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Sample records for regulatory axis treatment

  1. The Proline Regulatory Axis and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Phang, James Ming; Liu, Wei; Hancock, Chad; Christian, Kyle J., E-mail: phangj@mail.nih.gov [Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD (United States)

    2012-06-21

    Studies in metabolism and cancer have characterized changes in core pathways involving glucose and glutamine, emphasizing the provision of substrates for building cell mass. But recent findings suggest that pathways previously considered peripheral may play a critical role providing mechanisms for cell regulation. Several of these mechanisms involve the metabolism of non-essential amino acids, for example, the channeling of glycolytic intermediates into the serine pathway for one-carbon transfers. Historically, we proposed that the proline biosynthetic pathway participated in a metabolic interlock with glucose metabolism. The discovery that proline degradation is activated by p53 directed our attention to the initiation of apoptosis by proline oxidase/dehydrogenase. Now, however, we find that the biosynthetic mechanisms and the metabolic interlock may depend on the pathway from glutamine to proline, and it is markedly activated by the oncogene MYC. These findings add a new dimension to the proline regulatory axis in cancer and present attractive potential targets for cancer treatment.

  2. SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis.

    Science.gov (United States)

    Muhar, Matthias; Ebert, Anja; Neumann, Tobias; Umkehrer, Christian; Jude, Julian; Wieshofer, Corinna; Rescheneder, Philipp; Lipp, Jesse J; Herzog, Veronika A; Reichholf, Brian; Cisneros, David A; Hoffmann, Thomas; Schlapansky, Moritz F; Bhat, Pooja; von Haeseler, Arndt; Köcher, Thomas; Obenauf, Anna C; Popow, Johannes; Ameres, Stefan L; Zuber, Johannes

    2018-05-18

    Defining direct targets of transcription factors and regulatory pathways is key to understanding their roles in physiology and disease. We combined SLAM-seq [thiol(SH)-linked alkylation for the metabolic sequencing of RNA], a method for direct quantification of newly synthesized messenger RNAs (mRNAs), with pharmacological and chemical-genetic perturbation in order to define regulatory functions of two transcriptional hubs in cancer, BRD4 and MYC, and to interrogate direct responses to BET bromodomain inhibitors (BETis). We found that BRD4 acts as general coactivator of RNA polymerase II-dependent transcription, which is broadly repressed upon high-dose BETi treatment. At doses triggering selective effects in leukemia, BETis deregulate a small set of hypersensitive targets including MYC. In contrast to BRD4, MYC primarily acts as a selective transcriptional activator controlling metabolic processes such as ribosome biogenesis and de novo purine synthesis. Our study establishes a simple and scalable strategy to identify direct transcriptional targets of any gene or pathway. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  3. A CREB-MPP7-AMOT Regulatory Axis Controls Muscle Stem Cell Expansion and Self-Renewal Competence

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    Lydia Li

    2017-10-01

    Full Text Available Summary: Skeletal muscle regeneration requires resident muscle stem cells, termed satellite cells (SCs. SCs are largely quiescent during homeostasis yet become activated upon injury to supply myonuclei and self-renewed SCs. Molecular mechanisms underlying the competence of SCs to proliferate and self-renew in response to injury remain unclear. Here, we show that CREB activity establishes proliferative potential during SC quiescence. SCs with inhibited CREB activity remain quiescent and positioned in their niche, but upon injury, they cannot enter or maintain a proliferative state for expansion and self-renewal. We demonstrate mechanistically that Mpp7 is a CREB target and its functional mediator. MPP7 loss affects the level and sub-cellular localization of AMOT and YAP1 in quiescent SCs. Furthermore, MPP7 and AMOT are required for YAP1 nuclear accumulation, and the three are individually required for a proliferative state in myoblasts. We propose that the CREB-MPP7-AMOT-YAP1 axis establishes the competence of quiescent SCs to expand and self-renew, thereby preserving stem cell function. : Satellite cells are quiescent muscle stem cells that have the ability to regenerate muscles after injury. Li and Fan reveal an MPP7-AMOT-YAP1 regulatory axis that acts downstream of CREB to instill satellite cell competence. They also show how this regulatory axis prepares satellite cells for robust muscle regeneration after injury.

