Neuronal activity in the entopeduncular nucleus (EPN), one of the output nuclei of the rodent BG, was recorded in awake conditions to examine the mechanism of motor deficits. Cortically evoked inhibition in the EPN mediated by the cortico-striato-EPN direct pathway was mostly lost during suppression of D1R expression, whereas spontaneous firing rates and patterns remained unchanged. On the other hand, GPe activity changed little. These results suggest that D1R-mediated dopaminergic transmission maintains the information flow through the direct pathway to appropriately release motor actions.

  19. 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.

  20. Fish-specific duplicated dmrt2b contributes to a divergent function through Hedgehog pathway and maintains left-right asymmetry establishment function.

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    Sha Liu

    Full Text Available Gene duplication is thought to provide raw material for functional divergence and innovation. Fish-specific dmrt2b has been identified as a duplicated gene of the dmrt2a/terra in fish genomes, but its function has remained unclear. Here we reveal that Dmrt2b knockdown zebrafish embryos display a downward tail curvature and have U-shaped somites. Then, we demonstrate that Dmrt2b contributes to a divergent function in somitogenesis through Hedgehog pathway, because Dmrt2b knockdown reduces target gene expression of Hedgehog signaling, and also impairs slow muscle development and neural tube patterning through Hedgehog signaling. Moreover, the Dmrt2b morphants display defects in heart and visceral organ asymmetry, and, some lateral-plate mesoderm (LPM markers expressed in left side are randomized. Together, these data indicate that fish-specific duplicated dmrt2b contributes to a divergent function in somitogenesis through Hedgehog pathway and maintains the common function for left-right asymmetry establishment.

  1. 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

  2. The expression pattern of the Picea glauca Defensin 1 promoter is maintained in Arabidopsis thaliana, indicating the conservation of signalling pathways between angiosperms and gymnosperms.

    Science.gov (United States)

    Germain, Hugo; Lachance, Denis; Pelletier, Gervais; Fossdal, Carl Gunnar; Solheim, Halvor; Séguin, Armand

    2012-01-01

    A 1149 bp genomic fragment corresponding to the 5' non-coding region of the PgD1 (Picea glauca Defensin 1) gene was cloned, characterized, and compared with all Arabidopsis thaliana defensin promoters. The cloned fragment was found to contain several motifs specific to defence or hormonal response, including a motif involved in the methyl jasmonate reponse, a fungal elicitor responsive element, and TC-rich repeat cis-acting element involved in defence and stress responsiveness. A functional analysis of the PgD1 promoter was performed using the uidA (GUS) reporter system in stably transformed Arabidopsis and white spruce plants. The PgD1 promoter was responsive to jasmonic acid (JA), to infection by fungus and to wounding. In transgenic spruce embryos, GUS staining was clearly restricted to the shoot apical meristem. In Arabidopsis, faint GUS coloration was observed in leaves and flowers and a strong blue colour was observed in guard cells and trichomes. Transgenic Arabidopsis plants expressing the PgD1::GUS construct were also infiltrated with the hemibiotrophic pathogen Pseudomonas syringae pv. tomato DC3000. It caused a suppression of defensin expression probably resulting from the antagonistic relationship between the pathogen-stimulated salicylic acid pathway and the jasmonic acid pathway. It is therefore concluded that the PgD1 promoter fragment cloned appears to contain most if not all the elements for proper PgD1 expression and that these elements are also recognized in Arabidopsis despite the phylogenetic and evolutionary differences that separates them.

  3. Maintaining Learners’Motivation

    Institute of Scientific and Technical Information of China (English)

    SI Zi-han

    2015-01-01

    Foreign language learning is a complex process and its success is determined by a variety of factors. The prime one of them is motivation ,which, as everyone knows, could be controlled by external forces so as to be taken advantage of. Motivation could prompt the learner to have his own learning goals and let him finish his learning task autonomously. All of that shows the im⁃portance of maintaining learners’motivation. This paper will demonstrate not only the definition and the types of motivation, but al⁃so the methods that could be used to stimulate and maintain the motivation.

  4. Economy Maintains Good Health

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    China’s national economy has maintained rapid even growth in the first half of 2007, according to Xie Fuzhan, Commissioner of the National Bureau of Statistics. He was referring to major economic indicators of the January-June period that reveal that Chi

  5. Nuclear power plant maintainability.

    Science.gov (United States)

    Seminara, J L; Parsons, S O

    1982-09-01

    In the mid-1970s a general awareness of human factors engineering deficiencies associated with power plant control rooms took shape and the Electric Power Research Institute (EPRI) awarded the Lockheed Corporation a contract to review the human factors aspects of five representative operational control rooms and their associated simulators. This investigation revealed a host of major and minor deficiencies that assumed unforeseen dimensions in the post- Three Mile Island accident period. In the course of examining operational problems (Seminara et al, 1976) and subsequently the methods for overcoming such problems (Seminara et al, 1979, 1980) indications surfaced that power plants were far from ideal in meeting the needs of maintenance personnel. Accordingly, EPRI sponsored an investigation of the human factors aspects of power plant maintainability (Seminara, 1981). This paper provides an overview of the maintainability problems and issues encountered in the course of reviewing five nuclear power plants.

  6. Direct bonded space maintainers.

    Science.gov (United States)

    Santos, V L; Almeida, M A; Mello, H S; Keith, O

    1993-01-01

    The aim of this study was to evaluate clinically a bonded space maintainer, which would reduce chair-side time and cost. Sixty appliances were fabricated from 0.7 mm stainless steel round wire and bonded using light-cured composite to the two teeth adjacent to the site of extraction of a posterior primary tooth. Twenty males and sixteen females (age range 5-9-years-old) were selected from the Pedodontic clinic of the State University of Rio de Janeiro. The sixty space maintainers were divided into two groups according to the site in which they were placed: a) absent first primary molar and b) absent second primary molar. Impressions and study models were obtained prior to and 6 months after bonding the appliances. During this period only 8.3% of failures were observed, most of them from occlusal or facial trauma. Student t-test did not show statistically significant alterations in the sizes of the maintained spaces during the trial period.

  7. Oxidized ATM promotes abnormal proliferation of breast CAFs through maintaining intracellular redox homeostasis and activating the PI3K-AKT, MEK-ERK, and Wnt-β-catenin signaling pathways.

    Science.gov (United States)

    Tang, Shifu; Hou, Yixuan; Zhang, Hailong; Tu, Gang; Yang, Li; Sun, Yifan; Lang, Lei; Tang, Xi; Du, Yan-E; Zhou, Mingli; Yu, Tenghua; Xu, Liyun; Wen, Siyang; Liu, Chunming; Liu, Manran

    2015-01-01

    Abnormal proliferation is one characteristic of cancer-associated fibroblasts (CAFs), which play a key role in tumorigenesis and tumor progression. Oxidative stress (OS) is the root cause of CAFs abnormal proliferation. ATM (ataxia-telangiectasia mutated protein kinase), an important redox sensor, is involved in DNA damage response and cellular homeostasis. Whether and how oxidized ATM regulating CAFs proliferation remains unclear. In this study, we show that there is a high level of oxidized ATM in breast CAFs in the absence of double-strand breaks (DSBs) and that oxidized ATM plays a critical role in CAFs proliferation. The effect of oxidized ATM on CAFs proliferation is mediated by its regulation of cellular redox balance and the activity of the ERK, PI3K-AKT, and Wnt signaling pathways. Treating cells with antioxidant N-acetyl-cysteine (NAC) partially rescues the proliferation defect of the breast CAFs caused by ATM deficiency. Administrating cells with individual or a combination of specific inhibitors of the ERK, PI3K-AKT, and Wnt signaling pathways mimics the effect of ATM deficiency on breast CAF proliferation. This is mainly ascribed to the β-catenin suppression and down-regulation of c-Myc, thus further leading to the decreased cyclinD1, cyclinE, and E2F1 expression and the enhanced p21(Cip1) level. Our results reveal an important role of oxidized ATM in the regulation of the abnormal proliferation of breast CAFs. Oxidized ATM could serve as a potential target for treating breast cancer.

  8. 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.

  9. Modified bonded bridge space maintainer.

    Science.gov (United States)

    Liegeois, F; Limme, M

    1999-01-01

    The premature loss of primary teeth can create the need for space maintenance and restoration of function. This article presents a fixed bonded space maintainer, which allows space to be maintained with economy of dental tissues.

  10. Assessing optimal software architecture maintainability

    NARCIS (Netherlands)

    Bosch, Jan; Bengtsson, P.O.; Smedinga, Rein; Sousa, P; Ebert, J

    2000-01-01

    Over the last decade, several authors have studied the maintainability of software architectures. In particular, the assessment of maintainability has received attention. However, even when one has a quantitative assessment of the maintainability of a software architecture, one still does not have a

  11. Marshal: Maintaining Evolving Models Project

    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...

  12. Simple fixed functional space maintainer.

    Science.gov (United States)

    Goenka, Puneet; Sarawgi, Aditi; Marwah, Nikhil; Gumber, Parvind; Dutta, Samir

    2014-01-01

    Premature loss of a primary tooth is one of the most common etiology for malocclusion. Space maintainers are employed to prevent this complication. In anterior region, esthetics is an important concern along with function and space management. Fiber-reinforced composite (FRC) retained space maintainer solves all these purposes ef ficiently and ef fectively. In addition, the technique is simple and the appliance is very comfortable inside the oral cavity. Here is a case of premature loss of anterior primary tooth which was replaced by FRC retained esthetic functional space maintainer. The appliance was found to be functioning satisfactorily inside the oral cavity till the last visit (1 Year). How to cite this article: Goenka P, Sarawgi A, Marwah N, Gumber P, Dutta S. Simple Fixed Functional Space Maintainer. Int J Clin Pediatr Dent 2014;7(3):225-228.

  13. A Novel Polarization Maintaining Fiber

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    It introduces a novel elliptical jacket polarization maintaining fiber, whose SAP is like numeral "1". One preform can be drawn over 8km. Fiber's performances show that it is fit for fiber gyroscope and other sensors.

  14. A Novel Polarization Maintaining Fiber

    Institute of Scientific and Technical Information of China (English)

    Benjamin Xue

    2003-01-01

    It introduces a novel elliptical jacket polarization maintaining fiber, whose SAP is like numeral "1" One preform can be drawn over 8km. Fiber's performances show that it is fit for fiber gyroscope and other sensors.

  15. Simple Fixed Functional Space Maintainer

    OpenAIRE

    Goenka, Puneet; Sarawgi, Aditi; Marwah, Nikhil; Gumber, Parvind; Dutta, Samir

    2015-01-01

    ABSTRACT% Premature loss of a primary tooth is one of the most common etiology for malocclusion. Space maintainers are employed to prevent this complication. In anterior region, esthetics is an important concern along with function and space management. Fiber-reinforced composite (FRC) retained space maintainer solves all these purposes ef ficiently and ef fectively. In addition, the technique is simple and the appliance is very comfortable inside the oral cavity. Here is a case of premature ...

  16. Bulkloading and Maintaining XML Documents

    NARCIS (Netherlands)

    Schmidt, A.R.; Kersten, M.L.

    2002-01-01

    The popularity of XML as a exchange and storage format brings about massive amounts of documents to be stored, maintained and analyzed -- a challenge that traditionally has been tackled with Database Management Systems (DBMS). To open up the content of XML documents to analysis with declarative quer

  17. How homologous recombination maintains telomere integrity.

    Science.gov (United States)

    Tacconi, Eliana M C; Tarsounas, Madalena

    2015-06-01

    Telomeres protect the ends of linear chromosomes against loss of genetic information and inappropriate processing as damaged DNA and are therefore crucial to the maintenance of chromosome integrity. In addition to providing a pathway for genome-wide DNA repair, homologous recombination (HR) plays a key role in telomere replication and capping. Consistent with this, the genomic instability characteristic of HR-deficient cells and tumours is driven in part by telomere dysfunction. Here, we discuss the mechanisms by which HR modulates the response to intrinsic cellular challenges that arise during telomere replication, as well as its impact on the assembly of telomere protective structures. How normal and tumour cells differ in their ability to maintain telomeres is deeply relevant to the search for treatments that would selectively eliminate cells whose capacity for HR-mediated repair has been compromised.

  18. 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.

  19. NMG documentation, part 3: maintainer`s guide

    Energy Technology Data Exchange (ETDEWEB)

    Fritsch, F.N.; Dickinson, R.P. Jr.

    1996-07-01

    This is the third of a three-part report documenting NMG, the Numerical Mathematics Guide. Part I is aimed at the user of the systenL It contains an introduction, with an out- line of the complete report, and Chapter 1, User`s Point of View. Part II is aimed at the programmer and contains Chapter 2, How It Works. Part III is aimed at the maintainer of NMG and contains Chapter 3, Maintenance, and Chapter 4, Validation. Because its contents are so specialized, Part III will receive only limited distribution. Note that each chapter has its own page numbering and table of contents.

  20. Control Inflation while Maintain Growth

    Institute of Scientific and Technical Information of China (English)

    Yang Junsheng

    2008-01-01

    @@ Dragged by the U.S.subprime crisis and the soaring oil price, the global economy is slowing down,causing problems to China, the country which has continuously achieved miraculous economic growth.Apart from the accumulation of high inflation and risks of overheated economy, China is attacked by serious natural disasters ever since the beginning of 2008,including the snow disaster, the earthquake and the flood.It is obviously that China's priority now is to bring inflation under control so as to maintain the stable growth of economy.

  1. 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.

  2. Software Code Maintainability : A Literature Review

    Directory of Open Access Journals (Sweden)

    Berna Seref

    2016-05-01

    Full Text Available Software Maintainability is one of the most important quality attributes. To increase quality of a software, to manage software more efficient and to decrease cost of the software, maintainability, maintainability estimation and maintainability evaluation models have been proposed. However, the practical use of these models in software engineering tools and practice remained little due to their limitations or threats to validity. In this paper, results of our Literature Review about maintainability models, maintainability metrics and maintainability estimation are presented. Aim of this paper is providing a baseline for further searches and serving the needs of developers and customers.

  3. 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)

  4. 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.

  5. 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...

  6. Sources and Information: Maintaining Institutional Integrity.

    Science.gov (United States)

    Palmer, Jim; Zwemer, Diane

    1985-01-01

    Provides an annotated bibliography of ERIC materials dealing with the community college mission, educational quality, maintaining an effective faculty, effects and management of retrenchment, and the state role in community college education. (LAL)

  7. Space Maintainers in Dentistry: Past to Present

    OpenAIRE

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

    2013-01-01

    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 e...

  8. Molecular pathways

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine Terra

    2014-01-01

    that 45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection...... of fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases. Clin Cancer Res; 20(14); 3637-43. ©2014 AACR....

  9. 基于Keap1-Nrf2-ARE通路维持黏膜屏障完整探讨舒胃汤防治胃溃疡的研究%Study on Shuwei decoction prevention and treatment of gastric ulcer by regulating Keap1-Nrf2-ARE signal pathway to maintain the integrity of gastric mucosa

    Institute of Scientific and Technical Information of China (English)

    张琪; 梁海业; 陈世新; 张涛

    2016-01-01

    Objective It is to explore the prevention and treatment mechanism of Shuwei decoction on gastric ulcer by ob-serving the changes of Keap1-Nrf2-ARE signal pathway and the ultra structural in gastric mucosa before and after treat-ment.Methods It was a history control design trial.Thirty patients who conformed to diagnostic criteria, inclusion criteria and exclusion criteria were treated with Shuwei decoction for 6 weeks.The gastric mucosa ultra structure and apoptosis of epithelial cells were observed by electron microscope.The Keap1, Nrf2 ARE gene expression was detected by the fluorescence quantita-tive PCR.The expression of occludin and ZO-1 protein was detected by immunohistochemistry.Results Before treatment, gastric ulcer patients under electron microscope visible gastric mucosa epithelial microvillus sparse even shedding vanished, in-tercellular composite connections were loose or disappeared, nuclear pyknosis, nuclear week gaped, heterochromatin block distribution under nuclear membrane; mitochondrial swelling became larger, cristae fractured; rough endoplasmic reticulum expanded, cells were in the necrotic phase, there were a large number of cells autophagy.After treatment, gastric ulcer pa-tients under electron microscope visible gastric mucosa epithelial cell volume became small, nuclear chromatin margination, nuclear pyknosis, nuclear membrane broken nuclear fragmentation, organelles marked dilation of the swelling, fragmentation, vacuolization, formation of apoptotic bodies, autophagy was also found.After treatment,the levels of Keap1, Nrf2, ARE ex-pressions in gastric mucosa tissue, the positive distribution of ZO-1 and Occulidin protein were significantly higher than that before treatment(P<0.05).Conclusion Shuwei decoction exerts a distinct effect on curing gastric ulcer by regulating Keap1-Nrf2-ARE pathway, reducing oxidative stress injury, up-regulating the expression of ZO-1 and occludin protein.%目的 通过观察胃溃疡患者治疗前后Kelch

  10. Maintaining an Operational Flight Program (OFP)

    Science.gov (United States)

    1991-10-01

    Monitor And Control ( PMAC ), as an example, allows a maintainer to interact with his running OFP. Other specialized environment testing might indicate...paths on the F-15’s Central Computer. Processor Peculiar Tests Specialized testing for unique features of ECSs. Programmable Monitor And Control ( PMAC

  11. Maintaining Hope in the Face of Evil.

    Science.gov (United States)

    Miller, Geri

    2002-01-01

    P. G. Zimbardo (2001) and M. E. P. Seligman (in an interview with S. Carpenter, 2001) discuss evil and hope in response to the September 11, 2001, disaster. The implications for counseling are presented with an emphasis on how counselors can maintain hope for themselves and their clients in the face of evil. (Author)

  12. Maintaining strategic momentum : The CEO's agenda

    NARCIS (Netherlands)

    F.M. Maljers (Floris); C.W.F. Baden-Fuller (Charles); F.A.J. van den Bosch (Frans)

    1996-01-01

    textabstractThe question of how the CEO of a large complex organization maintain strategic momentum is addressed. This represents a great challenge when there are no obvious external threats, and no obvious reasons for having a concerted action. The inherent tensions which exist between stability an

  13. The randomized complexity of maintaining the minimum

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Chaudhuri, Shiva; Radhakrishnan, Jaikumar

    1996-01-01

    The complexity of maintaining a set under the operations Insert, Delete and FindMin is considered. In the comparison model it is shown that any randomized algorithm with expected amortized cost t comparisons per Insert and Delete has expected cost at least n/(e22t)-1 comparisons for FindMin. If F...

  14. 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...

  15. Treating Problem Behaviors Maintained by Negative Reinforcement.

    Science.gov (United States)

    Cipani, Ennio; Spooner, Fred

    1997-01-01

    Identifies four treatment techniques that may be applied when problem behavior is maintained by negative reinforcement: (1) functional communication training; (2) behavioral momentum; (3) differential reinforcement or an alternative escape behavior; and (4) errorless learning. Each of the techniques is defined, and applications and guidelines for…

  16. Maintaining ideal body weight counseling sessions

    Energy Technology Data Exchange (ETDEWEB)

    Brammer, S.H.

    1980-10-09

    The purpose of this program is to provide employees with the motivation, knowledge and skills necessary to maintain ideal body weight throughout life. The target audience for this program, which is conducted in an industrial setting, is the employee 40 years of age or younger who is at or near his/her ideal body weight.

  17. 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 ...

  18. How to Maintain a Social Reinforcement Program.

    Science.gov (United States)

    Arkin, Ronald; And Others

    This manual presents methodology for maintaining a social reinforcement system after supervisors in industrial environments have been trained in behavior modification theory and application. The maintenance manual discusses monitoring, evaluation, and integration of a company's employee performance system with the social reinforcement system…

  19. Designing pathways

    DEFF Research Database (Denmark)

    Scheuer, John Damm

    2010-01-01

    The theoretical background in this chapter is organizational studies and especially theories about design and design processes in organizations. The concept of design is defined as a particular kind of work aimed at making arrangements in order to change existing situations into desired ones....... The illustrative case example is the introduction of clinical pathways in a psychiatric department. The contribution to a general core of design research is the development of the concept of design work and a critical discussion of the role of technological rules in design work....

  20. A synthetic biochemistry molecular purge valve module that maintains redox balance.

    Science.gov (United States)

    Opgenorth, Paul H; Korman, Tyler P; Bowie, James U

    2014-06-17

    The greatest potential environmental benefit of metabolic engineering would be the production of high-volume commodity chemicals, such as biofuels. Yet, the high yields required for the economic viability of low-value chemicals is particularly hard to achieve in microbes owing to the myriad competing biochemical pathways. An alternative approach, which we call synthetic biochemistry, is to eliminate the organism by constructing biochemical pathways in vitro. Viable synthetic biochemistry, however, will require simple methods to replace the cellular circuitry that maintains cofactor balance. Here we design a simple purge valve module for maintaining NADP(+)/NADPH balance. We test the purge valve in the production of polyhydroxybutyryl bioplastic and isoprene--pathways where cofactor generation and utilization are unbalanced. We find that the regulatory system is highly robust to variations in cofactor levels and readily transportable. The molecular purge valve provides a step towards developing continuously operating, sustainable synthetic biochemistry systems.

  1. MOF maintains transcriptional programs regulating cellular stress response.

    Science.gov (United States)

    Sheikh, B N; Bechtel-Walz, W; Lucci, J; Karpiuk, O; Hild, I; Hartleben, B; Vornweg, J; Helmstädter, M; Sahyoun, A H; Bhardwaj, V; Stehle, T; Diehl, S; Kretz, O; Voss, A K; Thomas, T; Manke, T; Huber, T B; Akhtar, A

    2016-05-01

    MOF (MYST1, KAT8) is the major H4K16 lysine acetyltransferase (KAT) in Drosophila and mammals and is essential for embryonic development. However, little is known regarding the role of MOF in specific cell lineages. Here we analyze the differential role of MOF in proliferating and terminally differentiated tissues at steady state and under stress conditions. In proliferating cells, MOF directly binds and maintains the expression of genes required for cell cycle progression. In contrast, MOF is dispensable for terminally differentiated, postmitotic glomerular podocytes under physiological conditions. However, in response to injury, MOF is absolutely critical for podocyte maintenance in vivo. Consistently, we detect defective nuclear, endoplasmic reticulum and Golgi structures, as well as presence of multivesicular bodies in vivo in podocytes lacking Mof following injury. Undertaking genome-wide expression analysis of podocytes, we uncover several MOF-regulated pathways required for stress response. We find that MOF, along with the members of the non-specific lethal but not the male-specific lethal complex, directly binds to genes encoding the lysosome, endocytosis and vacuole pathways, which are known regulators of podocyte maintenance. Thus, our work identifies MOF as a key regulator of cellular stress response in glomerular podocytes.

  2. Operational handbook of the Bretby Maintainability Index

    Energy Technology Data Exchange (ETDEWEB)

    Rushworth, A.M.; Mason, S.; Talbot, C. (British Coal Corporation, Stanhope Bretby (United Kingdom). Technical Services and Research Executive, Ergonomics Branch)

    1994-01-01

    A substantial proportion of the injuries and costs in the mining industry, and in industry generally, occur during maintenance activities, particularly in work involving plant and machinery. A common thread linking the cause of these accidents and losses is a general deficiency in machine design, particularly the ergonomic aspects. This report concerns the Bretby Maintainability Index (BMI) which provides a comprehensive method of analysing and quantifying machinery maintainability in terms of health and safety and the financial implications associated with excessive downtime. The health and safety implications of poor machine design are discussed, as are the cost implications. The concept of the BMI is outlined and information on its application is given. Its detailed features are presented and guidance notes are provided.

  3. Maintaining Multimedia Data in a Geospatial Database

    Science.gov (United States)

    2012-09-01

    in a GIS are stored in two-dimensional space, which adds to the complexities faced in simulating a databases’ workload when the data is three...browsing, geocoding , reverse geocoding , flood risk, land information management, and toxic spill analysis. Jackpine was more in-depth than this thesis...benchmark testing. A. OVERVIEW In creating a GIS that maintains multimedia data, it is first important to note that the actual multimedia data is

  4. Maintainability Prediction and Analysis Study. Revision A

    Science.gov (United States)

    1978-07-01

    SS- 6b SECTION 1.0 INTRiODUCTION This document presents the results of a study to develop and document an improved maintainability prediction and...include operations on other RIs called out in the jth fault iscolation result . Tmujn Average time to perform the ruth corrective maintenance step for...of the study however, as the resulting time standards are used as Inputs In computing disassembly, interchange, and reassembly times for the

  5. Maintaining Wolbachia in Cell-free Medium

    OpenAIRE

    Gamston, Courtney; Rasgon, Jason

    2007-01-01

    In this video protocol, procedures are demonstrated to (1) purify Wolbachia symbionts out of cultured mosquito cells, (2) use a fluorescent assay to ascertain the viability of the purified Wolbachia and (3) maintain the now extracellular Wolbachia in cell-free medium. Purified Wolbachia remain alive in the extracellular phase but do not replicate until re-inoculated into eukaryotic cells. Extracellular Wolbachia purified in this manner will remain viable for at least a week at ...

  6. Maintaining genome stability in the nervous system.

    Science.gov (United States)

    McKinnon, Peter J

    2013-11-01

    Active maintenance of genome stability is a prerequisite for the development and function of the nervous system. The high replication index during neurogenesis and the long life of mature neurons highlight the need for efficient cellular programs to safeguard genetic fidelity. Multiple DNA damage response pathways ensure that replication stress and other types of DNA lesions, such as oxidative damage, do not affect neural homeostasis. Numerous human neurologic syndromes result from defective DNA damage signaling and compromised genome integrity. These syndromes can involve different neuropathology, which highlights the diverse maintenance roles that are required for genome stability in the nervous system. Understanding how DNA damage signaling pathways promote neural development and preserve homeostasis is essential for understanding fundamental brain function.

  7. 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.

  8. Take Control of Maintaining Your Mac

    CERN Document Server

    Kissell, Joe

    2009-01-01

    Keep your Mac running smoothly with our easy maintenance program! Regular maintenance is necessary to avoid problems and to ensure your Mac runs at peak performance, but it's hard to know what to do and when to do it. Best-selling author Joe Kissell has now applied his commonsense approach to the task of maintaining your Mac, whether you use Tiger or Leopard! Learn how to start on the right foot; what you should do daily, weekly, monthly, and yearly; and how to prepare for Mac OS X updates. Joe even explains how to monitor your Mac's health and debunks common panaceas. Read this book to lea

  9. 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. PMID:27688928

  10. Maintaining extensivity in evolutionary multiplex networks

    CERN Document Server

    Antonopoulos, Chris G

    2015-01-01

    In this Letter, we explore the role of network topology on its extensive character. We study analytically and numerically how the topology contributes to maintaining extensivity of entropy in multiplex networks, i.e. networks of subnetworks, by means of the sum of the positive Lyapunov exponents, $H_{KS}$, a quantity related to entropy. We show that extensivity relies not only on the interplay between the coupling strengths of the dynamics associated to the intra (short-range) and inter (long-range) interactions, but also on the sum of the intra-degrees of the nodes of the subnetworks. For the analytically treated networks of size $N$, if the sum of the intra-degrees (and the sum of inter-degrees) scales as $N^{\\theta+1}$, extensivity can be maintained if the intra-coupling (and the inter-coupling) strength scales as $N^{-\\theta}$, when evolution is driven by the maximization of $H_{KS}$. We then verify our analytical result by doing numerical simulations in multiplex networks formed by electrically and chemi...

  11. 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.

  12. STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.

    Directory of Open Access Journals (Sweden)

    Nelson W Chong

    Full Text Available BACKGROUND: STARS (STriated muscle Activator of Rho Signaling is a sarcomeric protein expressed early in cardiac development that acts as an acute stress sensor for pathological remodeling. However the role of STARS in cardiac development and function is incompletely understood. Here, we investigated the role of STARS in heart development and function in the zebrafish model and in vitro. METHODOLOGY AND PRINCIPAL FINDINGS: Expression of zebrafish STARS (zSTARS first occurs in the somites by the 16 somite stage [17 hours post fertilization (hpf]. zSTARS is expressed in both chambers of the heart by 48 hpf, and also in the developing brain, jaw structures and pectoral fins. Morpholino-induced knockdown of zSTARS alters atrial and ventricular dimensions and decreases ventricular fractional shortening (measured by high-speed video microscopy, with pericardial edema and decreased or absent circulation [abnormal cardiac phenotypes in 126/164 (77% of morpholino-injected embryos vs. 0/152 (0% of control morpholino embryos]. Co-injection of zsrf (serum response factor mRNA rescues the cardiac phenotype of zSTARS knockdown, resulting in improved fractional shortening and ventricular end-diastolic dimensions. Ectopic over-expression of STARS in vitro activates the STARS proximal promoter, which contains a conserved SRF site. Chromatin immunoprecipitation demonstrates that SRF binds to this site in vivo and the SRF inhibitor CCG-1423 completely blocks STARS proximal reporter activity in H9c2 cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates for the first time that STARS deficiency severely disrupts cardiac development and function in vivo and revealed a novel STARS-SRF feed-forward autoregulatory loop that could play an essential role in STARS regulation and cardiac function.

  13. 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...

  14. 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

  15. Motives for maintaining personal journal blogs.

    Science.gov (United States)

    Hollenbaugh, Erin E

    2011-01-01

    Although much has been learned about political and news blogs, there has been a lack of research on personal journal blogs. They deserve further research attention because of the implications blogs have in many bloggers' immediate social networks, as well as the opportunities for scientific inquiry in a rich and evolving communication environment. This study explored bloggers' motives for maintaining personal journal blogs, or blogs that resemble diaries about one's personal life. Stemming from the uses and gratifications perspective, antecedents (age, sex, loneliness, disclosiveness) and blogging motives composed a model for predicting the amount of blog use. Seven motives emerged from online survey data: helping/informing, social connection, pass time, exhibitionism, archiving/organizing, professionalism, and get feedback. Age, sex, loneliness, and disclosiveness predicted different motives, and the total model (age, sex, loneliness, disclosiveness, and motives) was useful for explaining 13% of the variance in the amount of blog use.

  16. 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.

  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 the Telescope Bibliography at Gemini Observatory

    Science.gov (United States)

    Zhang, X.

    2010-10-01

    The library profession benefits tremendously from ever-changing web technologies. In maintaining a telescope bibliography, web-publishing revolutionized the way librarians track relevant publications. Thanks to the search abilities provided by the NASA Astrophysics Data System, arXiv, publishers, as well as Google Scholar, and other such resources, online searching for Gemini-based publications has replaced the tedious perusing of print journals. However, we should keep in mind that online searching is neither flawless nor simple — different content providers require different search strategies. Sometimes the retrievals are not as complete as one expects. Information providers should be constantly improving their searching abilities in order to make the task of electronic publication tracking more reliable and efficient.

  19. Maintaining control is team's vital role.

    Science.gov (United States)

    Haywood, Liz; Frankel, Chris; Johns, Andrew

    2011-02-01

    In an environment where there is an ever-increasing use of reliable electronic control, it is easy to become complacent about the need for in-depth knowledge of how the controls actually work. After all, experts who can diagnose and fix such systems are only a phone call away, and a new unit can easily be fitted. Sometimes this is not the case at Bendigo Health, as we have a number of systems with a "black box" set of controls that can take days, or weeks, to fix, and cannot be fixed locally. To better manage and maintain our infrastructure, the Buildings & Infrastructure Department at Bendigo Health includes a number of employees who concentrate on building management systems (BMS). The BMS group plays a vital role in the complete lifecycle of projects that include control and monitoring of the plant within the hospital setting. A good example of this role was in the design, build, installation and commissioning, of two new negative pressure suites at Bendigo Health. The BMS group's involvement in this particular project included the door interlocking, the air conditioning and exhaust fan control, and a comprehensive alarm panel and overrides, all of which can be monitored centrally via the existing BMS system. The involvement of the BMS group, following the DHS guidelines, resulted in the architect and consulting engineers revisiting their designs and improving them to the benefit of both patient care and staff safety. The advantages of projects such as the negative pressure suites installed by the BMS group include the fact that that the hospital gains facilities that work correctly and according to industry guidelines; and the design, installation, and controls of the plant are understood by the people who will be maintaining the infrastructure. This paper will provide an overview of the work undertaken by the BMS group at Bendigo Health, using the negative pressure suites as an exemplar.

  20. Establishing and maintaining the Langerhans cell network.

    Science.gov (United States)

    Chopin, Michaël; Nutt, Stephen L

    2015-05-01

    Langerhans cells (LCs) are the unique antigen-presenting cell of the epidermis. LCs have long been depicted in textbooks as the archetypical dendritic cell that alerts the immune system upon pathogen induced skin barrier breakage, however recent findings argue instead for a more tolerogenic function. While the LCs that populate the epidermis in steady-state arise from progenitors that seed the skin during embryogenesis, it is now apparent that a second pathway generating LCs from a bone marrow derived progenitor is active in inflammatory settings. This review emphasizes the determinants underpinning the establishment of the LC network in steady-state and under inflammatory conditions, as well as the transcriptional machinery governing their differentiation. The dual origin of LCs raises important questions about the functional differences between these subsets in balancing the epidermal immune response between immunity and tolerance.

  1. Cancer and deregulation of stem cells pathways

    Directory of Open Access Journals (Sweden)

    Filipe Correia Martins

    2011-12-01

    Full Text Available Stem cells may have an important etiological role in cancer. Their classic regulatory pathways are deregulated in tumors, strengthening the stem cell theory of cancer. In this manuscript, we review Wnt, Notch and Hedhehog pathways, describing which of their factors may be responsible for the neoplastic development. Furthermore, we classify these elements as oncogenes or tumor suppressor genes, demonstrating their mutation implications in cancer. The activation of these pathways is associated with the expression of certain genes which maintain proliferation and apoptosis inhibition. Further work should be carried out in the future in order to control tumor development by controlling these signaling cascades.

  2. Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch.

    Science.gov (United States)

    Seidel, Hannah S; Kimble, Judith

    2015-11-09

    Many types of adult stem cells exist in a state of cell-cycle quiescence, yet it has remained unclear whether quiescence plays a role in maintaining the stem cell fate. Here we establish the adult germline of Caenorhabditis elegans as a model for facultative stem cell quiescence. We find that mitotically dividing germ cells--including germline stem cells--become quiescent in the absence of food. This quiescence is characterized by a slowing of S phase, a block to M-phase entry, and the ability to re-enter M phase rapidly in response to re-feeding. Further, we demonstrate that cell-cycle quiescence alters the genetic requirements for stem cell maintenance: The signaling pathway required for stem cell maintenance under fed conditions--GLP-1/Notch signaling--becomes dispensable under conditions of quiescence. Thus, cell-cycle quiescence can itself maintain stem cells, independent of the signaling pathway otherwise essential for such maintenance.

  3. Arteriolar niches maintain haematopoietic stem cell quiescence.

    Science.gov (United States)

    Kunisaki, Yuya; Bruns, Ingmar; Scheiermann, Christoph; Ahmed, Jalal; Pinho, Sandra; Zhang, Dachuan; Mizoguchi, Toshihide; Wei, Qiaozhi; Lucas, Daniel; Ito, Keisuke; Mar, Jessica C; Bergman, Aviv; Frenette, Paul S

    2013-10-31

    Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant three-dimensional associations in the mouse bone marrow among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2 (also known as CSPG4)(+) pericytes, distinct from sinusoid-associated leptin receptor (LEPR)(+) cells. Pharmacological or genetic activation of the HSC cell cycle alters the distribution of HSCs from NG2(+) periarteriolar niches to LEPR(+) perisinusoidal niches. Conditional depletion of NG2(+) cells induces HSC cycling and reduces functional long-term repopulating HSCs in the bone marrow. These results thus indicate that arteriolar niches are indispensable for maintaining HSC quiescence.

  4. MAVS maintains mitochondrial homeostasis via autophagy

    Science.gov (United States)

    Sun, Xiaofeng; Sun, Liwei; Zhao, Yuanyuan; Li, Ying; Lin, Wei; Chen, Dahua; Sun, Qinmiao

    2016-01-01

    Mitochondrial antiviral signalling protein (MAVS) acts as a critical adaptor protein to transduce antiviral signalling by physically interacting with activated RIG-I and MDA5 receptors. MAVS executes its functions at the outer membrane of mitochondria to regulate downstream antiviral signalling, indicating that the mitochondria provides a functional platform for innate antiviral signalling transduction. However, little is known about whether and how MAVS-mediated antiviral signalling contributes to mitochondrial homeostasis. Here we show that the activation of MAVS is sufficient to induce autophagic signalling, which may mediate the turnover of the damaged mitochondria. Importantly, we find MAVS directly interacts with LC3 through its LC3-binding motif ‘YxxI’, suggesting that MAVS might act as an autophagy receptor to mediate mitochondrial turnover upon excessive activation of RLR signalling. Furthermore, we provide evidence that both MAVS self-aggregation and its interaction with TRAF2/6 proteins are important for MAVS-mediated mitochondrial turnover. Collectively, our findings suggest that MAVS acts as a potential receptor for mitochondria-associated autophagic signalling to maintain mitochondrial homeostasis. PMID:27551434

  5. Arteriolar niches maintain haematopoietic stem cell quiescence

    Science.gov (United States)

    Kunisaki, Yuya; Bruns, Ingmar; Scheiermann, Christoph; Ahmed, Jalal; Pinho, Sandra; Zhang, Dachuan; Mizoguchi, Toshihide; Wei, Qiaozhi; Lucas, Daniel; Ito, Keisuke; Mar, Jessica C.; Bergman, Aviv; Frenette, Paul S.

    2013-01-01

    Cell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSCs in the bone marrow (BM) remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging techniques and computational modelling to analyse significant tridimensional associations among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal BM. These arterioles are ensheathed exclusively by rare NG2+ pericytes, distinct from sinusoid-associated LepR+ cells. Pharmacological or genetic activation of HSC cell cycle alters the distribution of HSCs from NG2+ peri-arteriolar niches to LepR+ peri-sinusoidal niches. Conditional depletion of NG2+ cells induces HSC cycling and reduces functional long-term repopulating HSCs in BM. These results thus indicate that arteriolar niches are indispensable to maintain HSC quiescence. PMID:24107994

  6. A corollary discharge maintains auditory sensitivity during sound production.

    Science.gov (United States)

    Poulet, James F A; Hedwig, Berthold

    2002-08-22

    Speaking and singing present the auditory system of the caller with two fundamental problems: discriminating between self-generated and external auditory signals and preventing desensitization. In humans and many other vertebrates, auditory neurons in the brain are inhibited during vocalization but little is known about the nature of the inhibition. Here we show, using intracellular recordings of auditory neurons in the singing cricket, that presynaptic inhibition of auditory afferents and postsynaptic inhibition of an identified auditory interneuron occur in phase with the song pattern. Presynaptic and postsynaptic inhibition persist in a fictively singing, isolated cricket central nervous system and are therefore the result of a corollary discharge from the singing motor network. Mimicking inhibition in the interneuron by injecting hyperpolarizing current suppresses its spiking response to a 100-dB sound pressure level (SPL) acoustic stimulus and maintains its response to subsequent, quieter stimuli. Inhibition by the corollary discharge reduces the neural response to self-generated sound and protects the cricket's auditory pathway from self-induced desensitization.

  7. A Maintainability Prediction Method Considering Environmental Impacts and Cost

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Maintainability prediction is one kind of primary maintainability action. Design deficiency would be found through predicting maintainability parameters under certain conditions. Now a maintainability prediction method that mainly considers maintenance time or maintenance man-hour is a kind of prediction method with a single index. With increasing product complexity and people's environmental consciousness, more attention is paid to environment impacts and maintenance cost or resource consumption in the maintenance process. It is necessary for a maintainability prediction method that can predict maintenance cost and maintenance environmental impacts. A new maintainability prediction method is presented in this paper based on analyzing existing maintainability prediction methods.The method is MABTCE (maintenance activity based timing/costing/environment impact assessment )and can predict maintenance time, maintenance costing and maintenance environmental impacts andthen improve maintainability design with prediction results.

  8. Research on Maintainability Evaluation Model Based on Fuzzy Theory

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Maintainability influencing attributes are analyzed, their weight and value calculating methods are given, and the maintainability fuzzy evaluation method is proposed based on the relative closeness. According to the maintenance task simulation operated in virtual environment, the maintainability virtual evaluation model is built by analyzing the maintenance task for each replaceable unit of product.At last, a case study is given based upon the main landing gear system of a certain type civil aircraft, and the result indicates that the model is suitable for maintainability qualitative evaluation and can support maintainability concurrent design.

  9. 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

  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. Arbovirus-mosquito interactions: RNAi pathway.

    Science.gov (United States)

    Olson, Ken E; Blair, Carol D

    2015-12-01

    Arthropod-borne (arbo) viruses infect hematophagous arthropods (vectors) to maintain virus transmission between vertebrate hosts. The mosquito vector actively controls arbovirus infection to minimize its fitness costs. The RNA interference (RNAi) pathway is the major antiviral response vectors use to restrict arbovirus infections. We know this because depleting RNAi gene products profoundly impacts arbovirus replication, the antiviral RNAi pathway genes undergo positive, diversifying selection and arboviruses have evolved strategies to evade the vector's RNAi responses. The vector's RNAi defense and arbovirus countermeasures lead to an arms race that prevents potential virus-induced fitness costs yet maintains arbovirus infections needed for transmission. This review will discuss the latest findings in RNAi-arbovirus interactions in the model insect (Drosophila melanogaster) and in specific mosquito vectors.

  12. 19 CFR 163.2 - Persons required to maintain records.

    Science.gov (United States)

    2010-04-01

    ... brokers. Each customs broker must also make and maintain records and make such records available in... 19 Customs Duties 2 2010-04-01 2010-04-01 false Persons required to maintain records. 163.2 Section 163.2 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND...

  13. Object Representations Maintain Attentional Control Settings across Space and Time

    Science.gov (United States)

    Schreij, Daniel; Olivers, Christian N. L.

    2009-01-01

    Previous research has revealed that we create and maintain mental representations for perceived objects on the basis of their spatiotemporal continuity. An important question is what type of information can be maintained within these so-called object files. We provide evidence that object files retain specific attentional control settings for…

  14. Polarization maintaining large-mode area photonic crystal fibre

    DEFF Research Database (Denmark)

    Folkenberg, Jacob Riis; Nielsen, Martin Dybendal; Mortensen, N.A.

    2004-01-01

    We report on a polarization maintaining large mode area photonic crystal fiber. Unlike, previous work on polarization maintaining photonic crystal fibers, birefringence is introduced using stress applying parts. This has allowed us to realize fibers, which are both single mode at any wavelength a...

  15. Coherent Beam Combination of Two Polarization Maintaining Ytterbium Fibre Amplifiers

    Institute of Scientific and Technical Information of China (English)

    HOU Jing; XIAO Rui; JIANG Zong-Fu; CHENG Xiang-Ai; SHU Bai-Hong; CHEN Jin-Bao; LIU Ze-Jin

    2005-01-01

    @@ We investigate coherent beam combination of fibre laser beams by phase locking. Phase noise of a polarization maintaining ytterbium fibre amplifier is inspected with a fibre interferometer. In a feed back control loop, two fibre polarization maintaining ytterbium amplifiers are phase locked and coherent combined when the phase noise is properly controlled by a LiNO3 phase modulator.