  4. HPA-axis stress reactivity in youth depression: evidence of impaired regulatory processes in depressed boys.

    Science.gov (United States)

    Lopez-Duran, Nestor L; McGinnis, Ellen; Kuhlman, Kate; Geiss, Elisa; Vargas, Ivan; Mayer, Stefanie

    2015-01-01

    Given the link between youth depression and stress exposure, efforts to identify related biomarkers have involved examinations of stress regulation systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Despite these vast efforts, the underlying mechanisms at play, as well as factors that may explain heterogeneity of past findings, are not well understood. In this study, we simultaneously examined separate components of the HPA-axis response (e.g. activation intensity, peak levels, recovery) to the Socially Evaluated Cold-Pressor Test in a targeted sample of 115 youth (age 9-16), recruited to overrepresent youth with elevated symptoms of depression. Among youth who displayed a cortisol response to the task, depression symptoms were associated with higher peak responses but not greater rate of activation or recovery in boys only. Among those who did not respond to the task, depression symptoms were associated with greater cortisol levels throughout the visit in boys and girls. Results suggest that depression symptoms are associated with a more prolonged activation of the axis and impaired recovery to psychosocial stressors primarily in boys. We discussed two potential mechanistic explanations of the link between depression symptoms and the duration of activation: (1) inhibitory shift (i.e. point at which the ratio of inhibitory and excitatory input into the axis shifts from greater excitatory to greater inhibitory input) or (2) inhibitory threshold (i.e. level of cortisol exposure required to activate the axis' feedback inhibition system).

  5. Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPARγ activation in high fructose diet-induced metabolic syndrome.

    Science.gov (United States)

    Cannizzaro, Luca; Rossoni, Giuseppe; Savi, Federica; Altomare, Alessandra; Marinello, Cristina; Saethang, Thammakorn; Carini, Marina; Payne, D Michael; Pisitkun, Trairak; Aldini, Giancarlo; Leelahavanichkul, Asada

    2017-01-01

    The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ). Rats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half. Rats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented. Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by

  6. Regulatory Support of Treatment of Savannah River Site Purex Waste

    International Nuclear Information System (INIS)

    Reid, L.T.

    2009-01-01

    This paper describes the support given by federal and state regulatory agencies to Savannah River Site (SRS) during the treatment of an organic liquid mixed waste from the Plutonium Extraction (Purex) process. The support from these agencies allowed (SRS) to overcome several technical and regulatory barriers and treat the Purex waste such that it met LDR treatment standards. (authors)

  7. The PDL1-PD1 Axis Converts Human Th1 Cells Into Regulatory T Cells

    Science.gov (United States)

    Amarnath, Shoba; Mangus, Courtney W.; Wang, James C.M.; Wei, Fang; He, Alice; Kapoor, Veena; Foley, Jason E.; Massey, Paul R.; Felizardo, Tania C.; Riley, James L.; Levine, Bruce L.; June, Carl H.; Medin, Jeffrey A.; Fowler, Daniel H.

    2011-01-01

    Immune surveillance by T helper type 1 (Th1) cells is critical for the host response to tumors and infection, but also contributes to autoimmunity and graft-versus-host disease (GvHD) after transplantation. The inhibitory molecule programmed death ligand-1 (PDL1) has been shown to anergize human Th1 cells, but other mechanisms of PDL1-mediated Th1 inhibition such as the conversion of Th1 cells to a regulatory phenotype have not been well characterized. We hypothesized that PDL1 may cause Th1 cells to manifest differentiation plasticity. Conventional T cells or irradiated K562 myeloid tumor cells overexpressing PDL1 converted TBET+ Th1 cells into FOXP3+ regulatory T cells (TREGS) in vivo, thereby preventing human-into-mouse xenogeneic GvHD (xGvHD). Either blocking PD1 expression on Th1 cells by siRNA targeting or abrogation of PD1 signaling by SHP1/2 pharmacologic inhibition stabilized Th1 cell differentiation during PDL1 challenge and restored the capacity of Th1 cells to mediate lethal xGVHD. PD1 signaling therefore induces human Th1 cells to manifest in vivo plasticity, resulting in a TREG phenotype that severely impairs cell-mediated immunity. Converting human Th1 cells to a regulatory phenotype with PD1 signaling provides a potential way to block GvHD after transplantation. Moreover, because this conversion can be prevented by blocking PD1 expression or pharmacologically inhibiting SHP1/2, this pathway provides a new therapeutic direction for enhancing T cell immunity to cancer and infection. PMID:22133721

  8. HPA axis response to psychological stress and treatment retention in residential substance abuse treatment: a prospective study.

    Science.gov (United States)

    Daughters, Stacey B; Richards, Jessica M; Gorka, Stephanie M; Sinha, Rajita

    2009-12-01

    Substance abuse treatment programs are often characterized by high rates of premature treatment dropout, which increases the likelihood of relapse to drug use. Negative reinforcement models of addiction emphasize an individual's inability to tolerate stress as a key factor for understanding poor substance use treatment outcomes, and evidence indicates that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis contributes to an individual's inability to respond adaptively to stress. The aim of the current study was to examine whether HPA axis response to stress is predictive of treatment retention among a sample of drug users in residential substance abuse treatment. Prospective study assessing treatment retention among 102 individuals enrolled in residential substance abuse treatment. Participants completed two computerized stress tasks, and HPA axis response to stress was measured via salivary cortisol at five time points from baseline (pre-stress) to 30 min post-stress exposure. The main outcome measures were treatment dropout (categorical) and total number of days in treatment (continuous). A significantly higher salivary cortisol response to stress was observed in treatment dropouts compared to treatment completers. Further, Cox proportional hazards survival analyses indicated that a higher peak cortisol response to stress was associated with a shorter number of days to treatment dropout. Results indicate that a higher salivary cortisol level in response to stress is associated with an inability to remain in substance abuse treatment. These findings are the first to document a biological marker of stress as a predictor of substance abuse treatment dropout, and support the development and implementation of treatments targeting this vulnerability.

  9. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2012-01-01

    Background Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress

  10. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Gordijn, Maartje S.; Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2015-01-01

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

  11. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2017-01-01

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

  12. Incorporating regulatory considerations into waste treatment technology development

    International Nuclear Information System (INIS)

    Siegel, M.R.; Powell, J.A.; Williams, T.A.; Kuusinen, T.L.; Lesperance, A.M.

    1991-02-01

    It is generally recognized that the development of new and innovative waste treatment technologies can significantly benefit the US Department of Energy's (DOE) environmental restoration and waste management program. DOE has established a research, development, demonstration, testing, and evaluation (RDDT ampersand E) program, managed by its Office of Technology Development, to encourage and direct the development of new waste treatment and management technologies. The treatment, storage, and disposal of hazardous and radioactive waste is heavily regulated both at the federal and state levels. In order to achieve the goals of applying the best new technologies in the fastest and most cost-effective manner possible, it is essential that regulatory factors be considered early and often during the development process. This paper presents a number of regulatory issues that are relevant to any program intended to encourage the development of new waste treatment and management technologies. It will also address how the use of these basic regulatory considerations can help ensure that technologies that are developed are acceptable to regulators and can therefore be deployed in the field. 2 refs

  13. Effects of natalizumab treatment on Foxp3+ T regulatory cells.

    Directory of Open Access Journals (Sweden)

    Max-Philipp Stenner

    Full Text Available BACKGROUND: Natalizumab, a monoclonal humanized antibody targeting the alpha-4 chain of very late activation antigen 4 (VLA-4 exerts impressive therapeutic effects in patients with relapsing-remitting multiple sclerosis. Our objective was to study impacts of Natalizumab therapy on Foxp3+ T regulatory cells (Tregs in multiple sclerosis (MS patients. METHODOLOGY: A combined approach of in vitro and ex vivo experiments using T cells isolated from the peripheral blood of healthy donors and Natalizumab treated MS patients was chosen. We determined binding of Natalizumab and its effects on the frequency, transmigratory behaviour and suppressive function of Tregs. PRINCIPAL FINDINGS: Binding of Natalizumab and expression of CD49d (alpha-4 chain of VLA-4 differed between non-regulatory and regulatory cells. Albeit Foxp3+ Tregs had lower levels of CD49d, Natalizumab blocked the transmigration of Foxp3+ Tregs similar to non-regulatory T cells. The frequency of peripheral blood Tregs was unaffected by Natalizumab treatment. Natalizumab does not alter the suppressive capacity of CD4+CD25(highCD127(lowFoxp3+ Tregs under in vitro conditions. Furthermore, the impaired function of Tregs in MS patients is not restored by Natalizumab treatment. CONCLUSIONS: We provide a first detailed analysis of Natalizumab effects on the regulatory T cell population. Our prospective study shows that Foxp3+ Tregs express lower levels of VLA-4 and bind less Natalizumab. We further the understanding of the mechanisms of action of Natalizumab by demonstrating that unlike other immunomodulatory drugs the beneficial therapeutic effects of the monoclonal antibody are largely independent of alterations in Treg frequency or function.