  16. 34 CFR 668.163 - Maintaining and accounting for funds.

    Science.gov (United States)

    2010-07-01

    ...) Accounting and internal control systems and financial records. (1) An institution must maintain accounting... financial records in accordance with the provisions under § 668.24. (e) Standard of conduct. An institution... 34 Education 3 2010-07-01 2010-07-01 false Maintaining and accounting for funds. 668.163...

  17. 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...

  18. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation.

    Science.gov (United States)

    Hilton, Matthew J; Tu, Xiaolin; Wu, Ximei; Bai, Shuting; Zhao, Haibo; Kobayashi, Tatsuya; Kronenberg, Henry M; Teitelbaum, Steven L; Ross, F Patrick; Kopan, Raphael; Long, Fanxin

    2008-03-01

    Postnatal bone marrow houses mesenchymal progenitor cells that are osteoblast precursors. These cells have established therapeutic potential, but they are difficult to maintain and expand in vitro, presumably because little is known about the mechanisms controlling their fate decisions. To investigate the potential role of Notch signaling in osteoblastogenesis, we used conditional alleles to genetically remove components of the Notch signaling system during skeletal development. We found that disruption of Notch signaling in the limb skeletogenic mesenchyme markedly increased trabecular bone mass in adolescent mice. Notably, mesenchymal progenitors were undetectable in the bone marrow of mice with high bone mass. As a result, these mice developed severe osteopenia as they aged. Moreover, Notch signaling seemed to inhibit osteoblast differentiation through Hes or Hey proteins, which diminished Runx2 transcriptional activity via physical interaction. These results support a model wherein Notch signaling in bone marrow normally acts to maintain a pool of mesenchymal progenitors by suppressing osteoblast differentiation. Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway.

  19. Use of porous space maintainers in staged mandibular reconstruction.

    Science.gov (United States)

    Henslee, Allan M; Spicer, Patrick P; Shah, Sarita R; Tatara, Alexander M; Kasper, F Kurtis; Mikos, Antonios G; Wong, Mark E

    2014-05-01

    The success of mandibular reconstructions depends not only on restoring the form and function of lost bone but also on the preservation of the overlying soft tissue layer. In this case study, 5 porous polymethylmethacrylate space maintainers fabricated via patient-specific molds were implanted initially to maintain the vitality of the overlying oral mucosa during staged mandibular reconstructions. Three of the 5 patients healed well; the other 2 patients developed dehiscences, likely due to a thin layer of soft tissue overlying the implant. The results presented provide evidence that a larger investigation of space maintainers fabricated using this method is warranted.

  20. Coastal Maintained Channels in US waters as of May 2013

    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...

  1. An Improved Functional Hierarchy Frame Model for System Maintainability

    Institute of Scientific and Technical Information of China (English)

    CHEN Dai-Lin; CHEN Dong-lin; WANG Ru-gen; ZHU Xue-ping

    2003-01-01

    By means of analogy, this paper analyses the present functional hierarchy frame model for system maintainability, and presents an improved model. Practical application indicates that the improved model is visualized, more convenient and perfected over the pervious models.

  2. Allocating SMART Reliability and Maintainability Goals to NASA Ground Systems

    Science.gov (United States)

    Gillespie, Amanda; Monaghan, Mark

    2013-01-01

    This paper will describe the methodology used to allocate Reliability and Maintainability (R&M) goals to Ground Systems Development and Operations (GSDO) subsystems currently being designed or upgraded.

  3. 36 CFR 1222.34 - How must agencies maintain records?

    Science.gov (United States)

    2010-07-01

    ... ADMINISTRATION RECORDS MANAGEMENT CREATION AND MAINTENANCE OF FEDERAL RECORDS Agency Recordkeeping Requirements... organizing and storing records; (b) Maintain electronic, audiovisual and cartographic, and microform records in accordance with 36 CFR parts 1236, 1237, and 1238 of this subchapter, respectively; (c)...

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

    OpenAIRE

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

    2014-01-01

    ABSTRACT Objectives: Of this in vivo study was to evaluate various space maintainers in terms of survival rate, gingival health and presence of caries. Design: 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). Results: Prefabricated bands with custom made loop showed maximum success rates (84.6%), whi...

  5. Band and loop space maintainer--made easy.

    Science.gov (United States)

    Nayak, U A; Loius, J; Sajeev, R; Peter, J

    2004-09-01

    Space maintainers have been used in Pediatric Dentistry for many years. The use of these appliances, however, in terms of indications, contraindications, design and construction has gained little attention from researchers. This paper highlights the construction of a new technique of fabrication of band and loop space maintainer. The advantages of this new Direct technique or Single sitting technique over the conventional technique are discussed.

  6. Kinesin-1 Acts with Netrin and DCC to Maintain Sensory Neuron Position in Caenorhabditis elegans

    Science.gov (United States)

    Barsi-Rhyne, Benjamin J.; Miller, Kristine M.; Vargas, Christopher T.; Thomas, Anthony B.; Park, Joori; Bremer, Martina; Jarecki, Jessica L.; VanHoven, Miri K.

    2013-01-01

    The organization of neurons and the maintenance of that arrangement are critical to brain function. Failure of these processes in humans can lead to severe birth defects, mental retardation, and epilepsy. Several kinesins have been shown to play important roles in cell migration in vertebrate systems, but few upstream and downstream pathway members have been identified. Here, we utilize the genetic model organism Caenorhabditis elegans to elucidate the pathway by which the C. elegans Kinesin-1 Heavy Chain (KHC)/KIF5 ortholog UNC-116 functions to maintain neuronal cell body position in the PHB sensory neurons. We find that UNC-116/KHC acts in part with the cell and axon migration molecules UNC-6/Netrin and UNC-40/DCC in this process, but in parallel to SAX-3/Robo. We have also identified several potential adaptor, cargo, and regulatory proteins that may provide insight into the mechanism of UNC-116/KHC’s function in this process. These include the cargo receptor UNC-33/CRMP2, the cargo adaptor protein UNC-76/FEZ and its regulator UNC-51/ULK, the cargo molecule UNC-69/SCOCO, and the actin regulators UNC-44/Ankyrin and UNC-34/Enabled. These genes also act in cell migration and axon outgrowth; however, many proteins that function in these processes do not affect PHB position. Our findings suggest an active posterior cell migration mediated by UNC-116/KHC occurs throughout development to maintain proper PHB cell body position and define a new pathway that mediates maintenance of neuronal cell body position. PMID:23475988

  7. Maintaining dental records: Are we ready for forensic needs?

    Directory of Open Access Journals (Sweden)

    Madhusudan Astekar

    2011-01-01

    Full Text Available Context: Dental remains are usually the last to get destroyed among body parts after death. They may be useful for personal identification in cases of mass disasters and decomposed unidentified bodies. Dental records may help in the identification of suspects in criminal investigations and in medicolegal cases. Maintenance of dental records is legally mandatory in most of the European and American countries. Unfortunately, the law is not very clear in India, and the awareness is very poor. Aims: To assess the awareness regarding the dental record maintenance among dentists in Rajasthan, to deduce the quality of average dental records kept by them and to evaluate the potential use of their maintained records, in any of forensic or medicolegal cases. Settings and Design: A cross-sectional survey was conducted among 100 dental practitioners of different cities in Rajasthan, India. Materials and Methods: Data were collected through a structured questionnaire, which was responded by the study population in the course of a telephonic interview. The questionnaire addressed on the mode of maintaining dental records in their regular practice. Statistical Analysis Used: The data so gathered were subjected for descriptive analysis. Results: As for knowledge or awareness about maintaining dental records, surprisingly a very low percentile (about 38% of surveyed dentists maintained records. Sixty-two percent of the dentists were maintaining no records at all. Conclusion : Nonmaintenance or poor quality of records maintained indicates that the dentists in Rajasthan are not prepared for any kind of forensic and medicolegal need if it arises.

  8. Persisting eicosanoid pathways in rheumatic diseases.

    Science.gov (United States)

    Korotkova, Marina; Jakobsson, Per-Johan

    2014-04-01

    An unmet clinical need exists for early treatment of rheumatic diseases and improved treatment strategies that can better maintain remission with reduced ongoing subclinical inflammation and bone destruction. Eicosanoids form one of the most complex networks in the body controlling many physiological and pathophysiological processes, including inflammation, autoimmunity and cancer. Persisting eicosanoid pathways are thought to be involved in the development of rheumatic diseases, and targeting this pathway might enable improved treatment strategies. Several enzymes of the arachidonic acid cascade as well as eicosanoid receptors (all part of the eicosanoid pathway) are today well-recognized targets for anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases. In this Review, we outline the evidence supporting pivotal roles of eicosanoid signalling in the pathogenesis of rheumatic diseases and discuss findings from studies in animals and humans. We focus first on rheumatoid arthritis and discuss the upregulation of the cyclooxygenase and lipoxygenase pathways as most data are available in this condition. Research into the roles of eicosanoids in other rheumatic diseases (osteoarthritis, idiopathic inflammatory myopathies, systemic lupus erythematosus and gout) is also progressing rapidly and is discussed. Finally, we summarize the prospects of targeting eicosanoid pathways as anti-inflammatory treatment strategies for patients with rheumatic diseases.

  9. Maintaining Discovered Frequent Itemsets: Cases for Changeable Database and Support

    Institute of Scientific and Technical Information of China (English)

    DU XiaoPing(杜孝平); TANG ShiWei(唐世渭); Akifumi Makinouchi(牧之内顕文)

    2003-01-01

    Mining frequent itemsets from large databases has played an essential role inmany data mining tasks. It is also important to maintain the discovered frequent itemsets forthese data mining tasks when the database is updated. All algorithms proposed so far for the maintenance of discovered frequent itemsets are only performed with a fixed minimum support,which is the same as that used to obtain the discovered frequent itemsets. That is, users cannot change the minimum support even if the new results are unsatisfactory to the users. In thispaper two new complementary algorithms, FMP (First Maintaining Process) and RMP (Repeated Maintaining Process), are proposed to maintain discovered frequent itemsets in the case that new transaction data are added to a transaction database. Both algorithms allow users to change theminimum support for the maintenance processes. FMP is used for the first maintaining process, andwhen the result derived from the FMP is unsatisfactory, RMP will be performed repeatedly untilsatisfactory results are obtained. The proposed algorithms re-use the previous results to cut downthe cost of maintenance. Extensive experiments have been conducted to assess the performance of the algorithms. The experimental results show that the proposed algorithms are very resultful compared with the previous mining and maintenance algorithms for maintenance of discovered frequent itemsets.

  10. 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.

  11. Innovative scheduling to maintain clinical pharmacy services despite budget retrenchment.

    Science.gov (United States)

    Siegel, J; Schneider, P J; Moore, T D

    1984-02-01

    A process is described in which staff scheduling was adjusted to maintain pharmaceutical services while achieving a 7% cutback in personnel costs. The pharmacy department in a 1000-bed university hospital was unable to achieve the necessary cost savings through reductions in sick leave and overtime hours. The pharmacy administration developed a plan that required pharmacists to work four 10-hour shifts per week and resulted in reduced hours of service. The pharmacists objected and proposed an alternative plan in which clinical service was maintained for 16 hours on weekdays and 12 hours on weekends. Pharmacist teams worked one flexible shift per week. Pharmacists developed an innovative staffing plan that allowed them to maintain a high level of practice and acceptable working hours.

  12. Functional analysis screening for problem behavior maintained by automatic reinforcement.

    Science.gov (United States)

    Querim, Angie C; Iwata, Brian A; Roscoe, Eileen M; Schlichenmeyer, Kevin J; Ortega, Javier Virués; Hurl, Kylee E

    2013-01-01

    A common finding in previous research is that problem behavior maintained by automatic reinforcement continues to occur in the alone condition of a functional analysis (FA), whereas behavior maintained by social reinforcement typically is extinguished. Thus, the alone condition may represent an efficient screening procedure when maintenance by automatic reinforcement is suspected. We conducted a series of 5-min alone (or no-interaction) probes for 30 cases of problem behavior and compared initial predictions of maintenance or extinction to outcomes obtained in subsequent FAs. Results indicated that data from the screening procedure accurately predicted that problem behavior was maintained by automatic reinforcement in 21 of 22 cases and by social reinforcement in 7 of 8 cases. Thus, results of the screening accurately predicted the function of problem behavior (social vs. automatic reinforcement) in 28 of 30 cases.

  13. Equilateral pentagon polarization maintaining photonic crystal fibre with low nonlinearity

    Institute of Scientific and Technical Information of China (English)

    Yang Han-Rui; Li Xu-You; Hong Wei; Hao Jin-Hui

    2012-01-01

    A new pentagon polarization maintaining photonic crystal fibre with low nonlinearity is introduced. The full vector finite element method was used to investigate the distribution and the effective area of modal field,the nonlinear properties,the effective indices of two orthogonal polarization modes and the birefringence of the new PM-PCF effectively.It is found that the birefringence of the new polarization maintaining photonic crystal fibre can easily achieve the order of 10-4,and it can obtain higher birefringence,larger effectively mode-field area and lower nonlinearity than traditional hexagonal polarization maintaining photonic crystal fibre with the same hole pitch,same hole diameter,and same ring number.It is important for sensing and communication applications,especially has potential application for fibre optical gyroscope.

  14. Validation Effectiveness of Develop Maintainability Allocation on Aircraft Mechanical Components

    Directory of Open Access Journals (Sweden)

    Wan Husain W.M.S.

    2016-01-01

    Full Text Available Maintainability Allocation is a process to identify the allowable maximum task time for each individual component. Consequently, this provides clear pictures to the designers to design and identify potential design improvement within allowable maintenance allocation time limits. During the design process elements such as missteps or misapplications most commonly occur. Here, the authors propose having the maximum target for each individual maintainability component. The main objective of this paper is to present the validation process of developed Maintainability Allocation to potentially eliminate previous problems. The process of validation begins with analysed all the data collected from Service Difficulty Reports (SDR for selected aircraft. This is to understand the problems from existing aircraft before a new design is proposed through the process of Maintainability Allocation prediction. The validation processes have discovered the importance of utilising historical information such as feedback information. The second area is looking at the element of quantifying the data collected from aircraft feedback information which contains various types of information that could be used for future improvement. Validation process shows that feedback information has helped to identify the critical and sensitive components that need more attention for further improvement. The study shows that the aircraft maintenance related feedback information systems analyses were very useful for deciding maintainability effectiveness; these include planning, organising maintenance and design improvement. There is no doubt that feedback information has the ability to contribute an important role in design activities. The results also show that maintainability is an important measure that can be used as a guideline for managing efforts made for the improvement of aircraft components.

  15. Maintaining realism in auditory length-perception experiments

    DEFF Research Database (Denmark)

    Kirkwood, Brent Christopher

    2005-01-01

    Humans are capable of hearing the lengths of wooden rods dropped onto hard floors. In an attempt to understand the influence of the stimulus presentation method for testing this kind of everyday listening task, listener performance was compared for three presentation methods in an auditory length......-estimation experiment. A comparison of the length-estimation accuracy for the three presentation methods indicates that the choice of presentation method is important for maintaining realism and for maintaining the acoustic cues utilized by listeners in perceiving length....

  16. 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.

  17. Sharing the sandbox: Evolutionary mechanisms that maintain bacterial cooperation.

    Science.gov (United States)

    Bruger, Eric; Waters, Christopher

    2015-01-01

    Microbes are now known to participate in an extensive repertoire of cooperative behaviors such as biofilm formation, production of extracellular public-goods, group motility, and higher-ordered multicellular structures. A fundamental question is how these cooperative tasks are maintained in the face of non-cooperating defector cells. Recently, a number of molecular mechanisms including facultative participation, spatial sorting, and policing have been discovered to stabilize cooperation. Often these different mechanisms work in concert to reinforce cooperation. In this review, we describe bacterial cooperation and the current understanding of the molecular mechanisms that maintain it.

  18. Maintaining Legitimacy: Controversies, Orders of Worth and Public Justifications

    NARCIS (Netherlands)

    Patriotta, G.; Gond, J.-P.; Schultz, F.

    2011-01-01

    We build on Boltanski and Thévenot's theory of justification to account for the ways in which different stakeholder groups actively engage with discourses and objects to maintain the legitimacy of institutions that are relevant to their activity. We use this framework to analyse a controversy emergi

  19. Maintaining Healthy Behaviors Following Weight Loss: A Grounded Theory Approach

    Science.gov (United States)

    Zunker, Christie; Cox, Tiffany L.; Ard, Jamy D.; Ivankova, Nataliya V.; Rutt, Candace D.; Baskin, Monica L.

    2011-01-01

    This study explored the process of how women maintained their healthy behaviors after a weight management program using a grounded theory approach. We conducted 2 focus groups and 23 interviews with a purposeful sample of African American and Caucasian women aged 30 and older who lost greater than 5% of their body weight during a weight management…

  20. Guidelines for Beginning and Maintaining a Toy Lending Library.

    Science.gov (United States)

    Rettig, Michael A.

    1998-01-01

    Toy-lending libraries provide parents and professionals with opportunities for shared play and the loan of toys. This article reviews the history of toy-lending libraries and the purpose of Lekoteks, the Swedish toy library. Guidelines and suggestions for developing and maintaining a toy-lending library are discussed. (JPB)

  1. Maintaining Equivalent Cut Scores for Small Sample Test Forms

    Science.gov (United States)

    Dwyer, Andrew C.

    2016-01-01

    This study examines the effectiveness of three approaches for maintaining equivalent performance standards across test forms with small samples: (1) common-item equating, (2) resetting the standard, and (3) rescaling the standard. Rescaling the standard (i.e., applying common-item equating methodology to standard setting ratings to account for…

  2. 4 CFR 200.14 - Responsibility for maintaining adequate safeguards.

    Science.gov (United States)

    2010-01-01

    ... identifiable personal data and automated systems shall be adequately trained in the security and privacy of... records in which identifiable personal data are processed or maintained, including all reports and output... personal records or data; must minimize, to the extent practicable, the risk that skilled technicians...

  3. Nuclear policy impacts at the national laboratories: maintaining the deterrence

    Energy Technology Data Exchange (ETDEWEB)

    Beck, James Bradley [Los Alamos National Laboratory

    2010-08-24

    In this presentation, the author will discuss recent nuclear policy impacts, including the 2010 Nuclear Posture Review, and the impacts they have on maintaining the nuclear deterrent. Specifically, he will highlight some of the remaining questions and challenges that remain to the nation and to the national laboratories. (auth)

  4. Beijing's Convention and Exhibition Industry Maintains Good Momentum

    Institute of Scientific and Technical Information of China (English)

    Xiong Jiuling

    2011-01-01

    @@ In recent years, Beijing's conven-tion and exhibition industry has maintained a good development momentum with expanding scale and improving facilities, becoming an inseparable part of the city's modern service sector.The development of the convention and exhibition industry has played an active role in perfecting the capital's functions, optimizing the industrial structure and enhancing the city's radiation capabilities.

  5. Establishing and Maintaining Boundaries in Teacher-Student Relationships

    Science.gov (United States)

    Bernstein-Yamashiro, Beth; Noam, Gil G.

    2013-01-01

    Because schools rarely provide guidelines for teachers that outline how they should conduct personal relationships with students, teachers must wrestle individually with how to establish, communicate, and maintain clear boundaries in their interactions. As schools work to become more personal environments, school administrators will need to help…

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

    Energy Technology Data Exchange (ETDEWEB)

    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. (ACR)

  7. 48 CFR 6.202 - Establishing or maintaining alternative sources.

    Science.gov (United States)

    2010-10-01

    ... emergency or industrial mobilization; (3) Be in the interest of national defense in establishing or maintaining an essential engineering, research, or development capability to be provided by an educational or... history of high demand; or (6) Satisfy a critical need for medical, safety, or emergency supplies....

  8. Free-end space maintainers: design, utilization and advantages.

    Science.gov (United States)

    Barbería, Elena; Lucavechi, Tania; Cárdenas, Dora; Maroto, Myriam

    2006-01-01

    Primary molars are a determining factor in the development of occlusion. Given their importance, when restorative treatment is notfeasible and a primary molar must be extracted, the practitioner should keep in mind the risk of losing space, and the consequent malocclusion. Preservation of the space can eliminate or reduce the needforprolonged orthodontic treatment. For that reason, there are various kinds of space maintainers and the pediatric dentist must decide which one to utilize, on the basis of general and local factors related to the child In the selection of a treatment option for space maintenance, the greatest complications occur when the first permanent molar has not yet erupted A large variety of appliances have been devised to deal with this situation. This article proposes the use of a removable space maintainer that is open on one end and can be employed to guide the first permanent molar, maintaining the integrity of the mucous membrane and serving as a prosthetic appliance, preventing the complications and contraindications often caused by sub-gingival maintainers.

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

    Science.gov (United States)

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

    2014-01-01

    ABSTRACT Objectives: Of this in vivo study was to evaluate various space maintainers in terms of survival rate, gingival health and presence of caries. Design: 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). Results: 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. PMID:25356008

  10. 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…

  11. Motivational Influences on Performance Maintained by Food Reinforcement

    Science.gov (United States)

    North, Stephen T.; Iwata, Brian A.

    2005-01-01

    In Study 1, we examined the independent effects of reinforcer consumption during sessions and meal consumption prior to sessions on performance maintained by food reinforcement. Nine individuals with developmental disabilities participated. On alternate days, a preferred edible item was delivered during (a) seven sessions conducted before lunch…

  12. 76 FR 79553 - Maintaining Access to Emergency Liquidity

    Science.gov (United States)

    2011-12-22

    ... Federal Reserve District Bank. 12 CFR 201.51. While the CLF is a special liquidity facility for the credit... ADMINISTRATION 12 CFR Part 741 RIN 3133-AD96 Maintaining Access to Emergency Liquidity AGENCY: National Credit... regulation to require federally insured credit unions (FICUs) to have access to backup federal...

  13. 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.

  14. The free energy cost of reducing noise while maintaining a high sensitivity

    CERN Document Server

    Sartori, Pablo

    2015-01-01

    Living systems need to be highly responsive, and also to keep fluctuations low. These goals are incompatible in equilibrium systems due to the Fluctuation Dissipation Theorem (FDT). Here, we show that biological sensory systems, driven far from equilibrium by free energy consumption, can reduce their intrinsic fluctuations while maintaining high responsiveness. By developing a continuum theory of the E. coli chemotaxis pathway, we demonstrate that adaptation can be understood as a non-equilibrium phase transition controlled by free energy dissipation, and it is characterized by a breaking of the FDT. We show that the maximum response at short time is enhanced by free energy dissipation. At the same time, the low frequency fluctuations and the adaptation error decrease with the free energy dissipation algebraically and exponentially, respectively.

  15. 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.

  16. The free energy cost of reducing noise while maintaining a high sensitivity

    Science.gov (United States)

    Sartori, Pablo; Tu, Yuhai

    2016-01-01

    Living systems need to be highly responsive, and also to keep fluctuations low. These goals are incompatible in equilibrium systems due to the Fluctuation Dissipation Theorem (FDT). Here, we show that biological sensory systems, driven far from equilibrium by free energy consumption, can reduce their intrinsic fluctuations while maintaining high responsiveness. By developing a continuum theory of the E. coli chemotaxis pathway, we demonstrate that adaptation can be understood as a non-equilibrium phase transition controlled by free energy dissipation, and it is characterized by a breaking of the FDT. We show that the maximum response at short time is enhanced by free energy dissipation. At the same time, the low frequency fluctuations and the adaptation error decrease with the free energy dissipation algebraically and exponentially, respectively. PMID:26406857

  17. Capu and Spire assemble a cytoplasmic actin mesh that maintains microtubule organization in the Drosophila oocyte.

    Science.gov (United States)

    Dahlgaard, Katja; Raposo, Alexandre A S F; Niccoli, Teresa; St Johnston, Daniel

    2007-10-01

    Mutants in the actin nucleators Cappuccino and Spire disrupt the polarized microtubule network in the Drosophila oocyte that defines the anterior-posterior axis, suggesting that microtubule organization depends on actin. Here, we show that Cappuccino and Spire organize an isotropic mesh of actin filaments in the oocyte cytoplasm. capu and spire mutants lack this mesh, whereas overexpressed truncated Cappuccino stabilizes the mesh in the presence of Latrunculin A and partially rescues spire mutants. Spire overexpression cannot rescue capu mutants, but prevents actin mesh disassembly at stage 10B and blocks late cytoplasmic streaming. We also show that the actin mesh regulates microtubules indirectly, by inhibiting kinesin-dependent cytoplasmic flows. Thus, the Capu pathway controls alternative states of the oocyte cytoplasm: when active, it assembles an actin mesh that suppresses kinesin motility to maintain a polarized microtubule cytoskeleton. When inactive, unrestrained kinesin movement generates flows that wash microtubules to the cortex.

  18. 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.

  19. 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... B, Vecchi A. Publication Autoimmun Rev. 2007 Nov;7(1):8-11. Epub 2007 Mar 26. Pathway - PNG File (.png) SVG

  20. The role of the Hippo pathway in melanocytes and melanoma

    Directory of Open Access Journals (Sweden)

    Bruce Charles Baguley

    2013-05-01

    Full Text Available The Hippo signalling pathway comprises a series of cytoplasmic tumour suppressor proteins including Merlin and the Lats1/2 and MST1/2 kinases, and is thought to play a critical role in determining the sizes of organs and tissues. The Hippo pathway is regulated upstream by extracellular mechanosensory signalling arising from cell shape and polarity, as well as by a variety of extracellular signalling molecules. When active, the pathway maintains the transcriptional activators YAP and TAZ in phosphorylated forms in the cytoplasm, preventing cell proliferation. When the Hippo pathway is inactivated, YAP and TAZ are translocated to the nucleus and induce the expression of a variety of proteins concerned with entry into the cell division cycle, such as cyclin D1 and Fox M1, as well as the inhibition of apoptosis. The failure of the Hippo pathway has been implicated in the development of many different types of cancer but there is limited information available as to its involvement in melanoma. We hypothesise here firstly that the Hippo pathway is involved in maintaining density of cutaneous melanocytes on the basement membrane at the junction of the epidermis and the dermis, and secondly, that its function is disturbed in melanoma. We have analysed a series of 23 low passage human melanoma lines as well as in cultures of normal melanocytes, and find that melanocytes, as well as all melanoma cell lines examined express TAZ. Melanocytes and most melanoma lines also express YAP. E-cadherin, an upstream regulator of the Hippo pathway, and Axl, a receptor tyrosine kinase regulated by the Hippo pathway, are expressed in melanocytes and in several melanoma cell lines. These observations, together with published evidence for the presence of Merlin, Lats1/2 and MST1/2 in melanocytes and melanoma cells, support the hypothesis that the Hippo pathway is an important component of melanocyte and melanoma behaviour.

  1. Clinical Pathway for Thyroidectomy.

    Science.gov (United States)

    Villar del Moral, Jesús María; Soria Aledo, Víctor; Colina Alonso, Alberto; Flores Pastor, Benito; Gutiérrez Rodríguez, María Teresa; Ortega Serrano, Joaquín; Parra Hidalgo, Pedro; Ros López, Susana

    2015-05-01

    Clinical pathways are care plans applicable to patient care procedures that present variations in practice and a predictable clinical course. They are designed not as a substitute for clinical judgment, but rather as a means to improve the effectiveness and efficiency of the procedures. This clinical pathway is the result of a collaborative work of the Sections of Endocrine Surgery and Quality Management of the Spanish Association of Surgeons. It attempts to provide a framework for standardizing the performance of thyroidectomy, the most frequently performed operation in endocrine surgery. Along with the usual documents of clinical pathways (temporary matrix, variance tracking and information sheets, assessment indicators and a satisfaction questionnaire) it includes a review of the scientific evidence around different aspects of pre, intra and postoperative management. Among others, antibiotic and antithrombotic prophylaxis, preoperative preparation in hyperthyroidism, intraoperative neuromonitoring and systems for obtaining hemostasis are included, along with management of postoperative hypocalcemia.

  2. The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms.

    Science.gov (United States)

    Chen, Chuck T; Domenichiello, Anthony F; Trépanier, Marc-Olivier; Liu, Zhen; Masoodi, Mojgan; Bazinet, Richard P

    2013-09-01

    Brain eicosapentaenoic acid (EPA) levels are 250- to 300-fold lower than docosahexaenoic acid (DHA), at least partly, because EPA is rapidly β-oxidized and lost from brain phospholipids. Therefore, we examined if β-oxidation was necessary for maintaining low EPA levels by inhibiting β-oxidation with methyl palmoxirate (MEP). Furthermore, because other metabolic differences between DHA and EPA may also contribute to their vastly different levels, this study aimed to quantify the incorporation and turnover of DHA and EPA into brain phospholipids. Fifteen-week-old rats were subjected to vehicle or MEP prior to a 5 min intravenous infusion of (14)C-palmitate, (14)C-DHA, or (14)C-EPA. MEP reduced the radioactivity of brain aqueous fractions for (14)C-palmitate-, (14)C-EPA-, and (14)C-DHA-infused rats by 74, 54, and 23%, respectively; while it increased the net rate of incorporation of plasma unesterified palmitate into choline glycerophospholipids and phosphatidylinositol and EPA into ethanolamine glycerophospholipids and phosphatidylserine. MEP also increased the synthesis of n-3 docosapentaenoic acid (n-3 DPA) from EPA. Moreover, the recycling of EPA into brain phospholipids was 154-fold lower than DHA. Therefore, the low levels of EPA in the brain are maintained by multiple redundant pathways including β-oxidation, decreased incorporation from plasma unesterified FA pool, elongation/desaturation to n-3 DPA, and lower recycling within brain phospholipids.

  3. FGF-dependent Notch signaling maintains the spinal cord stem zone

    Science.gov (United States)

    Akai, Jun; Halley, Pam A.; Storey, Kate G.

    2005-01-01

    Generation of the spinal cord relies on proliferation of undifferentiated cells located in a caudal stem zone. Although fibroblast growth factor (FGF) signaling is required to maintain this cell group, we do not know how it controls cell behavior in this context. Here we characterize an overlooked expression domain of the Notch ligand, Delta1, in the stem zone and demonstrate that this constitutes a proliferative cell group in which Notch signaling is active. We show that FGF signaling is required for expression of the proneural gene cash4 in the stem zone, which in turn induces Delta1. We further demonstrate that Notch signaling is required for cell proliferation within the stem zone; however, it does not regulate cell movement out of this region, nor is loss of Notch signaling sufficient to drive neuronal differentiation within this tissue. These data identify a novel role for the Notch pathway during vertebrate neurogenesis in which signaling between high Delta1-expressing cells maintains the neural precursor pool that generates the spinal cord. Our findings also suggest a mechanism for the establishment of the cell selection process, lateral inhibition: Mutual inhibition between Delta/Notch-expressing stem zone cells switches to single Delta1-presenting neurons as FGF activity declines in the newly formed neuroepithelium. PMID:16287717

  4. Notch maintains Drosophila type II neuroblasts by suppressing expression of the Fez transcription factor Earmuff.

    Science.gov (United States)

    Li, Xiaosu; Xie, Yonggang; Zhu, Sijun

    2016-07-15

    Notch signaling is crucial for maintaining neural stem cell (NSC) self-renewal and heterogeneity; however, the underlying mechanism is not well understood. In Drosophila, loss of Notch prematurely terminates the self-renewal of larval type II neuroblasts (NBs, the Drosophila NSCs) and transforms type II NBs into type I NBs. Here, we demonstrate that Notch maintains type II NBs by suppressing the activation of earmuff (erm) by Pointed P1 (PntP1). We show that loss of Notch or components of its canonical pathway leads to PntP1-dependent ectopic Erm expression in type II NBs. Knockdown of Erm significantly rescues the loss-of-Notch phenotypes, and misexpression of Erm phenocopies the loss of Notch. Ectopically expressed Erm promotes the transformation of type II NBs into type I NBs by inhibiting PntP1 function and expression in type II NBs. Our work not only elucidates a key mechanism of Notch-mediated maintenance of type II NB self-renewal and identity, but also reveals a novel function of Erm.

  5. Proanthocyanidins Inhibit Seed Germination by Maintaining a High Level of Abscisic Acid in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Liguo Jia; Jianhua Zhang; Qiuyu Wu; Nenghui Ye; Rui Liu; Lu Shi; Weifeng Xu; Hui Zhi; A. N. M. Rubaiyath Bin Rahman; Yiji Xia

    2012-01-01

    Proanthocyanidins (PAs) are the main products of the flavonoid biosynthetic pathway in seeds,but their biological function during seed germination is still unclear.We observed that seed germination is delayed with the increase of exogenous PA concentration in Arabidopsis.A similar inhibitory effect occurred in peeled Brassica napus seeds,which was observed by measuring radicle elongation.Using abscisic acid (ABA),a biosynthetic and metabolic inhibitor,and gene expression analysis by real-time polymerase chain reaction,we found that the inhibitory effect of PAs on seed germination is due to their promotion of ABA via de novo biogenesis,rather than by any inhibition of its degradation.Consistent with the relationship between PA content and ABA accumulation in seeds,PA-deficient mutants maintain a lower level of ABA compared with wild-types during germination.Our data suggest that PA distribution in the seed coat can act as a doorkeeper to seed germination.PA regulation of seed germination is mediated by the ABA signaling pathway.

  6. WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

    Science.gov (United States)

    Buckley, Catherine M.; Gopaldass, Navin; Bosmani, Cristina; Johnston, Simon A.; Insall, Robert H.

    2016-01-01

    Macropinocytosis is an ancient mechanism that allows cells to harvest nutrients from extracellular media, which also allows immune cells to sample antigens from their surroundings. During macropinosome formation, bulk plasma membrane is internalized with all its integral proteins. It is vital for cells to salvage these proteins before degradation, but the mechanisms for sorting them are not known. Here we describe the evolutionarily conserved recruitment of the WASH (WASP and SCAR homolog) complex to both macropinosomes and phagosomes within a minute of internalization. Using Dictyostelium, we demonstrate that WASH drives protein sorting and recycling from macropinosomes and is thus essential to maintain surface receptor levels and sustain phagocytosis. WASH functionally interacts with the retromer complex at both early and late phases of macropinosome maturation, but mediates recycling via retromer-dependent and -independent pathways. WASH mutants consequently have decreased membrane levels of integrins and other surface proteins. This study reveals an important pathway enabling cells to sustain macropinocytosis without bulk degradation of plasma membrane components. PMID:27647881

  7. 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......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...

  8. Motility and peristaltic flow in maintaining microbiome populations

    Science.gov (United States)

    Mirbagheri, Seyed Amir; Fu, Henry C.

    2016-11-01

    Bacteria are an important component of the microbiome in the digestive tract, and must be able to maintain their population despite the fact that the contents of the intestines are constantly flowing towards evacuation. Many bacteria accomplish this by colonizing the surfaces of the intestines where flows diminish, but some species live in the lumen. We attempt to address whether swimming motility of these species plays an important role in maintaining bacterial population in the face of peristaltic pumping out of the intestine. Using a two-dimensional model of peristaltic flows induced by small-amplitude traveling waves we examine the Lagrangian trajectories of passive bacteria as well as motile bacteria, which are treated as Brownian particles undergoing enhanced diffusion due to the bacteria's run-and-tumble motility. We examine how the densities of growing populations of bacteria depend on the combination of motility and peristaltic flow.

  9. 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.

  10. An intervention to help older adults maintain independence safely.

    Science.gov (United States)

    Ganong, Lawrence H; Coleman, Marilyn; Benson, Jacquelyn J; Snyder-Rivas, Linley A; Stowe, James D; Porter, Eileen J

    2013-05-01

    Older adults who live alone are at risk for problems (e.g., falling, sudden illness). To maintain themselves safely at home they may benefit from planning to prevent problems. The purpose of this study was to evaluate an intervention designed to train family members or friends as to how to help older adults who were living alone make plans to maintain independence safely in their homes and to make behavioral and household changes to enhance safety. Support network members of 19 older adults randomly assigned to the intervention group were taught to use multiple segment vignettes to assist the older adults in creating plans for living safely. Older adults in the control group (n = 21) were asked to engage in an unstructured discussion about home safety with their network members. Older adults in the intervention group developed safer plans and made more household and behavioral changes than did control group adults.

  11. 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...... confluence of chemical, artificial intelligence, and robotic approaches to artificial life.......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...

  12. 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....

  13. Maintaining dignity. The perspective of nursing home residents

    DEFF Research Database (Denmark)

    Høy, Bente

    2014-01-01

    Purpose. The overall purpose of this cross-country Nordic study was to gain further knowledge about dignity in nursing homes and the circumstances which may have an impact on it. The aim of this part of the study is to present the results, exploring nursing home residents’ experiences on how...... 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...... the perspective of the nursing home residents. Method. This qualitative study has an explorative design, based on qualitative individual research interviews. Twenty-eight nursing home residents were included from six nursing homes in Scandi-navia. A phenomenological-hermeneutic approach, inspired by Ricoeur...

  14. Artificial Intelligence Technology for the Maintainer’s Associate.

    Science.gov (United States)

    1986-12-01

    the term "Maintainer’s Associate," which was coined during The 1985 National Academy of Sciences Summer Study on Fault Isolation in Air Force Weapon...example, is paper-based and physicall ) 1 ri Ird insufficient cooperation between design eiir,,. of technical documentation have led to prubr’z, c; .1-t...in the 1985 National Academy of Sciences Summer Study on Fault Isolation in Air Force Weapon and Support Systems (National Academy Press, in press) to

  15. Designing for Supportability: Driving Reliability, Availability, and Maintainability In...

    Science.gov (United States)

    2012-04-01

    the initial operational test and evaluation ( IOT &E) process, and assessed against defined criteria. As illustrated in Figure 1, total ownership costs...Affordability Supportability Design Reviews, Tests and Evaluation ASR PDR CDR IOT &E Figure 2. Reliability, Availability, Maintainability —Life...Expended Cost Committed Concept & Engineering & Prod & Operations & Tech Dev Manufacturing Depl’mnt FRP Support Dev Decision OT&E Review A B C

  16. Maintaining plethodontid salamanders in the laboratory for regeneration studies.

    Science.gov (United States)

    Arenas, Claudia Marcela; Gómez-Molina, Andrea; Delgado, Jean Paul

    2015-01-01

    Limb regeneration studies have been extensively carried out in species of Ambystomatidae and Salamandridae families. So far limited research has been conducted in species belonging to the Plethodontidae family, where some of the species differs from other salamander families due to their direct development, thus absence of a larval life. Here, we describe a protocol to maintain the plethodontid salamanders of genus Bolitoglossa species under laboratory conditions to perform regeneration studies.

  17. Maintaining Spanish in an English-Speaking World

    OpenAIRE

    Juhasz, Audrey Constance

    2013-01-01

    As the Latino portion of the United States population continues to grow each year, more and more children in the United States leave their Spanish-speaking homes and enter English immersion schools. Throughout their lives, these children are likely to shift language preferences from their home language, to the language of the community. However, maintaining development in their first language would be a benefit to them in multiple ways. Identifying factors within bilingual homes that influenc...

  18. Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels

    OpenAIRE

    2015-01-01

    Mitochondria form a dynamic network within the cell as a result of balanced fusion and fission. Despite the established role of mitofusins (MFN1 and MFN2) in mitochondrial fusion, only MFN2 has been associated with metabolic and neurodegenerative diseases, which suggests that MFN2 is needed to maintain mitochondrial energy metabolism. The molecular basis for the mitochondrial dysfunction encountered in the absence of MFN2 is not understood. Here we show that loss of MFN2 leads to impaired mit...

  19. Maintaining the environmental-racial order in northern New Mexico

    OpenAIRE

    Wilmsen, Carl

    2007-01-01

    The environmental - racial order in northern New Mexico is maintained through a process of racial triangulation in which Anglos, Native Americans, and Hispanos are valued relative to one another along axes of environmental stewardship and victimization (Kim C J, 1999, "The racial triangulation of Asian Americans" Politics and Society 27 105 - 138). Both axes involve the juxtaposing of three long-standing images: (1) Spanish injustices to the Indians; (2) the inability of Mexicans to manage th...

  20. Erasure as a means of maintaining diglossia in Cyprus

    OpenAIRE

    2006-01-01

    The Greek speech community of Cyprus is characterized by classic diglossia, with the local varieties forming the L, and Standard Greek the H. It is argued here that this diglossic situation is maintained against what the sociopolitical and economic conditions would predict, because the prevailing linguistic ideology—according to which Cypriots are ethnically Greek, an ethnic identity that is primarily defined by the use of (an almost uniform) Greek language—has led to the erasure of diglossia...

  1. Maintaining Mobile Network Coverage Availability in Disturbance Scenarios

    Directory of Open Access Journals (Sweden)

    Joonas Säe

    2016-01-01

    Full Text Available Disturbance and disaster scenarios prevent the normal utilization of mobile networks. The aim of this study is to maintain the availability of cellular networks in disturbance scenarios. In order to extend the disaster time functionality, energy usage optimization is needed to maintain reasonable coverage and capacity. Simulations performed with different network layouts show the effects of choosing only a portion of evolved node B (eNB macrosites to operate at a time. Different sets of three to nine three-sectored eNB sites are selected to study how the network would perform with a limited number of eNB sites. Simulation results show how the mobile network availability duration can be sustained by selecting a set of eNB sites to operate at a time and still maintain a reasonable service level and availability in disturbance scenarios. An increase of 100% to 500% can be achieved in the duration of “backup coverage” in cellular networks with backup batteries when the percentage of active eNB sites is reduced down to 20%.

  2. 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.

  3. Helium POT System for Maintaining Sample Temperature after Cryocooler Deactivation

    Science.gov (United States)

    Haid, B. J.

    2006-04-01

    A system for maintaining a sample at a constant temperature below 10 K after deactivating the cooling source is demonstrated. In this system, the cooling source is a 4 K GM cryocooler that is joined with the sample through an extension that consists of a helium pot and a thermal resistance. Upon stopping the cryocooler, the power applied to a heater located on the sample side of the thermal resistance is decreased gradually to maintain an appropriate temperature rise across the thermal resistance as the helium pot warms. The sample temperature is held constant in this manner without the use of solid or liquid cryogens and without mechanically disconnecting the sample from the cooler. Shutting off the cryocooler significantly reduces sample motion that results from vibration and expansion/contraction of the cold-head housing. The reduction in motion permits certain procedures that are very sensitive to sample position stability, but are performed with limited duration. A proof-of-concept system was built and operated with the helium pot pressurized to the cryocooler's charge pressure. A sample with 200 mW of continuous heat dissipation was maintained at 7 K while the cryocooler operated intermittently with a duty cycle of 9.5 minutes off and 20 minutes on.