  14. Effects of natalizumab treatment on Foxp3+ T regulatory cells.

    Science.gov (United States)

    Stenner, Max-Philipp; Waschbisch, Anne; Buck, Dorothea; Doerck, Sebastian; Einsele, Hermann; Toyka, Klaus V; Wiendl, Heinz

    2008-10-06

    Natalizumab, a monoclonal humanized antibody targeting the alpha-4 chain of very late activation antigen 4 (VLA-4) exerts impressive therapeutic effects in patients with relapsing-remitting multiple sclerosis. Our objective was to study impacts of Natalizumab therapy on Foxp3+ T regulatory cells (Tregs) in multiple sclerosis (MS) patients. A combined approach of in vitro and ex vivo experiments using T cells isolated from the peripheral blood of healthy donors and Natalizumab treated MS patients was chosen. We determined binding of Natalizumab and its effects on the frequency, transmigratory behaviour and suppressive function of Tregs. Binding of Natalizumab and expression of CD49d (alpha-4 chain of VLA-4) differed between non-regulatory and regulatory cells. Albeit Foxp3+ Tregs had lower levels of CD49d, Natalizumab blocked the transmigration of Foxp3+ Tregs similar to non-regulatory T cells. The frequency of peripheral blood Tregs was unaffected by Natalizumab treatment. Natalizumab does not alter the suppressive capacity of CD4+CD25(high)CD127(low)Foxp3+ Tregs under in vitro conditions. Furthermore, the impaired function of Tregs in MS patients is not restored by Natalizumab treatment. We provide a first detailed analysis of Natalizumab effects on the regulatory T cell population. Our prospective study shows that Foxp3+ Tregs express lower levels of VLA-4 and bind less Natalizumab. We further the understanding of the mechanisms of action of Natalizumab by demonstrating that unlike other immunomodulatory drugs the beneficial therapeutic effects of the monoclonal antibody are largely independent of alterations in Treg frequency or function.

  15. The IL-33-ST2-MyD88 axis promotes regulatory T cell proliferation in the murine liver.

    Science.gov (United States)

    Xu, Lei; Li, Wei; Wang, Xiaofan; Zhang, Lina; Qi, Qianqian; Dong, Liyang; Wei, Chuan; Pu, Yanan; Li, Yalin; Zhu, Jifeng; Zhou, Sha; Liu, Feng; Chen, Xiaojun; Su, Chuan

    2018-05-05

    Hepatic Foxp3 + regulatory T (Treg) cells are crucial for maintaining local immune homeostasis in the liver. However, the environmental cues required for hepatic Treg cell homeostasis are unclear. In this study, we showed that the IL-33 receptor ST2 was preferentially expressed on Treg cells in the mouse liver, but it was more lowly expressed in the spleen, mesenteric lymph nodes, and blood. More importantly, we found that IL-33 promoted the proliferation of hepatic Treg cells through myeloid differentiation factor MyD88 signaling concomitant with increased CDK4 and cyclin D1 expression. These results suggested that IL-33 is a potential tissue-specific factor controlling Treg cell homeostasis via increased Treg proliferation in the liver. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Transcriptome analysis revealed the possible regulatory pathways initiating female geese broodiness within the hypothalamic-pituitary-gonadal axis

    Science.gov (United States)

    Wang, Jiwen; Li, Liang; Han, Chunchun; He, Hua; Xu, Hengyong

    2018-01-01

    Geese have the strongest tendency toward broodiness among all poultry. The mechanisms initiating broodiness within the goose hypothalamic-pituitary-gonadal axis (HPGA) are still unclear. Here, we reported the transcriptome differences between laying and initial nesting within the HPGA tissues of geese. We constructed a unigene database based on HPGA tissues and identified 128,148 unigenes, 100% of which have been annotated. By using Digital Gene Expression (DGE) sequencing, we screened 19, 110, 289, and 211 differentially expressed genes (DEGs) in the hypothalamus, pituitary gland, stroma ovarii, and follicles, respectively, between laying and nesting geese. Expression changes of hypocretin (HCRT) and pro-opiomelanocortin (POMC) in the hypothalamus of nesting geese may cause appetite reduction, which is possibly the first step and a prerequisite to initiate broodiness. In addition to prolactin (PRL), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), genes including oxytocin-neurophysin (OXT), chordin-like protein 1 (CHRDL1) and growth hormone (GH), expressed in the pituitary gland, are new candidate molecules that may be involved in broodiness in geese. Heme oxygenase 1 (HMOX1) in the pituitary gland, the proto-oncogene c-Fos (FOS), heat shock protein 90-alpha (HSP90AA), and cyclin-dependent kinase 1 (CDK1) in the ovary that may consolidate and transduce signals regulating the HPGA during broodiness in geese. PMID:29408859

  17. Transcriptome analysis revealed the possible regulatory pathways initiating female geese broodiness within the hypothalamic-pituitary-gonadal axis.

    Directory of Open Access Journals (Sweden)

    Hehe Liu

    Full Text Available Geese have the strongest tendency toward broodiness among all poultry. The mechanisms initiating broodiness within the goose hypothalamic-pituitary-gonadal axis (HPGA are still unclear. Here, we reported the transcriptome differences between laying and initial nesting within the HPGA tissues of geese. We constructed a unigene database based on HPGA tissues and identified 128,148 unigenes, 100% of which have been annotated. By using Digital Gene Expression (DGE sequencing, we screened 19, 110, 289, and 211 differentially expressed genes (DEGs in the hypothalamus, pituitary gland, stroma ovarii, and follicles, respectively, between laying and nesting geese. Expression changes of hypocretin (HCRT and pro-opiomelanocortin (POMC in the hypothalamus of nesting geese may cause appetite reduction, which is possibly the first step and a prerequisite to initiate broodiness. In addition to prolactin (PRL, follicle-stimulating hormone (FSH and luteinizing hormone (LH, genes including oxytocin-neurophysin (OXT, chordin-like protein 1 (CHRDL1 and growth hormone (GH, expressed in the pituitary gland, are new candidate molecules that may be involved in broodiness in geese. Heme oxygenase 1 (HMOX1 in the pituitary gland, the proto-oncogene c-Fos (FOS, heat shock protein 90-alpha (HSP90AA, and cyclin-dependent kinase 1 (CDK1 in the ovary that may consolidate and transduce signals regulating the HPGA during broodiness in geese.

  18. The Regulatory Factor ZFHX3 Modifies Circadian Function in SCN via an AT Motif-Driven Axis

    Science.gov (United States)

    Parsons, Michael J.; Brancaccio, Marco; Sethi, Siddharth; Maywood, Elizabeth S.; Satija, Rahul; Edwards, Jessica K.; Jagannath, Aarti; Couch, Yvonne; Finelli, Mattéa J.; Smyllie, Nicola J.; Esapa, Christopher; Butler, Rachel; Barnard, Alun R.; Chesham, Johanna E.; Saito, Shoko; Joynson, Greg; Wells, Sara; Foster, Russell G.; Oliver, Peter L.; Simon, Michelle M.; Mallon, Ann-Marie; Hastings, Michael H.; Nolan, Patrick M.

    2015-01-01

    Summary We identified a dominant missense mutation in the SCN transcription factor Zfhx3, termed short circuit (Zfhx3Sci), which accelerates circadian locomotor rhythms in mice. ZFHX3 regulates transcription via direct interaction with predicted AT motifs in target genes. The mutant protein has a decreased ability to activate consensus AT motifs in vitro. Using RNA sequencing, we found minimal effects on core clock genes in Zfhx3Sci/+ SCN, whereas the expression of neuropeptides critical for SCN intercellular signaling was significantly disturbed. Moreover, mutant ZFHX3 had a decreased ability to activate AT motifs in the promoters of these neuropeptide genes. Lentiviral transduction of SCN slices showed that the ZFHX3-mediated activation of AT motifs is circadian, with decreased amplitude and robustness of these oscillations in Zfhx3Sci/+ SCN slices. In conclusion, by cloning Zfhx3Sci, we have uncovered a circadian transcriptional axis that determines the period and robustness of behavioral and SCN molecular rhythms. PMID:26232227

  19. Adrenaline promotes epithelial-to-mesenchymal transition via HuR-TGFβ regulatory axis in pancreatic cancer cells and the implication in cancer prognosis.