  4. Space maintainer effects on intercanine arch width and length.

    Science.gov (United States)

    Dincer, M; Haydar, S; Unsal, B; Turk, T

    1996-01-01

    In order to investigate the effects of space maintainers in intercanine arch width and length, twenty cases, characterized with the early loss of mandibular primary molars were selected and divided into two groups. The treatment group used removable space maintainers, while the other ten cases served as the control group. The first dental casts of the treatment and control groups were obtained when the primary canines were in the mouth. After the eruption of permanent canines second dental casts were obtained in both groups. Six measurements were made on the dental casts of each patient. No parameter was found to be statistically significant in the treatment group. In the control group the increase in intercanine arch width and perimeter were found to be statistically significant. Also the increase at the buccal and lingual bone measurements were found to be statistically significant. These results showed that space maintainers might cease the increase in intercanine arch width and length during the transition period between the primary and permanent canines.

  5. Predictors of maintained high-risk behaviors among impoverished women.

    Science.gov (United States)

    Nyamathi, A M; Bennett, C; Leake, B

    1995-01-01

    The researchers sought to explore and describe the demographic, cognitive, psychosocial, and behavioral factors associated with the continued risky behavior of a convenience sample of homeless and drug-addicted women two to four weeks after they had completed an AIDS education program. The sample included 942 crack users and 767 women who had multiple sex partners. Analyses revealed that impoverished women who maintained multiple sexual partners were less likely to be in drug recovery programs than in homeless shelters. They were more likely to share needles and be involved sexually with male injection drug users compared with impoverished women who did not maintain multiple sexual partners. Persistent crack users were older than those who reported cessation of crack use, were more often African American, and were more likely to have sex partners who were injecting drug users. Women who demonstrated less improvement in depression and distress scores, concerns, use of affective coping, appraisal of threat, and social support were more likely to maintain crack use and multiple partners. The study's implications for the design of intervention programs aimed at risk reduction based on ethnicity are discussed.

  6. Immune cell trafficking from the brain maintains CNS immune tolerance.

    Science.gov (United States)

    Mohammad, Mohammad G; Tsai, Vicky W W; Ruitenberg, Marc J; Hassanpour, Masoud; Li, Hui; Hart, Prue H; Breit, Samuel N; Sawchenko, Paul E; Brown, David A

    2014-03-01

    In the CNS, no pathway dedicated to immune surveillance has been characterized for preventing the anti-CNS immune responses that develop in autoimmune neuroinflammatory disease. Here, we identified a pathway for immune cells to traffic from the brain that is associated with the rostral migratory stream (RMS), which is a forebrain source of newly generated neurons. Evaluation of fluorescently labeled leukocyte migration in mice revealed that DCs travel via the RMS from the CNS to the cervical LNs (CxLNs), where they present antigen to T cells. Pharmacologic interruption of immune cell traffic with the mononuclear cell-sequestering drug fingolimod influenced anti-CNS T cell responses in the CxLNs and modulated experimental autoimmune encephalomyelitis (EAE) severity in a mouse model of multiple sclerosis (MS). Fingolimod treatment also induced EAE in a disease-resistant transgenic mouse strain by altering DC-mediated Treg functions in CxLNs and disrupting CNS immune tolerance. These data describe an immune cell pathway that originates in the CNS and is capable of dampening anti-CNS immune responses in the periphery. Furthermore, these data provide insight into how fingolimod treatment might exacerbate CNS neuroinflammation in some cases and suggest that focal therapeutic interventions, outside the CNS have the potential to selectively modify anti-CNS immunity.

  7. Policies built upon pathways

    NARCIS (Netherlands)

    S. Musterd; Z. Kovács

    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 importa

  8. 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.

  9. 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.

  10. Mining biological pathways using WikiPathways web services.

    Directory of Open Access Journals (Sweden)

    Thomas Kelder

    Full Text Available WikiPathways is a platform for creating, updating, and sharing biological pathways [1]. Pathways can be edited and downloaded using the wiki-style website. Here we present a SOAP web service that provides programmatic access to WikiPathways that is complementary to the website. We describe the functionality that this web service offers and discuss several use cases in detail. Exposing WikiPathways through a web service opens up new ways of utilizing pathway information and assisting the community curation process.

  11. Mining biological pathways using WikiPathways web services.

    Science.gov (United States)

    Kelder, Thomas; Pico, Alexander R; Hanspers, Kristina; van Iersel, Martijn P; Evelo, Chris; Conklin, Bruce R

    2009-07-30

    WikiPathways is a platform for creating, updating, and sharing biological pathways [1]. Pathways can be edited and downloaded using the wiki-style website. Here we present a SOAP web service that provides programmatic access to WikiPathways that is complementary to the website. We describe the functionality that this web service offers and discuss several use cases in detail. Exposing WikiPathways through a web service opens up new ways of utilizing pathway information and assisting the community curation process.

  12. 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

  13. Diets, equipment, and techniques for maintaining crawfish in the laboratory

    Science.gov (United States)

    Tarshis, I.B.; Avault, James W.

    1978-01-01

    One commercial and 4 laboratory prepared extruded, water-stable diets were fed 3 times a week in 1-g portions to juvenile male and female White River crawfish, Procambarus acutus acutus (Girard), for 10 weeks. The. binding material in the laboratory preparation was alginate (Kelgin), whereas that in the commercial preparation was starch. No statistically significant weight differences developed between the groups of crawfish at the end of the 10-week period; all 5 diets were found satisfactory for feeding and maintaining P. acutus acutus in the laboratory, and all test crawfish survived throughout the experimental period. Weight gains were highest in a diet containing 50.5% protein; intermediate in those fed a diet with 46.0% protein; and lowest in those fed diets with 31.7 or 36.3% protein. Crawfish fed the commercial preparation of one of the 46.0% protein diets showed a slightly but not significantly higher weight gain than those fed the laboratory preparation of the diet. In an evaluation of the water stability of 5 commercially prepared animal chow diets and the commercial extruded diet, 2 of the commercial diets disintegrated after one hour exposure in water and the other 3 became bloated after one hour and remained on the surface throughout the 24-hour test. The commercial extruded diet maintained its water stability for the full 24 hours. The commercial preparation of the 46.0% protein diet was successfully used under laboratory conditions for feeding and maintaining the following crawfishes: Cambarellus shufeldtii (Faxon), Cambarus acuminatus Faxon, Orconectes limosus (Rafinesque), O. virilis (Hagen), Procambarus clarkii (Girard), and P. spiculifer (Le conte). In longevity experiments Cambarus diogenes diogenes Girard and Procambarus hinei (Ortmann) now have survived for 8 months on this diet in the laboratory.

  14. A nanofibrous electrospun patch to maintain human mesenchymal cell stemness.

    Science.gov (United States)

    Pandolfi, L; Furman, N Toledano; Wang, Xin; Lupo, C; Martinez, J O; Mohamed, M; Taraballi, F; Tasciotti, E

    2017-03-01

    Mesenchymal stem cells (MSCs) have been extensively investigated in regenerative medicine because of their crucial role in tissue healing. For these properties, they are widely tested in clinical trials, usually injected in cell suspension or in combination with tridimensional scaffolds. However, scaffolds can largely affect the fates of MSCs, inducing a progressive loss of functionality overtime. The ideal scaffold must delay MSCs differentiation until paracrine signals from the host induce their change. Herein, we proposed a nanostructured electrospun gelatin patch as an appropriate environment where human MSCs (hMSCs) can adhere, proliferate, and maintain their stemness. This patch exhibited characteristics of a non-linear elastic material and withstood degradation up to 4 weeks. As compared to culture and expansion in 2D, hMSCs on the patch showed a similar degree of proliferation and better maintained their progenitor properties, as assessed by their superior differentiation capacity towards typical mesenchymal lineages (i.e. osteogenic and chondrogenic). Furthermore, immunohistochemical analysis and longitudinal non-invasive imaging of inflammatory response revealed no sign of foreign body reaction for 3 weeks. In summary, our results demonstrated that our biocompatible patch favored the maintenance of undifferentiated hMSCs for up to 21 days and is an ideal candidate for tridimensional delivery of hMSCs. The present work reports a nanostructured patch gelatin-based able to maintain in vitro hMSCs stemness features. Moreover, hMSCs were able to differentiate toward osteo- and chondrogenic lineages once induces by differentiative media, confirming the ability of this patch to support stem cells for a potential in vivo application. These attractive properties together with the low inflammatory response in vivo make this patch a promising platform in regenerative medicine.

  15. Low-loss air-core polarization maintaining terahertz fiber.

    Science.gov (United States)

    Ren, Guobin; Gong, Yandong; Shum, Ping; Yu, Xia; Hu, JuanJuan; Wang, Guanghui; Ong Ling Chuen, Michael; Paulose, Varghese

    2008-09-01

    We propose a low-loss air-core polarization maintaining polymer fiber for terahertz (THz) wave guiding. The periodic arrangement of square holes with round corners in the cladding offers a bandgap effect for mode guiding. Numerical simulations show that the bandgap effect repels the modal power from the absorbent background polymers, resulting in a significant suppression of absorption loss of the polymers by a factor of more than 25. The phase-index birefringence of the proposed THz fiber is in the order of 10(-3).

  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. Integrated care pathways and task shifting

    Directory of Open Access Journals (Sweden)

    Linda Panton

    2014-11-01

    Full Text Available Delivery of HIV care has evolved over the last 10 years, and nurse specialists are a driving force in developing new pathways to enhance patient care. Despite the continued rise in numbers of people living with HIV, the financial constraints on the NHS have unfortunately resulted in a reduction in service provision. Experienced nurses are integral to patient care management. They not only provide standardized care for stable patients, therefore increasing consultant capacity for the more complex medical patient, but have a degree of flexibility that allows newly diagnosed patients quick access to care and support. With a strong emphasis being placed on an integrated and collaborative multidisciplinary team approach, to ensure patients receive the same standard of care, Scotland's HIV centres follow an integrated care pathway. The nurse oversees the completion of this document and co-ordinates the pathway of care depending on the clinical need. Nurses develop and maintain necessary partnerships between primary care, specialist care, psychological services, social care and third sector support services. The nurse case load continues to expand and diversify. Stable patients may be maintained on therapy but are living with a stigmatized long-term chronic condition and rely on the nurse as a point of contact to access advice and support readily. The more chaotic and vulnerable clients with complex care needs require the nurse to co-ordinate their care, ensuring the appropriate agencies remain involved. Overseeing the transition of care to other units and tracing patients who are lost to follow up is also a necessity, as retention in care is paramount for the continued improvement in clinical outcomes. The contribution that specialist nurses make to the provision of HIV care is valuable and will continue to play a large role in the delivery of such care.

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

    Science.gov (United States)

    Shitsukawa, Naoki; Ikari, Chihiro; Shimada, Sanae; Kitagawa, Satoshi; Sakamoto, Koichi; Saito, Hiroyuki; Ryuto, Hiromichi; Fukunishi, Nobuhisa; Abe, Tomoko; Takumi, Shigeo; Nasuda, Shuhei; Murai, Koji

    2007-04-01

    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.

  19. Nonlinear fitness landscape of a molecular pathway.

    Directory of Open Access Journals (Sweden)

    Lilia Perfeito

    2011-07-01

    Full Text Available Genes are regulated because their expression involves a fitness cost to the organism. The production of proteins by transcription and translation is a well-known cost factor, but the enzymatic activity of the proteins produced can also reduce fitness, depending on the internal state and the environment of the cell. Here, we map the fitness costs of a key metabolic network, the lactose utilization pathway in Escherichia coli. We measure the growth of several regulatory lac operon mutants in different environments inducing expression of the lac genes. We find a strikingly nonlinear fitness landscape, which depends on the production rate and on the activity rate of the lac proteins. A simple fitness model of the lac pathway, based on elementary biophysical processes, predicts the growth rate of all observed strains. The nonlinearity of fitness is explained by a feedback loop: production and activity of the lac proteins reduce growth, but growth also affects the density of these molecules. This nonlinearity has important consequences for molecular function and evolution. It generates a cliff in the fitness landscape, beyond which populations cannot maintain growth. In viable populations, there is an expression barrier of the lac genes, which cannot be exceeded in any stationary growth process. Furthermore, the nonlinearity determines how the fitness of operon mutants depends on the inducer environment. We argue that fitness nonlinearities, expression barriers, and gene-environment interactions are generic features of fitness landscapes for metabolic pathways, and we discuss their implications for the evolution of regulation.

  20. 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.

  1. Acquiring and maintaining a normal oral microbiome: current perspective.

    Science.gov (United States)

    Zaura, Egija; Nicu, Elena A; Krom, Bastiaan P; Keijser, Bart J F

    2014-01-01

    The oral microbiota survives daily physical and chemical perturbations from the intake of food and personal hygiene measures, resulting in a long-term stable microbiome. Biological properties that confer stability in the microbiome are important for the prevention of dysbiosis-a microbial shift toward a disease, e.g., periodontitis or caries. Although processes that underlie oral diseases have been studied extensively, processes involved in maintaining of a normal, healthy microbiome are poorly understood. In this review we present our hypothesis on how a healthy oral microbiome is acquired and maintained. We introduce our view on the prenatal development of tolerance for the normal oral microbiome: we propose that development of fetal tolerance toward the microbiome of the mother during pregnancy is the major factor for a successful acquisition of a normal microbiome. We describe the processes that influence the establishment of such microbiome, followed by our perspective on the process of sustaining a healthy oral microbiome. We divide microbiome-maintenance factors into host-derived and microbe-derived, while focusing on the host. Finally, we highlight the need and directions for future research.

  2. Maintaining Aura's Orbit Requirements Under New Maneuver Operations

    Science.gov (United States)

    Johnson, Megan; Petersen, Jeremy D.

    2014-01-01

    The Earth Observing System (EOS) Afternoon Constellation consists of five member missions (GCOM-W1, Aqua, CALIPSO, CloudSat, and Aura), each of which maintain a frozen, sun-synchronous orbit with a 16-day repeating ground track that follows the Worldwide Reference System-2 (WRS-2). Under nominal science operations for Aura, the propulsion system is oriented such that the resultant thrust vector is aligned 13.493 degrees away from the velocity vector along the yaw axis. When performing orbit maintenance maneuvers, the spacecraft performs a yaw slew to align the thrust vector in the appropriate direction. A new Drag Make Up (DMU) maneuver operations scheme has been implemented for Aura alleviating the need for the 13.493 degree yaw slew. The focus of this investigation is to assess the impact that no-slew DMU maneuver operations will have on Auras Mean Local Time (MLT) which drives the required along track separation between Aura and the constellation members, as well as Auras frozen orbit properties, eccentricity and argument of perigee. Seven maneuver strategies were analyzed to determine the best operational approach. A mirror pole strategy, with maneuvers alternating at the North and South poles, was implemented operationally to minimize impact to the MLT. Additional analysis determined that the mirror pole strategy could be further modified to include frozen orbit maneuvers and thus maintain both MLT and the frozen orbit properties under no-slew operations

  3. Extending Access Management to maintain audit logs in cloud computing

    Directory of Open Access Journals (Sweden)

    Ajay Prasad

    2014-01-01

    Full Text Available Considering the most often talked about security risks in cloud computing, like, security and compliance, viability, lack of transparency, reliability and performance issues. Bringing strong auditability in cloud services can reduce these risks to a great extent. Also, auditing, both internally and externally is generally required and sometimes unavoidable looking into the present day competition in the business arena. Auditing in web based and cloud based usage environments focuses mainly on cost of a service which determines the overall expenditure of the user organization. However, the expenditure can be controlled by a collaborative approach between the provider company and the user organization by constantly monitoring the end user access and usage of subscribed cloud services. Though, many cloud providers will claim of having a robust auditable feature, the generic verifiability with sustainable long term recording of usage logs do not exist at all. Certain access management models can be perfectly extended to maintain audit logs for long terms. However, maintaining long term logs certainly has storage implications, especially with larger organizations. The storage implications need to be studied.

  4. Landscape irrigation management for maintaining an aquifer and economic returns.

    Science.gov (United States)

    Kovacs, Kent Forrest; Mancini, Mattia; West, Grant

    2015-09-01

    Expanding irrigated agriculture and dryer climatic conditions has led to large-scale withdrawals of groundwater and the decline in shallow aquifers. Policy makers must wrestle with the challenge of maintaining economic growth while conserving the groundwater resource. A spatially explicit landscape level model analyzes consequences of optimally chosen crop mix patterns on an aquifer and economic returns. The model of the groundwater use incorporates irrigation needs of the crops grown, initial aquifer thickness, hydro-conductivity of the aquifer, and distance to surrounding grid cells. The economic model incorporates the site specific yield, crop mix, and irrigation practice investments to predict economic returns. A tradeoff occurs between the volume of the aquifer and economic returns due to groundwater withdrawal for irrigation, but the farm's ability to grow profitable lower irrigation crops dampens the intensity of this tradeoff. Allowing for multiple unconventional irrigation practices that are yield increasing and water conserving significantly increases the economic returns of a given crop mix while maintaining the aquifer.

  5. Lifelong Bilingualism Maintains White Matter Integrity in Older Adults

    Science.gov (United States)

    Luk, Gigi; Bialystok, Ellen; Craik, Fergus I. M.; Grady, Cheryl L.

    2012-01-01

    Previous research has shown that bilingual speakers have higher levels of cognitive control than comparable monolinguals, especially at older ages. The present study investigates a possible neural correlate of this behavioral effect. Given that white matter (WM) integrity decreases with age in adulthood, we tested the hypothesis that bilingualism is associated with maintenance of WM in older people. Using diffusion tensor imaging, we found higher WM integrity in older people who were lifelong bilinguals than in monolinguals. This maintained integrity was measured by fractional anisotropy (FA) and was found in the corpus callosum extending to the superior and inferior longitudinal fasciculi. We also hypothesized that stronger WM connections would be associated with more widely distributed patterns of functional connectivity in bilinguals. We tested this by assessing the resting-state functional connectivity of frontal lobe regions adjacent to WM areas with group differences in FA. Bilinguals showed stronger anterior to posterior functional connectivity compared to monolinguals. These results are the first evidence that maintained WM integrity is related to lifelong naturally occurring experience; the resulting enhanced structural and functional connectivity may provide a neural basis for “brain reserve.” PMID:22090506

  6. Acquiring and maintaining a normal oral microbiome: current perspective

    Directory of Open Access Journals (Sweden)

    Egija eZaura

    2014-06-01

    Full Text Available The oral microbiota survives daily physical and chemical perturbations from the intake of food and personal hygiene measures, resulting in a long-term stable microbiome. Biological properties that confer stability in the microbiome are important for the prevention of dysbiosis – a microbial shift towards a disease, e.g., periodontitis or caries. Although processes that underlie oral diseases have been studied extensively, processes involved in maintaining of a normal, healthy microbiome are poorly understood. In this review we present our hypothesis on how a healthy oral microbiome is acquired and maintained. We introduce our view on the prenatal development of tolerance for the normal oral microbiome: we propose that development of fetal tolerance towards the microbiome of the mother during pregnancy is the major factor for a successful acquisition of a normal microbiome. We describe the processes that influence the establishment of such microbiome, followed by our perspective on the process of sustaining a healthy oral microbiome. We divide microbiome-maintenance factors into host-derived and microbe-derived, while focusing on the host. Finally, we highlight the need and directions for future research.

  7. Lifelong bilingualism maintains white matter integrity in older adults.

    Science.gov (United States)

    Luk, Gigi; Bialystok, Ellen; Craik, Fergus I M; Grady, Cheryl L

    2011-11-16

    Previous research has shown that bilingual speakers have higher levels of cognitive control than comparable monolinguals, especially at older ages. The present study investigates a possible neural correlate of this behavioral effect. Given that white matter (WM) integrity decreases with age in adulthood, we tested the hypothesis that bilingualism is associated with maintenance of WM in older people. Using diffusion tensor imaging, we found higher WM integrity in older people who were lifelong bilinguals than in monolinguals. This maintained integrity was measured by fractional anisotropy (FA) and was found in the corpus callosum extending to the superior and inferior longitudinal fasciculi. We also hypothesized that stronger WM connections would be associated with more widely distributed patterns of functional connectivity in bilinguals. We tested this by assessing the resting-state functional connectivity of frontal lobe regions adjacent to WM areas with group differences in FA. Bilinguals showed stronger anterior to posterior functional connectivity compared to monolinguals. These results are the first evidence that maintained WM integrity is related to lifelong naturally occurring experience; the resulting enhanced structural and functional connectivity may provide a neural basis for "brain reserve."

  8. 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.

  9. Microtubules contribute to maintain nucleus shape in epithelial cell monolayer

    Science.gov (United States)

    Tremblay, Dominique; Andrzejewski, Lukasz; Pelling, Andrew

    2013-03-01

    INTRODUCTION: Tissue strains can result in significant nuclear deformations and may regulate gene expression. However, the precise role of the cytoskeleton in regulating nuclear mechanics remains poorly understood. Here, we investigate the nuclear deformability of Madin-Darky canine kidney cells (MDCK) under various stretching conditions to clarify the role of the microtubules and actin network on the mechanical behavior of the nucleus. METHODS: A custom-built cell-stretching device allowing for real time imaging of MDCK nuclei was used. Cells were seeded on a silicone membrane coated with rat-tail collagen I. A nuclear stain, Hoechst-33342, was used to image nuclei during stretching. We exposed cells to a compressive and non-compressive stretching strain field of 25%. Nocodazole and cytochalasin-D were used to depolymerize the microtubules and actin network. RESULTS: Nuclei in control cells stretched more along their minor axis than major axis with a deformation of 5% and 2% respectively. This anisotropy vanished completely in microtubule-deprived cells and these cells showed a very high nuclear deformability along the minor axis when exposed to a compressive stretching strain field. CONCLUSIONS: The microtubules drive the anisotropic deformability of MDCK nuclei in a monolayer and maintain nuclear shape when exposed to compressive strain. Such intrinsic mechanical behavior indicates that microtubules are essential to maintain nuclear shape and may prevent down regulation of gene expression.

  10. 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.

  11. Outcomes of Phacoemulsification with Anterior Chamber Maintainer in Vitrectomized Eyes

    Directory of Open Access Journals (Sweden)

    Elif Betül Türkoğlu

    2012-07-01

    Full Text Available Pur po se: To evaluate the outcomes of phacoemulsification with anterior chamber maintainer in vitrectomized eyes with complicated cataract. Ma te ri al and Met hod: Twenty eyes of 20 patients who developed complicated cataract after pars plana vitrectomy (PPV were included in the study. Phacoemulsification with clear corneal incision and foldable intraocular lens implantation was performed. In group 1, anterior chamber maintainer (ACM was used during phacoemusification and in group 2, ACM was not used. Pre- and postoperative visual acuities as well as per- and postoperative complications were reviewed retrospectively. Re sults: Anterior chamber maintainer was used during the surgery in 12 (60% cases and was not used in 8 (40% cases. Phacoemulsification was performed 16.5±9.2 (4-40 months after PPV. Best-corrected visual acuities were between hand motions and 0.4 preoperatively and between counting fingers from 1 meter and 1.0 postoperatively in group 1. Best-corrected visual acuities were between hand motions and 0.1 preoperatively and between counting fingers from 1 meter and 0.8 postoperatively in group 2. Posterior capsule was ruptured in 1 eye peroperatively in group 1. In group 2, phacoemulsification was more difficult due to deep anterior chamber in 8 eyes and intraoperative complications were iris sphincter rupture in 1 eye and posterior capsule rupture in 1 eye. Mild corneal edema in 7 (58.3% eyes, fibrin reaction in 2 (16.6%, intraocular lens decentralization in 1 (8.3% and posterior capsule opacification in 4 (33.3% eyes were the postoperative complications in group 1. Mild corneal edema in 5 (62.5% eyes, fibrin reaction in 1 (12.5% and posterior capsule opacification in 2 (25% eyes were the postoperative complications in group 2. Dis cus si on: Complicated cataracts which may develop after PPV can be treated safely with phacoemulsification. Continuous irrigation during the surgery may provide a stable anterior chamber and prevents

  12. 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

  13. Conservation of PHO pathway in ascomycetes and the role of Pho84

    Indian Academy of Sciences (India)

    Parul Tomar; Sinha Sinha

    2014-06-01

    In budding yeast, Saccharomyces cerevisiae, the phosphate signalling and response pathway, known as PHO pathway, monitors phosphate cytoplasmic levels by controlling genes involved in scavenging, uptake and utilization of phosphate. Recent attempts to understand the phosphate starvation response in other ascomycetes have suggested the existence of both common and novel components of the budding yeast PHO pathway in these ascomycetes. In this review, we discuss the components of PHO pathway, their roles in maintaining phosphate homeostasis in yeast and their conservation across ascomycetes. The role of high-affinity transporter, Pho84, in sensing and signalling of phosphate has also been discussed.

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

    OpenAIRE

    Garg, A.; Samadi, F.; J N Jaiswal; Saha, S.

    2014-01-01

    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...

  15. Reliability and Maintainability Data for Liquid Metal Cooling Systems

    Energy Technology Data Exchange (ETDEWEB)

    Cadwallader, Lee Charles [Idaho National Laboratory

    2015-05-01

    One of the coolants of interest for future fusion breeding blankets is lead-lithium. As a liquid metal it offers the advantages of high temperature operation for good station efficiency, low pressure, and moderate flow rate. This coolant is also under examination for use in test blanket modules to be used in the ITER international project. To perform reliability, availability, maintainability and inspectability (RAMI) assessment as well as probabilistic safety assessment (PSA) of lead-lithium cooling systems, component failure rate data are needed to quantify the system models. RAMI assessment also requires repair time data and inspection time data. This paper presents a new survey of the data sets that are available at present to support RAMI and PSA quantification. Recommendations are given for the best data values to use when quantifying system models.

  16. The critical power to maintain thermally stable molecular junctions

    Science.gov (United States)

    Wang, Yanlei; Xu, Zhiping

    2014-07-01

    With the rise of atomic-scale devices such as molecular electronics and scanning probe microscopies, energy transport processes through molecular junctions have attracted notable research interest recently. In this work, heat dissipation and transport across diamond/benzene/diamond molecular junctions are explored by performing atomistic simulations. We identify the critical power Pcr to maintain thermal stability of the junction through efficient dissipation of local heat. We also find that the molecule-probe contact features a power-dependent interfacial thermal resistance RK in the order of 109 kW-1. Moreover, both Pcr and RK display explicit dependence on atomic structures of the junction, force and temperature. For instance, Pcr can be elevated in multiple-molecule junctions, and streching the junction enhances RK by a factor of 2. The applications of these findings in molecular electronics and scanning probing measurements are discussed, providing practical guidelines in their rational design.

  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. 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.

  19. NiTi bonded space regainer/maintainer.

    Science.gov (United States)

    Negi, K S

    2010-01-01

    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.

  20. Neural correlates of establishing, maintaining, and switching brain states.

    Science.gov (United States)

    Tang, Yi-Yuan; Rothbart, Mary K; Posner, Michael I

    2012-06-01

    Although the study of brain states is an old one in neuroscience, there has been growing interest in brain state specification owing to MRI studies tracing brain connectivity at rest. In this review, we summarize recent research on three relatively well-described brain states: the resting, alert, and meditation states. We explore the neural correlates of maintaining a state or switching between states, and argue that the anterior cingulate cortex and striatum play a critical role in state maintenance, whereas the insula has a major role in switching between states. Brain state may serve as a predictor of performance in a variety of perceptual, memory, and problem solving tasks. Thus, understanding brain states is critical for understanding human performance.

  1. 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.

  2. Propagation of Optical Pulses in Polarization Maintaining Highly Birefringent Fibers

    Science.gov (United States)

    Leiva, Ariel; Olivares, Ricardo

    2008-04-01

    The propagation of Gaussian optical pulses through optical PM-HiBi (Polarization Maintaining Highly Birefringent) fibers is analyzed and simulated. Based upon a model of propagation as described by Marcuse, et al., [1] and Sunnerud, et al., [2], and the use of PMD (Polarization Mode Dispersion) compensators and emulators used by Kogelnik, et al. [2], [3] and Lima, et al. [4], we construct a simple model that allows graphical representation of the distortion experienced by optical pulses when propagating in a PM-HiBi fiber for different initial polarizations. The results of our analysis have the benefit of being identical to the more elaborate models of [1], [2], while also providing the additional advantage of simple graphical representation.

  3. Hierarchically nanotextured surfaces maintaining superhydrophobicity under severely adverse conditions

    Science.gov (United States)

    Maitra, Tanmoy; Antonini, Carlo; Auf der Mauer, Matthias; Stamatopoulos, Christos; Tiwari, Manish K.; Poulikakos, Dimos

    2014-07-01

    Superhydrophobic surfaces are highly desirable for a broad range of technologies and products affecting everyday life. Despite significant progress in recent years in understanding the principles of hydrophobicity, mostly inspired by surface designs found in nature, many man-made surfaces employ readily processable materials, ideal to demonstrate principles, but with little chance of survivability outside a very limited range of well-controlled environments. Here we focus on the rational development of robust, hierarchically nanostructured, environmentally friendly, metal-based (aluminum) superhydrophobic surfaces, which maintain their performance under severely adverse conditions. Based on their functionality, we superpose selected hydrophobic layers (i.e. self-assembled monolayers, thin films, or nanofibrous coatings) on hierarchically textured aluminum surfaces, collectively imparting high level robustness of superhydrophobicity under adverse conditions. These surfaces simultaneously exhibit chemical stability, mechanical durability and droplet impalement resistance. They impressively maintained their superhydrophobicity after exposure to severely adverse chemical environments like strong alkaline (pH ~ 9-10), acidic (pH ~ 2-3), and ionic solutions (3.5 weight% of sodium chloride), and could simultaneously resist water droplet impalement up to an impact velocity of 3.2 m s-1 as well as withstand standard mechanical durability tests.Superhydrophobic surfaces are highly desirable for a broad range of technologies and products affecting everyday life. Despite significant progress in recent years in understanding the principles of hydrophobicity, mostly inspired by surface designs found in nature, many man-made surfaces employ readily processable materials, ideal to demonstrate principles, but with little chance of survivability outside a very limited range of well-controlled environments. Here we focus on the rational development of robust, hierarchically

  4. Teaching and maintaining ethical behavior in a professional organization.

    Science.gov (United States)

    Brodhead, Matthew T; Higbee, Thomas S

    2012-01-01

    In addition to continuing education mandates by the Behavior Analyst Certification Board (BACB), behavior-analytic professional organizations may adopt systems that teach and maintain ethical behavior in its employees. Systems of ethical supervision and management may allow for an organization to customize training that prevents ethical misconduct by employees. These systems may also allow supervisors to identify ethical problems in their infancy, allowing the organization to mitigate concerns before they further develop. Systems of ethical management and supervision also may help to improve services and promote consumer protection. Additional benefits might include both avoiding litigation and loss of consumers and income. These systems may promote the field of Behavior Analysis as a desirable, consumer-friendly approach to solving socially significant behavior problems.

  5. Maintaining photonic quantum polarisation entanglement in nanoscale waveguides

    CERN Document Server

    Li, Ming; Ren, Xi-Feng; Xiong, Xiao; Cai, Yong-Jing; Guo, Guo-Ping; Tong, Li-Min; Guo, Guang-Can

    2014-01-01

    In this work, we demonstrate for the first time the maintaining of quantum polarisation entanglement in both a nanoscale dielectric tapered fibre and a plasmonic waveguide. Entangled photons are coupled into these waveguides, and quantum state tomography is used to verify that the transmitted states have fidelities of 0.958 and 0.932 with the maximally polarisation entangled state Phi^{+}, respectively. Furthermore, the Clauser, Horne, Shimony, and Holt (CHSH) inequality tests performed, resulting in values of$2.588\\pm0.141>2 and 2.495\\pm0.147>2, respectively, demonstrate the violation of the hidden variable model. Our investigations pave the way toward a quantum near-field micro/nano-scope, which can realize high spatial resolution, ultra-sensitive, fibre-integrated, and plasmon-enhanced detection, as well as bridge nanophotonics and quantum metrology.

  6. Creating and maintaining chemical artificial life by robotic symbiosis.

    Science.gov (United States)

    Hanczyc, Martin M; Parrilla, Juan M; Nicholson, Arwen; Yanev, Kliment; Stoy, Kasper

    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 droplet that it creates. The robot can then use this categorization to autonomously detect the current state of the droplet and respond. The robot is programmed to visually track the droplet and either inject more chemical fuel to sustain a motile state or introduce a new chemical component that results in a state change (e.g., division). Coupling inexpensive open source hardware with sensing and feedback allows for replicable real-time manipulation and monitoring of nonequilibrium systems that would be otherwise tedious, expensive, and error-prone. This system is a first step towards the practical confluence of chemical, artificial intelligence, and robotic approaches to artificial life.

  7. Sociable mobile robots through self-maintained energy

    DEFF Research Database (Denmark)

    Ngo, Trung Dung; Schiøler, Henrik

    2006-01-01

    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...... 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...... 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...

  8. Balanced polarization maintaining fiber Sagnac interferometer vibration sensor.

    Science.gov (United States)

    Wada, Kenji; Narui, Hirokazu; Yamamoto, Daiki; Matsuyama, Tetsuya; Horinaka, Hiromichi

    2011-10-24

    To achieve a nearly zero-delay operating point in a polarization-maintaining (PM) fiber Sagnac interferometer, two identical PM fibers were incorporated so that their two main axes were orthogonally coupled to each other. A simple fiber vibration sensor system was constructed with a light emitting diode and a balanced PM fiber Sagnac interferometer, in which one of the PM fibers was used as a sensing cable and the other as a reference cable. The vibration sensor was confirmed to be temperature-compensated and generated a phase shift per unit length and unit strain of the sensor of 4.7 milliradian/(m·με) when mechanical vibrations with 1 kHz sinusoidal and triangular waves were stably observed under an input power of 10 μW.

  9. 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

  10. Maintaining skin integrity in the aged: a systematic review.

    Science.gov (United States)

    Kottner, J; Lichterfeld, A; Blume-Peytavi, U

    2013-09-01

    Ageing is associated with structural and functional changes of the skin that result in increased vulnerability. The aim of this systematic review is to synthesize empirical evidence about the efficacy and effectiveness of basic skin care interventions for maintaining skin integrity in the aged. The databases Medline, EMBASE, CINAHL (1990-2012), Scopus, SCI (February 2013) and reference lists were searched. Inclusion criteria were primary intervention studies using skin care products in physiologically aged skin (lower age limit 50 years). Study and sample characteristics, interventions and outcomes were extracted. The methodological quality was assessed and a level of evidence was assigned. From 1535 screened articles 188 were read in full text. From these, 33 articles were included reporting results on treating dry skin conditions, and preventing incontinence-associated dermatitis and superficial ulcerations. Most studies had lower levels of evidence of 3 or 4. Skin-cleansing products containing syndets or amphoteric surfactants compared with standard soap and water washing improved skin dryness and demonstrated skin-protecting effects. Moisturizers containing humectants consistently showed statistically significant improvements in skin dryness. Skin barrier products containing occlusives reduced the occurrence of skin injuries compared with standard or no treatment. Owing to methodological limitations the current evidence base for basic skin care in the aged is weak. Using low-irritating cleansing products and humectant- or occlusive-containing moisturizers seems to be the best strategy for maintaining the skin barrier function and integrity. We know little about the effects of cleansing regimens and about the benefits of moisturizers when compared with each other.

  11. Distributed Amplify and Forward Cooperation While Maintaining Transmission Freedom

    Directory of Open Access Journals (Sweden)

    L. Chen

    2011-01-01

    Full Text Available Problem statement: This study proposes a novel Distributed Amplify and-Forward (DAF cooperative scheme, achieving higher diver¬sity order and yet maintaining the same transmission freedom as the conventional Amplify-and-Forward (AF scheme. In the DAF scheme, a user’s transmitted symbols are partitioned into several sequences in order to be relayed by different users. Approach: In the cooperative network, each user still uses half of their transmission for relaying others’ signals. But instead of relaying one user’s entire transmitted sequence, it helps different users for the relaying. Theoretical analysis of the DAF scheme is carried out in order to justify its advantages over the existing schemes. The outage behavior and Diversity-Multiplexing Tradeoff (DMT analyses of the DAF scheme are presented. Results: Through outage behavior analysis, it is shown the DAF scheme achieves substantial diversity gains over the AF scheme. Furthermore, the DMT analysis justices both the scheme’s achievable diversity gains and its ability to maintain the same multiplexing gain as the AF scheme. The theoretical analyses are then extended to a general cooperative network consisting of N (N≥2 relays, showing the diversity order can be increased with respect to the number of relays but not at the expense of each user’s multiplexing gain. Conclusion: Finally, a practical coded cooperative system that integrates the DAF scheme with the concatenated Reed-Solomon Convolution Codes (RSCC is proposed, validating the achievable performance gain offered by the DAF scheme.

  12. 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.

  13. Role of microRNAs in maintaining cancer stem cells.

    Science.gov (United States)

    Garofalo, Michela; Croce, Carlo M

    2015-01-01

    Increasing evidence sustains that the establishment and maintenance of many, if not all, human cancers are due to cancer stem cells (CSCs), tumor cells with stem cell properties, such as the capacity to self-renew or generate progenitor and differentiated cells. CSCs seem to play a major role in tumor metastasis and drug resistance, but albeit the potential clinical importance, their regulation at the molecular level is not clear. Recent studies have highlighted several miRNAs to be differentially expressed in normal and cancer stem cells and established their role in targeting genes and pathways supporting cancer stemness properties. This review focuses on the last advances on the role of microRNAs in the regulation of stem cell properties and cancer stem cells in different tumors.

  14. Identifying dysregulated pathways in cancers from pathway interaction networks

    Directory of Open Access Journals (Sweden)

    Liu Ke-Qin

    2012-06-01

    Full Text Available Abstract Background Cancers, a group of multifactorial complex diseases, are generally caused by mutation of multiple genes or dysregulation of pathways. Identifying biomarkers that can characterize cancers would help to understand and diagnose cancers. Traditional computational methods that detect genes differentially expressed between cancer and normal samples fail to work due to small sample size and independent assumption among genes. On the other hand, genes work in concert to perform their functions. Therefore, it is expected that dysregulated pathways will serve as better biomarkers compared with single genes. Results In this paper, we propose a novel approach to identify dysregulated pathways in cancer based on a pathway interaction network. Our contribution is three-fold. Firstly, we present a new method to construct pathway interaction network based on gene expression, protein-protein interactions and cellular pathways. Secondly, the identification of dysregulated pathways in cancer is treated as a feature selection problem, which is biologically reasonable and easy to interpret. Thirdly, the dysregulated pathways are identified as subnetworks from the pathway interaction networks, where the subnetworks characterize very well the functional dependency or crosstalk between pathways. The benchmarking results on several distinct cancer datasets demonstrate that our method can obtain more reliable and accurate results compared with existing state of the art methods. Further functional analysis and independent literature evidence also confirm that our identified potential pathogenic pathways are biologically reasonable, indicating the effectiveness of our method. Conclusions Dysregulated pathways can serve as better biomarkers compared with single genes. In this work, by utilizing pathway interaction networks and gene expression data, we propose a novel approach that effectively identifies dysregulated pathways, which can not only be used

  15. 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.

  16. Sequestration of mutated alpha1-antitrypsin into inclusion bodies is a cell-protective mechanism to maintain endoplasmic reticulum function.

    Science.gov (United States)

    Granell, Susana; Baldini, Giovanna; Mohammad, Sameer; Nicolin, Vanessa; Narducci, Paola; Storrie, Brian; Baldini, Giulia

    2008-02-01

    A variant alpha1-antitrypsin with E342K mutation has a high tendency to form intracellular polymers, and it is associated with liver disease. In the hepatocytes of individuals carrying the mutation, alpha1-antitrypsin localizes both to the endoplasmic reticulum (ER) and to membrane-surrounded inclusion bodies (IBs). It is unclear whether the IBs contribute to cell toxicity or whether they are protective to the cell. We found that in hepatoma cells, mutated alpha1-antitrypsin exited the ER and accumulated in IBs that were negative for autophagosomal and lysosomal markers, and contained several ER components, but not calnexin. Mutated alpha1-antitrypsin induced IBs also in neuroendocrine cells, showing that formation of these organelles is not cell type specific. In the presence of IBs, ER function was largely maintained. Increased levels of calnexin, but not of protein disulfide isomerase, inhibited formation of IBs and lead to retention of mutated alpha1-antitrypsin in the ER. In hepatoma cells, shift of mutated alpha1-antitrypsin localization to the ER by calnexin overexpression lead to cell shrinkage, ER stress, and impairment of the secretory pathway at the ER level. We conclude that segregation of mutated alpha1-antitrypsin from the ER to the IBs is a protective cell response to maintain a functional secretory pathway.

  17. 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.

  18. Issues and Methods for Assessing COTS Reliability, Maintainability, and Availability

    Science.gov (United States)

    Schneidewind, Norman F.; Nikora, Allen P.

    1998-01-01

    Many vendors produce products that are not domain specific (e.g., network server) and have limited functionality (e.g., mobile phone). In contrast, many customers of COTS develop systems that am domain specific (e.g., target tracking system) and have great variability in functionality (e.g., corporate information system). This discussion takes the viewpoint of how the customer can ensure the quality of COTS components. In evaluating the benefits and costs of using COTS, we must consider the environment in which COTS will operate. Thus we must distinguish between using a non-mission critical application like a spreadsheet program to produce a budget and a mission critical application like military strategic and tactical operations. Whereas customers will tolerate an occasional bug in the former, zero tolerance is the rule in the latter. We emphasize the latter because this is the arena where there are major unresolved problems in the application of COTS. Furthermore, COTS components may be embedded in the larger customer system. We refer to these as embedded systems. These components must be reliable, maintainable, and available, and must be with the larger system in order for the customer to benefit from the advertised advantages of lower development and maintenance costs. Interestingly, when the claims of COTS advantages are closely examined, one finds that to a great extent these COTS components consist of hardware and office products, not mission critical software [1]. Obviously, COTS components are different from custom components with respect to one or more of the following attributes: source, development paradigm, safety, reliability, maintainability, availability, security, and other attributes. However, the important question is whether they should be treated differently when deciding to deploy them for operational use; we suggest the answer is no. We use reliability as an example to justify our answer. In order to demonstrate its reliability, a COTS

  19. Tractor Mechanics. Maintaining and Servicing the Power Train, Learning Activity Packages 49-53; Maintaining and Servicing the Clutch, Learning Activity Packages 54-59; Maintaining and Servicing the Transmission and Differential, Learning Activity Packages 60-68; Maintaining and Servicing the Final Drive, Learning Activity Packages 69-77.

    Science.gov (United States)

    Clemson Univ., SC. Vocational Education Media Center.

    This series of learning activity packages focuses on four areas of tractor mechanics: (1) maintaining and servicing the power train, (2) maintaining and servicing the clutch, (3) maintaining and servicing the transmission and differential, and (4) maintaining and servicing the final drive. Each of the twenty-nine illustrated learning activity…

  20. Mixed-lineage kinase inhibitors require the activation of Trk receptors to maintain long-term neuronal trophism and survival.