    Science.gov (United States)

    Pu, Jun; Zhang, Xiaorui; Luo, Huiwen; Xu, Lijuan; Lu, Xiaozhao; Lu, Jianguo

    2017-11-25

    Psychological stress has recently been described as a risk factor in the development of pancreatic cancer. Here, we reported that increased neurotransmitter adrenaline was associated with the poor survival in pancreatic cancer patients. Moreover, in the cell model study, we found adrenaline promoted pancreatic cell PANC-1 migration in a dose dependent manner. Block of the β2-adrenoreceptor with ICI118,551, significantly reduced cell migration. Further study found that adrenaline induced a cytoplasmic translocation of RNA binding protein HuR, which in turn activated TGFβ, as shown by the SBE luciferase assay and phosphorylation of Smad2/3. Either HuR knockdown or TGFβ inhibition reduced cell migration induced by adrenaline. Taken together, our study here revealed that adrenaline-HuR-TGFβ regulatory axis at least partially contributes to the psychological stress induced metastasis in PANC-1 cells, shedding light on therapeutic targeting psychological stress in improving the prognosis of pancreatic cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The neuro-immune axis: Prospect for novel treatments for mental disorders

    NARCIS (Netherlands)

    Kraneveld, Aletta D.; de Theije, Caroline G.M.; van Heesch, Floor; Borre, Yuliya; de Kivit, Sander; Olivier, Berend; Korte, Mechiel; Garssen, Johan

    2014-01-01

    Disturbed bidirectional pathways between the (central) nervous system and immune system have been implicated in various mental disorders, including depressive and neurodevelopmental disorders. In this minireview, the role of the neuro-immune axis and its targetability in relation to major depression

  1. Transcriptional regulatory dynamics of the hypothalamic-pituitary-gonadal axis and its peripheral pathways as impacted by the 3-beta HSD inhibitor Trilostane in zebrafish (Danio rerio)

    Science.gov (United States)

    To identify transcription factors (TFs), members of hypothalamic-pituitary- gonadal axis (HPG-axis), TF networks and signaling pathways underlying generalized effects of 3-beta hydroxysteroid dehydrogenase (HSD3B) inhibition, reproductively mature zebrafish (Danio rerio) were exp...

  2. The treatment of uncertainties in risk for regulatory decision making

    International Nuclear Information System (INIS)

    Baybutt, P.; Cox, D.C.; Denning, R.S.; Kurth, R.E.; Fraley, D.W.; Heaberlin, S.W.

    1982-01-01

    This paper describes research conducted in an ongoing program at Battelle to develop and adapt decision analysis methods for regulatory decision making. A general approach to risk-based decision making is discussed. The nature of uncertainties in risk assessment is described and methods for their inclusion in decision making are proposed. The use of decision analysis methods in regulatory decision making and the consideration of uncertainties is illustrated in a realistic case study

  3. An Alternative Technique in the Treatment of Celiac Axis Stenosis Diagnosed During Pancreaticoduodenectomy

    Directory of Open Access Journals (Sweden)

    Marcel C. C. Machado

    1998-01-01

    Full Text Available Celiac compression is usually a benign condition, but when surgery necessitates division of collaterals from the superior mesenteric artery, it may cause life-threatening celiac organ ischemia. Celiac axis obstruction is found in 12.5% to 49.7% of patients during abdominal angiography. In such patients, the arterial blood supply to the stomach, spleen, and liver is sustained through extraordinarily welldeveloped pathways in the pancreas.

  4. 78 FR 56719 - Challenging Regulatory and Reimbursement Paradigms for Medical Devices in the Treatment of...

    Science.gov (United States)

    2013-09-13

    ...] Challenging Regulatory and Reimbursement Paradigms for Medical Devices in the Treatment of Metabolic Diseases... announcing a public workshop entitled ``Changing Regulatory and Reimbursement Paradigms for Medical Devices... registration information on the AGA Web site. If you need special accommodations due to a disability, please...

  5. 78 FR 69694 - Changing Regulatory and Reimbursement Paradigms for Medical Devices in the Treatment of Obesity...

    Science.gov (United States)

    2013-11-20

    ...] Changing Regulatory and Reimbursement Paradigms for Medical Devices in the Treatment of Obesity and... Administration (FDA) is announcing a public workshop entitled ``Changing Regulatory and Reimbursement Paradigms... information on the AGA Web site. If you need special accommodations due to a disability, please contact...

  6. TWEAK/Fn14 axis: a promising target for the treatment of cardiovascular diseases.

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    Luis Miguel Blanco-Colio

    2014-01-01

    Full Text Available Cardiovascular diseases (CVD are the first cause of mortality in Western countries. CVD include several pathologies such as coronary heart disease, stroke or cerebrovascular accident, congestive heart failure, peripheral arterial disease and aortic aneurysm, among others. Interaction between members of the tumor necrosis factor (TNF superfamily and their receptors elicits several biological actions that could participate in CVD. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK and its functional receptor, fibroblast growth factor-inducible molecule 14 (Fn14, are two proteins belonging to the TNF superfamily that activate NF-κB by both canonical and non-canonical pathways and regulate several cell functions such as proliferation, migration, differentiation, cell death, inflammation, and angiogenesis. TWEAK/Fn14 axis plays a beneficial role in tissue repair after acute injury. However, persistent TWEAK/Fn14 activation mediated by blocking experiments or overexpression experiments in animal models has shown an important role of this axis in the pathological remodeling underlying CVD. In this review, we summarize the role of TWEAK/Fn14 pathway in the development of CVD, focusing on atherosclerosis and stroke and the molecular mechanisms by which TWEAK/Fn14 interaction participates in these pathologies. We also review the role of the soluble form of TWEAK as a biomarker for the diagnosis and prognosis of CVD. Finally, we highlight the results obtained with other members of the TNF superfamily that also activate canonical and non-canonical NF-κB pathway.

  7. Low-Intensity Pulsed Ultrasound and Halo Immobilization Is an Effective Treatment for Nonunion Following Traumatic Spondylolisthesis of the Axis.

    Science.gov (United States)

    Oda, Kohtaroh; Ohba, Tetsuro; Ebata, Shigeto; Haro, Hirotaka

    2017-10-01

    This case report describes a unique case involving traumatic spondylolisthesis of the axis that resulted in nonunion, angulation, and displacement after conservative treatment with a cervical collar, but which was successfully achieved union with halo immobilization and low-intensity pulsed ultrasound (LIPUS). Halo immobilization of a traumatic spondylolisthesis in a 20-year-old patient, that previously failed to improve after wearing a cervical collar for 3 months, was immediately followed by treatment with a LIPUS device (SAFHS 4000J; Teijin Pharma, Tokyo, Japan) 20 minutes once daily to the right and left fracture sites which were located using fluoroscopic guidance. Radiographs and computed tomography showed conclusive evidence of bone union after 10 weeks of treatment with halo immobilization. No adverse events were observed. To the best of our knowledge, this is the first report describing that the combination of halo immobilization and LIPUS therapy might be a safe, effective, and feasible method by which to treat cervical spine fractures.

  8. Treatment of differing professional opinions in the regulatory review process

    International Nuclear Information System (INIS)

    Shapar, H.K.

    1978-01-01

    The Nuclear Regulatory Commission is an independent body whose purpose is to assure that civilian nuclear activities are consistent with the public health and safety and environmental protection. To this effect, Congress has vested it with the necessary control powers. The question here is how to reconcile diverging opinions expressed within NRC by executives and technicians during the enquiry pocedure for licensing of nuclear installations. The diversity of professional viewpoints should be viewed as a positive factor strengthening the regulatory process and should therefore be maintained. However, decisions must be made; therefore some viewpoints will not prevail but that should not be construed as a signal that the internal discussion process is condemned. NRC staff are entitled to express their views and not subjected to professional and administrative sanctions for doing so. (NEA) [fr

  9. 1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis.