    Science.gov (United States)

    Wang, Leo H; Paden, Andrew J; Johnson, Eugene M

    2005-03-01

    Small-molecule mixed-lineage kinase (MLK) inhibitors, such as CEP-1347 [3,9-bis[(ethylthio)methyl]-(8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H, 11H-2,7b,11a-triazadibenzo(a,g)cycloocta(cde)trinden-1-one] and CEP-11004 [3,9-bis-[(isopropylthio)methyl]-(8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo(a,g)cycloocta(cde)trinden-1-one], prevent c-Jun NH(2)-terminal kinase (JNK) pathway activation as well as the consequent neuronal cell death in many cell culture and animal models. In the cell culture model of nerve growth factor (NGF)-deprived sympathetic neurons, we find that CEP-11004 induced a approximately 3-fold increase in the mRNA and protein levels of TrkA, the NGF receptor. This resulted in ligand-independent activation of the TrkA receptor and the downstream phosphatidylinositol 3-kinase (PI3-kinase) pathway. Addition of the Trk inhibitor K252a [(8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo(a,g)cycloocta(cde)-trinden-1-one] or the PI3-kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] significantly decreased the protein synthesis rates, mitochondrial function, and neuronal survival maintained by CEP-11004. In contrast to sympathetic neurons, MLK inhibitors maintain only short-term survival of potassium- and serum-deprived rat cerebellar granule neurons (CGNs), despite continuous inhibition of the JNK pathway. We found that similar to sympathetic neurons, CEP-11004 increased the levels of the Trk receptor expressed in CGNs, TrkB. However, CGNs required the addition of the exogenous ligand brain-derived neurotrophic factor (BDNF) to activate the PI3-kinase pathway and to maintain long-term survival. BDNF activated TrkB, but caused rapid down-regulation of activated receptors and maintained only minimal survival. Therefore, increase in TrkB levels

  1. Different Pathways Leading to Integrase Inhibitors Resistance

    Science.gov (United States)

    Thierry, Eloïse; Deprez, Eric; Delelis, Olivier

    2017-01-01

    Integrase strand-transfer inhibitors (INSTIs), such as raltegravir (RAL), elvitegravir, or dolutegravir (DTG), are efficient antiretroviral agents used in HIV treatment in order to inhibit retroviral integration. By contrast to RAL treatments leading to well-identified mutation resistance pathways at the integrase level, recent clinical studies report several cases of patients failing DTG treatment without clearly identified resistance mutation in the integrase gene raising questions for the mechanism behind the resistance. These compounds, by impairing the integration of HIV-1 viral DNA into the host DNA, lead to an accumulation of unintegrated circular viral DNA forms. This viral DNA could be at the origin of the INSTI resistance by two different ways. The first one, sustained by a recent report, involves 2-long terminal repeat circles integration and the second one involves expression of accumulated unintegrated viral DNA leading to a basal production of viral particles maintaining the viral information. PMID:28123383

  2. Sororin actively maintains sister chromatid cohesion.

    Science.gov (United States)

    Ladurner, Rene; Kreidl, Emanuel; Ivanov, Miroslav P; Ekker, Heinz; Idarraga-Amado, Maria Helena; Busslinger, Georg A; Wutz, Gordana; Cisneros, David A; Peters, Jan-Michael

    2016-03-15

    Cohesion between sister chromatids is established during DNA replication but needs to be maintained to enable proper chromosome-spindle attachments in mitosis or meiosis. Cohesion is mediated by cohesin, but also depends on cohesin acetylation and sororin. Sororin contributes to cohesion by stabilizing cohesin on DNA. Sororin achieves this by inhibiting WAPL, which otherwise releases cohesin from DNA and destroys cohesion. Here we describe mouse models which enable the controlled depletion of sororin by gene deletion or auxin-induced degradation. We show that sororin is essential for embryonic development, cohesion maintenance, and proper chromosome segregation. We further show that the acetyltransferases ESCO1 and ESCO2 are essential for stabilizing cohesin on chromatin, that their only function in this process is to acetylate cohesin's SMC3 subunit, and that DNA replication is also required for stable cohesin-chromatin interactions. Unexpectedly, we find that sororin interacts dynamically with the cohesin complexes it stabilizes. This implies that sororin recruitment to cohesin does not depend on the DNA replication machinery or process itself, but on a property that cohesin acquires during cohesion establishment.

  3. Reliability and maintainability analysis of electrical system of drum shearers

    Institute of Scientific and Technical Information of China (English)

    SEYED Hadi Hoseinie; MOHAMMAD Ataei; REZA Khalokakaie; UDAY Kumar

    2011-01-01

    The reliability and maintainability of electrical system of drum shearer at Parvade.l Coal Mine in central Iran was analyzed. The maintenance and failure data were collected during 19 months of shearer operation. According to trend and serial correlation tests, the data were independent and identically distributed (iid) and therefore the statistical techniques were used for modeling. The data analysis show that the time between failures (TBF) and time to repair (TTR) data obey the lognormal and Weibull 3 parameters distribution respectively. Reliability-based preventive maintenance time intervals for electrical system of the drum shearer were calculated with regard to reliability plot. The reliability-based maintenance intervals for 90%, 80%, 70% and 50% reliability level are respectively 9.91, 17.96, 27.56 and 56.1 h. Also the calculations show that time to repair (TTR) of this system varies in range 0.17-4 h with 1.002 h as mean time to repair (MTTR). There is a 80% chance that the electrical system of shearer of Parvade.l mine repair will be accomplished within 1.45 h.

  4. Maintaining boundaries in psychotherapy: Covert narcissistic personality characteristics and psychotherapists.

    Science.gov (United States)

    Luchner, Andrew F; Mirsalimi, Hamid; Moser, Casey J; Jones, Rebecca A

    2008-03-01

    The psychological literature to date has identified more than one form of narcissism: the more well-known grandiose form, and the less familiar and recognized covert form. Although the distinction between these two narcissistic types has been identified with regard to better conceptualizing client dynamics, there has been much less written about how covert narcissistic tendencies and traits may affect psychotherapists and psychotherapy. This paper uses psychodynamic theory to highlight the role that covert narcissistic characteristics may have on the psychotherapists' ability to maintain boundaries, potentially leading to boundary transgressions (existing along a continuum from therapeutically useful to maladaptive and anti-therapeutic). Specific therapeutic situations have been delineated to increase therapists' recognition and awareness of themes that may emerge and compromise the boundaries between themselves and their clients. Areas of focus include narcissism and its forms, the possible connection between covert narcissism in psychotherapists and the impact on managing boundaries, the potential therapeutic implications of covert narcissistic tendencies in psychotherapists, and the implications of covert narcissistic personality characteristics on treatment, supervision, and training. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  5. FUNGICIDE APPLICATION FOR MAINTAINING POSTHARVEST QUALITY IN TOMATO FRUITS

    Directory of Open Access Journals (Sweden)

    D. M. Vani

    2014-07-01

    Full Text Available Tomato fruits are usually consumed soon after harvest, however, as they are mainly comprised of water, and its walls are fragile, facilitates the emergence of diseases, making necessary the use of preventive measures in the field in order to reduce incidence of disease. The objective is then to evaluate the effect of foliar application of fungicides on the final quality of tomato fruits in postharvest. There were 13 applications of foliar fungicides Azoxystrobin+Cyproconazol and Boscalida, 7 applications Tebuconazol+Trifoxistrobin and 17 applications of Propamocarb+Fluopicolide (Control. We analyzed the incidence of Fusarium sp. in fruits, decay percentage of fruit weight (g and Brix. For incidence of Fusarium sp. in fruits, treatments Tebuconazol+Trifoxistrobin and Azoxistrobin+Ciproconazol reduced by 14.3%, the pathogen in fruits. There was a decrease of 82% in the deterioration of fruits treated with Tebuconazol+Trifoxistrobin and 91% in those treated with Azoxistrobin+Ciproconazol. As for the weight gain, treatments Tebuconazol+Trifoxistrobin, Boscalida and Azoxistrobin+Ciproconazol reduced the weight gain in 8.12%, 20.8% and 38.8%, respectively, compared to the control. ° Brix values of fruits treated with Tebuconazol+Trifoxistrobin and Boscalida were higher than those treated with Azoxistrobin+Ciproconazol and Control (Propamocarb+Fluopicolide. It is concluded that the treatment carried out with Tebuconazol+Trifoxistrobin afforded the greatest benefits in maintaining the tomato fruits in harvest.

  6. Translational activation maintains germline tissue homeostasis during adulthood.

    Science.gov (United States)

    Nousch, Marco; Eckmann, Christian R

    2015-01-01

    Adult tissue maintenance is achieved through a tightly controlled equilibrium of 2 opposing cell fates: stem cell proliferation and differentiation. In recent years, the germ line emerged as a powerful in vivo model tissue to investigate the underlying gene expression mechanisms regulating this balance. Studies in numerous organisms highlighted the prevalence of post-transcriptional mRNA regulation, which relies on RNA-targeting factors that influence mRNA fates (e.g. decay or translational efficiency). Conserved translational repressors were identified that build negative feedback loops to ensure one or the other cell fate. However, to facilitate a fast and efficient transition between 2 opposing cell fates, translational repression per se appears not to be sufficient, suggesting the involvement of additional modes of gene expression regulation. Cytoplasmic poly(A) polymerases (cytoPAPs) represent a unique class of post-transcriptional mRNA regulators that modify mRNA 3' ends and positively influence cytoplasmic mRNA fates. We recently discovered that the 2 main cytoPAPs, GLD-2 and GLD-4, use distinct mechanisms to promote gene expression and that cytoPAP-mediated mRNA activation is important for regulating the size of the proliferative germ cell pool in the adult Caenorhabditis elegans gonad. Here, we comment on the different mechanisms of the 2 cytoPAPs as translational activators in germ cell development and focus on their biological roles in maintaining the balance between germline stem cell proliferation and differentiation in the Caenorhabditis elegans gonad.

  7. 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

    2011-05-12

    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 δ(3)-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.

  8. YAP/TAZ initiate and maintain Schwann cell myelination

    Science.gov (United States)

    Grove, Matthew; Kim, Hyukmin; Santerre, Maryline; Krupka, Alexander J; Han, Seung Baek; Zhai, Jinbin; Cho, Jennifer Y; Park, Raehee; Harris, Michele; Kim, Seonhee; Sawaya, Bassel E; Kang, Shin H; Barbe, Mary F; Cho, Seo-Hee; Lemay, Michel A; Son, Young-Jin

    2017-01-01

    Nuclear exclusion of the transcriptional regulators and potent oncoproteins, YAP/TAZ, is considered necessary for adult tissue homeostasis. Here we show that nuclear YAP/TAZ are essential regulators of peripheral nerve development and myelin maintenance. To proliferate, developing Schwann cells (SCs) require YAP/TAZ to enter S-phase and, without them, fail to generate sufficient SCs for timely axon sorting. To differentiate, SCs require YAP/TAZ to upregulate Krox20 and, without them, completely fail to myelinate, resulting in severe peripheral neuropathy. Remarkably, in adulthood, nuclear YAP/TAZ are selectively expressed by myelinating SCs, and conditional ablation results in severe peripheral demyelination and mouse death. YAP/TAZ regulate both developmental and adult myelination by driving TEAD1 to activate Krox20. Therefore, YAP/TAZ are crucial for SCs to myelinate developing nerve and to maintain myelinated nerve in adulthood. Our study also provides a new insight into the role of nuclear YAP/TAZ in homeostatic maintenance of an adult tissue. DOI: http://dx.doi.org/10.7554/eLife.20982.001 PMID:28124973

  9. Microstructure and properties of novel polarization maintaining fiber

    Institute of Scientific and Technical Information of China (English)

    LI Mei-cheng; LIU Li-hua; XUE Jian-jun; XIAO Tian-peng; LIANG Le-tian; ZHAO Lian-cheng

    2005-01-01

    An improved type of elliptical jacket polarization maintaining fiber was developed by using a modified chemical vapor deposition method with special treatment. Different from conventional elliptical jacket, the shape of the stress jacket was transmuted. The cross-section of fiber consists of 5 layers: substrate, outer cladding, stress jacket, inner cladding and core. The cross sectional component distribution was investigated by electron probe microscopy and energy dispersive spectrum. The finite element method was used to calculate the stress birefringence. Based on the analyses of the microstructure, the technological process is improved. The temperature cycling test of the fiber wound into gyroscope coils was performed. The results show that the fiber possesses superior performance at high and low temperatures compared with other fibers. The high homogeneity is achieved by well-controlled modified chemical vapor deposition process. A homogeneous length of 8 km fiber is obtained. With advantages in homogeneity and length, the fiber has great potential in applications such as fiber gyroscopes, fiber hydrophone and other optical fiber sensors.

  10. Role of SUPERMAN in maintaining Arabidopsis floral whorl boundaries.

    Science.gov (United States)

    Sakai, H; Medrano, L J; Meyerowitz, E M

    1995-11-09

    The Arabidopsis gene SUPERMAN (SUP) is necessary for the proper spatial development of reproductive floral tissues. Recessive mutations cause extra stamens to form interior to the normal third whorl stamens, at the expense of fourth whorl carpel development. The mutant phenotype is associated with the ectopic expression of the B function genes, AP3 and PI, in the altered floral region, closer to the centre of the flower than in the wild type, and ap3 sup and pi sup double mutants exhibit a phenotype similar to ap3 and pi single mutants. These findings led to SUP being interpreted as an upstream negative regulator of the B function organ-identity genes, acting in the fourth whorl, to establish a boundary between stamen and carpel whorls. Here we show, using molecular cloning and analysis, that it is expressed in the third whorl and acts to maintain this boundary in developing flowers. The putative SUPERMAN protein contains one zinc-finger and a region resembling a basic leucine zipper motif, suggesting a function in transcriptional regulation.

  11. 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.

  12. Maintaining the will to live of patients with advanced cancer.

    Science.gov (United States)

    Khan, Luluel; Wong, Rebecca; Li, Madeline; Zimmermann, Camilla; Lo, Chris; Gagliese, Lucia; Rodin, Gary

    2010-01-01

    The will to live is a natural instinct experienced by all human beings. It tends to persist in humans, despite marked adversity such as that associated with advanced cancer. The will to live may be measured directly, or indirectly, by assessing the desire for hastened death. Factors that may affect it include age, life stage, and physical and psychological distress. In particular, states of depression and hopelessness may precede the loss of the will to live. Other psychosocial variables that may affect the will to live include physical suffering, attachment security, self-esteem, and spiritual well-being. A number of screening tools are available to identify risk factors for the loss of the will to live. Awareness of these factors can guide interventions to preserve morale and maintain hope in patients faced with a terminal illness. Critical among these are the alleviation of physical and psychosocial distress and the establishment of a therapeutic alliance that is sensitive to the specific support needs of individual patients. Comfort and facility with such supportive interventions in oncology will require greater attention to the development of communication and relationship skills at both undergraduate and postgraduate levels of training.

  13. 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.

  14. Web-Based Environment for Maintaining Legacy Software

    Science.gov (United States)

    Tigges, Michael; Thompson, Nelson; Orr, Mark; Fox, Richard

    2007-01-01

    Advanced Tool Integration Environment (ATIE) is the name of both a software system and a Web-based environment created by the system for maintaining an archive of legacy software and expertise involved in developing the legacy software. ATIE can also be used in modifying legacy software and developing new software. The information that can be encapsulated in ATIE includes experts documentation, input and output data of tests cases, source code, and compilation scripts. All of this information is available within a common environment and retained in a database for ease of access and recovery by use of powerful search engines. ATIE also accommodates the embedment of supporting software that users require for their work, and even enables access to supporting commercial-off-the-shelf (COTS) software within the flow of the experts work. The flow of work can be captured by saving the sequence of computer programs that the expert uses. A user gains access to ATIE via a Web browser. A modern Web-based graphical user interface promotes efficiency in the retrieval, execution, and modification of legacy code. Thus, ATIE saves time and money in the support of new and pre-existing programs.

  15. IGF-I maintains calpastatin expression and attenuates apoptosis in several models of photoreceptor cell death.

    Science.gov (United States)

    Arroba, Ana I; Wallace, Deborah; Mackey, Ashley; de la Rosa, Enrique J; Cotter, Thomas G

    2009-09-01

    Retinitis pigmentosa is a heterogeneous group of inherited retinal dystrophies in which the loss of photoreceptor cells via apoptosis leads to blindness. In this study we have experimentally mimicked this condition by treating 661W cells and wild-type mouse retinal explants with a Ca(2+) ionophore. Ca(2+) overload induced apoptosis, which was correlated with calpain-2 activation, loss of calpastatin, its endogenous inhibitor, as well as the loss of its transcriptional activator, phospho-cAMP response element binding (CREB). All are similar changes to those observed in the rd1 mouse model of retinitis pigmentosa. Insulin like-growth factor-I (IGF-I) attenuated this Ca(2+)-induced apoptosis, as well as decreased the activation of calpain-2 and maintained calpastatin levels through the activation of the Akt-CREB pathway. Similarly, IGF-I decreased photoreceptor apoptosis in rd1 mouse retinal explants in parallel with reduced activation of calpain-2 and increased levels of calpastatin and activation of phospho-CREB. In conclusion, IGF-I seems to protect neural cells following a physiopathological or an experimental increase in intracellular Ca(2+), an observation that may have therapeutic consequences in neurodegenerative diseases such as retinitis pigmentosa.

  16. CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo

    Directory of Open Access Journals (Sweden)

    Benjamin T. Spike

    2014-04-01

    Full Text Available Little is known about the extracellular signaling factors that govern mammary stem cell behavior. Here, we identify CRIPTO and its cell-surface receptor GRP78 as regulators of stem cell behavior in isolated fetal and adult mammary epithelial cells. We develop a CRIPTO antagonist that promotes differentiation and reduces self-renewal of mammary stem cell-enriched populations cultured ex vivo. By contrast, CRIPTO treatment maintains the stem cell phenotype in these cultures and yields colonies with enhanced mammary gland reconstitution capacity. Surface expression of GRP78 marks CRIPTO-responsive, stem cell-enriched fetal and adult mammary epithelial cells, and deletion of GRP78 from adult mammary epithelial cells blocks their mammary gland reconstitution potential. Together, these findings identify the CRIPTO/GRP78 pathway as a developmentally conserved regulator of fetal and adult mammary stem cell behavior ex vivo, with implications for the stem-like cells found in many cancers.

  17. CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo

    Science.gov (United States)

    Spike, Benjamin T.; Kelber, Jonathan A.; Booker, Evan; Kalathur, Madhuri; Rodewald, Rose; Lipianskaya, Julia; La, Justin; He, Marielle; Wright, Tracy; Klemke, Richard; Wahl, Geoffrey M.; Gray, Peter C.

    2014-01-01

    Summary Little is known about the extracellular signaling factors that govern mammary stem cell behavior. Here, we identify CRIPTO and its cell-surface receptor GRP78 as regulators of stem cell behavior in isolated fetal and adult mammary epithelial cells. We develop a CRIPTO antagonist that promotes differentiation and reduces self-renewal of mammary stem cell-enriched populations cultured ex vivo. By contrast, CRIPTO treatment maintains the stem cell phenotype in these cultures and yields colonies with enhanced mammary gland reconstitution capacity. Surface expression of GRP78 marks CRIPTO-responsive, stem cell-enriched fetal and adult mammary epithelial cells, and deletion of GRP78 from adult mammary epithelial cells blocks their mammary gland reconstitution potential. Together, these findings identify the CRIPTO/GRP78 pathway as a developmentally conserved regulator of fetal and adult mammary stem cell behavior ex vivo, with implications for the stem-like cells found in many cancers. PMID:24749068

  18. ETAA1 acts at stalled replication forks to maintain genome integrity.

    Science.gov (United States)

    Bass, Thomas E; Luzwick, Jessica W; Kavanaugh, Gina; Carroll, Clinton; Dungrawala, Huzefa; Glick, Gloria G; Feldkamp, Michael D; Putney, Reid; Chazin, Walter J; Cortez, David

    2016-11-01

    The ATR checkpoint kinase coordinates cellular responses to DNA replication stress. Budding yeast contain three activators of Mec1 (the ATR orthologue); however, only TOPBP1 is known to activate ATR in vertebrates. We identified ETAA1 as a replication stress response protein in two proteomic screens. ETAA1-deficient cells accumulate double-strand breaks, sister chromatid exchanges, and other hallmarks of genome instability. They are also hypersensitive to replication stress and have increased frequencies of replication fork collapse. ETAA1 contains two RPA-interaction motifs that localize ETAA1 to stalled replication forks. It also interacts with several DNA damage response proteins including the BLM/TOP3α/RMI1/RMI2 and ATR/ATRIP complexes. It binds ATR/ATRIP directly using a motif with sequence similarity to the TOPBP1 ATR-activation domain; and like TOPBP1, ETAA1 acts as a direct ATR activator. ETAA1 functions in parallel to the TOPBP1/RAD9/HUS1/RAD1 pathway to regulate ATR and maintain genome stability. Thus, vertebrate cells contain at least two ATR-activating proteins.

  19. ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes

    Directory of Open Access Journals (Sweden)

    Hsiao P.J. Voon

    2015-04-01

    Full Text Available Histone H3.3 is a replication-independent histone variant, which replaces histones that are turned over throughout the entire cell cycle. H3.3 deposition at euchromatin is dependent on HIRA, whereas ATRX/Daxx deposits H3.3 at pericentric heterochromatin and telomeres. The role of H3.3 at heterochromatic regions is unknown, but mutations in the ATRX/Daxx/H3.3 pathway are linked to aberrant telomere lengthening in certain cancers. In this study, we show that ATRX-dependent deposition of H3.3 is not limited to pericentric heterochromatin and telomeres but also occurs at heterochromatic sites throughout the genome. Notably, ATRX/H3.3 specifically localizes to silenced imprinted alleles in mouse ESCs. ATRX KO cells failed to deposit H3.3 at these sites, leading to loss of the H3K9me3 heterochromatin modification, loss of repression, and aberrant allelic expression. We propose a model whereby ATRX-dependent deposition of H3.3 into heterochromatin is normally required to maintain the memory of silencing at imprinted loci.

  20. ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes.

    Science.gov (United States)

    Voon, Hsiao P J; Hughes, Jim R; Rode, Christina; De La Rosa-Velázquez, Inti A; Jenuwein, Thomas; Feil, Robert; Higgs, Douglas R; Gibbons, Richard J

    2015-04-21

    Histone H3.3 is a replication-independent histone variant, which replaces histones that are turned over throughout the entire cell cycle. H3.3 deposition at euchromatin is dependent on HIRA, whereas ATRX/Daxx deposits H3.3 at pericentric heterochromatin and telomeres. The role of H3.3 at heterochromatic regions is unknown, but mutations in the ATRX/Daxx/H3.3 pathway are linked to aberrant telomere lengthening in certain cancers. In this study, we show that ATRX-dependent deposition of H3.3 is not limited to pericentric heterochromatin and telomeres but also occurs at heterochromatic sites throughout the genome. Notably, ATRX/H3.3 specifically localizes to silenced imprinted alleles in mouse ESCs. ATRX KO cells failed to deposit H3.3 at these sites, leading to loss of the H3K9me3 heterochromatin modification, loss of repression, and aberrant allelic expression. We propose a model whereby ATRX-dependent deposition of H3.3 into heterochromatin is normally required to maintain the memory of silencing at imprinted loci.

  1. Apoptotic pathways as a therapeutic target for colorectal cancer treatment

    Institute of Scientific and Technical Information of China (English)

    Aman M Abraha; Ezra B Ketema

    2016-01-01

    Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment.

  2. SMARCAL1 maintains telomere integrity during DNA replication.

    Science.gov (United States)

    Poole, Lisa A; Zhao, Runxiang; Glick, Gloria G; Lovejoy, Courtney A; Eischen, Christine M; Cortez, David

    2015-12-01

    The SMARCAL1 (SWI/SNF related, matrix-associated, actin-dependent, regulator of chromatin, subfamily A-like 1) DNA translocase is one of several related enzymes, including ZRANB3 (zinc finger, RAN-binding domain containing 3) and HLTF (helicase-like transcription factor), that are recruited to stalled replication forks to promote repair and restart replication. These enzymes can perform similar biochemical reactions such as fork reversal; however, genetic studies indicate they must have unique cellular activities. Here, we present data showing that SMARCAL1 has an important function at telomeres, which present an endogenous source of replication stress. SMARCAL1-deficient cells accumulate telomere-associated DNA damage and have greatly elevated levels of extrachromosomal telomere DNA (C-circles). Although these telomere phenotypes are often found in tumor cells using the alternative lengthening of telomeres (ALT) pathway for telomere elongation, SMARCAL1 deficiency does not yield other ALT phenotypes such as elevated telomere recombination. The activity of SMARCAL1 at telomeres can be separated from its genome-maintenance activity in bulk chromosomal replication because it does not require interaction with replication protein A. Finally, this telomere-maintenance function is not shared by ZRANB3 or HLTF. Our results provide the first identification, to our knowledge, of an endogenous source of replication stress that requires SMARCAL1 for resolution and define differences between members of this class of replication fork-repair enzymes.

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

    Science.gov (United States)

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

    2013-10-01

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

  4. Pathway-Based Genomics Prediction using Generalized Elastic Net.

    Directory of Open Access Journals (Sweden)

    Artem Sokolov

    2016-03-01

    Full Text Available We present a novel regularization scheme called The Generalized Elastic Net (GELnet that incorporates gene pathway information into feature selection. The proposed formulation is applicable to a wide variety of problems in which the interpretation of predictive features using known molecular interactions is desired. The method naturally steers solutions toward sets of mechanistically interlinked genes. Using experiments on synthetic data, we demonstrate that pathway-guided results maintain, and often improve, the accuracy of predictors even in cases where the full gene network is unknown. We apply the method to predict the drug response of breast cancer cell lines. GELnet is able to reveal genetic determinants of sensitivity and resistance for several compounds. In particular, for an EGFR/HER2 inhibitor, it finds a possible trans-differentiation resistance mechanism missed by the corresponding pathway agnostic approach.

  5. Pathway-Based Genomics Prediction using Generalized Elastic Net

    Science.gov (United States)

    Sokolov, Artem; Carlin, Daniel E.; Paull, Evan O.; Baertsch, Robert; Stuart, Joshua M.

    2016-01-01

    We present a novel regularization scheme called The Generalized Elastic Net (GELnet) that incorporates gene pathway information into feature selection. The proposed formulation is applicable to a wide variety of problems in which the interpretation of predictive features using known molecular interactions is desired. The method naturally steers solutions toward sets of mechanistically interlinked genes. Using experiments on synthetic data, we demonstrate that pathway-guided results maintain, and often improve, the accuracy of predictors even in cases where the full gene network is unknown. We apply the method to predict the drug response of breast cancer cell lines. GELnet is able to reveal genetic determinants of sensitivity and resistance for several compounds. In particular, for an EGFR/HER2 inhibitor, it finds a possible trans-differentiation resistance mechanism missed by the corresponding pathway agnostic approach. PMID:26960204

  6. Pathway-Based Genomics Prediction using Generalized Elastic Net.

    Science.gov (United States)

    Sokolov, Artem; Carlin, Daniel E; Paull, Evan O; Baertsch, Robert; Stuart, Joshua M

    2016-03-01

    We present a novel regularization scheme called The Generalized Elastic Net (GELnet) that incorporates gene pathway information into feature selection. The proposed formulation is applicable to a wide variety of problems in which the interpretation of predictive features using known molecular interactions is desired. The method naturally steers solutions toward sets of mechanistically interlinked genes. Using experiments on synthetic data, we demonstrate that pathway-guided results maintain, and often improve, the accuracy of predictors even in cases where the full gene network is unknown. We apply the method to predict the drug response of breast cancer cell lines. GELnet is able to reveal genetic determinants of sensitivity and resistance for several compounds. In particular, for an EGFR/HER2 inhibitor, it finds a possible trans-differentiation resistance mechanism missed by the corresponding pathway agnostic approach.

  7. Pathways to Global Markets

    DEFF Research Database (Denmark)

    Smith, David E.; Mitry, Darryl J.

    2011-01-01

    . An important case study is McDonald‘s corporation, the world‘s largest fast food restaurant chain. This company has employed divergent marketing and economic strategies in both domestic and the international markets to become a leader in the global marketplace. An overview of the company‘s background......, organizational structures, mission and vision illustrate McDonald‘s strategic focus on its proactive evolution from a small drive-through operation to a global fast-food giant. The strategy is based on its ability to adapt to the cultural differences of the markets that McDonald‘s serves while preserving its......For marketing and economic researchers, an important aspect of globalization is the degree to which various consumer behavior dimensions and consumption patterns in different parts of the world are becoming similar, and how multinational companies have identified pathways to global success...

  8. Receptor activator of nuclear factor-κB ligand and osteoprotegerin: maintaining the balance to prevent bone loss

    Directory of Open Access Journals (Sweden)

    Anne-Priscille Trouvin

    2010-11-01

    Full Text Available Anne-Priscille Trouvin, Vincent GoëbDepartment of Rheumatology, Rouen University Hospital, Rouen, FranceAbstract: Bone remodeling requires a precise balance between resorption and formation. It is a complex process that involves numerous factors: hormones, growth factors, vitamins, and cytokines, and notably osteoprotegerin (OPG and receptor activator for nuclear factor-κB (RANK ligand. The signaling pathway OPG/RANK/RANKL is key to regulation for maintaining the balance between the activity of osteoblasts and osteoclasts in order to prevent bone loss and ensure a normal bone turnover. In this review, the RANK/RANKL/OPG pathway is described. The multiple interactions of various factors (hormones, cytokines, growth factors, and vitamins with the OPG/RANK/RANKL pathway are also commented on. Finally, the effects of denosumab, a human monoclonal antibody that binds to RANKL and thereby inhibits the activation of osteoclasts, and of strontium ranelate are also described. Indeed, these two new drugs afford appreciable assistance in daily care practice, helping to prevent bone loss in patients with osteoporosis.Keywords: osteoprotegerin, OPG, RANK, RANKL, denosumab, strontium ranelate, osteoporosis

  9. Signal Transduction Pathways of EMT Induced by TGF-β, SHH, and WNT and Their Crosstalks

    Science.gov (United States)

    Zhang, Jingyu; Tian, Xiao-Jun; Xing, Jianhua

    2016-01-01

    Epithelial-to-mesenchymal transition (EMT) is a key step in development, wound healing, and cancer development. It involves cooperation of signaling pathways, such as transformation growth factor-β (TGF-β), Sonic Hedgehog (SHH), and WNT pathways. These signaling pathways crosstalk to each other and converge to key transcription factors (e.g., SNAIL1) to initialize and maintain the process of EMT. The functional roles of multi-signaling pathway crosstalks in EMT are sophisticated and, thus, remain to be explored. In this review, we focused on three major signal transduction pathways that promote or regulate EMT in carcinoma. We discussed the network structures, and provided a brief overview of the current therapy strategies and drug development targeted to these three signal transduction pathways. Finally, we highlighted systems biology approaches that can accelerate the process of deconstructing complex networks and drug discovery. PMID:27043642

  10. The Verriest Lecture: Short-wave-sensitive cone pathways across the life span.

    Science.gov (United States)

    Werner, John S

    2016-03-01

    Structurally and functionally, the short-wave-sensitive (S) cone pathways are thought to decline more rapidly with normal aging than the middle- and long-wave-sensitive cone pathways. This would explain the celebrated results by Verriest and others demonstrating that the largest age-related color discrimination losses occur for stimuli on a tritan axis. Here, we challenge convention, arguing from psychophysical data that selective S-cone pathway losses do not cause declines in color discrimination. We show substantial declines in chromatic detection and discrimination, as well as in temporal and spatial vision tasks, that are mediated by S-cone pathways. These functional losses are not, however, unique to S-cone pathways. Finally, despite reduced photon capture by S cones, their postreceptoral pathways provide robust signals for the visual system to renormalize itself to maintain nearly stable color perception across the life span.

  11. Signal Transduction Pathways of EMT Induced by TGF-β, SHH, and WNT and Their Crosstalks.

    Science.gov (United States)

    Zhang, Jingyu; Tian, Xiao-Jun; Xing, Jianhua

    2016-03-28

    Epithelial-to-mesenchymal transition (EMT) is a key step in development, wound healing, and cancer development. It involves cooperation of signaling pathways, such as transformation growth factor-β (TGF-β), Sonic Hedgehog (SHH), and WNT pathways. These signaling pathways crosstalk to each other and converge to key transcription factors (e.g., SNAIL1) to initialize and maintain the process of EMT. The functional roles of multi-signaling pathway crosstalks in EMT are sophisticated and, thus, remain to be explored. In this review, we focused on three major signal transduction pathways that promote or regulate EMT in carcinoma. We discussed the network structures, and provided a brief overview of the current therapy strategies and drug development targeted to these three signal transduction pathways. Finally, we highlighted systems biology approaches that can accelerate the process of deconstructing complex networks and drug discovery.

  12. Signal Transduction Pathways of EMT Induced by TGF-β, SHH, and WNT and Their Crosstalks

    Directory of Open Access Journals (Sweden)

    Jingyu Zhang

    2016-03-01

    Full Text Available Epithelial-to-mesenchymal transition (EMT is a key step in development, wound healing, and cancer development. It involves cooperation of signaling pathways, such as transformation growth factor-β (TGF-β, Sonic Hedgehog (SHH, and WNT pathways. These signaling pathways crosstalk to each other and converge to key transcription factors (e.g., SNAIL1 to initialize and maintain the process of EMT. The functional roles of multi-signaling pathway crosstalks in EMT are sophisticated and, thus, remain to be explored. In this review, we focused on three major signal transduction pathways that promote or regulate EMT in carcinoma. We discussed the network structures, and provided a brief overview of the current therapy strategies and drug development targeted to these three signal transduction pathways. Finally, we highlighted systems biology approaches that can accelerate the process of deconstructing complex networks and drug discovery.

  13. Mitochondrial genome regulates mitotic fidelity by maintaining centrosomal homeostasis.

    Science.gov (United States)

    Donthamsetty, Shashikiran; Brahmbhatt, Meera; Pannu, Vaishali; Rida, Padmashree C G; Ramarathinam, Sujatha; Ogden, Angela; Cheng, Alice; Singh, Keshav K; Aneja, Ritu

    2014-01-01

    Centrosomes direct spindle morphogenesis to assemble a bipolar mitotic apparatus to enable error-free chromosome segregation and preclude chromosomal instability (CIN). Amplified centrosomes, a hallmark of cancer cells, set the stage for CIN, which underlies malignant transformation and evolution of aggressive phenotypes. Several studies report CIN and a tumorigenic and/or aggressive transformation in mitochondrial DNA (mtDNA)-depleted cells. Although several nuclear-encoded proteins are implicated in centrosome duplication and spindle organization, the involvement of mtDNA encoded proteins in centrosome amplification (CA) remains elusive. Here we show that disruption of mitochondrial function by depletion of mtDNA induces robust CA and mitotic aberrations in osteosarcoma cells. We found that overexpression of Aurora A, Polo-like kinase 4 (PLK4), and Cyclin E was associated with emergence of amplified centrosomes. Supernumerary centrosomes in rho0 (mtDNA-depleted) cells resulted in multipolar mitoses bearing "real" centrosomes with paired centrioles at the multiple poles. This abnormal phenotype was recapitulated by inhibition of respiratory complex I in parental cells, suggesting a role for electron transport chain (ETC) in maintaining numeral centrosomal homeostasis. Furthermore, rho0 cells displayed a decreased proliferative capacity owing to a G 2/M arrest. Downregulation of nuclear-encoded p53 in rho0 cells underscores the importance of mitochondrial and nuclear genome crosstalk and may perhaps underlie the observed mitotic aberrations. By contrast, repletion of wild-type mtDNA in rho0 cells (cybrid) demonstrated a much lesser extent of CA and spindle multipolarity, suggesting partial restoration of centrosomal homeostasis. Our study provides compelling evidence to implicate the role of mitochondria in regulation of centrosome duplication, spindle architecture, and spindle pole integrity.

  14. Maintaining cholesterol homeostasis:Sterol regulatory element-binding proteins

    Institute of Scientific and Technical Information of China (English)

    Lutz W. Weber; Meinrad Boll; Andreas Stampfl

    2004-01-01

    The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane proteins are members of the basic helix-loop-helix-leucine zipper (bHLHZip) family of transcription factors. They activate the expression of at least 30 genes involved in the synthesis of cholesterol and lipids. SREBPs are synthesized as precursor proteins in the endoplasmic reticulum (ER), where they form a complex with another protein, SREBP cleavage activating protein (SCAP).The SCAP molecule contains a sterol sensory domain. In the presence of high cellular sterol concentrations SCAP confines SREBP to the ER. With low cellular concentrations, SCAP escorts SREBP to activation in the Golgi. There, SREBP undergoes two proteolytic cleavage steps to release the mature, biologically active transcription factor, nuclear SREBP (nSREBP). nSREBP translocates to the nucleus and binds to sterol response elements (SRE) in the promoter/enhancer regions of target genes. Additional transcription factors are required to activate transcription of these genes. Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBP-1a and -1c are isoforms produced from a single gene by alternate splicing. SREBP-2is encoded by a different gene and does not display any isoforms. It appears that SREBPs alone, in the sequence described above, can exert complete control over cholesterol synthesis, whereas many additional factors (hormones,cytokines, etc.) are required for complete control of lipid metabolism. Medicinal manipulation of the SREBP/SCAP system is expected to prove highly beneficial in the management of cholesterol-related disease.

  15. Human STEAP3 maintains tumor growth under hypoferric condition

    Energy Technology Data Exchange (ETDEWEB)

    Isobe, Taichi, E-mail: tisobe@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Baba, Eishi, E-mail: e-baba@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Arita, Shuji, E-mail: arita.s@nk-cc.go.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Komoda, Masato, E-mail: komoda@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tamura, Shingo, E-mail: tamshin@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Shirakawa, Tsuyoshi, E-mail: t-w-r@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Ariyama, Hiroshi, E-mail: hariyama@kyumed.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Takaishi, Shigeo, E-mail: takaishi@med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Kusaba, Hitoshi, E-mail: hkusaba@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); and others

    2011-11-01

    Iron is essential in cellular proliferation and survival based on its crucial roles in DNA and ATP synthesis. Tumor cells proliferate rapidly even in patients with low serum iron, although their actual mechanisms are not well known. To elucidate molecular mechanisms of efficient tumor progression under the hypoferric condition, we studied the roles of six-transmembrane epithelial antigen of the prostate family member 3 (STEAP3), which was reported to facilitate iron uptake. Using Raji cells with low STEAP3 mRNA expression, human STEAP3-overexpressing cells were established. The impact of STEAP3 expression was analyzed about the amount of iron storage, the survival under hypoferric conditions in vitro and the growth of tumor in vivo. STEAP3 overexpression increased ferritin, an indicator of iron storage, in STEAP3-overexpressing Raji cells. STEAP3 gave Raji cells the resistance to iron deprivation-induced apoptosis. These STEAP3-overexpressing Raji cells preserved efficient growth even in hypoferric mice, while parental Raji cells grew less rapidly. In addition, iron deficiency enhanced STEAP3 mRNA expression in tumor cells. Furthermore, human colorectal cancer tissues exhibited more STEAP3 mRNA expression and iron storage compared with normal colon mucosa. These findings indicate that STEAP3 maintains iron storage in human malignant cells and tumor proliferation under the hypoferric condition. -- Highlights: {yields} STEAP3 expression results in increment of stored intracellular iron. {yields} Iron deprivation induces expression of STEAP3. {yields} Colorectal cancer expresses STEAP3 highly and stores iron much. {yields} STEAP3 expressing tumors preserves growth even in mice being hypoferremia.

  16. 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.

  17. 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

  18. A pathway to spirituality.

    Science.gov (United States)

    Shaw, Jon A

    2005-01-01

    The phenomenology of mystical experiences has been described throughout all the ages and in all religions. All mystical traditions identify some sense of union with the absolute as the ultimate spiritual goal. I assume that the pathway to both theistic and secular spirituality and our readiness to seek a solution in a psychological merger with something beyond the self evolves out of our human experience. Spirituality is one of man's strategies for dealing with the limitations of the life cycle, separation and loss, biological fragility, transience, and non-existence. Spirituality may serve as the affective component to a belief system or myth that is not rooted in scientific evidence but is lived as if it is true. Spirituality may take many forms, but I will suggest that in some instances it may serve as a reparative process in which one creates in the external world, through symbolic form, a nuance or facet of an internalized mental representation which has become lost or is no longer available to the self; or it may represent the continuity of the self-representation after death through a self-object merger. Lastly I will illustrate from the writings of two of our greatest poets, Dante Alighieri and William Wordsworth, how their poetry became interwoven with a profound spirituality. In Dante we will see the elaboration of a religious spirituality, while in the writings of Wordsworth a secular spirituality emerges interwoven with nature and belatedly his identification with "tragic man" as his mythos.

  19. 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 provid

  20. Autism: Many Genes, Common Pathways?

    OpenAIRE

    Geschwind, Daniel H.

    2008-01-01

    Autism is a heterogeneous neurodevelopmental syndrome with a complex genetic etiology. It is still not clear whether autism comprises a vast collection of different disorders akin to intellectual disability or a few disorders sharing common aberrant pathways. Unifying principles among cases of autism are likely to be at the level of brain circuitry in addition to molecular pathways.

  1. Autism: many genes, common pathways?

    Science.gov (United States)

    Geschwind, Daniel H

    2008-10-31

    Autism is a heterogeneous neurodevelopmental syndrome with a complex genetic etiology. It is still not clear whether autism comprises a vast collection of different disorders akin to intellectual disability or a few disorders sharing common aberrant pathways. Unifying principles among cases of autism are likely to be at the level of brain circuitry in addition to molecular pathways.

  2. Biogenetic Pathways for Marine Terpenoids

    Institute of Scientific and Technical Information of China (English)

    郑其煌; 苏镜娱; 黄起鹏; 王植材; 刘璇; 高碧; 曾陇梅; 郑德炫

    1994-01-01

    A reasonable theoretical elucidation of biogenetic pathways is given for marine ter-penoids——halogenated terpenoids,cernbranolides and tetracyclic tetraterpenoids in marine organisms ac-cording to biogenesis,and the possibility of studying biogenetic pathways by chemical synthesis and molecu-lar probe method is discussed.

  3. KeyPathwayMinerWeb

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  4. Novel protein regulates ERK pathway

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ The ERK (extracellular signal-regulated kinase) pathway plays a critical role in the vital processes of living cells such as proliferation and differentiation.Recently, CAS scientists in Shanghai have discovered a novel mechanism of spatial regulation on ERK pathway. The result was published in the 4 September issue of the Proceedings of National Academy of Sciences(PNAS).

  5. The Role of Filtration in Maintaining Clean Heat Exchanger Coils

    Energy Technology Data Exchange (ETDEWEB)

    Li Yang; James E. Braun; Eckhard A. Groll

    2004-06-30

    The main purpose of the study was to investigate the role of filtration in maintaining clean heat exchanger coils and overall performance. Combinations of 6 different levels of filtration (MERV 14, 11, 8, 6, 4, and no filter) and 4 different coils (an eight-row lanced-fin coil, HX8L), (an eight-row wavy-fin coil, HX8W), (a four-row lanced-fin coil, HX4L) and (a two-row lanced-fin coil, HX2L) were tested at 4 different air velocities (1.52, 2.03, 2.54,3.05 m/s (300, 400, 500, 600 ft/min)). The fouled conditions were obtained after injection of 600 grams of ASHRAE standard dust upstream of the filter/coil combination. This magnitude of dust is representative of a year of normal operation for an air conditioning system. The air-side pressure drops of the coils and filters and air-side heat transfer coefficients of the coils were determined from the measurements under the clean and fouled conditions. Depending upon the filter and coil test, the coil pressure drops increased in the range of 6%-30% for an air velocity at 2.54 m/s (500 ft/min). The impact was significantly greater for tests performed without a filter. The largest relative effect of fouling on pressure drop occurs for coils with fewer rows and having lanced fins. Coils with a greater number of rows can hold more dust so that a fixed amount of dust has a relatively smaller impact. The impact of fouling on air-side heat transfer coefficients was found to be relatively small. In some cases, heat transfer was actually enhanced due to additional turbulence caused by the presence of dust. The experimental results for pressure drops and heat transfer coefficients were correlated and the correlations were implemented within computer models of prototypical rooftop air conditioners and used to evaluate the impact of fouling on cooling capacity and EER. The equipment cooling capacity is reduced with fouling primarily because of a decrease in air flow due to the increase pressure drop rather than due to changes in h

  6. The Cryptococcus neoformans alkaline response pathway: identification of a novel rim pathway activator.

    Directory of Open Access Journals (Sweden)

    Kyla S Ost

    2015-04-01

    Full Text Available The Rim101/PacC transcription factor acts in a fungal-specific signaling pathway responsible for sensing extracellular pH signals. First characterized in ascomycete fungi such as Aspergillus nidulans and Saccharomyces cerevisiae, the Rim/Pal pathway maintains conserved features among very distantly related fungi, where it coordinates cellular adaptation to alkaline pH signals and micronutrient deprivation. However, it also directs species-specific functions in fungal pathogens such as Cryptococcus neoformans, where it controls surface capsule expression. Moreover, disruption of the Rim pathway central transcription factor, Rim101, results in a strain that causes a hyper-inflammatory response in animal infection models. Using targeted gene deletions, we demonstrate that several genes encoding components of the classical Rim/Pal pathway are present in the C. neoformans genome. Many of these genes are in fact required for Rim101 activation, including members of the ESCRT complex (Vps23 and Snf7, ESCRT-interacting proteins (Rim20 and Rim23, and the predicted Rim13 protease. We demonstrate that in neutral/alkaline pH, Rim23 is recruited to punctate regions on the plasma membrane. This change in Rim23 localization requires upstream ESCRT complex components but does not require other Rim101 proteolysis components, such as Rim20 or Rim13. Using a forward genetics screen, we identified the RRA1 gene encoding a novel membrane protein that is also required for Rim101 protein activation and, like the ESCRT complex, is functionally upstream of Rim23-membrane localization. Homologs of RRA1 are present in other Cryptococcus species as well as other basidiomycetes, but closely related genes are not present in ascomycetes. These findings suggest that major branches of the fungal Kingdom developed different mechanisms to sense and respond to very elemental extracellular signals such as changing pH levels.

  7. Refining the quantitative pathway of the Pathways to Mathematics model.

    Science.gov (United States)

    Sowinski, Carla; LeFevre, Jo-Anne; Skwarchuk, Sheri-Lynn; Kamawar, Deepthi; Bisanz, Jeffrey; Smith-Chant, Brenda

    2015-03-01

    In the current study, we adopted the Pathways to Mathematics model of LeFevre et al. (2010). In this model, there are three cognitive domains--labeled as the quantitative, linguistic, and working memory pathways--that make unique contributions to children's mathematical development. We attempted to refine the quantitative pathway by combining children's (N=141 in Grades 2 and 3) subitizing, counting, and symbolic magnitude comparison skills using principal components analysis. The quantitative pathway was examined in relation to dependent numerical measures (backward counting, arithmetic fluency, calculation, and number system knowledge) and a dependent reading measure, while simultaneously accounting for linguistic and working memory skills. Analyses controlled for processing speed, parental education, and gender. We hypothesized that the quantitative, linguistic, and working memory pathways would account for unique variance in the numerical outcomes; this was the case for backward counting and arithmetic fluency. However, only the quantitative and linguistic pathways (not working memory) accounted for unique variance in calculation and number system knowledge. Not surprisingly, only the linguistic pathway accounted for unique variance in the reading measure. These findings suggest that the relative contributions of quantitative, linguistic, and working memory skills vary depending on the specific cognitive task.

  8. Tractor Mechanics. Maintaining and Servicing the Cooling System, Learning Activity Packages 34-40; Maintaining and Servicing Hydraulic Systems, Learning Activity Packages 41-48.

    Science.gov (United States)

    Clemson Univ., SC. Vocational Education Media Center.

    This series of learning activity packages focuses on two areas of tractor mechanics: (1) maintaining and servicing the cooling system and (2) maintaining and servicing hydraulic systems. Each of the fifteen illustrated learning activity packages follows a typical format: introduction, directions, objectives, learning activities, tools and…

  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. 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.

  11. 14 CFR 119.43 - Certificate holder's duty to maintain operations specifications.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Certificate holder's duty to maintain... Chapter § 119.43 Certificate holder's duty to maintain operations specifications. (a) Each certificate holder shall maintain a complete and separate set of its operations specifications at its principal...

  12. 34 CFR 607.31 - How does a grantee maintain its eligibility?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false How does a grantee maintain its eligibility? 607.31... Grantee Meet? § 607.31 How does a grantee maintain its eligibility? (a) A grantee shall maintain its... set forth in its grant application including, if applicable, the institution's success...

  13. 34 CFR 606.31 - How does a grantee maintain its eligibility?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false How does a grantee maintain its eligibility? 606.31... Conditions Must a Grantee Meet? § 606.31 How does a grantee maintain its eligibility? (a) A grantee shall maintain its eligibility under the requirements in § 606.2, except for § 606.2(a)(3) and (4), for...

  14. 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

  15. Transgenic Chickens Overexpressing Aromatase Have High Estrogen Levels but Maintain a Predominantly Male Phenotype.

    Science.gov (United States)

    Lambeth, Luke S; Morris, Kirsten R; Wise, Terry G; Cummins, David M; O'Neil, Terri E; Cao, Yu; Sinclair, Andrew H; Doran, Timothy J; Smith, Craig A

    2016-01-01

    Estrogens play a key role in sexual differentiation of both the gonads and external traits in birds. The production of estrogen occurs via a well-characterized steroidogenic pathway, which is a multistep process involving several enzymes, including cytochrome P450 aromatase. In chicken embryos, the aromatase gene (CYP19A1) is expressed female-specifically from the time of gonadal sex differentiation. Ectopic overexpression of aromatase in male chicken embryos induces gonadal sex reversal, and male embryos treated with estradiol become feminized; however, this is not permanent. To test whether a continuous supply of estrogen in adult chickens could induce stable male to female sex reversal, 2 transgenic male chickens overexpressing aromatase were generated using the Tol2/transposase system. These birds had robust ectopic aromatase expression, which resulted in the production of high serum levels of estradiol. Transgenic males had female-like wattle and comb growth and feathering, but they retained male weights, displayed leg spurs, and developed testes. Despite the small sample size, this data strongly suggests that high levels of circulating estrogen are insufficient to maintain a female gonadal phenotype in adult birds. Previous observations of gynandromorph birds and embryos with mixed sex chimeric gonads have highlighted the role of cell autonomous sex identity in chickens. This might imply that in the study described here, direct genetic effects of the male chromosomes largely prevailed over the hormonal profile of the aromatase transgenic birds. This data therefore support the emerging view of at least partial cell autonomous sex development in birds. However, a larger study will confirm this intriguing observation.

  16. Genetic modification of dividing cells using episomally maintained S/MAR DNA vectors.

    Science.gov (United States)

    Wong, Suet-Ping; Harbottle, Richard Paul

    2013-08-13

    The development of episomally maintained DNA vectors to genetically modify dividing cells efficiently and stably, without the risk of integration-mediated genotoxicity, should prove to be a valuable tool in genetic research. In this study, we demonstrate the utility of Scaffold/Matrix Attachment Region (S/MAR) DNA vectors to model the restoration of a functional wild-type copy of the gene folliculin (FLCN) implicated in the renal cancer Birt-Hogg-Dubé (BHD). Inactivation of FLCN has been shown to be involved in the development of sporadic renal neoplasia in BHD. S/MAR-modified BHD tumor cells (named UOK257-FS) show restored stable FLCN expression and have normalized downstream TGFβ signals. We demonstrate that UOK257-FS cells show a reduced growth rate in vitro and suppression of xenograft tumor development in vivo, compared with the original FLCN-null UOK257 cell line. In addition, we demonstrate that mTOR signaling in serum-starved FLCN-restored cells is differentially regulated compared with the FLCN-deficient cell. The novel UOK257-FS cell line will be useful for studying the signaling pathways affected in BHD pathogenesis. Significantly, this study demonstrates the suitability of S/MAR vectors to successfully model the functional expression of a therapeutic gene in a cancer cell line and will aid the identification of novel cancer markers for diagnosis and therapy.Molecular Therapy-Nucleic Acids (2013) 2, e115; doi:10.1038/mtna.2013.40; published online 13 August 2013.

  17. Capu and Spire Assemble a Cytoplasmic Actin Mesh that Maintains Microtubule Organization in the Drosophila Oocyte

    Science.gov (United States)

    Dahlgaard, Katja; Raposo, Alexandre A.S.F.; Niccoli, Teresa; St Johnston, Daniel

    2007-01-01

    Summary Mutants in the actin nucleators Cappuccino and Spire disrupt the polarized microtubule network in the Drosophila oocyte that defines the anterior-posterior axis, suggesting that microtubule organization depends on actin. Here, we show that Cappuccino and Spire organize an isotropic mesh of actin filaments in the oocyte cytoplasm. capu and spire mutants lack this mesh, whereas overexpressed truncated Cappuccino stabilizes the mesh in the presence of Latrunculin A and partially rescues spire mutants. Spire overexpression cannot rescue capu mutants, but prevents actin mesh disassembly at stage 10B and blocks late cytoplasmic streaming. We also show that the actin mesh regulates microtubules indirectly, by inhibiting kinesin-dependent cytoplasmic flows. Thus, the Capu pathway controls alternative states of the oocyte cytoplasm: when active, it assembles an actin mesh that suppresses kinesin motility to maintain a polarized microtubule cytoskeleton. When inactive, unrestrained kinesin movement generates flows that wash microtubules to the cortex. PMID:17925229

  18. 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.

  19. Jasmonate Signal Pathway in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yi Shan; Zhi-Long Wang; Daoxin Xie

    2007-01-01

    Jasmonates (JAs), which include jasmonic acid and its cyclopentane derivatives are synthesized from the octadecanoid pathway and widely distributed throughout the plant kingdom. JAs modulate the expression of numerous genes and mediate responses to stress, wounding, insect attack, pathogen infection, and UV damage. They also affect a variety of processes in many plant developmental processes. The JA signal pathway involves two important events: the biosynthesis of JA and the transduction of JA signal. Several important Arabidopsis mutants in jasmonate signal pathway were described in this review.

  20. Plasticity within non-cerebellar pathways rapidly shapes motor performance in vivo

    Science.gov (United States)

    Mitchell, Diana E.; Della Santina, Charles C.; Cullen, Kathleen E.

    2016-01-01

    Although cerebellar mechanisms are vital to maintain accuracy during complex movements and to calibrate simple reflexes, recent in vitro studies have called into question the widely held view that synaptic changes within cerebellar pathways exclusively guide alterations in motor performance. Here we investigate the vestibulo-ocular reflex (VOR) circuitry by applying temporally precise activation of vestibular afferents in awake-behaving monkeys to link plasticity at different neural sites with changes in motor performance. Behaviourally relevant activation patterns produce rapid attenuation of direct pathway VOR neurons, but not their nerve input. Changes in the strength of this pathway are sufficient to induce a lasting decrease in the evoked VOR. In addition, indirect brainstem pathways display complementary nearly instantaneous changes, contributing to compensating for the reduced sensitivity of primary VOR neurons. Taken together, our data provide evidence that multiple sites of plasticity within VOR pathways can rapidly shape motor performance in vivo. PMID:27157829

  1. An assay for the mannan-binding lectin pathway of complement activation

    DEFF Research Database (Denmark)

    Petersen, Steen Vang; Thiel, S; Jensen, L;

    2001-01-01

    The mannan-binding lectin (MBL) pathway of complement activation has been established as the third pathway of complement activation. MBL is a carbohydrate-binding serum protein, which circulates in complex with serine proteases known as mannan-binding lectin associated serine proteases (MASPs...... activation. Therefore, in a generally applicable complement activation assay specific for the MBL pathway, the activity of the classical pathway must be inhibited. This can be accomplished by exploiting the finding that high ionic strength buffers inhibit the binding of C1q to immune complexes and disrupt...... the C1 complex, whereas the carbohydrate-binding activity of MBL and the integrity of the MBL complex is maintained under hypertonic conditions. In the assay described here, the specific C4b-depositing capacity of the MBL pathway was determined by incubating serum diluted in buffer containing 1 M Na...

  2. Glass fiber-reinforced composite resin as a space maintainer: A clinical study

    Directory of Open Access Journals (Sweden)

    Subramaniam P

    2008-12-01

    Full Text Available The aim of this study is to evaluate the use of glass fiber-reinforced composite resin (GFRCR as a space maintainer and to compare it with a conventional band-and-loop space maintainer. A total of 30 children (23 boys and 7 girls aged 6-8 years were selected for the study. Each of these children required maintenance of space due to premature loss of primary first molars in at least two quadrants. In one quadrant, a GFRCR space maintainer was applied and in the other quadrant a band-and-loop space maintainer was cemented. Patients were recalled at regular intervals over 12 months and retention of both the types of space maintainers was evaluated. The retention of the GFRCR space maintainer was found to be superior to that of the band-and-loop space maintainer, but this difference was not statistically significant.

  3. Glass fiber-reinforced composite resin as a space maintainer: a clinical study.

    Science.gov (United States)

    Subramaniam, P; Babu, Gkl; Sunny, R

    2008-01-01

    The aim of this study is to evaluate the use of glass fiber-reinforced composite resin (GFRCR) as a space maintainer and to compare it with a conventional band-and-loop space maintainer. A total of 30 children (23 boys and 7 girls) aged 6-8 years were selected for the study. Each of these children required maintenance of space due to premature loss of primary first molars in at least two quadrants. In one quadrant, a GFRCR space maintainer was applied and in the other quadrant a band-and-loop space maintainer was cemented. Patients were recalled at regular intervals over 12 months and retention of both the types of space maintainers was evaluated. The retention of the GFRCR space maintainer was found to be superior to that of the band-and-loop space maintainer, but this difference was not statistically significant.

  4. Regulation of Arginine-Ornithine Exchange and the Arginine Deiminase Pathway in Streptococcus lactis

    NARCIS (Netherlands)

    POOLMAN, B; DRIESSEN, AJM; KONINGS, WN

    1987-01-01

    Streptococcus lactis metabolizes arginine by the argiqine deiminase (ADI) pathway. Resting cells of S. lactis grown in the presence of galactose and arginine maintain a high intracellular ornithine pool in the absence of arginine and other exogenous energy sources. Addition of arginine results in a

  5. Rapamycin Attenuated Cardiac Hypertrophy Induced by Isoproterenol and Maintained Energy Homeostasis via Inhibiting NF-κB Activation

    Directory of Open Access Journals (Sweden)

    Xi Chen

    2014-01-01

    Full Text Available Rapamycin, also known as sirolimus, is an immunosuppressant drug used to prevent rejection organ (especially kidney transplantation. However, little is known about the role of Rapa in cardiac hypertrophy induced by isoproterenol and its underlying mechanism. In this study, Rapa was administrated intraperitoneally for one week after the rat model of cardiac hypertrophy induced by isoproterenol established. Rapa was demonstrated to attenuate isoproterenol-induced cardiac hypertrophy, maintain the structure integrity and functional performance of mitochondria, and upregulate genes related to fatty acid metabolism in hypertrophied hearts. To further study the implication of NF-κB in the protective role of Rapa, cardiomyocytes were pretreated with TNF-α or transfected with siRNA against NF-κB/p65 subunit. It was revealed that the upregulation of extracellular circulating proinflammatory cytokines induced by isoproterenol was able to be reversed by Rapa, which was dependent on NF-κB pathway. Furthermore, the regression of cardiac hypertrophy and maintaining energy homeostasis by Rapa in cardiomyocytes may be attributed to the inactivation of NF-κB. Our results shed new light on mechanisms underlying the protective role of Rapa against cardiac hypertrophy induced by isoproterenol, suggesting that blocking proinflammatory response by Rapa might contribute to the maintenance of energy homeostasis during the progression of cardiac hypertrophy.

  6. α-Spectrin and integrins act together to regulate actomyosin and columnarization, and to maintain a monolayered follicular epithelium.

    Science.gov (United States)

    Ng, Bing Fu; Selvaraj, Gokul Kannan; Santa-Cruz Mateos, Carmen; Grosheva, Inna; Alvarez-Garcia, Ines; Martín-Bermudo, María Dolores; Palacios, Isabel M

    2016-04-15

    The spectrin cytoskeleton crosslinks actin to the membrane, and although it has been greatly studied in erythrocytes, much is unknown about its function in epithelia. We have studied the role of spectrins during epithelia morphogenesis using the Drosophila follicular epithelium (FE). As previously described, we show that α-Spectrin and β-Spectrin are essential to maintain a monolayered FE, but, contrary to previous work, spectrins are not required to control proliferation. Furthermore, spectrin mutant cells show differentiation and polarity defects only in the ectopic layers of stratified epithelia, similar to integrin mutants. Our results identify α-Spectrin and integrins as novel regulators of apical constriction-independent cell elongation, as α-Spectrin and integrin mutant cells fail to columnarize. Finally, we show that increasing and reducing the activity of the Rho1-Myosin II pathway enhances and decreases multilayering of α-Spectrin cells, respectively. Similarly, higher Myosin II activity enhances the integrin multilayering phenotype. This work identifies a primary role for α-Spectrin in controlling cell shape, perhaps by modulating actomyosin. In summary, we suggest that a functional spectrin-integrin complex is essential to balance adequate forces, in order to maintain a monolayered epithelium.

  7. Multiple pathways regulate shoot branching

    Directory of Open Access Journals (Sweden)

    Catherine eRameau

    2015-01-01

    Full Text Available Shoot branching patterns result from the spatio-temporal regulation of axillary bud outgrowth. Numerous endogenous, developmental and environmental factors are integrated at the bud and plant levels to determine numbers of growing shoots. Multiple pathways that converge to common integrators are most probably involved. We propose several pathways involving not only the classical hormones auxin, cytokinins and strigolactones, but also other signals with a strong influence on shoot branching such as gibberellins, sugars or molecular actors of plant phase transition. We also deal with recent findings about the molecular mechanisms and the pathway involved in the response to shade as an example of an environmental signal controlling branching. We propose the TCP transcription factor TB1/BRC1 and the polar auxin transport stream in the stem as possible integrators of these pathways. We finally discuss how modeling can help to represent this highly dynamic system by articulating knowledges and hypothesis and calculating the phenotype properties they imply.

  8. Minimized human telomerase maintains telomeres and resolves endogenous roles of H/ACA proteins, TCAB1, and Cajal bodies.

    Science.gov (United States)

    Vogan, Jacob M; Zhang, Xiaozhu; Youmans, Daniel T; Regalado, Samuel G; Johnson, Joshua Z; Hockemeyer, Dirk; Collins, Kathleen

    2016-08-15

    We dissected the importance of human telomerase biogenesis and trafficking pathways for telomere maintenance. Biological stability of human telomerase RNA (hTR) relies on H/ACA proteins, but other eukaryotes use other RNP assembly pathways. To investigate additional rationale for human telomerase assembly as H/ACA RNP, we developed a minimized cellular hTR. Remarkably, with only binding sites for telomerase reverse transcriptase (TERT), minimized hTR assembled biologically active enzyme. TERT overexpression was required for cellular interaction with minimized hTR, indicating that H/ACA RNP assembly enhances endogenous hTR-TERT interaction. Telomere maintenance by minimized telomerase was unaffected by the elimination of the telomerase holoenzyme Cajal body chaperone TCAB1 or the Cajal body scaffold protein Coilin. Surprisingly, wild-type hTR also maintained and elongated telomeres in TCAB1 or Coilin knockout cells, with distinct changes in telomerase action. Overall, we elucidate trafficking requirements for telomerase biogenesis and function and expand mechanisms by which altered telomere maintenance engenders human disease.

  9. Prolyl-4-Hydroxylase 2 Potentially Contributes to Hepatocellular Carcinoma-Associated Erythrocytosis by Maintaining Hepatocyte Nuclear Factor-4α Expression

    Directory of Open Access Journals (Sweden)

    Wenwen Sun

    2015-12-01

    Full Text Available Background: Increased red blood cell count (Erythrocytosis is an important paraneoplastic syndrome of hepatocellular carcinoma (HCC and is a significant risk factor for lethal lung artery thromboembolism. HCC-associated erythrocytosis is partially caused by the ability of several HCC cells to produce erythropoietin (EPO. Prolyl-4-hydroxylase 2 (PHD2 is an enzyme encoded by the gene EGLN1. The best-known function of PHD2 is to mediate the oxygen-dependent degradation of the labile α-subunit of hypoxia-inducible factor (HIF. However, there is increasing evidence that PHD2 also regulates HIF-independent pathways by interacting with other substrates. Methods: In the EPO-producing human HCC cell line HepG2, the expression of PHD2 gene was silenced with siRNA. EPO production was estimated using quantitative PCR and ELISA. Results: In HepG2 cells, PHD2 suppresses the activity of TGF-β1 pathway and consequently maintains the expression of hepatocyte nuclear factor-4α (HNF-4α, an important transcription factor promoting the EPO expression in hepatocytes. PHD2 knockdown caused a marked reduction of EPO production. HIF seemed not to be involved in this biology. Conclusion: Our findings show that PHD2 represents a potential contributing factor for HCC-associated erythrocytosis. Selective inhibition of PHD2 in HCC cells might be considered as a new way to manage erythrocytosis in HCC patients.

  10. The sclerophyllous Eucalyptus camaldulensis and herbaceous Nicotiana tabacum have different mechanisms to maintain high rates of photosynthesis

    Directory of Open Access Journals (Sweden)

    Wei Huang

    2016-11-01

    Full Text Available It is believed that high levels of mesophyll conductance (gm largely contribute to the high rates of photosynthesis in herbaceous C3 plants. However, some sclerophyllous C3 plants that display low levels of gm have high rates of photosynthesis, and the underlying mechanisms responsible for high photosynthetic rates in sclerophyllous C3 plants are unclear. In the present study, we examined photosynthetic characteristics in two high-photosynthesis plants (the sclerophyllous Eucalyptus camaldulensis and the herbaceous Nicotiana tabacum using measurements of gas exchange and chlorophyll fluorescence. Under saturating light intensities, both species had similar rates of CO2 assimilation at 400 μmol mol-1 CO2 (A400. However, E. camaldulensis exhibited significantly lower gm and chloroplast CO2 concentration (Cc than N. tabacum. A quantitative analysis revealed that, in E. camaldulensis, the gm limitation was the most constraining factor for photosynthesis. By comparison, in N. tabacum, the biochemical limitation was the strongest, followed by gm and gs limitations. In conjunction with a lower Cc, E. camaldulensis up-regulated the capacities of photorespiratory pathway and alternative electron flow. Furthermore, the rate of alternative electron flow was positively correlated with the rates of photorespiration and ATP supply from other flexible mechanisms, suggesting the important roles of photorespiratory pathway and alternative electron flow in sustaining high rate of photosynthesis in E. camaldulensis. These results highlight the different mechanisms used to maintain high rates of photosynthesis in the sclerophyllous E. camaldulensis and the herbaceous N. tabacum.

  11. The Sclerophyllous Eucalyptus camaldulensis and Herbaceous Nicotiana tabacum Have Different Mechanisms to Maintain High Rates of Photosynthesis

    Science.gov (United States)

    Huang, Wei; Tong, You-Gui; Yu, Guo-Yun; Yang, Wei-Xian

    2016-01-01

    It is believed that high levels of mesophyll conductance (gm) largely contribute to the high rates of photosynthesis in herbaceous C3 plants. However, some sclerophyllous C3 plants that display low levels of gm have high rates of photosynthesis, and the underlying mechanisms responsible for high photosynthetic rates in sclerophyllous C3 plants are unclear. In the present study, we examined photosynthetic characteristics in two high-photosynthesis plants (the sclerophyllous Eucalyptus camaldulensis and the herbaceous Nicotiana tabacum) using measurements of gas exchange and chlorophyll fluorescence. Under saturating light intensities, both species had similar rates of CO2 assimilation at 400 μmol mol−1 CO2 (A400). However, E. camaldulensis exhibited significantly lower gm and chloroplast CO2 concentration (Cc) than N. tabacum. A quantitative analysis revealed that, in E. camaldulensis, the gm limitation was the most constraining factor for photosynthesis. By comparison, in N. tabacum, the biochemical limitation was the strongest, followed by gm and gs limitations. In conjunction with a lower Cc, E. camaldulensis up-regulated the capacities of photorespiratory pathway and alternative electron flow. Furthermore, the rate of alternative electron flow was positively correlated with the rates of photorespiration and ATP supply from other flexible mechanisms, suggesting the important roles of photorespiratory pathway, and alternative electron flow in sustaining high rate of photosynthesis in E. camaldulensis. These results highlight the different mechanisms used to maintain high rates of photosynthesis in the sclerophyllous E. camaldulensis and the herbaceous N. tabacum. PMID:27933083

  12. Exonuclease 1 is essential for maintaining genomic stability and the proliferative capacity of neural but not hematopoietic stem cells

    Directory of Open Access Journals (Sweden)

    Junling Zhang

    2014-01-01

    Full Text Available Exonuclease 1 (Exo1 has been implicated in the regulation of DNA damage responses in stem cells with dysfunctional telomeres. However, it is unclear whether Exo1-mediated DNA maintenance pathways play a role in the maintenance of genomic stability and the self-renewal of tissue stem cells in mice with functional telomeres. Here, we analyzed the proliferative capacity of neural stem cells (NSCs and hematopoietic stem cells (HSCs from Exo1−/− mice. Our study shows that Exo1 deficiency impairs the maintenance of genomic stability and proliferative capacity in NSCs but not HSCs. In line with these results, we detected a decrease in proliferation and an up-regulation of p21 expression levels in Exo1-deficient NSCs but not Exo1-deficient HSCs. Our data provide experimental evidence that Exo1 deficiency has a differential impact on the homeostasis and proliferative capacity of tissue stem cells in the brain and bone marrow, suggesting that different tissue stem cells utilize distinct mechanisms for maintaining their genomic stability. Our current study provides important insight into the role of Exo1-mediated DNA maintenance pathways in the maintenance of genomic stability and the proliferative capacity of tissue stem cells.

  13. Hipk2 and PP1c Cooperate to Maintain Dvl Protein Levels Required for Wnt Signal Transduction

    Directory of Open Access Journals (Sweden)

    Nobuyuki Shimizu

    2014-09-01

    Full Text Available The phosphoprotein Dishevelled (Dvl is a common essential component of Wnt/β-catenin and Wnt/planar cell polarity (PCP signaling pathways. However, the regulation and significance of Dvl phosphorylation are not fully understood. Here, we show that homeodomain-interacting protein kinase 2 (Hipk2 facilitates protein phosphatase 1 catalytic subunit (PP1c-mediated dephosphorylation of Dvl via its C-terminal domain and that this dephosphorylation blocks ubiquitination and consequent degradation mediated by the E3 ubiquitin ligase Itch, which targets the phosphorylated form of Dvl proteins. Inhibition of Hipk2 or PP1c function reduces Dvl protein levels and suppresses Wnt/β-catenin and Wnt/PCP pathway-dependent events in mammalian cells and zebrafish embryos, suggesting that Hipk2 and PP1c are essential for maintaining Dvl protein levels that are sufficient to activate Wnt signaling. We also show that Wnt-3a, a Wnt/β-catenin ligand, induces dissociation of the Dvl-Hipk2-PP1c complex and Dvl degradation under high-cell-density conditions. This regulation may be a negative feedback mechanism that fine-tunes Wnt/β-catenin signaling.

  14. The Oxylipin Pathway in Arabidopsis

    OpenAIRE

    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...

  15. Session on computation in biological pathways

    Energy Technology Data Exchange (ETDEWEB)

    Karp, P.D. [SRI International, Menlo Park, CA (United States); Riley, M. [Marine Biological Lab., Woods Hole, MA (United States)

    1996-12-31

    The papers in this session focus on the development of pathway databases and computational tools for pathway analysis. The discussion involves existing databases of sequenced genomes, as well as techniques for studying regulatory pathways.

  16. 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.

  17. Synthetic Routes to Methylerythritol Phosphate Pathway Intermediates and Downstream Isoprenoids

    Science.gov (United States)

    Jarchow-Choy, Sarah K; Koppisch, Andrew T; Fox, David T

    2014-01-01

    Isoprenoids constitute the largest class of natural products with greater than 55,000 identified members. They play essential roles in maintaining proper cellular function leading to maintenance of human health, plant defense mechanisms against predators, and are often exploited for their beneficial properties in the pharmaceutical and nutraceutical industries. Most impressively, all known isoprenoids are derived from one of two C5-precursors, isopentenyl diphosphate (IPP) or dimethylallyl diphosphate (DMAPP). In order to study the enzyme transformations leading to the extensive structural diversity found within this class of compounds there must be access to the substrates. Sometimes, intermediates within a biological pathway can be isolated and used directly to study enzyme/pathway function. However, the primary route to most of the isoprenoid intermediates is through chemical catalysis. As such, this review provides the first exhaustive examination of synthetic routes to isoprenoid and isoprenoid precursors with particular emphasis on the syntheses of intermediates found as part of the 2C-methylerythritol 4-phosphate (MEP) pathway. In addition, representative syntheses are presented for the monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), triterpenes (C30) and tetraterpenes (C40). Finally, in some instances, the synthetic routes to substrate analogs found both within the MEP pathway and downstream isoprenoids are examined. PMID:25009443

  18. 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

  19. Exploring levels of hexosamine biosynthesis pathway intermediates and protein kinase C isoforms in muscle and fat tissue of Zucker Diabetic Fatty rats.

    NARCIS (Netherlands)

    Bosch, R.R.; Janssen, S.W.J.; Span, P.N.; Olthaar, A.J.; Emst-de Vries, S.E. van; Willems, P.H.G.M.; Martens, G.J.M.; Hermus, A.R.M.M.; Sweep, C.G.J.

    2003-01-01

    Many studies suggest that insulin resistance develops and/or is maintained by an increased flux of glucose through the hexosamine biosynthesis pathway. This pathway may attenuate insulin-stimulated glucose uptake by activating protein kinase C (PKC). Therefore, we investigated whether the concentrat

  20. Space maintainer for the loss of a permanent molar in the adolescent patient: report of case.

    Science.gov (United States)

    Lindemeyer, R G; Glavich, G G

    1996-01-01

    An adolescent patient who loses a permanent first molar presents a clinical challenge for the practitioner. The ideal space maintainer should not only maintain the edentulous space, but it should also maintain inter-arch integrity. An esthetic, inexpensive unilateral space maintainer has been designed for the replacement of a permanent first molar in an adolescent patient. The appliance has demonstrated high patient satisfaction, as well as, a good clinical result. This appliance is designed to remain in place until the patient is old enough to receive an implant or a more permanent prosthetic replacement.

  1. New Therapeutic Approaches for the Treatment of Rheumatoid Arthritis may Rise from the Cholinergic Anti-Inflammatory Pathway and Antinociceptive Pathway

    Directory of Open Access Journals (Sweden)

    Xiao Hua Pan

    2010-01-01

    Full Text Available Due to the complex etiology of rheumatoid arthritis (RA, it is difficult to be completely cured at the current stage although many approaches have been applied in clinics, especially the wide application of nonsteroidal anti-inflammatory drugs (NSAIDs and disease-modifying antirheumatic drugs (DMARDs. New drug discovery and development via the recently discovered cholinergic anti-inflammatory and antinociceptive pathways should be promising. Based on the above, the nicotinic acetylcholine receptor agonists maintain the potential for the treatment of RA. Therefore, new therapeutic approaches may rise from these two newly discovered pathways. More preclinical experiments and clinical trials are required to confirm our viewpoint.

  2. Maintaining Growth

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    China's GDP grew 9.2 percent in 2011,a remarkable achievement outshining many other countries.However,the current condition of the national economy is less than appealing.The sequential quarterly GDP growth rates for 2011 stood at 9.7 percent,9.5 percent,9.1 percent and 8.9 percent,showing a trend of deceleration.A consensus has been made that stabilizing growth should be the primary goal for China's economic development.

  3. LXR signaling pathways and atherosclerosis

    Science.gov (United States)

    Calkin, Anna; Tontonoz, Peter

    2010-01-01

    First discovered as orphan receptors, liver X receptors (LXRs) were subsequently identified as the nuclear receptor target of the cholesterol metabolites, oxysterols.1 There are 2 LXR receptors encoded by distinct genes: LXRα is most highly expressed in the liver, adipose, kidney, adrenal tissues and macrophages, and LXRβ is ubiquitously expressed. Despite differential tissue distribution, these isoforms have 78% homology in their ligand-binding domain and appear to respond to the same endogenous ligands. Work over the past 10 years has shown that the LXR pathway regulates lipid metabolism and inflammation via both the induction and repression of target genes. Given the importance of cholesterol regulation and inflammation in the development of cardiovascular disease, it is not surprising that activation of the LXR pathway attenuates various mechanisms underlying atherosclerotic plaque development.2 In this minireview we will discuss the impact of the LXR pathway on both cholesterol metabolism and atherosclerosis. PMID:20631351

  4. Tissue factor pathway inhibitor endocytosis.

    Science.gov (United States)

    Schwartz, A L; Broze, G J

    1997-10-01

    Tissue factor pathway inhibitor (TFPI), a 42 kD protein, provides the physiological inhibition of tissue factor initiated coagulation by inhibition of both factor Xa and factor VIIa/tissue factor. In plasma, most TFPI is lipoprotein bound with an additional "releasable" pool bound to the endothelial cell surface. TFPI clearance is via receptor mediated endocytosis into liver. Heparin sulfate proteoglycans and LRP (low density lipoprotein receptor-related protein), an extremely large (∼600 kD) cell surface protein, primarily mediate this clearance, although additional TFPI binding sites and endocytosis pathways exist. (Trends Cardiovasc Med 1997; 7:234-239). © 1997, Elsevier Science Inc.

  5. [Pathways of flowering regulation in plants].

    Science.gov (United States)

    Liu, Yongping; Yang, Jing; Yang, Mingfeng

    2015-11-01

    Flowering, the floral transition from vegetative growth to reproductive growth, is induced by diverse endogenous and exogenous cues, such as photoperiod, temperature, hormones and age. Precise flowering time is critical to plant growth and evolution of species. The numerous renewal molecular and genetic results have revealed five flowering time pathways, including classical photoperiod pathway, vernalization pathway, autonomous pathway, gibberellins (GA) pathway and newly identified age pathway. These pathways take on relatively independent role, and involve extensive crosstalks and feedback loops. This review describes the complicated regulatory network of this floral transition to understand the molecular mechanism of flowering and provide references for further research in more plants.

  6. China Maintains World No.1in Terms of Auto Production and Sales in2010%China Maintains World No.1in Terms of Auto Production and Sales in 2010

    Institute of Scientific and Technical Information of China (English)

    Li Zao

    2011-01-01

    @@ Figures from the China Association of Automobile Manufacturers show that the auto industry of China maintained the development tendency of the last year in2010 under the accumulation effect of many consumption encouraging policies such as purchase tax concession,old for new service,car subsidy program for rural areas,energy-saving products discount,both the auto production and the sales exceeding 18 million units,maintaining its position as the world No.1,achieving 18.2647 million units and 18.0619 million units respectively,with an increase of 32.44% and 32.37% on a year-on-year basis.

  7. 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...

  8. 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... § 11.713 Requirements for maintaining current knowledge of waters to be navigated. (a) If a first class... current knowledge of the route. Persons using this method of re-familiarization shall certify,...

  9. The use of space maintainers at a UK pediatric dentistry department.

    Science.gov (United States)

    Qudeimat, M A; Fayle, S A

    1999-01-01

    Space maintainers have been in use in pediatric dentistry for many years. The use of these appliances, however, in terms of indications, contraindications, design, and construction, has gained little attention from researchers. It is clearly essential that when space maintainers are fitted, it is the result of careful planning and appropriate prescriptions.

  10. The Role of the School Business Official in Maintaining School District Financial Solvency

    Science.gov (United States)

    Williams, Ann C.

    2012-01-01

    The purpose of this study was to identify the job responsibilities perceived as most important in maintaining school district financial solvency. Additionally, the study sought to identify specific financial management strategies school business officials (SBO) could consider to maintain financial solvency in their school districts. A total of 208…

  11. 12 CFR 559.10 - How must separate corporate identities be maintained?

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false How must separate corporate identities be... corporate identities be maintained? (a) Each savings association and subordinate organization thereof must be operated in a manner that demonstrates to the public that each maintains a separate...

  12. 41 CFR 102-74.180 - What illumination levels must Federal agencies maintain on Federal facilities?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What illumination levels... illumination levels must Federal agencies maintain on Federal facilities? Except where special circumstances exist, Federal agencies must maintain illumination levels at— (a) 50 foot-candles at work...

  13. Simultaneous demodulation of polarization mode coupling and fiber Bragg grating within a polarization maintaining fiber

    Science.gov (United States)

    Zhao, Yanshuang; Liu, Yanlei; Zhang, Jianzhong; Yang, Jun; Canning, John; Peng, G. D.; Chen, Yujin; Yuan, Libo

    2015-09-01

    We propose a simultaneous demodulation scheme of polarization mode coupling and fiber Bragg grating in a polarization maintaining fiber based on a white light interferometer. A polarization maintaining fiber with two inscribed fiber Bragg gratings is used to demonstrate the feasibility.

  14. On the impact of DSL tools on the maintainability of language implementations

    NARCIS (Netherlands)

    Klint, P.; Storm, T. van der; Vinju, J.J.; Brabrand, C.; Moreau, P.-E.

    2010-01-01

    Does the use of DSL tools improve the maintainability of language implementations compared to implementations from scratch? We present empirical results on aspects of maintainability of six implementations of the same DSL using different languages (Java, JavaScript, C#) and DSL tools (ANTLR, OMeta,

  15. 13 CFR 126.500 - How does a qualified HUBZone SBC maintain HUBZone certification?

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false How does a qualified HUBZone SBC... ADMINISTRATION HUBZONE PROGRAM Maintaining HUBZone Status § 126.500 How does a qualified HUBZone SBC maintain HUBZone certification? Any qualified HUBZone SBC seeking to remain on the List must recertify every...

  16. 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)...

  17. 27 CFR 31.163 - Requirements when a wholesale dealer in liquors maintains a retail department.

    Science.gov (United States)

    2010-04-01

    ... wholesale dealer in liquors maintains a retail department. 31.163 Section 31.163 Alcohol, Tobacco Products... wholesale dealer in liquors maintains a retail department. (a) Constructive receipt and sale. When a... spirits, and the retail sales of distilled spirits normally represent 90 percent or more of the volume...

  18. 13 CFR 120.829 - Job Opportunity average a CDC must maintain.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Job Opportunity average a CDC must... Job Opportunity average a CDC must maintain. (a) A CDC's portfolio must maintain a minimum average of one Job Opportunity per an amount of 504 loan funding that will be specified by SBA from time to...

  19. Loco signaling pathway in longevity.

    Science.gov (United States)

    Lin, Yuh-Ru; Parikh, Hardik; Park, Yongkyu

    2011-05-01

    Despite the various roles of regulator of G protein signaling (RGS) protein in the G protein signaling pathway that have been defined, the function of RGS has not been characterized in longevity signaling pathways. We found that reduced expression of Loco, a Drosophila RGS protein, resulted in a longer lifespan of flies with stronger resistance to stress, higher MnSOD activity and increased fat content. In contrast, overexpression of the loco gene shortened the fly lifespan significantly, lowered stress resistance and reduced fat content, also indicating that the RGS domain containing GTPase-activating protein (GAP) activity is related to the regulation of longevity. Interestingly, expressional changes of yeast RGS2 and rat RGS14, homologs to the fly Loco, also affected oxidative stress resistance and longevity in the respective species. It is known that Loco inactivates inhibitory Gαi•GTP protein to reduce activity of adenylate cyclase (AC) and RGS14 interacts with activated H-Ras and Raf-1 kinases, which subsequently inhibits ERK phosphorylation. We propose that Loco/RGS14 protein may regulate stress resistance and longevity as an activator in AC-cAMP-PKA pathway and/or as a molecular scaffold that sequesters active Ras and Raf from Ras•GTP-Raf-MEK-ERK signaling pathway. Consistently, our data showed that downregulation of Loco significantly diminishes cAMP amounts and increases p-ERK levels with higher resistance to the oxidative stress.

  20. 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. Solvents and vapor intrusion pathways.

    Science.gov (United States)

    Phillips, Scott D; Krieger, Gary R; Palmer, Robert B; Waksman, Javier C

    2004-08-01

    Vapor intrusion must be recognized appropriately as a separate pathway of contamination. Although many issues resemble those of other forms of contamination (particularly its entryway, which is similar to that of radon seepage), vapor intrusion stands apart as a unique risk requiring case-specific action. This article addresses these issues and the current understanding of the most appropriate and successful remedial actions.

  2. 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...

  3. Auditory pathways: anatomy and physiology.

    Science.gov (United States)

    Pickles, James O

    2015-01-01

    This chapter outlines the anatomy and physiology of the auditory pathways. After a brief analysis of the external, middle ears, and cochlea, the responses of auditory nerve fibers are described. The central nervous system is analyzed in more detail. A scheme is provided to help understand the complex and multiple auditory pathways running through the brainstem. The multiple pathways are based on the need to preserve accurate timing while extracting complex spectral patterns in the auditory input. The auditory nerve fibers branch to give two pathways, a ventral sound-localizing stream, and a dorsal mainly pattern recognition stream, which innervate the different divisions of the cochlear nucleus. The outputs of the two streams, with their two types of analysis, are progressively combined in the inferior colliculus and onwards, to produce the representation of what can be called the "auditory objects" in the external world. The progressive extraction of critical features in the auditory stimulus in the different levels of the central auditory system, from cochlear nucleus to auditory cortex, is described. In addition, the auditory centrifugal system, running from cortex in multiple stages to the organ of Corti of the cochlea, is described.

  4. 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.

  5. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma.

    Science.gov (United States)

    Peacock, Craig D; Wang, Qiuju; Gesell, Gregory S; Corcoran-Schwartz, Ian M; Jones, Evan; Kim, Jynho; Devereux, Wendy L; Rhodes, Jonathan T; Huff, Carol A; Beachy, Philip A; Watkins, D Neil; Matsui, William

    2007-03-01

    The cancer stem cell hypothesis suggests that malignant growth depends on a subset of tumor cells with stem cell-like properties of self-renewal. Because hedgehog (Hh) signaling regulates progenitor cell fate in normal development and homeostasis, aberrant pathway activation might be involved in the maintenance of such a population in cancer. Indeed, mutational activation of the Hh pathway is associated with medulloblastoma and basal cell carcinoma; pathway activity is also critical for growth of other tumors lacking such mutations, although the mechanism of pathway activation is poorly understood. Here we study the role and mechanism of Hh pathway activation in multiple myeloma (MM), a malignancy with a well defined stem cell compartment. In this model, rare malignant progenitors capable of clonal expansion resemble B cells, whereas the much larger tumor cell population manifests a differentiated plasma cell phenotype that pathologically defines the disease. We show that the subset of MM cells that manifests Hh pathway activity is markedly concentrated within the tumor stem cell compartment. The Hh ligand promotes expansion of MM stem cells without differentiation, whereas the Hh pathway blockade, while having little or no effect on malignant plasma cell growth, markedly inhibits clonal expansion accompanied by terminal differentiation of purified MM stem cells. These data reveal that Hh pathway activation is heterogeneous across the spectrum of MM tumor stem cells and their more differentiated progeny. The potential existence of similar relationships in other adult cancers may have important biologic and clinical implications for the study of aberrant Hh signaling.

  6. Alternate pathways of thyroid hormone metabolism.

    Science.gov (United States)

    Wu, Sing-Yung; Green, William L; Huang, Wen-Sheng; Hays, Marguerite T; Chopra, Inder J

    2005-08-01

    The major thyroid hormone (TH) secreted by the thyroid gland is thyroxine (T(4)). Triiodothyronine (T(3)), formed chiefly by deiodination of T(4), is the active hormone at the nuclear receptor, and it is generally accepted that deiodination is the major pathway regulating T(3) bioavailability in mammalian tissues. The alternate pathways, sulfation and glucuronidation of the phenolic hydroxyl group of iodothyronines, the oxidative deamination and decarboxylation of the alanine side chain to form iodothyroacetic acids, and ether link cleavage provide additional mechanisms for regulating the supply of active hormone. Sulfation may play a general role in regulation of iodothyronine metabolism, since sulfation of T(4) and T(3) markedly accelerates deiodination to the inactive metabolites, reverse triiodothyronine (rT(3)) and T(2). Sulfoconjugation is prominent during intrauterine development, particularly in the precocial species in the last trimester including humans and sheep, where it may serve both to regulate the supply of T(3), via sulfation followed by deiodination, and to facilitate maternal-fetal exchange of sulfated iodothyronines (e.g., 3,3'-diiodothyronine sulfate [T(2)S]). The resulting low serum T(3) may be important for normal fetal development in the late gestation. The possibility that T(2)S or its derivative, transferred from the fetus and appearing in maternal serum or urine, can serve as a marker of fetal thyroid function is being studied. Glucuronidation of TH often precedes biliary-fecal excretion of hormone. In rats, stimulation of glucuronidation by various drugs and toxins may lead to lower T(4) and T(3) levels, provocation of thyrotropin (TSH) secretion, and goiter. In man, drug induced stimulation of glucuronidation is limited to T(4), and does not usually compromise normal thyroid function. However, in hypothyroid subjects, higher doses of TH may be required to maintain euthyroidism when these drugs are given. In addition, glucuronidates and

  7. 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.

  8. A novel role for extracellular signal-regulated kinase in maintaining long-term memory-relevant excitability changes.

    Science.gov (United States)

    Cohen-Matsliah, Sivan Ida; Brosh, Inbar; Rosenblum, Kobi; Barkai, Edi

    2007-11-14

    Pyramidal neurons in the piriform cortex from olfactory-discrimination-trained rats show enhanced intrinsic neuronal excitability that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the postburst afterhyperpolarization (AHP), which is generated by repetitive spike firing. AHP reduction is attributable to decreased conductance of a calcium-dependent potassium current, the sI(AHP). We have previously shown that such learning-induced AHP reduction is maintained by PKC activation. However, the molecular machinery underlying such long-lasting modulation of intrinsic excitability is yet to be fully described. Here we examine whether the extracellular signal-regulated kinase I/II (ERKI/II) pathway, which is known to be crucial in learning, memory, and synaptic plasticity processes, is instrumental for the long-term maintenance of learning-induced AHP reduction. PD98059 or UO126, which selectively block MEK, the upstream kinase of ERK, increased the AHP in neurons from trained rats but not in neurons from naive and pseudo-trained rats. Consequently, the differences in AHP amplitude and neuronal adaptation between neurons from trained rats and controls were abolished. This effect was not mediated by modulation of basic membrane properties. In accordance with its effect on neuronal excitability, the level of activated ERK in the membranal fraction was significantly higher in piriform cortex samples taken from trained rats. In addition, the PKC activator OAG (1-oleoyl-20acety-sn-glycerol), which was shown to reduce the AHP in neurons from control rats, had no effect on these neurons in the presence of PD98059. Our data show that ERK has a key role in maintaining long-lasting learning-induced enhancement of neuronal excitability.

  9. 1,25-dihydroxyvitamin D3 treatment delays cellular aging in human mesenchymal stem cells while maintaining their multipotent capacity.

    Directory of Open Access Journals (Sweden)

    Barbara Klotz

    Full Text Available 1,25-dihydroxyvitamin D3 (1,25D3 was reported to induce premature organismal aging in fibroblast growth factor-23 (Fgf23 and klotho deficient mice, which is of main interest as 1,25D3 supplementation of its precursor cholecalciferol is used in basic osteoporosis treatment. We wanted to know if 1,25D3 is able to modulate aging processes on a cellular level in human mesenchymal stem cells (hMSC. Effects of 100 nM 1,25D3 on hMSC were analyzed by cell proliferation and apoptosis assay, β-galactosidase staining, VDR and surface marker immunocytochemistry, RT-PCR of 1,25D3-responsive, quiescence- and replicative senescence-associated genes. 1,25D3 treatment significantly inhibited hMSC proliferation and apoptosis after 72 h and delayed the development of replicative senescence in long-term cultures according to β-galactosidase staining and P16 expression. Cell morphology changed from a fibroblast like appearance to broad and rounded shapes. Long term treatment did not induce lineage commitment in terms of osteogenic pathways but maintained their clonogenic capacity, their surface marker characteristics (expression of CD73, CD90, CD105 and their multipotency to develop towards the chondrogenic, adipogenic and osteogenic pathways. In conclusion, 1,25D3 delays replicative senescence in primary hMSC while the pro-aging effects seen in mouse models might mainly be due to elevated systemic phosphate levels, which propagate organismal aging.

  10. DMPD: Signalling pathways mediating type I interferon gene expression. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17904888 Signalling pathways mediating type I interferon gene expression. Edwards M...csml) Show Signalling pathways mediating type I interferon gene expression. PubmedID 17904888 Title Signalling pathways media

  11. Fiber reinforced composite loop space maintainer: An alternative to the conventional band and loop

    Directory of Open Access Journals (Sweden)

    Ramakrishna Yeluri

    2012-01-01

    Full Text Available The stainless steel band and loop appliance is the most commonly used fixed space maintainer in pediatric dentistry. But there are several disadvantages with this appliance such as the need for a cast or a working model, decalcification of the abutment tooth, loosening because of breakage or dissolution of the luting agent, tendency to get embedded in the soft tissue and the possibility of metal allergy. The purpose of this article is to present a simple, laboratory design of a "Fiber Reinforced Composite" (FRC loop space maintainer and discuss the advantages over the traditional band and loop space maintainers.

  12. Glass fiber-reinforced composite resin as a space maintainer: A clinical study

    OpenAIRE

    Subramaniam P; Babu GKL; Sunny R

    2008-01-01

    The aim of this study is to evaluate the use of glass fiber-reinforced composite resin (GFRCR) as a space maintainer and to compare it with a conventional band-and-loop space maintainer. A total of 30 children (23 boys and 7 girls) aged 6-8 years were selected for the study. Each of these children required maintenance of space due to premature loss of primary first molars in at least two quadrants. In one quadrant, a GFRCR space maintainer was applied and in the other quadrant a band-and-loop...

  13. Fiber reinforced composite loop space maintainer: An alternative to the conventional band and loop.

    Science.gov (United States)

    Yeluri, Ramakrishna; Munshi, Autar Krishen

    2012-04-01

    The stainless steel band and loop appliance is the most commonly used fixed space maintainer in pediatric dentistry. But there are several disadvantages with this appliance such as the need for a cast or a working model, decalcification of the abutment tooth, loosening because of breakage or dissolution of the luting agent, tendency to get embedded in the soft tissue and the possibility of metal allergy. The purpose of this article is to present a simple, laboratory design of a "Fiber Reinforced Composite" (FRC) loop space maintainer and discuss the advantages over the traditional band and loop space maintainers.

  14. Current perspectives of the signaling pathways directing neural crest induction.

    Science.gov (United States)

    Stuhlmiller, Timothy J; García-Castro, Martín I

    2012-11-01

    The neural crest is a migratory population of embryonic cells with a tremendous potential to differentiate and contribute to nearly every organ system in the adult body. Over the past two decades, an incredible amount of research has given us a reasonable understanding of how these cells are generated. Neural crest induction involves the combinatorial input of multiple signaling pathways and transcription factors, and is thought to occur in two phases from gastrulation to neurulation. In the first phase, FGF and Wnt signaling induce NC progenitors at the border of the neural plate, activating the expression of members of the Msx, Pax, and Zic families, among others. In the second phase, BMP, Wnt, and Notch signaling maintain these progenitors and bring about the expression of definitive NC markers including Snail2, FoxD3, and Sox9/10. In recent years, additional signaling molecules and modulators of these pathways have been uncovered, creating an increasingly complex regulatory network. In this work, we provide a comprehensive review of the major signaling pathways that participate in neural crest induction, with a focus on recent developments and current perspectives. We provide a simplified model of early neural crest development and stress similarities and differences between four major model organisms: Xenopus, chick, zebrafish, and mouse.

  15. Hydrogen sulfide in signaling pathways.

    Science.gov (United States)

    Olas, Beata

    2015-01-15

    For a long time hydrogen sulfide (H₂S) was considered a toxic compound, but recently H₂S (at low concentrations) has been found to play an important function in physiological processes. Hydrogen sulfide, like other well-known compounds - nitric oxide (NO) and carbon monoxide (CO) is a gaseous intracellular signal transducer. It regulates the cell cycle, apoptosis and the oxidative stress. Moreover, its functions include neuromodulation, regulation of cardiovascular system and inflammation. In this review, I focus on the metabolism of hydrogen sulfide (including enzymatic pathways of H₂S synthesis from l- and d-cysteine) and its signaling pathways in the cardiovascular system and the nervous system. I also describe how hydrogen sulfide may be used as therapeutic agent, i.e. in the cardiovascular diseases.

  16. Evolution of variation in presence and absence of genes in bacterial pathways

    Directory of Open Access Journals (Sweden)

    Francis Andrew R

    2012-04-01

    Full Text Available Abstract Background Bacterial genomes exhibit a remarkable degree of variation in the presence and absence of genes, which probably extends to the level of individual pathways. This variation may be a consequence of the significant evolutionary role played by horizontal gene transfer, but might also be explained by the loss of genes through mutation. A challenge is to understand why there would be variation in gene presence within pathways if they confer a benefit only when complete. Results Here, we develop a mathematical model to study how variation in pathway content is produced by horizontal transfer, gene loss and partial exposure of a population to a novel environment. Conclusions We discuss the possibility that variation in gene presence acts as cryptic genetic variation on which selection acts when the appropriate environment occurs. We find that a high level of variation in gene presence can be readily explained by decay of the pathway through mutation when there is no longer exposure to the selective environment, or when selection becomes too weak to maintain the genes. In the context of pathway variation the role of horizontal gene transfer is probably the initial introduction of a complete novel pathway rather than in building up the variation in a genome without the pathway.

  17. The Hippo pathway regulates homeostatic growth of stem cell niche precursors in the Drosophila ovary.

    Science.gov (United States)

    Sarikaya, Didem P; Extavour, Cassandra G

    2015-02-01

    The Hippo pathway regulates organ size, stem cell proliferation and tumorigenesis in adult organs. Whether the Hippo pathway influences establishment of stem cell niche size to accommodate changes in organ size, however, has received little attention. Here, we ask whether Hippo signaling influences the number of stem cell niches that are established during development of the Drosophila larval ovary, and whether it interacts with the same or different effector signaling pathways in different cell types. We demonstrate that canonical Hippo signaling regulates autonomous proliferation of the soma, while a novel hippo-independent activity of Yorkie regulates autonomous proliferation of the germ line. Moreover, we demonstrate that Hippo signaling mediates non-autonomous proliferation signals between germ cells and somatic cells, and contributes to maintaining the correct proportion of these niche precursors. Finally, we show that the Hippo pathway interacts with different growth pathways in distinct somatic cell types, and interacts with EGFR and JAK/STAT pathways to regulate non-autonomous proliferation of germ cells. We thus provide evidence for novel roles of the Hippo pathway in establishing the precise balance of soma and germ line, the appropriate number of stem cell niches, and ultimately regulating adult female reproductive capacity.

  18. 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.

  19. Identification of Metabolic Pathway Systems

    Directory of Open Access Journals (Sweden)

    Sepideh eDolatshahi

    2016-02-01

    Full Text Available The estimation of parameters in even moderately large biological systems is a significant challenge. This challenge is greatly exacerbated if the mathematical formats of appropriate process descriptions are unknown. To address this challenge, the method of dynamic flux estimation (DFE was proposed for the analysis of metabolic time series data. Under ideal conditions, the first phase of DFE yields numerical representations of all fluxes within a metabolic pathway system, either as values at each time point or as plots against their substrates and modulators. However, this numerical result does not reveal the mathematical format of each flux. Thus, the second phase of DFE selects functional formats that are consistent with the numerical trends obtained from the first phase. While greatly facilitating metabolic data analysis, DFE is only directly applicable if the pathway system contains as many dependent variables as fluxes. Because most actual systems contain more fluxes than metabolite pools, this requirement is seldom satisfied. Auxiliary methods have been proposed to alleviate this issue, but they are not general. Here we propose strategies that extend DFE toward general, slightly underdetermined pathway systems.

  20. Imbalanced kynurenine pathway in schizophrenia.

    Science.gov (United States)

    Kegel, Magdalena E; Bhat, Maria; Skogh, Elisabeth; Samuelsson, Martin; Lundberg, Kristina; Dahl, Marja-Liisa; Sellgren, Carl; Schwieler, Lilly; Engberg, Göran; Schuppe-Koistinen, Ina; Erhardt, Sophie

    2014-01-01

    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.

  1. Pathways to Shape the Bioeconomy

    Directory of Open Access Journals (Sweden)

    Carmen Priefer

    2017-02-01

    Full Text Available In view of the increasing depletion of fossil fuel resources, the concept “bioeconomy” aims at the gradual replacement of fossil fuels by renewable feedstock. Seen as a comprehensive societal transition, the bioeconomy is a complex field that includes a variety of sectors, actors, and interests and is related to far-reaching changes in today’s production systems. While the objectives pursued—such as reducing dependence on fossil fuels, mitigating climate change, ensuring global food security, and increasing the industrial use of biogenic resources—are not generally contentious, there is fierce controversy over the possible pathways for achieving these objectives. Based on a thorough literature review, the article identifies major lines of conflict in the current discourse. Criticism of the prevalent concept refers mainly to the strong focus on technology, the lack of consideration given to alternative implementation pathways, the insufficient differentiation of underlying sustainability requirements, and the inadequate participation of societal stakeholders. Since today it cannot be predicted which pathway will be the most expedient—the one already being taken or one of the others proposed—this paper suggests pursuing a strategy of diversity concerning the approaches to shape the bioeconomy, the funding of research topics, and the involvement of stakeholders.

  2. Identification of Metabolic Pathway Systems.

    Science.gov (United States)

    Dolatshahi, Sepideh; Voit, Eberhard O

    2016-01-01

    The estimation of parameters in even moderately large biological systems is a significant challenge. This challenge is greatly exacerbated if the mathematical formats of appropriate process descriptions are unknown. To address this challenge, the method of dynamic flux estimation (DFE) was proposed for the analysis of metabolic time series data. Under ideal conditions, the first phase of DFE yields numerical representations of all fluxes within a metabolic pathway system, either as values at each time point or as plots against their substrates and modulators. However, this numerical result does not reveal the mathematical format of each flux. Thus, the second phase of DFE selects functional formats that are consistent with the numerical trends obtained from the first phase. While greatly facilitating metabolic data analysis, DFE is only directly applicable if the pathway system contains as many dependent variables as fluxes. Because most actual systems contain more fluxes than metabolite pools, this requirement is seldom satisfied. Auxiliary methods have been proposed to alleviate this issue, but they are not general. Here we propose strategies that extend DFE toward general, slightly underdetermined pathway systems.

  3. The updated RGD Pathway Portal utilizes increased curation efficiency and provides expanded pathway information.

    Science.gov (United States)

    Hayman, G Thomas; Jayaraman, Pushkala; Petri, Victoria; Tutaj, Marek; Liu, Weisong; De Pons, Jeff; Dwinell, Melinda R; Shimoyama, Mary

    2013-02-05

    The RGD Pathway Portal provides pathway annotations for rat, human and mouse genes and pathway diagrams and suites, all interconnected via the pathway ontology. Diagram pages present the diagram and description, with diagram objects linked to additional resources. A newly-developed dual-functionality web application composes the diagram page. Curators input the description, diagram, references and additional pathway objects. The application combines these with tables of rat, human and mouse pathway genes, including genetic information, analysis tool and reference links, and disease, phenotype and other pathway annotations to pathway genes. The application increases the information content of diagram pages while expediting publication.

  4. Parking lots owned and maintained by the U.S. Fish and Wildlife Service

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — U.S. Fish and Wildlife Service parking lot inventory includes parking lots owned and maintained by the U.S. Fish and Wildlife Service on National Wildlife Refuges,...

  5. Older people maintaining well-being: an International Appreciative Inquiry study.

    Science.gov (United States)

    Reed, Jan; Richardson, Elsie; Marais, Sandra; Moyle, Wendy

    2008-03-01

    This paper reports on the progress of an international study investigating older people's strategies for maintaining well-being in the UK, Germany, South Africa and Australia. It uses an Appreciative Inquiry framework for investigation.

  6. Clinical evaluation of simple fixed space maintainers bonded with flow composite resin.

    Science.gov (United States)

    Simsek, Sera; Yilmaz, Yucel; Gurbuz, Taskin

    2004-01-01

    The aim of this study was to evaluate the clinical performance of simple fixed space maintainers bonded by using a flow composite resin (Tetric Flow) to prevent space resulting from early extracted primary teeth. For that reason, 64 fixed space maintainers (34 in the lower jaw and 30 in the upper jaw) were applied to 45 patients. The patients followed up for 12 to 18 months. Survival rate, prevention ability of that space, and whether damage to the abutment teeth occurred were evaluated. Five percent of space maintainers were determined to be unsuccessful at the end of the control period. During this period, loss of space among the abutment teeth was found to be statistically insignificant (P > .05). Finally, it was observed that the use of simple fixed space maintainers was successful due to operator experience and the choosing of favorable patient groups.

  7. 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 qu

  8. 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...... benefit. Agents are divided into firms and individuals, which can be either maintainer or user-developers. A maintainer is an agent responsible for releasing new versions of a program and a user-developer is an agent who use but may also become a developer. It is observed through the model that the three...... 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....

  9. Transcriptomic and Metabolomic Studies Disclose Key Metabolism Pathways Contributing to Well-maintained Photosynthesis under the Drought and the Consequent Drought-Tolerance in Rice

    OpenAIRE

    Ma, Xiaosong; Xia, Hui; Liu, Yunhua; Wei, Haibin; Zheng, Xiaoguo; Song, Congzhi; Chen, Liang; Liu, Hongyan; Luo, Lijun

    2016-01-01

    In contrast to wild species, drought-tolerance in crops requires a fully functional metabolism during drought (particularly photosynthetic processes). However, the link between drought-tolerance, photosynthetic regulation during drought, and the associated transcript and metabolic foundation, remains largely unknown. For this study, we used two rice cultivars with contrasting drought-tolerance (the drought-intolerant cultivar IRAT109 and the drought-tolerant cultivar IAC1246) to explore trans...

  10. Molecular dynamics simulation study on zwitterionic structure to maintain the normal conformations of Glutathione

    Institute of Scientific and Technical Information of China (English)

    YAN; Han; ZHU; HaoMiao; SHEN; Jian

    2007-01-01

    Molecular dynamics simulations were applied to normal conformational Glutathione (GSH) and GSH over zwitterionic and hydrophobic surfaces respectively. Conformational analysis of GSH during the simulation time on RMSD, conformational flexibility and dihedral distribution were performed. The results showed that zwitterionic structure maintains the normal conformations of GSH to a better extent, which should be a first good proof of the hypothesis of "maintain of normal structure".

  11. FEDERAL DOWNSIZING: Agency Officials’ Views on Maintaining Performance During Downsizing at Selected Agencies.

    Science.gov (United States)

    1998-03-01

    of Representatives March 1998 FEDERAL DOWNSIZING Agency Officials’ Views on Maintaining Performance During Downsizing at Selected Agencies M) 2Tc...effective workforce, you asked us to review these five agencies to obtain information on the effects downsizing has had on their performance and what actions... downsized and to what extent; (2) determine what actions were taken to maintain performance for one selected downsized component at each parent agency

  12. Fixed functional space maintainer: novel aesthetic approach for missing maxillary primary anterior teeth.

    Science.gov (United States)

    Khare, Vikram; Nayak, Prathibha Anand; Khandelwal, Vishal; Nayak, Ullal Anand

    2013-06-03

    The first-line treatment of non-restorable traumatically injured or carious deciduous teeth is extraction which may be a curse for the future dentition as well as social activity of a child. Various therapeutic modalities from removable partial dentures to fixed space maintainer can be used for replacement of such lost teeth. Two types of fixed aesthetic space maintainers for replacing premature loss of maxillary deciduous incisors in 4-year-old children are discussed.

  13. A Comparative Study of Biodegradation of Nickel and Chromium from Space Maintainers: An in vitro Study

    OpenAIRE

    Anand, Ashish; Sharma, Arun; Kumar, Piush; Sandhu, Meera; Sachdeva, Shobhit; Sachdev, Vinod

    2015-01-01

    ABSTRACT Objective: The aim of the study was to compare and evaluate the in vitro biodegradation of nickel and chromium from space maintainers, made of three different companies, i.e (Dantaurum, Rocky mountain and Dtech) in artificial saliva. Materials and methods: The study comprised of 30 space maintainers out of which 10 were fabricated using Dantaurum, 10 using Rocky mountain and 10 using Dtech band materials. Stainless steel wire (Dantaurum, Rocky mountain and Konark) was used for making...

  14. Fixed functional space maintainer: novel aesthetic approach for missing maxillary primary anterior teeth

    OpenAIRE

    Khare, Vikram; Nayak, Prathibha Anand; Khandelwal, Vishal; Nayak, Ullal Anand

    2013-01-01

    The first-line treatment of non-restorable traumatically injured or carious deciduous teeth is extraction which may be a curse for the future dentition as well as social activity of a child. Various therapeutic modalities from removable partial dentures to fixed space maintainer can be used for replacement of such lost teeth. Two types of fixed aesthetic space maintainers for replacing premature loss of maxillary deciduous incisors in 4-year-old children are discussed.

  15. Space maintainer using fiber-reinforced composite and natural tooth--a non-invasive technique.

    Science.gov (United States)

    Tayab, Tabassum; Vizhi, Kayal; Srinivasan, Ila

    2011-04-01

    Dental traumatic injuries are widespread in the population and are a frequent pathology among children and teenagers. Dentists and especially pediatric dentists are commonly confronted with managing dental crown root fractures on a regular basis. Fiber-reinforced composite (FRC) have been used as an alternative to conventional space maintainers in pediatric dentistry. We present here a case of a 11-year-old boy with oblique crown root fracture, treated by placing extracted natural crown with FRC as space maintainer.

  16. 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

  17. The effects of response cost in the treatment of aberrant behavior maintained by negative reinforcement.

    OpenAIRE

    Keeney, K M; Fisher, W W; Adelinis, J D; Wilder, D A

    2000-01-01

    Positive reinforcement contingencies can sometimes be used to decrease problem behavior maintained by negative reinforcement (e.g., escape). In the current study, we evaluated the extent to which response cost (i.e., contingent removal of a preferred stimulus) would compete with the negative reinforcer maintaining destructive behavior. The response cost contingency reduced destructive behavior by 87% from baseline levels even though the negative reinforcement contingency (i.e., escape) remain...

  18. Space maintainers placed from 2008 to 2011 at the School of Dentistry, University of Costa Rica

    OpenAIRE

    Gutiérrez Marín, Natalia; López Soto, Andrea

    2014-01-01

    The objective of this investigation was to determinate both the type and quantity of space maintainers in pediatric dentistry performed by three generations of graduates from 2008 to 2011 at the School of Dentistry of the University of Costa Rica. 146 student registers were analyzed with a population of 1646 patients. The students placed 340 space maintainers; including band and loop, lingual arch, Nance arch, distal shoe, fixed prosthesis, transpalatal and removables. The most commonly used ...

  19. Sympathetic Nerve Activity Maintains an Anti-Inflammatory State in Adipose Tissue in Male Mice by Inhibiting TNF-α Gene Expression in Macrophages.

    Science.gov (United States)

    Tang, Lijun; Okamoto, Shiki; Shiuchi, Tetsuya; Toda, Chitoku; Takagi, Kazuyo; Sato, Tatsuya; Saito, Kumiko; Yokota, Shigefumi; Minokoshi, Yasuhiko

    2015-10-01

    Adipose tissue macrophages (ATMs) play an important role in the inflammatory response in obese animals. How ATMs are regulated in lean animals has remained elusive, however. We now show that the sympathetic nervous system (SNS) is necessary to maintain the abundance of the mRNA for the proinflammatory cytokine TNF-α at a low level in ATMs of lean mice. Intracerebroventricular injection of agouti-related neuropeptide increased the amount of TNF-α mRNA in epididymal (epi) white adipose tissue (WAT), but not in interscapular brown adipose tissue (BAT), through inhibition of sympathetic nerve activity in epiWAT. The surgical denervation and β-adrenergic antagonist propranolol up-regulated TNF-α mRNA in both epiWAT and BAT in vivo. Signaling by the β2-adrenergic receptor (AR) and protein kinase A down-regulated TNF-α mRNA in epiWAT explants and suppressed lipopolysaccharide-induced up-regulation of TNF-α mRNA in the stromal vascular fraction of this tissue. β-AR-deficient (β-less) mice manifested an increased plasma TNF-α concentration and increased TNF-α mRNA abundance in epiWAT and BAT. TNF-α mRNA abundance was greater in ATMs (CD11b(+) cells of the stromal vascular fraction) from epiWAT or BAT of wild-type mice than in corresponding CD11b(-) cells, and β2-AR mRNA abundance was greater in ATMs than in CD11b(-) cells of epiWAT. Our results show that the SNS and β2-AR-protein kinase A pathway maintain an anti-inflammatory state in ATMs of lean mice in vivo, and that the brain melanocortin pathway plays a role in maintaining this state in WAT of lean mice via the SNS.

  20. Cell homeostasis in a Leishmania major mutant overexpressing the spliced leader RNA is maintained by an increased proteolytic activity.

    Science.gov (United States)

    Toledo, Juliano S; Ferreira, Tiago R; Defina, Tânia P A; Dossin, Fernando de M; Beattie, Kenneth A; Lamont, Douglas J; Cloutier, Serge; Papadopoulou, Barbara; Schenkman, Sergio; Cruz, Angela K

    2010-10-01

    Although several stage-specific genes have been identified in Leishmania, the molecular mechanisms governing developmental gene regulation in this organism are still not well understood. We have previously reported an attenuation of virulence in Leishmania major and L. braziliensis carrying extra-copies of the spliced leader RNA gene. Here, we surveyed the major differences in proteome and transcript expression profiles between the spliced leader RNA overexpressor and control lines using two-dimensional gel electrophoresis and differential display reverse transcription PCR, respectively. Thirty-nine genes related to stress response, cytoskeleton, proteolysis, cell cycle control and proliferation, energy generation, gene transcription, RNA processing and post-transcriptional regulation have abnormal patterns of expression in the spliced leader RNA overexpressor line. The evaluation of proteolytic pathways in the mutant revealed a selective increase of cysteine protease activity and an exacerbated ubiquitin-labeled protein population. Polysome profile analysis and measurement of cellular protein aggregates showed that protein translation in the spliced leader RNA overexpressor line is increased when compared to the control line. We found that L. major promastigotes maintain homeostasis in culture when challenged with a metabolic imbalance generated by spliced leader RNA surplus through modulation of intracellular proteolysis. However, this might interfere with a fine-tuned gene expression control necessary for the amastigote multiplication in the mammalian host.

  1. Patients experiences of maintaining mental well-being and hope within Motor Neurone Disease: A thematic synthesis

    Directory of Open Access Journals (Sweden)

    Andrew eSoundy

    2015-05-01

    Full Text Available Research is required that can synthesize the experiences of patients with Motor Neurone Disease (MND. One value of being able to do this is to understand the psychological experiences and processes involved in maintaining mental well-being and hope. A qualitative thematic synthesis of studies was undertaken. Studies were electronically searched from inception until June 2014. Twenty-nine studies with 342 (175 male unique individuals with MND were identified. Five themes were identified: (1The effects of the disease on interactions, relationships, roles and meaningful activities, (2 Responses that relate to the expression of hope, (3 Factors which disable hope, (4 Factors which enable hope, and (5 Cognitive and Practical adaptation that enabled hope, control and coping. Finally, a model of hope enablement was identified that considers the psychological pathways undertaken by a patient which influence mental well-being and hope. Within this review article evidence is provided which illustrates the central importance of relationships and social support for individuals with MND. Further it has been identified that periods of coping are possible and are likely associated with greater mental well-being for patients with MND

  2. Fiber technology in space maintainer: a clinical follow-up study.

    Science.gov (United States)

    Saravanakumar, M S; Siddaramayya, Jayaraman; Sajjanar, Arunkumar B; Godhi, Brinda Suhas; Reddy, N Simhachalam; Krishnam, Raju P

    2013-11-01

    Various space maintainers are used in pediatric dentistry. However, their construction requires time consuming laboratory procedures. Recently fiber-reinforced composite resin (FRCR) has been introduced for various application in dentistry. Polyethylene fibers appear to have the best properties in elasticity, translucency, adaptability, tenaciousness, resistance to traction and to impact. The purpose of this study was to clinically evaluate the long-term effect of FRCR space maintainer made with Ribbond(®) bondable reinforcement ribbon in children over a period of 18 months. A total of thirty FRCR space maintainers were applied to 30 children between the age group of 6 to 9 years old, follow-up visits were done at 1, 6, 12 and 18 months. The data obtained was subjected to statistical analysis. Maxillary appliances survived more than mandibular appliances. Mean survival time of space maintainer were found to be 12 months (minimum 1 and maximum 18 months). The present study suggested that FRCR space maintainers (Ribbond(®)), which was observed for up to 18 months, can be accepted as a successful alternative to conventional band-loop space maintainer only for short periods.

  3. Influence of conditioned reinforcement on the response-maintaining effects of quinpirole in rats.

    Science.gov (United States)

    Collins, Gregory T; Woods, James H

    2009-09-01

    D2-like agonists, such as quinpirole, maintain responding in monkeys, rats, and mice when they are substituted for cocaine. This study examined the influence of operant history and cocaine-paired stimuli (CS) on quinpirole-maintained responding in rats trained to nose poke for cocaine. Upon acquisition of responding for cocaine, substitutions were performed in the presence or absence of injection-CS pairings. Although cocaine maintained responding regardless of whether injections were accompanied by CS, quinpirole maintained responding only when CS were paired with injections. To assess the influence of operant history, injections of cocaine, quinpirole, remifentanil, nicotine, or saline were made available on a previously inactive lever, while nose pokes continued to result in CS presentation. Although responding was reallocated from the nose poke to the lever when cocaine or remifentanil was available, lever presses remained low, and nose poking persisted when quinpirole or nicotine was made contingent upon lever presses. Finally, quinpirole pretreatments resulted in high rates of nose poking when nose pokes resulted in CS presentation alone, but failed to maintain nose poking when the CS was omitted. Taken together, these results suggest that the response-maintaining effects of quinpirole are primarily mediated by an enhancement of the conditioned reinforcing effects of earlier CS, rather than by a reinforcing effect of quinpirole.

  4. Enhanced fatty acid accumulation in Isochrysis galbana by inhibition of the mitochondrial alternative oxidase pathway under nitrogen deprivation.

    Science.gov (United States)

    Zhang, Litao; Liu, Jianguo

    2016-07-01

    The purpose of this study was to clarify the interrelation between the mitochondrial alternative oxidase (AOX) pathway and fatty acid accumulation in marine microalga Isochrysis galbana. Under normal conditions, the activity of the AOX pathway was maintained at a low level in I. galbana. Compared with the normal condition, nitrogen deprivation significantly increased the AOX pathway activity and fatty acid accumulation. Under nitrogen deprivation, the inhibition of the AOX pathway by salicylhydroxamic acid caused the accumulation of reducing equivalents and the over-reduction of chloroplasts in I. galbana cells, leading to a decrease in the photosynthetic O2 evolution rate. The over-production of reducing equivalents due to the inhibition of the AOX pathway under nitrogen deprivation further enhanced the accumulation of fatty acids in I. galbana cells.

  5. 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

    -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......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...

  6. 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 memb

  7. Primary Metabolic Pathways and Metabolic Flux Analysis

    DEFF Research Database (Denmark)

    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...

  8. A brain cancer pathway in clinical practice

    DEFF Research Database (Denmark)

    Laursen, Emilie Lund; Rasmussen, Birthe Krogh

    2012-01-01

    Danish healthcare seeks to improve cancer survival through improved diagnostics, rapid treatment and increased focus on cancer prevention and early help-seeking. In neuro-oncology, this has resulted in the Integrated Brain Cancer Pathway (IBCP). The paper explores how the pathway works...... in the initial phase in a clinical setting with emphasis on pathway criteria....

  9. KEGG PATHWAY / Acute myeloid leukemia [KEGG

    Lifescience Database Archive (English)

    Full Text Available PATHWAY: map05221 Entry map05221Pathway Name Acute myeloid leukemia Description Acute...Class Human Diseases; Cancers Pathwaymap map05221Acute myeloid leukemia Disease H00003Acute myeloid leukemia...inkDB DBGET integrated database retrieval system KEGG PATHWAY / Acute myeloid leukemia ...

  10. Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression

    DEFF Research Database (Denmark)

    Wang, Qian; Bailey, Charles G; Ng, Cynthia

    2011-01-01

    L-Type amino acid transporters such as LAT1 and LAT3 mediate the uptake of essential amino acids. Here, we report that prostate cancer cells coordinate the expression of LAT1 and LAT3 to maintain sufficient levels of leucine needed for mTORC1 signaling and cell growth. Inhibiting LAT function...... transporter pathways vital for tumor outgrowth....

  11. The Retinoblastoma pathway regulates stem cell proliferation in freshwater planarians.

    Science.gov (United States)

    Zhu, Shu Jun; Pearson, Bret J

    2013-01-15

    Freshwater planarians are flatworms of the Lophotrochozoan superphylum and are well known for their regenerative abilities, which rely on a large population of pluripotent adult stem cells. However, the mechanisms by which planarians maintain a precise population of adult stem cells while balancing proliferation and cell death, remain to be elucidated. Here we have identified, characterized, and functionally tested the core Retinoblastoma (Rb) pathway components in planarian adult stem cell biology. The Rb pathway is an ancient and conserved mechanism of proliferation control from plants to animals and is composed of three core components: an Rb protein, and a transcription factor heterodimer of E2F and DP proteins. Although the planarian genome contains all components of the Rb pathway, we found that they have undergone gene loss from the ancestral state, similar to other species in their phylum. The single Rb homolog (Smed-Rb) was highly expressed in planarian stem cells and was required for stem cell maintenance, similar to the Rb-homologs p107 and p130 in vertebrates. We show that planarians and their phylum have undergone the most severe reduction in E2F genes observed thus far, and the single remaining E2F was predicted to be a repressive-type E2F (Smed-E2F4-1). Knockdown of either Smed-E2F4-1 or its dimerization partner Dp (Smed-Dp) by RNAi resulted in temporary hyper-proliferation. Finally, we showed that known Rb-interacting genes in other systems, histone deacetylase 1 and cyclinD (Smed-HDAC1; Smed-cycD), were similar to Rb in expression and phenotypes when knocked down by RNAi, suggesting that these established interactions with Rb may also be conserved in planarians. Together, these results showed that planarians use the conserved components of the Rb tumor suppressor pathway to control proliferation and cell survival.

  12. Pathways involved in Drosophila and human cancer development: the Notch, Hedgehog, Wingless, Runt, and Trithorax pathway.

    Science.gov (United States)

    Geissler, Klaus; Zach, Otto

    2012-05-01

    Animal models are established tools to study basic questions of biology in a systematic way. They have greatly facilitated our understanding of the mechanisms by which nature forms and maintains organisms. Much of the knowledge on molecular changes underlying the development of organisms originates from research in the fruit fly model Drosophila melanogaster. Vertebrate models including the mouse and zebrafish model, but also other animal models coming from different corners of the animal kingdom have shown that much of the basic machinery of development is essentially identical, not just in all vertebrates but in all major phyla of invertebrates too. Moreover, key elements of this machinery have been demonstrated to be involved in recurrent molecular abnormalities detected in tumor-tissue from patients, indicating their implication in the genesis of human cancer. Thus, research in this field has become a common topic for both biologists and hemato-oncologists. In this review, we summarize current knowledge on some of these key elements and molecular pathways such as Notch, Hedgehog, Wingless, Runt, and Trithorax that have been originally described and studied in animal models and which seem to play a major role in the pathophysiology and targeted management of human cancer.

  13. Apoptotic engulfment pathway and schizophrenia.

    Directory of Open Access Journals (Sweden)

    Xiangning Chen

    Full Text Available 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.

  14. 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.

  15. Fibromyalgia and the serotonin pathway.

    Science.gov (United States)

    Juhl, J H

    1998-10-01

    Fibromyalgia syndrome is a musculoskeletal pain and fatigue disorder manifested by diffuse myalgia, localized areas of tenderness, fatigue, lowered pain thresholds, and nonrestorative sleep. Evidence from multiple sources support the concept of decreased flux through the serotonin pathway in fibromyalgia patients. Serotonin substrate supplementation, via L-tryptophan or 5-hydroxytryptophan (5-HTP), has been shown to improve symptoms of depression, anxiety, insomnia and somatic pains in a variety of patient cohorts. Identification of low serum tryptophan and serotonin levels may be a simple way to identify persons who will respond well to this approach.

  16. A Comparative Study of Biodegradation of Nickel and Chromium from Space Maintainers: An in vitro Study

    Science.gov (United States)

    Anand, Ashish; Sharma, Arun; Kumar, Piush; Sachdeva, Shobhit; Sachdev, Vinod

    2015-01-01

    ABSTRACT Objective: The aim of the study was to compare and evaluate the in vitro biodegradation of nickel and chromium from space maintainers, made of three different companies, i.e (Dantaurum, Rocky mountain and Dtech) in artificial saliva. Materials and methods: The study comprised of 30 space maintainers out of which 10 were fabricated using Dantaurum, 10 using Rocky mountain and 10 using Dtech band materials. Stainless steel wire (Dantaurum, Rocky mountain and Konark) was used for making loops and Leone solder and flux was used for soldering. Each group was further divided into four subgroups containing 1, 2, 3 and 4 space maintainers respectively. The space maintainers in each subgroup were placed in separate glass beakers containing 100 ml of artificial saliva at 37°C for 4 weeks. Salivary samples from each beaker was analyzed for nickel and chromium ions separately on days 1, 7, 14, 21 and 28 days using inductively coupled plasma-optical emission spectrophotometer. Results: Total release of nickel and chromium from all band and loop space maintainers ranged from 0.020 to 1.524 ppm and 0.002 to 0.289 ppm respectively. The release of nickel and chromium between the groups and within the groups was not significant (p space maintainers made of Dantaurum, Rocky mountain and Dtech which could cause any toxicity. How to cite this article: Anand A, Sharma A, Kumar P, Sandhu M, Sachdeva S, Sachdev V. A Comparative Study of Biodegradation of Nickel and Chromium from Space Maintainers: An in vitro Study. Int J Clin Pediatr Dent 2015; 8(1):37-41. PMID:26124579

  17. The p53 pathway in hematopoiesis: lessons from mouse models, implications for humans

    OpenAIRE

    Pant, Vinod; Quintás-Cardama, Alfonso; Lozano, Guillermina

    2012-01-01

    Aberrations in the p53 tumor suppressor pathway are associated with hematologic malignancies. p53-dependent cell cycle control, senescence, and apoptosis functions are actively involved in maintaining hematopoietic homeostasis under normal and stress conditions. Whereas loss of p53 function promotes leukemia and lymphoma development in humans and mice, increased p53 activity inhibits hematopoietic stem cell function and results in myelodysplasia. Thus, exquisite regulation of p53 activity is ...

  18. Oxylipin Pathway in Rice and Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    E. Wassim Chehab; John V. Perea; Banu Gopalan; Steve Theg; Katayoon Dehesh

    2007-01-01

    Plants have evolved complex signaling pathways to coordinate responses to developmental and environmental information. The oxylipin pathway is one pivotal lipid-based signaling network, composed of several competing branch pathways, that determines the plant's ability to adapt to various stimuli. Activation of the oxylipin pathway induces the de novo synthesis of biologically active metabolltes called "oxylipins". The relative levels of these metabolltes are a distinct indicator of each plant species and determine the ability of plants to adapt to different stimuli. The two major branches of the oxylipln pathway, allene oxide synthase (AOS) and hydroperoxide lyase (HPL) are responsible for production of the signaling compounds,jasmonates and aldehydes respectively. Here, we compare and contrast the regulation of AOS and HPL branch pathways in rice and Arabidopsis as model monocotyledonous and dicotyledonous systems. These analyses provide new Insights into the evolution of JAs and aldehydes signaling pathways, and the complex network of processes responsible for stress adaptations in monocots and dicots.

  19. An evaluation of survival of space maintainers: a six-year follow-up study.

    Science.gov (United States)

    Tulunoglu, Ozlem; Ulusu, Tezer; Genç, Yasemin

    2005-02-15

    The aim of this study was to evaluate the median survival time of fixed and removable space maintainers related to age groups, gender, and their distribution in upper and lower dental arches. The adherence of patients to a periodic recall program and the success rate of different types of space maintainers related to different arches were also evaluated. This study included 663 patients aged between 4-15 years old that were treated between the years of 1997 and 2002. The patients were categorized into four main groups: lost to follow-up, failed, successful, and censored at the end of study. Three hundred forty-five space maintainers were considered lost to follow-up, 83 were considered failed, 206 successful, and 20 censored-at-end. The overall median survival time of the appliances was 6.51 months. Median survival time was 7.25 months in the 4-6 age group, 6.35 months in the 7-12 age group, and 7.0 months in the 13+ age groups. Median survival time was 5.76 months in girls and 7.11 months in boys. Median survival time of space maintainers was 7.17 months for maxilla and 6.69 months in the mandible. Median survival time was 5.25 months for space maintainers fabricated in both arches.

  20. Dysmegakaryocytopoiesis and maintaining platelet count in patients with plasma cell neoplasm

    Directory of Open Access Journals (Sweden)

    Yasmin Mair

    2013-01-01

    Full Text Available Background: Dysmegakaryocytopoiesis in patients with the plasma cell neoplasm (PCN is rarely discussed in the literature. The puzzling phenomenon, which PCN patients maintaining normal platelet count even when the marrow is mostly replaced by plasma cells, is hardly explored. Aim: This study was aimed to determine the frequency of dysmegakaryocytopoiesis in PCN and the relationships between bone marrow (BM plasma cell percentage, plasma cell immunomarkers, the severity of dysmegakaryocytopoiesis, and peripheral blood platelet count in PCN. Materials and Methods: We randomly selected 16 cases of PCN, among which 4 were with monoclonal gammopathy of undetermined significance and 12 were with plasma cell myeloma. Results: Our study showed that: (1 Dysmegakaryocytopoiesis was present in all the selected cases of PCN and its severity was not correlated with the percentage of the plasma cells in BM; (2 almost all patients maintained normal platelet count even when BM was mostly replaced by plasma cells; (3 immunomarkers of the neoplastic plasma cells were not associated with dysmegakaryocytopoiesis or maintaining of platelet count. The possible mechanisms behind dysmegakaryocytopoiesis and maintaining of platelet count were also discussed. Conclusion: Despite the universal presence of dysmegakaryocytopoiesis in PCN, the platelet count is maintained at normal range.

  1. Dolphins can maintain vigilant behavior through echolocation for 15 days without interruption or cognitive impairment.

    Directory of Open Access Journals (Sweden)

    Brian K Branstetter

    Full Text Available In dolphins, natural selection has developed unihemispheric sleep where alternating hemispheres of their brain stay awake. This allows dolphins to maintain consciousness in response to respiratory demands of the ocean. Unihemispheric sleep may also allow dolphins to maintain vigilant states over long periods of time. Because of the relatively poor visibility in the ocean, dolphins use echolocation to interrogate their environment. During echolocation, dolphin produce clicks and listen to returning echoes to determine the location and identity of objects. The extent to which individual dolphins are able to maintain continuous vigilance through this active sense is unknown. Here we show that dolphins may continuously echolocate and accurately report the presence of targets for at least 15 days without interruption. During a total of three sessions, each lasting five days, two dolphins maintained echolocation behaviors while successfully detecting and reporting targets. Overall performance was between 75 to 86% correct for one dolphin and 97 to 99% correct for a second dolphin. Both animals demonstrated diel patterns in echolocation behavior. A 15-day testing session with one dolphin resulted in near perfect performance with no significant decrement over time. Our results demonstrate that dolphins can continuously monitor their environment and maintain long-term vigilant behavior through echolocation.

  2. An ongoing role for structural sarcomeric components in maintaining Drosophila melanogaster muscle function and structure.

    Directory of Open Access Journals (Sweden)

    Alexander D Perkins

    Full Text Available Animal muscles must maintain their function while bearing substantial mechanical loads. How muscles withstand persistent mechanical strain is presently not well understood. The basic unit of muscle is the sarcomere, which is primarily composed of cytoskeletal proteins. We hypothesized that cytoskeletal protein turnover is required to maintain muscle function. Using the flight muscles of Drosophila melanogaster, we confirmed that the sarcomeric cytoskeleton undergoes turnover throughout adult life. To uncover which cytoskeletal components are required to maintain adult muscle function, we performed an RNAi-mediated knockdown screen targeting the entire fly cytoskeleton and associated proteins. Gene knockdown was restricted to adult flies and muscle function was analyzed with behavioural assays. Here we analyze the results of that screen and characterize the specific muscle maintenance role for several hits. The screen identified 46 genes required for muscle maintenance: 40 of which had no previously known role in this process. Bioinformatic analysis highlighted the structural sarcomeric proteins as a candidate group for further analysis. Detailed confocal and electron microscopic analysis showed that while muscle architecture was maintained after candidate gene knockdown, sarcomere length was disrupted. Specifically, we found that ongoing synthesis and turnover of the key sarcomere structural components Projectin, Myosin and Actin are required to maintain correct sarcomere length and thin filament length. Our results provide in vivo evidence of adult muscle protein turnover and uncover specific functional defects associated with reduced expression of a subset of cytoskeletal proteins in the adult animal.

  3. Dolphins can maintain vigilant behavior through echolocation for 15 days without interruption or cognitive impairment.

    Science.gov (United States)

    Branstetter, Brian K; Finneran, James J; Fletcher, Elizabeth A; Weisman, Brian C; Ridgway, Sam H

    2012-01-01

    In dolphins, natural selection has developed unihemispheric sleep where alternating hemispheres of their brain stay awake. This allows dolphins to maintain consciousness in response to respiratory demands of the ocean. Unihemispheric sleep may also allow dolphins to maintain vigilant states over long periods of time. Because of the relatively poor visibility in the ocean, dolphins use echolocation to interrogate their environment. During echolocation, dolphin produce clicks and listen to returning echoes to determine the location and identity of objects. The extent to which individual dolphins are able to maintain continuous vigilance through this active sense is unknown. Here we show that dolphins may continuously echolocate and accurately report the presence of targets for at least 15 days without interruption. During a total of three sessions, each lasting five days, two dolphins maintained echolocation behaviors while successfully detecting and reporting targets. Overall performance was between 75 to 86% correct for one dolphin and 97 to 99% correct for a second dolphin. Both animals demonstrated diel patterns in echolocation behavior. A 15-day testing session with one dolphin resulted in near perfect performance with no significant decrement over time. Our results demonstrate that dolphins can continuously monitor their environment and maintain long-term vigilant behavior through echolocation.

  4. Safety, reliability, maintainability and quality provisions for the Space Shuttle program

    Science.gov (United States)

    1990-01-01

    This publication establishes common safety, reliability, maintainability and quality provisions for the Space Shuttle Program. NASA Centers shall use this publication both as the basis for negotiating safety, reliability, maintainability and quality requirements with Shuttle Program contractors and as the guideline for conduct of program safety, reliability, maintainability and quality activities at the Centers. Centers shall assure that applicable provisions of the publication are imposed in lower tier contracts. Centers shall give due regard to other Space Shuttle Program planning in order to provide an integrated total Space Shuttle Program activity. In the implementation of safety, reliability, maintainability and quality activities, consideration shall be given to hardware complexity, supplier experience, state of hardware development, unit cost, and hardware use. The approach and methods for contractor implementation shall be described in the contractors safety, reliability, maintainability and quality plans. This publication incorporates provisions of NASA documents: NHB 1700.1 'NASA Safety Manual, Vol. 1'; NHB 5300.4(IA), 'Reliability Program Provisions for Aeronautical and Space System Contractors'; and NHB 5300.4(1B), 'Quality Program Provisions for Aeronautical and Space System Contractors'. It has been tailored from the above documents based on experience in other programs. It is intended that this publication be reviewed and revised, as appropriate, to reflect new experience and to assure continuing viability.

  5. 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.

  6. DMPD: Pathways connecting inflammation and cancer. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18325755 Pathways connecting inflammation and cancer. Allavena P, Garlanda C, Borre...llo MG, Sica A, Mantovani A. Curr Opin Genet Dev. 2008 Feb;18(1):3-10. Epub 2008 Mar 5. (.png) (.svg) (.html) (.csml) Show Pathway...s connecting inflammation and cancer. PubmedID 18325755 Title Pathways connecting infl...ni A. Publication Curr Opin Genet Dev. 2008 Feb;18(1):3-10. Epub 2008 Mar 5. Pathway - PNG File (.png) SVG F

  7. 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.

  8. Further Evaluation of the Use of Multiple Schedules for Behavior Maintained by Negative Reinforcement.

    Science.gov (United States)

    Campos, Claudia; Leon, Yanerys; Sleiman, Andressa; Urcuyo, Beatriz

    2017-03-01

    One potential limitation of functional communication training (FCT) is that after the functional communication response (FCR) is taught, the response may be emitted at high rates or inappropriate times. Thus, schedule thinning is often necessary. Previous research has demonstrated that multiple schedules can facilitate schedule thinning by establishing discriminative control of the communication response while maintaining low rates of problem behavior. To date, most applied research evaluating the clinical utility of multiple schedules has done so in the context of behavior maintained by positive reinforcement (e.g., attention or tangible items). This study examined the use of a multiple schedule with alternating Fixed Ratio (FR 1)/extinction (EXT) components for two individuals with developmental disabilities who emitted escape-maintained problem behavior. Although problem behavior remained low during all FCT and multiple schedule phases, the use of the multiple schedule alone did not result in discriminated manding.

  9. Live-social-video reward maintains joystick task performance in bonnet macaques.

    Science.gov (United States)

    Andrews, M W; Rosenblum, L A

    1993-12-01

    A number of studies have now indicated that monkeys of several species will perform hundreds of food-rewarded joystick tasks on a daily basis. Our goal in this study was to identify the level of joystick task performance that could be maintained by 10 sec. of live, color video of a conspecific social group contingent upon the completion of a joystick task. The subjects were five individually housed bonnet macaques that were highly experienced on joystick tasks. Performance with social-video reward was compared to that maintained by a 190-mg banana-flavored pellet reward and to a nonreward condition. Comparable levels of task activity were maintained by both video and pellet reward, whereas task activity nearly ceased in the absence of reward. Four of the five monkeys increased their levels of task activity between the first and second weeks of social-video reward.

  10. 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.

  11. A comparison of positive and negative reinforcement for compliance to treat problem behavior maintained by escape.

    Science.gov (United States)

    Slocum, Sarah K; Vollmer, Timothy R

    2015-09-01

    Previous research has shown that problem behavior maintained by escape can be treated using positive reinforcement. In the current study, we directly compared functional (escape) and nonfunctional (edible) reinforcers in the treatment of escape-maintained problem behavior for 5 subjects. In the first treatment, compliance produced a break from instructions. In the second treatment, compliance produced a small edible item. Neither treatment included escape extinction. Results suggested that the delivery of a positive reinforcer for compliance was effective for treating escape-maintained problem behavior for all 5 subjects, and the delivery of escape for compliance was ineffective for 3 of the 5 subjects. Implications and future directions related to the use of positive reinforcers in the treatment of escape behavior are discussed.

  12. Research of the coating resin performance of the polarization-maintaining fiber coil

    Science.gov (United States)

    Meng, Zhaokui; Shao, Hongfeng; Xu, Hongjie; Yang, Yuanhong

    2006-11-01

    The coating resin performance of the Polarization-Maintaining fiber coil is an important fact to affect the performance of the FOG. It is one of some problems in the fact during the industrialization of the FOG. From the action and effect on the two important performance parameters such as temperature and vibration of the fiber ring and Fiber Optical Gyroscope (FOG). In allusion to the factual conditions of the FOG, all aspects of experiments are done and the experiment results are analyzed. The experiment and analysis results show that the facts to affect coating resin performance of the Polarization-Maintaining fiber coil is brought due to the unsuitable coating adhesive. The amount and uniformity of coating resin are the two main facts of the effect. In addition, the temperature performance of the resin and the remaining stress which are the facts to affect the coating resin performance of the Polarization-Maintaining fiber coil can not be ignored.

  13. Establishing and maintaining cell polarity with mRNA localization in Drosophila.

    Science.gov (United States)

    Barr, Justinn; Yakovlev, Konstantin V; Shidlovskii, Yulii; Schedl, Paul

    2016-03-01

    How cell polarity is established and maintained is an important question in diverse biological contexts. Molecular mechanisms used to localize polarity proteins to distinct domains are likely context-dependent and provide a feedback loop in order to maintain polarity. One such mechanism is the localized translation of mRNAs encoding polarity proteins, which will be the focus of this review and may play a more important role in the establishment and maintenance of polarity than is currently known. Localized translation of mRNAs encoding polarity proteins can be used to establish polarity in response to an external signal, and to maintain polarity by local production of polarity determinants. The importance of this mechanism is illustrated by recent findings, including orb2-dependent localized translation of aPKC mRNA at the apical end of elongating spermatid tails in the Drosophila testis, and the apical localization of stardust A mRNA in Drosophila follicle and embryonic epithelia.

  14. Shared care and implementation of a pediatric clinical pathway

    DEFF Research Database (Denmark)

    Langfrits, Mette Sørensen; Thomsen, RW; Rubak, Jens Mørck

    Background: Asthma is the most common chronic disease among Danish children. The role of the health care professional is to evaluate the current level of asthma control (based on symptoms and lung function) and then adjust asthma treatment to gain and maintain control of the disease and ensure few...... (Viborg Hospital) and at all affiliated general practitioners (GP´s). Our hypothesis is that it can improve intersectional collaboration between health care professionals treating children with asthma based on a shared responsibility of the treatment called Shared Care. Aim: We aim to examine in 4...... observational studies if implementation of clinical pathways and shared care lead to improvement of the following outcomes: Study 1) An increased proportion of asthmatic children followed at the right place, i.e. the well-controlled asthmatic children should be followed in general practice and children...

  15. 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.

  16. Forging new pathways for research on language learning motivation

    Directory of Open Access Journals (Sweden)

    Raby Françoise

    2015-01-01

    Full Text Available Research on motivation in the field of applied linguistics seeks to better understand how and why learners become involved in learning activities and maintain their efforts in this regard. Dörnyei provided a seminal model drawing essentially from cognitive and social psychology (Dörnyei, 2001. In the wake of his reflection, and after investigating motivation in a range of academic contexts, we are now able to present our own model, which is dynamic, weighted, and polytomic (Raby, 2007. After presenting cognitive ergonomics as a new pathway for research in second language acquisition, we shall present the results of our investigations in foreign language learning motivation in technologically enhanced contexts, outlining major methodological difficulties pertaining to this sort of this grounded research.

  17. Roles of MAP kinase signaling pathway in oocyte meiosis

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Mitogen-activated protein kinase (MAPK) is a family of Ser/Thr protein kinases expressed widely in eukaryotic cells. MAPK is activated by a cascade of protein kinase phosphorylation and plays pivotal roles in regulating meiosis process in oocytes. As an important physical substrate of MAPK, p90rsk mediates numerous MAPK functions. MAPK was activated at G2/M transition during meiosis. Its activity reached the peak at MⅠ stage and maintained at this level until the time before the pronuclear formation after fertilization. There is complex interplay between MAPK and MPF in the meiosis regulation. Furthermore, other intracellular signal transducers, such as cAMP, protein kinase C and protein phosphotase, ect., also regulated the activity of MAPK at different stages during meiosis in oocytes. In the present article, the roles of MAPK signaling pathway in oocyte meiosis are reviewed and discussed.

  18. The Role of Ubiquitine Proteasome Pathway in Carcinogenesis

    Directory of Open Access Journals (Sweden)

    N.Ceren Sumer Turanligil

    2010-02-01

    Full Text Available Ubiquitin works as a marker protein which targets misfolded or injured proteins to cellular degradation. It brings the abnormal proteins to a subcellular organelle named proteasome and it maintains the degradation of proteins in limited lenghts of peptides by leaving the process withuout being changed. Mistakes in ubiquitin-dependent proteolysis in various steps of carcinogenesis is known. In this review, we dealed with the effects of ubiquitin-proteasome pathway (UPP on carcinogenesis via intercellular signaling molecules like Ras, transcription factors like NF-kB, cytokines like TNF-alfa Tumor necrosis factor, protooncogenes like p53 and MDM2(murine double minute 2, components of cell cycle and DNA repair proteins like BRCA1. We also focused on the relationship of UPP on antigen presentation which is active in immune response and its place in the aetiology of colon cancer to provide a specific example. [Archives Medical Review Journal 2010; 19(1.000: 36-55

  19. Kekuatan Geser dan Pola Patahan Loop Space Maintainer yang Dibuat dengan Teknik Spot Welding Elektrik

    Directory of Open Access Journals (Sweden)

    Elin Karlina

    2015-10-01

    Full Text Available The aim of this research was to study the effect of spot variations on shear strength of spot welds in an electric loop space maintainer. Stainless steel wire of 0.8 mm diameter and nickel chromium crwon for lower second molar of temporary teeth were used. A loop 1 cm wide, made of 3.5 cm stainless steel wire, was welded with 3 dots on the crown using an electric spot welder. Each dot for each group took different spot variations from 1 X – 4 X. A loop space maintainer made with the usual materials and techniques as applied at the IKGA FKG UI Clinic was used as a control, with a torch as heat source. Ten specimens each were prepared for shear testing and three spesimens each for metallography. Universal testing machine was used for shear strength testing at a crosshead speed of 0.5 mm/min, and SEM/EDS was used for metallography and fractography. The data were statistically analyzed with one-way ANOVA at p = 0.05, and Tukey post hoc test. The results show that the shear strength of the welded loop space maintainer was higher than that of a soldered loop space maintainer, although the difference was not statistically significant with spot variation 1 X. SEM/EDS analysis suggests that a new alloy forms at the contact area of welded and soldered loop space maintainer. Fractography of the joints suggests that welds are better than soldered joints, with higher ductility and toughness, as can be seen from the dimpled pattern of the welded joint and cleavage patterns in the control joints. In conclusion, the loop space maintainer is better made by welding than by soldering.

  20. [Evaluation of clinical efficiency of various space maintainers in premature loss of deciduous molars].

    Science.gov (United States)

    Davydov, B N; Bakernikova, T M; Lavrikov, V G; Chumakov, A N

    2015-01-01

    The paper presents the results of two years observation of clinical application of three variants of space maintainers in early primary molars loss. Sixty-five children aged 6-12 years were included in the study. The most common problems when using fixed space maintainers is a deformation of intermediate part seen in 58.3% of children when applying crown (ring) with bracer. Support elements debonding at stabilizing devise fixed directly to tooth enamel is registered in 49.6% of children. Cementation releasing of support elements is observed by the application of crown (ring) with bracer at 45.8% of children.

  1. A simple and effective way of maintaining the microvascular field clean and dry during anastomosis

    Directory of Open Access Journals (Sweden)

    G I Nambi

    2013-01-01

    Full Text Available During microvascular anastomosis, it is important to maintain the microsurgical field irrigated yet dry so as to achieve a good view of the vessels for approximation. In this method, an infant feeding tube (size 4, with its tip sandwiched between layers of dry gauze and a surgical glove component placed in the anastomotic field and the other end connected to a suction apparatus, is used to maintain the microsurgical field free from flooding. It also has the additional advantage of providing a stable platform for microvascular anastomosis.

  2. Phase sensitivity to temperature of the guiding mode in polarization-maintaining photonic crystal fiber.

    Science.gov (United States)

    Song, Jingming; Sun, Kang; Li, Shuai; Cai, Wei

    2015-08-20

    The propagating phase changing of a polarization-maintaining photonic crystal fiber (PM-PCF) caused by temperature variation is theoretically studied, as well as compared with conventional PANDA fiber. As to verifying numerical analysis, a platform based on a Michelson interferometer for phase versus temperature measurement was built for both kinds of fiber. Experiments show that PM-PCF has similar temperature sensitivity with conventional polarization-maintaining fiber. With optimized PM-PCF design (thinner coating layer and coating material with smaller thermal expansion coefficient), the sensitivity could be further reduced to about 80% of the present level.

  3. Kekuatan Geser dan Pola Patahan Loop Space Maintainer yang Dibuat dengan Teknik Spot Welding Elektrik

    OpenAIRE

    Elin Karlina; Ellyza Herda; Heriandi Sutadi

    2015-01-01

    The aim of this research was to study the effect of spot variations on shear strength of spot welds in an electric loop space maintainer. Stainless steel wire of 0.8 mm diameter and nickel chromium crwon for lower second molar of temporary teeth were used. A loop 1 cm wide, made of 3.5 cm stainless steel wire, was welded with 3 dots on the crown using an electric spot welder. Each dot for each group took different spot variations from 1 X – 4 X. A loop space maintainer made with the usual mat...

  4. The micro and the macro: How discourse of control maintains HIV-related stigma.

    Science.gov (United States)

    Ranjbar, Vania; McKinlay, Andy; McVittie, Chris

    2016-02-01

    In this article, we examine how HIV/AIDS caregivers negotiate stigma in their discourse of providing care to HIV-positive individuals. Using interview data, we demonstrate how participants employed discourse of control in attempting to avoid and counter HIV-related stigma: participants rejected fear of associating with HIV-positive individuals by drawing on their knowledge of HIV transmission and their ability to control and avoid infection. Such discourses backfire, however, as the concept of HIV infection being controllable and thus avoidable maintains accountability for the disease. Thus, participants' micro discourse of control can maintain the macro discourse that produces HIV-related stigma.

  5. Maintained aggressive behavior in gonadectomized male Siamese fighting fish (Betta splendens).

    Science.gov (United States)

    Weiss, C S; Coughlin, J P

    1979-07-01

    Adult male Betta splendens were gonadectomized and tested twice for aggressive behavior two weeks later. In a mutual viewing test environment, it was found that gonadectomized animals maintained their aggressive behavior on all six indices of aggression at a level equal to controls. Animals that showed some testis regeneration and sham operated fish were also equal to controls. The results are interpreted to mean that adult aggressive behavior in male B. splendens may not be under the control of gonadal hormones. Pituitary gonadotropins, interrenal gland, and critical period hypotheses are given as possible explanations of the maintained aggressiveness following castration.

  6. Sharing the sandbox: Evolutionary mechanisms that maintain bacterial cooperation [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Eric Bruger

    2015-12-01

    Full Text Available Microbes are now known to participate in an extensive repertoire of cooperative behaviors such as biofilm formation, production of extracellular public-goods, group motility, and higher-ordered multicellular structures. A fundamental question is how these cooperative tasks are maintained in the face of non-cooperating defector cells. Recently, a number of molecular mechanisms including facultative participation, spatial sorting, and policing have been discovered to stabilize cooperation. Often these different mechanisms work in concert to reinforce cooperation. In this review, we describe bacterial cooperation and the current understanding of the molecular mechanisms that maintain it.

  7. Systems and methods for maintaining multiple objects within a camera field-of-view

    Science.gov (United States)

    Gans, Nicholas R.; Dixon, Warren

    2016-03-15

    In one embodiment, a system and method for maintaining objects within a camera field of view include identifying constraints to be enforced, each constraint relating to an attribute of the viewed objects, identifying a priority rank for the constraints such that more important constraints have a higher priority that less important constraints, and determining the set of solutions that satisfy the constraints relative to the order of their priority rank such that solutions that satisfy lower ranking constraints are only considered viable if they also satisfy any higher ranking constraints, each solution providing an indication as to how to control the camera to maintain the objects within the camera field of view.

  8. 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.)

  9. Adaptation pathways of global wheat production: Importance of strategic adaptation to climate change.

    Science.gov (United States)

    Tanaka, Akemi; Takahashi, Kiyoshi; Masutomi, Yuji; Hanasaki, Naota; Hijioka, Yasuaki; Shiogama, Hideo; Yamanaka, Yasuhiro

    2015-09-16

    Agricultural adaptation is necessary to reduce the negative impacts of climate change on crop yields and to maintain food production. However, few studies have assessed the course of adaptation along with the progress of climate change in each of the current major food producing countries. Adaptation pathways, which describe the temporal sequences of adaptations, are helpful for illustrating the timing and intensity of the adaptation required. Here we present adaptation pathways in the current major wheat-producing countries, based on sequential introduction of the minimum adaptation measures necessary to maintain current wheat yields through the 21st century. We considered two adaptation options: (i) expanding irrigation infrastructure; and (ii) switching crop varieties and developing new heat-tolerant varieties. We find that the adaptation pathways differ markedly among the countries. The adaptation pathways are sensitive to both the climate model uncertainty and natural variability of the climate system, and the degree of sensitivity differs among countries. Finally, the negative impacts of climate change could be moderated by implementing adaptations steadily according to forecasts of the necessary future adaptations, as compared to missing the appropriate timing to implement adaptations.

  10. The Wnt signaling pathway in cellular proliferation and differentiation: A tale of two coactivators.

    Science.gov (United States)

    Teo, Jia-Ling; Kahn, Michael

    2010-09-30

    Wnt signaling pathways play divergent roles during development, normal homeostasis and disease. The responses that result from the activation of the pathway control both proliferation and differentiation. Tight regulation and controlled coordination of the Wnt signaling cascade is required to maintain the balance between proliferation and differentiation. The non-redundant roles of the coactivator proteins CBP and p300, within the context of Wnt signaling are discussed. We highlight their roles as integrators of the various inputs that a cell receives to elicit the correct and coordinated response. We propose that essentially all cellular information - i.e. from other signaling pathways, nutrient levels, etc. - is funneled down into a choice of coactivators usage, either CBP or p300, by their interacting partner beta-catenin (or catenin-like molecules in the absence of beta-catenin) to make the critical decision to either remain quiescent, or once entering cycle to proliferate without differentiation or to initiate the differentiation process.

  11. Crosstalk between Inflammation and ROCK/MLCK Signaling Pathways in Gastrointestinal Disorders with Intestinal Hyperpermeability

    Science.gov (United States)

    Du, Lijun; Kim, John J.; Shen, Jinhua

    2016-01-01

    The barrier function of the intestine is essential for maintaining the normal homeostasis of the gut and mucosal immune system. Abnormalities in intestinal barrier function expressed by increased intestinal permeability have long been observed in various gastrointestinal disorders such as Crohn's disease (CD), ulcerative colitis (UC), celiac disease, and irritable bowel syndrome (IBS). Imbalance of metabolizing junction proteins and mucosal inflammation contributes to intestinal hyperpermeability. Emerging studies exploring in vitro and in vivo model system demonstrate that Rho-associated coiled-coil containing protein kinase- (ROCK-) and myosin light chain kinase- (MLCK-) mediated pathways are involved in the regulation of intestinal permeability. With this perspective, we aim to summarize the current state of knowledge regarding the role of inflammation and ROCK-/MLCK-mediated pathways leading to intestinal hyperpermeability in gastrointestinal disorders. In the near future, it may be possible to specifically target these specific pathways to develop novel therapies for gastrointestinal disorders associated with increased gut permeability.

  12. Longevity pathways and memory ageing

    Directory of Open Access Journals (Sweden)

    Ilias eGkikas

    2014-06-01

    Full Text Available The ageing process has been associated with numerous pathologies at the cellular, tissue, and organ level. Decline or loss of brain functions, including learning and memory, is one of the most devastating and feared aspects of ageing. Learning and memory are fundamental processes by which animals adjust to environmental changes, evaluate various sensory signals based on context and experience, and make decisions to generate adaptive behaviours. Age-related memory impairment is an important phenotype of brain ageing. Understanding the molecular mechanisms underlying age-related memory impairment is crucial for the development of therapeutic strategies that may eventually lead to the development of drugs to combat memory loss. Studies in invertebrate animal models have taught us much about the physiology of ageing and its effects on learning and memory. In this review we survey recent progress relevant to conserved molecular pathways implicated in both ageing and memory formation and consolidation.

  13. Pathways towards ferroelectricity in hafnia

    Science.gov (United States)

    Huan, Tran Doan; Sharma, Vinit; Rossetti, George A.; Ramprasad, Rampi

    2014-08-01

    The question of whether one can systematically identify (previously unknown) ferroelectric phases of a given material is addressed, taking hafnia (HfO2) as an example. Low free energy phases at various pressures and temperatures are identified using a first-principles based structure search algorithm. Ferroelectric phases are then recognized by exploiting group theoretical principles for the symmetry-allowed displacive transitions between nonpolar and polar phases. Two orthorhombic polar phases occurring in space groups Pca21 and Pmn21 are singled out as the most viable ferroelectric phases of hafnia, as they display low free energies (relative to known nonpolar phases), and substantial switchable spontaneous electric polarization. These results provide an explanation for the recently observed surprising ferroelectric behavior of hafnia, and reveal pathways for stabilizing ferroelectric phases of hafnia as well as other compounds.

  14. Signalling pathways in pemphigus vulgaris.

    Science.gov (United States)

    Li, Xiaoguang; Ishii, Norito; Ohata, Chika; Furumura, Minao; Hashimoto, Takashi

    2014-03-01

    Acantholysis in pemphigus vulgaris is induced by binding of autoantibodies to desmoglein 3 (Dsg3). The roles of signalling pathways on development of acantholysis have recently been extensively studied. In the study by Sayar et al., recently published in Exp Dermatol, epidermal growth factor receptor (EGFR) signalling was activated in both in vivo and in vitro pemphigus vulgaris experimental models. However, while EGFR inhibitors suppressed activity of p38 mitogen-activated protein kinase (p38MAPK) linearly, they suppressed activity of c-Myc and acantholysis in a non-linear, V-shaped relationship. These findings indicated complicated interactions among EGFR, p38MAPK and c-Myc in pemphigus vulgaris pathology.

  15. Fuel Dependence of Benzene Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H; Eddings, E; Sarofim, A; Westbrook, C

    2008-07-14

    The relative importance of formation pathways for benzene, an important precursor to soot formation, was determined from the simulation of 22 premixed flames for a wide range of equivalence ratios (1.0 to 3.06), fuels (C{sub 1}-C{sub 12}), and pressures (20 to 760 torr). The maximum benzene concentrations in 15 out of these flames were well reproduced within 30% of the experimental data. Fuel structural properties were found to be critical for benzene production. Cyclohexanes and C{sub 3} and C{sub 4} fuels were found to be among the most productive in benzene formation; and long-chain normal paraffins produce the least amount of benzene. Other properties, such as equivalence ratio and combustion temperatures, were also found to be important in determining the amount of benzene produced in flames. Reaction pathways for benzene formation were examined critically in four premixed flames of structurally different fuels of acetylene, n-decane, butadiene, and cyclohexane. Reactions involving precursors, such as C{sub 3} and C{sub 4} species, were examined. Combination reactions of C{sub 3} species were identified to be the major benzene formation routes with the exception of the cyclohexane flame, in which benzene is formed exclusively from cascading fuel dehydrogenation via cyclohexene and cyclohexadiene intermediates. Acetylene addition makes a minor contribution to benzene formation, except in the butadiene flame where C{sub 4}H{sub 5} radicals are produced directly from the fuel, and in the n-decane flame where C{sub 4}H{sub 5} radicals are produced from large alkyl radical decomposition and H atom abstraction from the resulting large olefins.

  16. 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.

  17. 41 CFR 102-118.170 - Will GSA continue to maintain a centralized numbering system for Government transportation...

    Science.gov (United States)

    2010-07-01

    ... maintain a centralized numbering system for Government transportation documents? 102-118.170 Section 102-118.170 Public Contracts and Property Management Federal Property Management Regulations System... centralized numbering system for Government transportation documents? Yes, GSA will maintain a...

  18. 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; Tauqeer Alam, Mohammad; Keller, Markus A; Breitenbach, Michael; Brindle, Kevin M; Rabinowitz, Joshua D; Ralser, Markus

    2015-08-01

    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 parasite

  19. Coordination of insulin and Notch pathway activities by microRNA miR-305 mediates adaptive homeostasis in the intestinal stem cells of the Drosophila gut.

    Science.gov (United States)

    Foronda, David; Weng, Ruifen; Verma, Pushpa; Chen, Ya-Wen; Cohen, Stephen M

    2014-11-01

    Homeostasis of the intestine is maintained by dynamic regulation of a pool of intestinal stem cells. The balance between stem cell self-renewal and differentiation is regulated by the Notch and insulin signaling pathways. Dependence on the insulin pathway places the stem cell pool under nutritional control, allowing gut homeostasis to adapt to environmental conditions. Here we present evidence that miR-305 is required for adaptive homeostasis of the gut. miR-305 regulates the Notch and insulin pathways in the intestinal stem cells. Notably, miR-305 expression in the stem cells is itself under nutritional control via the insulin pathway. This link places regulation of Notch pathway activity under nutritional control. These findings provide a mechanism through which the insulin pathway controls the balance between stem cell self-renewal and differentiation that is required for adaptive homeostasis in the gut in response to changing environmental conditions.

  20. Pathway-Based Functional Analysis of Metagenomes

    Science.gov (United States)

    Bercovici, Sivan; Sharon, Itai; Pinter, Ron Y.; Shlomi, Tomer

    Metagenomic data enables the study of microbes and viruses through their DNA as retrieved directly from the environment in which they live. Functional analysis of metagenomes explores the abundance of gene families, pathways, and systems, rather than their taxonomy. Through such analysis researchers are able to identify those functional capabilities most important to organisms in the examined environment. Recently, a statistical framework for the functional analysis of metagenomes was described that focuses on gene families. Here we describe two pathway level computational models for functional analysis that take into account important, yet unaddressed issues such as pathway size, gene length and overlap in gene content among pathways. We test our models over carefully designed simulated data and propose novel approaches for performance evaluation. Our models significantly improve over current approach with respect to pathway ranking and the computations of relative abundance of pathways in environments.

  1. Mesenchymal stem cells maintain TGF-beta-mediated chondrogenic phenotype in alginate bead culture

    DEFF Research Database (Denmark)

    Mehlhorn, A T; Schmal, H; Kaiser, S

    2006-01-01

    This article addresses the stability of chondrogenic phenotype and the transdifferentiation potential of bone marrow-derived mesenchymal stem cells (MSCs) at distinct stages of differentiation. Differentiated MSCs were expected to maintain cartilage-like gene expression pattern in the absence of ...

  2. Work-Life Balance: Strategies for Attaining and Maintaining Work-Life Balance

    Science.gov (United States)

    Winkler, Josette Chinchiolo

    2010-01-01

    Purpose: It was the purpose of this study (a) to identify and describe the elements of balance that elementary principals perceive as most important to their personal and professional lives; (b) to identify the strategies elementary principals perceive as most important to maintain balance in their personal and professional lives; (c) to determine…

  3. Hypertension guidelines: Evidence-based treatments for maintaining blood pressure control.

    Science.gov (United States)

    Davis, Leslie Louise

    2015-06-11

    Approximately one in three adults in the United States has hypertension. This article provides an update on the latest JNC-8 guideline for treating hypertension in adults. Emphasis is placed on new and updated information and implications for primary care clinicians to help patients achieve and maintain better blood pressure control.

  4. Setting apart the amateur from the professional: maintaining the value of standardised representational photography.

    Science.gov (United States)

    Banks, Debbie

    2014-10-01

    The purpose of this paper is to discuss the importance of standard representational photography in clinical photography and its aid in maintaining the gold standard in the medical illustration profession. it is important that professionals are aware of potential threats to good practice with many areas identified in the article.

  5. Influence of Motivating Operations and Discriminative Stimuli on Challenging Behavior Maintained by Positive Reinforcement

    Science.gov (United States)

    Edrisinha, Chaturi; O'Reilly, Mark; Sigafoos, Jeff; Lancioni, Giulio; Choi, Ha Young

    2011-01-01

    We examined the effects of an establishing operation (EO) and abolishing operation (AO) on stimulus control of challenging behavior. Two participants with developmental disabilities and challenging behavior participated. In Phase I, a functional analysis was conducted to identify the consequences maintaining challenging behavior. In Phase II, a…

  6. Hanford Site guide for preparing and maintaining generator group pollution prevention program documentation

    Energy Technology Data Exchange (ETDEWEB)

    Place, B. G.

    1997-11-25

    This document provides guidance to contractor generator groups for developing and maintaining documentation of Pollution Prevention/Waste. Minimization (P2/WMin) Program activities. The program documentation is intended to demonstrate generator compliance with U.S. Department of Energy (DOE) requirements as well as state and Federal regulations.

  7. Critical Issue Bibliography (CRIB) Sheet: Maintaining Financial Health--Tuition Strategies, Cost Containment, and Fundraising.

    Science.gov (United States)

    ERIC Clearinghouse on Higher Education, Washington, DC.

    This CRitical Issue Bibliography (CRIB) Sheet lists resources that focus on maintaining the financial health of an institution of higher education. It describes resources in three areas: (1) tuition strategies; (2) cost containment; and (3) fundraising. The focus of the bibliography, however, is on cost containment and efficiency, and it details…

  8. Antinociceptive effects of high-dose remifentanil in male methadone-maintained patients.

    Science.gov (United States)

    Hay, Justin L; White, Jason M; Bochner, Felix; Somogyi, Andrew A

    2008-10-01

    The treatment of acute pain in patients maintained on methadone is difficult due to increased pain sensitivity (hyperalgesia) and cross-tolerance to other opioids. This study aimed to investigate whether remifentanil elicits antinociception in methadone-maintained subjects in a dose-dependent manner. Eight chronic methadone-maintained subjects attended the testing session approximately 20 h after their normal methadone dose (range 50-110 mgday(-1)). Following a 20 min saline infusion, subjects were administered intravenous remifentanil in seven increasing doses ranging from 0.5 to 3.5 microgkg(-1)min(-1), each for 2 0min. Testing was performed in the last 10 min of each infusion. The testing measures included nociception, as measured by the cold pressor test, withdrawal using the subjective opiate withdrawal scale (SOWS), and subjective opioid effects using the morphine-benzedrine group scale (MBG). Results showed dose-dependent increase in cold pressor tolerance time from baseline of 15.6+/-3.5 (mean+/-SEM)s up to 77.3+/-24.7s during this dosing protocol. During the infusion typical mu-opioid receptor agonist side effects were observed, but with no withdrawal. Methadone-maintained patients demonstrate significant tolerance to remifentanil and may require opioid doses 20-30 higher than required for the treatment of acute pain in opioid-naïve patients.

  9. Tractor Mechanics: Maintaining and Servicing the Fuel System. Learning Activity Packages 20-33.

    Science.gov (United States)

    Clemson Univ., SC. Vocational Education Media Center.

    Learning activity packages are presented for instruction in tractor mechanics. The packages deal with the duties involved in maintaining the fuel system. The following fourteen learning activity packages are included: servicing fuel and air filters, servicing fuel tanks and lines, adjusting a carburetor, servicing a carburetor, servicing the…

  10. Stepparents' Affinity-Seeking and Affinity-Maintaining Strategies with Stepchildren.

    Science.gov (United States)

    Ganong, Lawrence; Coleman, Marilyn; Fine, Mark; Martin, Patricia

    1999-01-01

    Examines the strategies that stepparents use to develop and maintain affinity with stepchildren and the effects that these strategies have on the development of stepparent-stepchildren relationships. Thirty-one affinity-seeking strategies are identified. Results show that dyadic activities worked best, but it is important that stepchildren…

  11. Metabolic and hemodynamic effects of saline infusion to maintain volemia on temporary abdominal aortic occlusion

    Directory of Open Access Journals (Sweden)

    Fábio Ferreira Amorim

    2002-10-01

    Full Text Available OBJECTIVE: To analyze hemodynamic and metabolic effects of saline solution infusion in the maintenance of blood volume in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. METHODS: We studied 20 dogs divided into 2 groups: the ischemia-reperfusion group (IRG, n=10 and the ischemia-reperfusion group with saline solution infusion aiming at maintaining mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, n=10. All animals were anesthetized with sodium thiopental and maintained on spontaneous ventilation. Occlusion of the supraceliac aorta was obtained with inflation of a Fogarty catheter inserted through the femoral artery. After 60 minutes of ischemia, the balloon was deflated, and the animals were observed for another 60 minutes of reperfusion. RESULTS: IRG-SS dogs did not have hemodynamic instability after aortic unclamping, and the mean systemic blood pressure and heart rate were maintained. However, acidosis worsened, which was documented by a greater reduction of arterial pH that occurred especially due to the absence of a respiratory response to metabolic acidosis that was greater with the adoption of this procedure. CONCLUSION: Saline solution infusion to maintain blood volume avoided hemodynamic instability after aortic unclamping. This procedure, however, caused worsening in metabolic acidosis in this experimental model.

  12. Standard methods for maintaining adult Apis mellifera in cages under in vitro laboratory conditions

    NARCIS (Netherlands)

    Williams, G.R.; Alaux, C.; Costa, C.; Csaki, C.; Steen, van der J.J.M.

    2013-01-01

    Adult honey bees are maintained in vitro in laboratory cages for a variety of purposes. For example, researchers may wish to perform experiments on honey bees caged individually or in groups to study aspects of parasitology, toxicology, or physiology under highly controlled conditions, or they may c

  13. 14 CFR 243.9 - Procedures for collecting and maintaining the information.

    Science.gov (United States)

    2010-01-01

    ... collecting and maintaining the information. Covered airlines may use any method or procedure to collect... segment. (c) The contact information collected pursuant to section 243.7(a)(2) of this part shall be kept... to obtain this information. (d) The contact information collected pursuant to section 243.7(a)(2)...

  14. Surface treatments and coatings to maintain fresh cut mango quality in storage

    Science.gov (United States)

    Edible coatings prevent moisture loss and may decrease gas exchange, thereby retaining moisture and flavor of fresh-cut fruit. Previous experiments showed that carboxymethylcellulose (CMC) with added maltodextrin maintained visual quality of stored mango slices also treated with calcium ascorbate an...

  15. Treatment of Escape-Maintained Behavior with Positive Reinforcement: The Role of Reinforcement Contingency and Density

    Science.gov (United States)

    Ingvarsson, Einar T.; Hanley, Gregory P.; Welter, Katherine M.

    2009-01-01

    Functional analyses suggested that the disruptive behavior of three preschool children was maintained by escape from demands. While keeping the escape contingency intact, we conducted (a) a density analysis in which the children earned preferred items for task completion according to two schedules that varied in reinforcement density, and (b) a…

  16. We're All Adults Here: Clarifying and Maintaining Boundaries with Adult Learners

    Science.gov (United States)

    Booth, Melanie; Schwartz, Harriet L.

    2012-01-01

    Working with adult learners presents a unique set of interpersonal boundary questions. In this chapter, the authors discuss the characteristics of working with adult learners that have led them to explore questions about boundaries between them and their students. They then identify how they might define, set, maintain, adjust, and work close to…

  17. NT-proBNP as a predictor of intradialytichypotension among maintaining hemodialysis patients

    Institute of Scientific and Technical Information of China (English)

    余金波

    2012-01-01

    Objective To assess the risk factors of intradialytichypotension (IDH) among maintaining hemodialysis (MHD) patients and to explore the relation between NTproBNP and IDH,thus to provide clinical evidence for the prevention and treatment of IDH. Methods A total of 202 MHD patients during March

  18. Voucher-Based Contingent Reinforcement of Smoking Abstinence among Methadone-Maintained Patients: A Pilot Study

    Science.gov (United States)

    Dunn, Kelly E.; Sigmon, Stacey C.; Thomas, Colleen S.; Heil, Sarah H.; Higgins, Stephen T.

    2008-01-01

    This study evaluated the efficacy of a contingency management (CM) intervention to promote smoking cessation in methadone-maintained patients. Twenty participants, randomized into contingent (n = 10) or noncontingent (n = 10) experimental conditions, completed the 14-day study. Abstinence was determined using breath carbon monoxide and urine…

  19. Maintaining Ecclesial Identity in Christian Higher Education: Some Thoughts from the Catholic Experience

    Science.gov (United States)

    Dosen, Anthony J.

    2012-01-01

    By the mid-19th century, liberal protestant universities had allowed their religious identity to slip away. During the same period, Catholic institutions had maintained their religious identity. Catholicism's stance against modernist thought had held the day. In the 1960s, the Aristotelian-Thomistic hegemony was broken, allowing for a pluralistic…

  20. 42 CFR 424.516 - Additional provider and supplier requirements for enrolling and maintaining active enrollment...

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Additional provider and supplier requirements for... Billing Privileges § 424.516 Additional provider and supplier requirements for enrolling and maintaining... active enrollment status for a provider or supplier when that provider or supplier certifies that...

  1. Performance of Polarizers and Coupler in an All Polarization Maintaining Fiber Interferometer

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhe; LIAO Yanbiao; HU Yongrning; LI Xiujian; MENG Zhou

    2000-01-01

    It is given mathematical models and analyze the performance of polarizers and coupler in an all polarization maintaining fiber (PMF) Michelson interferometer. The optical coherent signal to noise ratio (CSNR) of the interferometer is calculated by means of the Jones matrix with cross coupling matrix elements.

  2. How to Maintain an Operational Reserve? Further Engaging Army Reserve Component Forces in the Coming Decade

    Science.gov (United States)

    2015-02-17

    with mobilizing Reserve Component units for overseas missions. This flexibility will allow the Army to meet ongoing mission requirements , while... reserve will impose an increased cost on the Army. First (and most obviously), the Army will have to fund the additional pay and allowances required ...AIR WAR COLLEGE AIR UNIVERSITY HOW TO MAINTAIN AN OPERATIONAL RESERVE ? FURTHER ENGAGING ARMY RESERVE COMPONENT FORCES IN

  3. A Swarm Intelligent Algorithm Based Route Maintaining Protocol for Mobile Sink Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Xiaoming Wu

    2015-01-01

    Full Text Available Recent studies have shown that mobile sink can be a solution to solve the problem that energy consumption of sensor nodes is not balanced in wireless sensor networks (WSNs. Caused by the sink mobility, the paths between the sensor nodes and the sink change frequently and have profound influence on the lifetime of WSN. It is necessary to design a protocol that can find efficient routings between the mobile sink and nodes but does not consume too many network resources. In this paper, we propose a swarm intelligent algorithm based route maintaining protocol to resolve this issue. The protocol utilizes the concentric ring mechanism to guide the route researching direction and adopts the optimal routing selection to maintain the data delivery route in mobile sink WSN. Using the immune based artificial bee colony (IABC algorithm to optimize the forwarding path, the routing maintaining protocol could find an alternative routing path quickly and efficiently when the coordinate of sink is changed in WSN. The results of our extensive experiments demonstrate that our proposed route maintaining protocol is able to balance the network traffic load and prolong the network lifetime.

  4. Digital Avionics Information System (DAIS): Reliability and Maintainability Model. Final Report.

    Science.gov (United States)

    Czuchry, Andrew J.; And Others

    The reliability and maintainability (R&M) model described in this report represents an important portion of a larger effort called the Digital Avionics Information System (DAIS) Life Cycle Cost (LCC) Study. The R&M model is the first of three models that comprise a modeling system for use in LCC analysis of avionics systems. The total…

  5. 31 CFR 1.30 - Application to system of records maintained by Government contractors.

    Science.gov (United States)

    2010-07-01

    ... by Government contractors. When a component contracts for the operation of a system of records, to... 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...

  6. 9 CFR 201.29 - Market agencies, packers and dealers required to file and maintain bonds.

    Science.gov (United States)

    2010-01-01

    ... packer purchasing livestock, directly or through an affiliate or employee or a wholly-owned subsidiary... bond. In the event a packer maintains a wholly-owned subsidiary or affiliate to conduct its livestock buying, the wholly-owned subsidiary or affiliate shall be registered as a packer buyer for its...

  7. A transition space maintainer for the adolescent dentition: a case report.

    Science.gov (United States)

    Levine, N; Sigal, M J; Creighton, J M; Maeda, T

    1990-12-01

    Premature loss of teeth in posterior segments of the primary, mixed or permanent dentition may lead to space loss in an anterior-posterior dimension. This article illustrates how a simple, aesthetic and effective space maintainer can be used to prevent space loss in the permanent dentition.

  8. Maintaining Switzerland's Top Innovation Capacity. OECD Economics Department Working Papers, No. 487

    Science.gov (United States)

    Jaumotte, Florence

    2006-01-01

    Despite some weakening in the 1990s, partly due to sluggish trend growth, the Swiss innovation performance has been very strong. There are, however, areas in which policy reforms could strengthen innovation further and help Switzerland maintain its lead in the face of a changing global environment. Boosting competition, simplifying administrative…

  9. Teacher Collaborative Curriculum Design in Technical Vocational Colleges: A Strategy for Maintaining Curriculum Consistency?

    Science.gov (United States)

    Albashiry, Nabeel M.; Voogt, Joke M.; Pieters, Jules 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 quality and relevance of their programmes to the…

  10. Configuration maintaining control of three-body ring tethered system based on thrust compensation

    Science.gov (United States)

    Huang, Panfeng; Liu, Binbin; Zhang, Fan

    2016-06-01

    Space multi-tethered systems have shown broad prospects in remote observation missions. This paper mainly focuses on the dynamics and configuration maintaining control of space spinning three-body ring tethered system for such mission. Firstly, we establish the spinning dynamic model of the three-body ring tethered system considering the elasticity of the tether using Newton-Euler method, and then validate the suitability of this model by numerical simulation. Subsequently, LP (Likins-Pringle) initial equilibrium conditions for the tethered system are derived based on rigid body's equilibrium theory. Simulation results show that tether slack, snapping and interaction between the tethers exist in the three-body ring system, and its' configuration can not be maintained without control. Finally, a control strategy based on thrust compensation, namely thrust to simulate tether compression under LP initial equilibrium conditions is designed to solve the configuration maintaining control problem. Control effects are verified by numerical simulation compared with uncontrolled situation. Simulation results show that the configuration of the three-body ring tethered system could maintain under this active control strategy.

  11. Women Vietnamese Refugees in the United States: Maintaining Balance between Two Cultures. Senior Division Winner.

    Science.gov (United States)

    Marino, Katherine

    1998-01-01

    Focuses on how the migration of Vietnamese to the United States affected the women's roles within their families and society. Discusses how Vietnamese women ensured familial stability by maintaining a balance between U.S. and Vietnamese cultures. Provides an annotated bibliography. (CMK)

  12. Evaluation of a web-based lifestyle coach designed to maintain a healthy bodyweight

    NARCIS (Netherlands)

    Kelders, Saskia M.; Gemert-Pijnen, van Julia E.W.C.; Werkman, Andrea; Seydel, Erwin R.

    2010-01-01

    We evaluated a web-based intervention, the Healthy Weight Assistant (HWA), which was designed to help people with a healthy bodyweight, or those who are slightly overweight, to achieve and maintain a healthy weight. Four evaluation methods were used: (1) pre- and post-test questionnaires; (2) real t

  13. An Approach for Maintaining Models of an E-Commerce Collaboration

    NARCIS (Netherlands)

    Bodenstaff, L.; Wombacher, A.; Wieringa, R.J.; Reichert, M.U.

    2008-01-01

    To keep an overview on complex e-commerce collaborations several models are used to describe them. When models overlap in describing a collaboration, the overlapping information should not contradict. Models are of different nature and maintained by different people. Therefore, keeping model-overlap

  14. Femtosecond all-polarization-maintaining fiber laser operating at 1028 nm

    DEFF Research Database (Denmark)

    Olsson, R.K.; Andersen, T.V.; Leick, Lasse;

    2008-01-01

    We present an effective solution for an all-polarization-maintaining modelocked femtosecond fiber laser operating at the central wavelength of 1028 nm. The laser is based on an Yb-doped active fiber. Modelocking is enabled by a semiconductor saturable absorber mirror, and the central wavelength...

  15. Failure to maintain set as a predictor of childhood depression within a children's psychiatric inpatient sample.

    Science.gov (United States)

    Kavanaugh, Brian C; Gaudet, Charles E; Dupont-Frechette, Jennifer A; Tellock, Perrin P; Maher, Isolde D; Haisley, Lauren D; Holler, Karen A

    2016-12-30

    Despite a wealth of studies in adults and adolescents, only a handful of studies have examined executive function in childhood depression. This study utilized retrospective chart review of a children's psychiatric inpatient program to evaluate executive function via Wisconsin Card Sorting Test (WCST) in 33 children (6-12 years old) with a depressive disorder and 61 age/sex-matched children without a depressive disorder referred for neuropsychological evaluation. WCST categories, perseverative errors, and failure to maintain set errors were examined as potential predictors of depressive disorder diagnosis and self-reported depressive symptoms. After controlling for age, length of hospital stay, and ADHD, failure to maintain set significantly predicted depressive disorder diagnosis. Failure to maintain set was also significantly associated with self-reported depressive symptoms. Current findings provide preliminary evidence to suggest that failure to maintain set may reflect a core deficit of childhood depression. While findings are preliminary, this may have important implications for the diagnosis and treatment of childhood depression.

  16. [Mycelial fungi maintained in the Russia Collection of Microorganisms (VKM IBPM RAS)].

    Science.gov (United States)

    Ozerskaia, S M; Kochkina, G A; Ivanushkina, N E; Zaprometova, K M; Eremina, S S

    2005-01-01

    Information on application of diversity of mycelial fungi maintained in the Russia Collection of Microorganisms (VKM) at the Institute for Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences to research and biotechnology as producers is presented, as well as data on additions to the basic collection.

  17. Worms Eat My Garbage. How To Set Up and Maintain a Worm Composting System. First Edition.

    Science.gov (United States)

    Appelhof, Mary

    This book is a resource for parents and teachers who want to teach about recycling and composting by setting up and maintaining a worm composting system. It is designed to be a detailed yet simple manual of vermicomposting. The manual covers the basics of vermicomposting and answers such questions as where to store a composting container, what…

  18. Keeping the Rust at Bay: How To Maintain and Develop Your Language Skills.

    Science.gov (United States)

    Marriott, Helen

    1994-01-01

    Discusses measures language teachers can use to maintain and develop their communicative language ability. Introduces strategies teachers can adopt and mentions ways in which educational systems and universities can assist teachers. The model presented is relevant to teachers of any language. (13 references) (Author/CK)

  19. Evaluation of antibiotic releasing porous polymethylmethacrylate space maintainers in an infected composite tissue defect model

    NARCIS (Netherlands)

    Spicer, P.P.; Shah, S.R.; Henslee, A.M.; Watson, B.M.; Kinard, L.A.; Kretlow, J.D.; Bevil, K.; Kattchee, L.; Bennett, G.N.; Demian, N.; Mende, K.; Murray, C.K.; Jansen, J.A.; Wong, M.E.; Mikos, A.G.; Kasper, F.K.

    2013-01-01

    This study evaluated the in vitro and in vivo performance of antibiotic-releasing porous polymethylmethacrylate (PMMA)-based space maintainers comprising a gelatin hydrogel porogen and a poly(dl-lactic-co-glycolic acid) (PLGA) particulate carrier for antibiotic delivery. Colistin was released in vit

  20. 30 CFR 250.109 - What documents must I prepare and maintain related to welding?

    Science.gov (United States)

    2010-07-01

    ... related to welding? 250.109 Section 250.109 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF... Performance Standards § 250.109 What documents must I prepare and maintain related to welding? (a) You must submit a Welding Plan to the District Manager before you begin drilling or production activities on...

  1. Tunable polarisation-maintaining filter based on liquid crystal photonic bandgap fibre

    DEFF Research Database (Denmark)

    Scolari, Lara; Olausson, Christina Bjarnal Thulin; Weirich, Johannes

    2008-01-01

    A tunable and polarisation-maintaining all-in-fibre filter based on a liquid crystal photonic bandgap fibre is demonstrated. Its polarisation extinction ratio reaches 14 dB at 1550 nm wavelength. Its spectral tunability range spans over 250 nm in the temperature range 30–70°C. The measured...

  2. 76 FR 51041 - Hemoglobin Standards and Maintaining Adequate Iron Stores in Blood Donors; Public Workshop

    Science.gov (United States)

    2011-08-17

    ... HUMAN SERVICES Food and Drug Administration Hemoglobin Standards and Maintaining Adequate Iron Stores in... workshop. The Food and Drug Administration (FDA) is announcing a public workshop entitled: ``Hemoglobin... discuss blood donor hemoglobin and hematocrit qualification standards in the United States, its impact...

  3. Male sterility of triticale lines generated through recombination of triticale and rye maintainers

    Directory of Open Access Journals (Sweden)

    Tomasz Warzecha

    2014-11-01

    Full Text Available The Triticum timopheevi cytoplasmic male sterility (cms system in triticale (xTriticosecale Wittmack suffers from a low frequency of maintainers and environmental instability of the male sterility. On the other hand, the Pampa cms system in rye (Secale cereale exhibits strong male sterility and a low frequency of restorers. Here, we report generating hybrids between maintainers of the T. timopheevi cms system in triticale and maintainers of the rye Pampa cms system. Ten hybrids were obtained. Their hybridity was verified by PCR (polymerase chain reaction using ISSR (inter simple sequence repeats primers. The cms maintaining ability of F2 individuals and their progeny was tested. The F2 plants were crossed to male sterile lines of triticale carrying the T. timopheevi cytoplasm. Among 180 G1 offspring of these crosses, 71 (39.4% were completely male sterile. Fourteen F2 individuals (7.8%, as well as their F2S1 and progeny, generated stable male sterility in G1, G1BC1 and G1BC2 generations after the crosses. Our results suggest that it is possible to produce a more stable cms system in triticale based on the T. timopheevi cytoplasm as compared to the existing one.

  4. Increasing complexity while maintaining a high degree of symmetry in nanocrystal growth.

    Science.gov (United States)

    Liz-Marzán, Luis M

    2015-03-23

    Learning from classics: Crystal growth is a complex process, and there are multiple paths for going from dissolved ions to solid crystals. Highlighted herein is the application of traditional chemistry concepts to new ways for increasing the complexity of nanocrystals while maintaining a high degree of symmetry.

  5. Furloughs and Faculty Management of Time: Maintaining Quality in an Economic Crisis

    Science.gov (United States)

    Jones, Loring; Hohman, Melinda; Mathiesen, Sally; Finnegan, Daniel

    2014-01-01

    An anonymous Web-based survey was used to gather the perceptions and experiences from 114 faculty members teaching in 16 social work programs in the California State University system about the effect of severe budget cuts on their educational activities. Most respondents reported they worked on their furlough days and maintained the same or…

  6. Demonstration of Pelvic Anatomy by Modified Midline Transection that Maintains Intact Internal Pelvic Organs

    Science.gov (United States)

    Steinke, Hanno; Saito, Toshiyuki; Herrmann, Gudrun; Miyaki, Takayoshi; Hammer, Niels; Sandrock, Mara; Itoh, Masahiro; Spanel-Borowski, Katharina

    2010-01-01

    Gross dissection for demonstrating anatomy of the human pelvis has traditionally involved one of two approaches, each with advantages and disadvantages. Classic hemisection in the median plane through the pelvic ring transects the visceral organs but maintains two symmetric pelvic halves. An alternative paramedial transection compromises one side…

  7. An Evaluation of Response Cost in the Treatment of Inappropriate Vocalizations Maintained by Automatic Reinforcement

    Science.gov (United States)

    Falcomata, Terry S.; Roane, Henry S.; Hovanetz, Alyson N.; Kettering, Tracy L.; Keeney, Kris M.

    2004-01-01

    In the current study, we examined the utility of a procedure consisting of noncontingent reinforcement with and without response cost in the treatment of inappropriate vocalizations maintained by automatic reinforcement. Results are discussed in terms of examining the variables that contribute to the effectiveness of response cost as treatment for…

  8. 46 CFR 12.25-45 - GMDSS At-sea Maintainer.

    Science.gov (United States)

    2010-10-01

    ... Engine Department § 12.25-45 GMDSS At-sea Maintainer. An applicant is eligible to have his or her STCW... outlined in Section B-IV/2 of the STCW Code (incorporated by reference in § 12.01-3) for training...

  9. 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.

  10. Reconstructing fungal natural product biosynthetic pathways.

    Science.gov (United States)

    Lazarus, C M; Williams, K; Bailey, A M

    2014-10-01

    Large scale fungal genome sequencing has revealed a multitude of potential natural product biosynthetic pathways that remain uncharted. Here we describe some of the methods that have been used to explore them via heterologous gene expression. We focus on filamentous fungal hosts and discuss the technological challenges and successes behind the reconstruction of fungal natural product pathways. Optimised, efficient heterologous expression of reconstructed biosynthetic pathways promises progress in the discovery of novel compounds that could be utilised by the pharmaceutical and agrochemical industries.

  11. Coherent band pathways between knots and links

    CERN Document Server

    Buck, Dorothy

    2014-01-01

    We categorise coherent band (aka nullification) pathways between knots and 2-component links. Additionally, we characterise the minimal coherent band pathways (with intermediates) between any two knots or 2-component links with small crossing number. We demonstrate these band surgeries for knots and links with small crossing number. We apply these results to place lower bounds on the minimum number of recombinant events separating DNA configurations, restrict the recombination pathways and determine chirality and/or orientation of the resulting recombinant DNA molecules.

  12. CREB pathway links PGE2 signaling with macrophage polarization.

    Science.gov (United States)

    Luan, Bing; Yoon, Young-Sil; Le Lay, John; Kaestner, Klaus H; Hedrick, Susan; Montminy, Marc

    2015-12-22

    Obesity is thought to promote insulin resistance in part via activation of the innate immune system. Increases in proinflammatory cytokine production by M1 macrophages inhibit insulin signaling in white adipose tissue. In contrast, M2 macrophages have been found to enhance insulin sensitivity in part by reducing adipose tissue inflammation. The paracrine hormone prostaglandin E2 (PGE2) enhances M2 polarization in part through activation of the cAMP pathway, although the underlying mechanism is unclear. Here we show that PGE2 stimulates M2 polarization via the cyclic AMP-responsive element binding (CREB)-mediated induction of Krupple-like factor 4 (KLF4). Targeted disruption of CREB or the cAMP-regulated transcriptional coactivators 2 and 3 (CRTC2/3) in macrophages down-regulated M2 marker gene expression and promoted insulin resistance in the context of high-fat diet feeding. As re-expression of KLF4 rescued M2 marker gene expression in CREB-depleted cells, our results demonstrate the importance of the CREB/CRTC pathway in maintaining insulin sensitivity in white adipose tissue via its effects on the innate immune system.

  13. Standardized Markerless Gene Integration for Pathway Engineering in Yarrowia lipolytica.

    Science.gov (United States)

    Schwartz, Cory; Shabbir-Hussain, Murtaza; Frogue, Keith; Blenner, Mark; Wheeldon, Ian

    2016-12-22

    The yeast Yarrowia lipolytica is a promising microbial host due to its native capacity to produce lipid-based chemicals. Engineering stable production strains requires genomic integration of modified genes, avoiding episomal expression that requires specialized media to maintain selective pressures. Here, we develop a CRISPR-Cas9-based tool for targeted, markerless gene integration into the Y. lipolytica genome. A set of genomic loci was screened to identify sites that were accepting of gene integrations without impacting cell growth. Five sites were found to meet these criteria. Expression levels from a GFP expression cassette were consistent when inserted into AXP, XPR2, A08, and D17, with reduced expression from MFE1. The standardized tool is comprised of five pairs of plasmids (one homologous donor plasmid and a CRISPR-Cas9 expression plasmid), with each pair targeting gene integration into one of the characterized sites. To demonstrate the utility of the tool we rapidly engineered a semisynthetic lycopene biosynthesis pathway by integrating four different genes at different loci. The capability to integrate multiple genes without the need for marker recovery and into sites with known expression levels will enable more rapid and reliable pathway engineering in Y. lipolytica.

  14. The Lipocalin LPR-1 Cooperates with LIN-3/EGF Signaling To Maintain Narrow Tube Integrity in Caenorhabditis elegans.

    Science.gov (United States)

    Pu, Pu; Stone, Craig E; Burdick, Joshua T; Murray, John I; Sundaram, Meera V

    2016-12-30

    Lipocalins are secreted cup-shaped glycoproteins that bind sterols, fatty acids, and other lipophilic molecules. Lipocalins have been implicated in a wide array of processes related to lipophilic cargo transport, sequestration and signaling, and several are used as biomarkers for human disease, but the functions of most lipocalins remain poorly understood. Here we show that the C. elegans lipocalin LPR-1 is required to maintain apical membrane integrity and a continuous lumen in two narrow, unicellular tubes, the excretory duct and pore, during a period of rapid lumen elongation. LPR-1 fusion protein is expressed by the duct and pore and accumulates both intracellularly and in apical extracellular compartments, but it can also function cell non-autonomously when provided from outside of the excretory system. lpr-1 mutant defects can be rescued by increased signaling through the Epidermal growth factor (EGF) - Ras - Extracellular signal regulated kinase (ERK) pathway, which promotes the more elongated duct vs. less elongated pore tube fate. Spatial and temporal rescue experiments indicate that Ras signaling acts within the duct and pore tubes during or prior to cell fate determination to bypass the requirement for LPR-1. lpr-1 mutations did not disrupt LIN-3/EGF-dependent duct fate specification, prevent functioning of any specific LIN-3/EGF isoform, or alter LET-23/EGFR localization, and reduced signaling did not phenocopy or enhance lpr-1 mutant defects. These data suggest that LPR-1 protects lumen integrity through a LIN-3/EGF-independent mechanism, but that increased signaling upregulates some target(s) that can compensate for lpr-1 absence.

  15. Reciprocal regulation between O-GlcNAcylation and tribbles pseudokinase 2 (TRIB2) maintains transformative phenotypes in liver cancer cells.

    Science.gov (United States)

    Yao, Bingjie; Xu, Yanli; Wang, Jiayi; Qiao, Yongxia; Zhang, Yue; Zhang, Xiao; Chen, Yan; Wu, Qi; Zhao, Yinghui; Zhu, Guoqing; Sun, Fenyong; Li, Zhi; Yuan, Hong

    2016-11-01

    TRIB2 has been identified as an onco-protein, and O-GlcNAcylation of target proteins has been reported to stimulate transformative phenotypes in liver cancer cells. However, the relationships between TRIB2 and O-GlcNAcylation are still unknown. The aim of this study was to investigate whether and how O-GlcNAcylation and TRIB2 regulate each other. We found that stimulation of O-GlcNAcylation elevates TRIB2 by enhancing its protein stability. TRIB2 can be O-GlcNAcylated by the hexosamine biosynthesis pathway (HBP). Also, O-GlcNAcylation boosting of transformative phenotypes of liver cancer cells might occur in a TRIB2-dependent manner. Interestingly, TRIB2 stimulated the metabolism of HBP, demonstrating that TRIB2 has positive feedback on O-GlcNAcylation. Notably, TRIB2 was found to maintain the stability of guanylate cyclase 1 alpha 3 (GUCY1A3), a key component of HBP, by interacting GUCY1A3 and reducing its ubiquitination. Importantly, TRIB2-dependent regulation of metabolism, transformative phenotypes, and O-GlcNAcylation all rely on GUCY1A3. Mouse experiments demonstrate that O-GlcNAcylation of TRIB2 is much higher in the livers of diabetic mice compared to control mice, suggesting that O-GlcNAcylation of TRIB2 might be critical for diabetes-associated liver cancer. Collectively, we have uncovered a positive auto-regulatory feedback between O-GlcNAcylation and TRIB2, which might be regarded as a promising therapeutic target for liver cancer.

  16. Tcf3 represses Wnt-β-catenin signaling and maintains neural stem cell population during neocortical development.

    Directory of Open Access Journals (Sweden)

    Atsushi Kuwahara

    Full Text Available During mouse neocortical development, the Wnt-β-catenin signaling pathway plays essential roles in various phenomena including neuronal differentiation and proliferation of neural precursor cells (NPCs. Production of the appropriate number of neurons without depletion of the NPC population requires precise regulation of the balance between differentiation and maintenance of NPCs. However, the mechanism that suppresses Wnt signaling to prevent premature neuronal differentiation of NPCs is poorly understood. We now show that the HMG box transcription factor Tcf3 (also known as Tcf7l1 contributes to this mechanism. Tcf3 is highly expressed in undifferentiated NPCs in the mouse neocortex, and its expression is reduced in intermediate neuronal progenitors (INPs committed to the neuronal fate. We found Tcf3 to be a repressor of Wnt signaling in neocortical NPCs in a reporter gene assay. Tcf3 bound to the promoter of the proneural bHLH gene Neurogenin1 (Neurog1 and repressed its expression. Consistent with this, Tcf3 repressed neuronal differentiation and increased the self-renewal activity of NPCs. We also found that Wnt signal stimulation reduces the level of Tcf3, and increases those of Tcf1 (also known as Tcf7 and Lef1, positive mediators of Wnt signaling, in NPCs. Together, these results suggest that Tcf3 antagonizes Wnt signaling in NPCs, thereby maintaining their undifferentiated state in the neocortex and that Wnt signaling promotes the transition from Tcf3-mediated repression to Tcf1/Lef1-mediated enhancement of Wnt signaling, constituting a positive feedback loop that facilitates neuronal differentiation.

  17. Expanding antitumor therapeutic windows by targeting cancer-specific nicotinamide adenine dinucleotide phosphate-biogenesis pathways

    Directory of Open Access Journals (Sweden)

    Chakrabarti G

    2015-03-01

    Full Text Available Gaurab Chakrabarti,1,2,4 David E Gerber,3,4 David A Boothman1,2,4 1Department of Pharmacology, 2Department of Radiation Oncology, 3Division of Hematology and Oncology, 4Harold C Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA Abstract: Nicotinamide adenine dinucleotide phosphate (NADPH biogenesis is an essential mechanism by which both normal and cancer cells maintain redox balance. While antitumor approaches to treat cancers through elevated reactive oxygen species (ROS are not new ideas, depleting specific NADPH-biogenesis pathways that control recovery and repair pathways are novel, viable approaches to enhance cancer therapy. However, to elicit efficacious therapies exploiting NADPH-biogenic pathways, it is crucial to understand and specifically define the roles of NADPH-biogenesis pathways used by cancer cells for survival or recovery from cell stress. It is equally important to select NADPH-biogenic pathways that are expendable or not utilized in normal tissue to avoid unwanted toxicity. Here, we address recent literature that demonstrates specific tumor-selective NADPH-biogenesis pathways that can be exploited using agents that target specific cancer cell pathways normally not utilized in normal cells. Defining NADPH-biogenesis profiles of specific cancer-types should enable novel strategies to exploit these therapeutic windows for increased efficacy against recalcitrant neoplastic disease, such as pancreatic cancers. Accomplishing the goal of using ROS as a weapon against cancer cells will also require agents, such as NQO1 bioactivatable drugs, that selectively induce elevated ROS levels in cancer cells, while normal cells are protected. Keywords: reactive oxygen species (ROS, NQO1-bioactivatable drugs, nicotinamide adenine dinucleotide phosphate (NADPH, glutathione (GSH, biogenic pathways, antioxidant

  18. Fiber-reinforced composites as a fixed space maintainer in case of primary tooth loss.

    Science.gov (United States)

    Acharya, Sonu; Tandon, Shobha

    2011-01-01

    Restorative dentistry is continually changing, with ground-breaking treatments developing based on new materials, techniques, and technologies. Composite materials are a leading example, and the introduction of fiber reinforcement has further increased the possible uses of composites in restorative dentistry. Maintaining arch length during primary, mixed, and early permanent dentition is essential for the development of occlusion. In an effort to prevent future problems, appliances may be placed to retain space resulting from early loss of teeth. In case of primary teeth loss, fixed space maintainers are being used, but these are time consuming to fabricate, and incorporated wires may lead to soft tissue trauma. This clinical case uses fiber-reinforced composite as a space maintainer, thus reducing the time required to complete treatment. In spite of best efforts of practicing dentists, there still remains a large percentage of the population who do not present for treatment, except with pain or other condition. Unfortunately some of those individuals are children, who are not in a position to make the difficult decision to visit the dentist independently. Often by the time they are examined, there is no chance of saving the involved tooth, necessitating extraction and space maintenance. To prevent closure of space and arch length deficiency, appliances may be placed to retain space. Different appliances may be used for space maintenance, such as the removable and fixed space maintainers, but they are difficult and time consuming to construct. Also, the attention span of a child patient is insufficient for this treatment protocol. Considering these difficulties, the clinician could choose the option of a space maintainer, which is less time consuming to fabricate, and for which patient acceptance is optimal.

  19. Effects of PDT on the endocytic pathway

    Science.gov (United States)

    Kessel, David

    2010-02-01

    Two lines of evidence point to an early effect of photodamage on membrane trafficking. [1] Internalization of a fluorescent probe for hydrophobic membrane loci was impaired by prior photodamage. [2] Interference with the endocytic pathway by the PI-3 kinase antagonist wortmannin led to accumulation of cytoplasmic vacuoles suggesting a block in the recycling of plasma membrane components. Prior photodamage blocked this pathway so that no vacuoles were formed upon exposure of cells to wortmannin. In a murine hepatoma line, the endocytic pathway was preferentially sensitive to lysosomal photodamage. The role of photodamage to the endocytic pathway as a factor in PDT efficacy remains to be assessed.

  20. Female offenders’ pathways to prison in Belgium

    Directory of Open Access Journals (Sweden)

    Nuytiens An

    2012-01-01

    Full Text Available This paper examines some results of a research on female offenders’ life histories and pathways to prison in Belgium. Women’s pathways into crime will be presented and the connection of these pathways to their life histories will be explored. The study reveals that the greater part of the research population are adult-onset offenders. The authors argue that the importance of adult-onset pathways for female offenders might be explained by the emergence of (gendered vulnerabilities within the women’s lives, often accumulated not before adulthood.

  1. Maintaining Genetic Integrity Under Extreme Conditions: Novel DNA Damage Repair Biology in the Archaea

    Science.gov (United States)

    2013-11-23

    11/23/2013 Final Report DISTRIBUTION A: Distribution approved for public release. AIR FORCE RESEARCH LABORATORY AF OFFICE OF SCIENTIFIC RESEARCH...damaging agents, the genetic interactions with known DNA repair pathways and, crucially, the observed delay in DSB repair visualised by PFGE confirm the

  2. Working Memory Benefits Creative Insight, Musical Improvisation, and Original Ideation Through Maintained Task-Focused Attention

    NARCIS (Netherlands)

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

    2012-01-01

    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 pers

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

    NARCIS (Netherlands)

    de Dreu, C.K.W.; Nijstad, B.A.; Baas, M.; Wolsink, I.; Roskes, M.

    2012-01-01

    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 pers

  4. New insights into transduction pathways that regulate boar sperm function.

    Science.gov (United States)

    Hurtado de Llera, A; Martin-Hidalgo, D; Gil, M C; Garcia-Marin, L J; Bragado, M J

    2016-01-01

    Detailed molecular mechanisms mediating signal transduction cascades that regulate boar sperm function involving Ser/Thr and tyrosine phosphorylation of proteins have been reviewed previously. Therefore, this review will focus in those kinase pathways identified recently (boar spermatozoa that regulate different functional spermatozoa processes. AMP-activated protein kinase (AMPK) is a cell energy sensor kinase that was first identified in mammalian spermatozoa in 2012, and since then it has emerged as an essential regulator of boar sperm function. Signaling pathways leading to AMPK activation in boar sperm are highlighted in this review (PKA, CaMKKα/β, and PKC as well as Ca(2+) and cAMP messengers as upstream regulators). Interestingly, stimuli considered as cell stress (hyperosmotic stress, inhibition of mitochondrial activity, absence of intracellular Ca(2+)) markedly activate AMPK in boar spermatozoa. Moreover, AMPK plays a remarkable and necessary regulatory role in mammalian sperm function, controlling essential boar sperm functional processes such as motility, viability, mitochondrial membrane potential, organization and fluidity of plasma membrane, and outer acrosome membrane integrity. These mentioned processes are all required under fluctuating environment of spermatozoa when transiting through the female reproductive tract to achieve fertilization. An applied role of AMPK in artificial insemination techniques is also suggested as during boar seminal doses preservation at 17 °C, physiological levels of AMPK activity markedly increase (maximum on Day 7) and result essential to maintain the aforementioned fundamental sperm processes. Moreover, regulation of sperm function exerted by the glycogen synthase kinase 3 and Src family kinase pathways is summarized.

  5. 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.

  6. Identification of a sotolon pathway in dry white wines.

    Science.gov (United States)

    Pons, Alexandre; Lavigne, Valérie; Landais, Yannick; Darriet, Philippe; Dubourdieu, Denis

    2010-06-23

    Sotolon (3-hydroxy-4,5-dimethyl-2(5H)-furanone) is a chiral furanone, an aroma compound known to be responsible for premature-aging flavor in dry white wines. Sotolon generally results from mild oxygenation during bottle aging, and until now, its formation pathways had not been elucidated. The ability of the main precursors described in the literature under very different experimental conditions to produce sotolon was tested. In model wine solution maintained at 40 degrees C for 6 months, sotolon was produced by the oxidative degradation of ascorbic acid. By use of GC-MS, 2-ketobutyric acid, produced by the oxidative degradation of the ascorbic acid in the model wine solution, was identified as a potent precursor of sotolon in this pathway. Ascorbic acid is an exogenous compound, added before bottling, but 2-ketobutyric acid was found even in white wines that had not been supplemented. Consequently, this sotolon formation pathway is also valid in white wines with no added ascorbic acid. In addition, we showed that Saccharomyces cerevisiae strains were capable of producing variable concentrations of this ketone during alcoholic fermentation. In model wine solution, certain yeast strains released large quantities of 2-ketobutyric acid, similar to those found in oxidized dry white wines. In view of these results, the role of yeast strains in this premature-aging phenomenon of dry white wines is discussed. Finally, these investigations revealed that one chemical mechanism responsible for the low concentrations of sotolon found in prematurely aged white wines made from various grape varieties was an aldol condensation between 2-ketobutyric acid and acetaldehyde.

  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. 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.

  9. 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...... several network perturbation techniques and over a range of perturbation degrees. In addition, users may now provide a gold-standard set to determine how enriched extracted pathways are with relevant genes compared to randomized versions of the original network....

  10. T Cell Receptor and Cytokine Signaling Can Function at Different Stages to Establish and Maintain Transcriptional Memory and Enable T Helper Cell Differentiation

    Science.gov (United States)

    Bevington, Sarah L.; Cauchy, Pierre; Withers, David R.; Lane, Peter J. L.; Cockerill, Peter N.

    2017-01-01

    Experienced T cells exhibit immunological memory via a rapid recall response, responding to restimulation much faster than naïve T cells. The formation of immunological memory starts during an initial slow response, when naïve T cells become transformed to proliferating T blast cells, and inducible immune response genes are reprogrammed as active chromatin domains. We demonstrated that these active domains are supported by thousands of priming elements which cooperate with inducible transcriptional enhancers to enable efficient responses to stimuli. At the conclusion of this response, a small proportion of these cells return to the quiescent state as long-term memory T cells. We proposed that priming elements can be established in a hit-and-run process dependent on the inducible factor AP-1, but then maintained by the constitutive factors RUNX1 and ETS-1. This priming mechanism may also function to render genes receptive to additional differentiation-inducing factors such as GATA3 and TBX21 that are encountered under polarizing conditions. The proliferation of recently activated T cells and the maintenance of immunological memory in quiescent memory T cells are also dependent on various cytokine signaling pathways upstream of AP-1. We suggest that immunological memory is established by T cell receptor signaling, but maintained by cytokine signaling.

  11. T Cell Receptor and Cytokine Signaling Can Function at Different Stages to Establish and Maintain Transcriptional Memory and Enable T Helper Cell Differentiation.

    Science.gov (United States)

    Bevington, Sarah L; Cauchy, Pierre; Withers, David R; Lane, Peter J L; Cockerill, Peter N

    2017-01-01

    Experienced T cells exhibit immunological memory via a rapid recall response, responding to restimulation much faster than naïve T cells. The formation of immunological memory starts during an initial slow response, when naïve T cells become transformed to proliferating T blast cells, and inducible immune response genes are reprogrammed as active chromatin domains. We demonstrated that these active domains are supported by thousands of priming elements which cooperate with inducible transcriptional enhancers to enable efficient responses to stimuli. At the conclusion of this response, a small proportion of these cells return to the quiescent state as long-term memory T cells. We proposed that priming elements can be established in a hit-and-run process dependent on the inducible factor AP-1, but then maintained by the constitutive factors RUNX1 and ETS-1. This priming mechanism may also function to render genes receptive to additional differentiation-inducing factors such as GATA3 and TBX21 that are encountered under polarizing conditions. The proliferation of recently activated T cells and the maintenance of immunological memory in quiescent memory T cells are also dependent on various cytokine signaling pathways upstream of AP-1. We suggest that immunological memory is established by T cell receptor signaling, but maintained by cytokine signaling.

  12. Optic pathway degeneration in Japanese black cattle.

    Science.gov (United States)

    Chiba, Shiori; Funato, Shingo; Horiuchi, Noriyuki; Matsumoto, Kotaro; Inokuma, Hisashi; Furuoka, Hidefumi; Kobayashi, Yoshiyasu

    2015-02-01

    Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy.

  13. Fuel Pathway Integration Technical Team Roadmap

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-06-01

    The Fuel Pathway Integration Technical Team (FPITT) supports the U.S. DRIVE Partnership (the Partnership) in the identification and evaluation of implementation scenarios for fuel cell technology pathways, including hydrogen and fuel cell electric vehicles in the transportation sector, both during a transition period and in the long term.

  14. Opportunities for pharmaceutical care with critical pathways.

    Science.gov (United States)

    Koch, K E

    1995-01-01

    Critical pathways are multidisciplinary tools designed to improve patient care and efficiency. Almost every path requires some type of pharmacotherapeutic intervention, from selection of surgical prophylaxis to management of anticoagulation. Pharmacists should become involved with the critical pathway process because it offers an excellent opportunity to incorporate pharmaceutical care and to meet Joint Commission on Accreditation of Healthcare Organization compliance criteria.

  15. Modeling cancer progression via pathway dependencies.

    Directory of Open Access Journals (Sweden)

    Elena J Edelman

    2008-02-01

    Full Text Available Cancer is a heterogeneous disease often requiring a complexity of alterations to drive a normal cell to a malignancy and ultimately to a metastatic state. Certain genetic perturbations have been implicated for initiation and progression. However, to a great extent, underlying mechanisms often remain elusive. These genetic perturbations are most likely reflected by the altered expression of sets of genes or pathways, rather than individual genes, thus creating a need for models of deregulation of pathways to help provide an understanding of the mechanisms of tumorigenesis. We introduce an integrative hierarchical analysis of tumor progression that discovers which a priori defined pathways are relevant either throughout or in particular steps of progression. Pathway interaction networks are inferred for these relevant pathways over the steps in progression. This is followed by the refinement of the relevant pathways to those genes most differentially expressed in particular disease stages. The final analysis infers a gene interaction network for these refined pathways. We apply this approach to model progression in prostate cancer and melanoma, resulting in a deeper understanding of the mechanisms of tumorigenesis. Our analysis supports previous findings for the deregulation of several pathways involved in cell cycle control and proliferation in both cancer types. A novel finding of our analysis is a connection between ErbB4 and primary prostate cancer.

  16. Mining the Wnt pathway for cancer therapeutics.

    NARCIS (Netherlands)

    Barker, N.; Clevers, J.C.

    2006-01-01

    Aberrant activation of the Wnt pathway is implicated in driving the formation of various human cancers, particularly those of the digestive tract. Inhibition of aberrant Wnt pathway activity in cancer cell lines efficiently blocks their growth, highlighting the great potential of therapeutics design

  17. 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.

  18. 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

  19. Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival.

    Science.gov (United States)

    He, Jingquan; Zhang, Feng; Tay, Li Wei Rachel; Boroda, Salome; Nian, Weiqi; Levental, Kandice R; Levental, Ilya; Harris, Thurl E; Chang, Jeffrey T; Du, Guangwei

    2017-03-27

    Cancer cells reprogram their metabolism to increase the synthesis of macromolecules for rapid proliferation. Compared to fatty acids, much less is known about the synthesis of phospholipids, which is essential for membrane biogenesis in cancer cells. We found that LPIN1, which encodes lipin-1, a phosphatidic acid phosphatase (PAP) controlling the rate-limiting step in the phospholipid synthesis pathway, is highly up-regulated in basal-like triple-negative breast cancer (TNBC). Moreover, high LPIN1 expression correlates with the poor prognosis of these patients. Knockdown of LPIN1 increases apoptosis in basal-like TNBC cell lines, whereas it has minimal or less effect on normal human mammary gland epithelial cells (HMECs) and estrogen receptor-positive breast cancer cell lines. Fatty acid incorporation and lipidomics analyses showed that LPIN1 knockdown blocks phospholipid synthesis and changes membrane lipid compositions that ultimately induce the activation of 1 of the 3 branches of unfolded protein responses, the inositol-requiring enzyme-1α pathway. We also show for the first time, to our knowledge, that lipin-1 knockdown significantly inhibits tumor growth in vivo using an orthotopic xenograft breast mouse model. Our results suggest that lipin-1 is a potential target for cancer therapy.-He, J., Zhang, F., Tay, L. W. R., Boroda, S., Nian, W., Levental, K. R., Levental, I., Harris, T. E., Chang, J. T., Du, G. Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival.

  20. Assistance in Maintaining a Positive Self-image in People with Dementia

    Directory of Open Access Journals (Sweden)

    Franciscus Robert Hogeeveen

    2015-08-01

    Full Text Available Dementia is a disrupting disease, most of all for those suffering from it. In essence, the disease increasingly dismantles the patient as an autonomously acting and thinking person. People with dementia continue being aware of their deterioration to varying degrees during the course of their disease. Feelings of loss of control, uncertainty, fear and grief are experienced, permanently threatening their well-being. In these difficult circumstances, maintaining a positive self-image can contribute to an optimal quality of life. Up until now little research has been done on the effectiveness of interventions that could contribute to maintaining a positive self-image. The authors will systematically discuss a number of possible interventions by means of real-life case histories. They will make recommendations for further research.