    Science.gov (United States)

    Wei, Chunyan; Mei, Jie; Tang, Lingli; Liu, Yukai; Li, Dajin; Li, Mingqing; Zhu, Xiaoyong

    2016-12-01

    Foxp3 + regulatory T (T reg ) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal T reg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal T reg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment. After adding 1-methyl-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), to the co-culture system, we found that the differentiation of T reg cells, mainly IL-10 + T reg cells, decreased. Therefore, 1-MT-pretreated ESCs-educated T reg cells performed impaired suppressive function. Moreover, estrogen promoted the differentiation of T reg cells by elevating IDO1 expression in the ectopic lesion. Subsequently, we examined mannose receptor C, type 2 (MRC2), which is an up-stream molecule of IL-10, by bioinformatics analysis and real-time PCR validation. MRC2 expression in ectopic ESCs was notably lower than that in normal ESCs, which further negatively regulated the expression of IDO1 and Ki-67 in ESCs. Furthermore, MRC2 is required for T reg differentiation in the ectopic lesion, especially that for CD4 high T reg . Therefore, MRC2-silenced ESCs-educated T reg manifested a stronger suppressive function in vitro. Consistently, the percentage of T reg increased when MRC2-shRNA was administered in the peritoneal cavity of endometriosis-disease mice model. Besides, 1-MT improved the condition of endometriosis, in terms of reducing the number and weight of total ectopic lesions in vivo. These results indicate that the estrogen-IDO1-MRC2 axis participates in the differentiation and function of T reg and is involved in the development of

  10. Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats.

    Science.gov (United States)

    Oliveira, Ariclecio Cunha de; Andreotti, Sandra; Sertie, Rogério António Laurato; Campana, Amanda Baron; de Proença, André Ricardo Gomes; Vasconcelos, Renata Prado; Oliveira, Keciany Alves de; Coelho-de-Souza, Andrelina Noronha; Donato-Junior, José; Lima, Fábio Bessa

    2018-04-15

    Melatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis. At the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0.2 mg/kg body weight) added to drinking water at night or associated with insulin (NHP, 1.5 U/100 g/day) or only insulin. Animals were then euthanized, and the subcutaneous (SC), epididymal (EP), and retroperitoneal (RP) fat pads were excised, weighed and processed for adipocyte isolation for morphometric analysis as well as for measuring glucose uptake, oxidation, and incorporation of glucose into lipids. Hypothalamus was collected for gene expression and blood samples were collected for biochemical assays. The treatment with melatonin plus insulin (MI) was capable of maintaining glycemic control. In epididymal (EP) and subcutaneous (SC) adipocytes, the melatonin plus insulin (MI) treatment group recovered the insulin responsiveness. In the hypothalamus, melatonin treatment alone promoted a significant reduction in kisspeptin-1, neurokinin B and androgen receptor mRNA levels, in relation to control group. Combined treatment with melatonin and insulin promoted a better glycemic control, improving insulin sensitivity in white adipose tissue (WAT). Indeed, melatonin treatment reduced hypothalamic genes related to reproductive function. Copyright © 2017. Published by Elsevier Inc.

  11. The regulatory treatment of liquidity risk in South Africa

    Directory of Open Access Journals (Sweden)

    Johann Jacobs

    2012-08-01

    Full Text Available The Basel accord describes the regulatory capital requirements for credit, market and operational risk. The accord aims to provide guidelines to level the playing field for all internationally active banks and to protect consumers against these risks. Despite the growing significance to bank solvency of liquidity risk, it is omitted from the new accord2. Banks are not required to measure and manage this risk yet they are often considerably exposed to the threat of severely diminished liquidity. This omission from the accord could have dire consequences for banks and the economy in which they operate: liquidity crises can occur without warning and spread quickly to other parts of the financial system. This article critically explores current practices in South Africa and proposes guidelines for effective liquidity risk regulation.

  12. Verification of Treatment Planning System (TPS) on Beam Axis of Co-60 Teletherapy

    International Nuclear Information System (INIS)

    Nunung-Nuraeni; Budhy-Kurniawan; Purwanto; Sugiyantari; Heru-Prasetio; Nasukha

    2001-01-01

    Cancer diseases up to now can be able to be treated by using surgery, chemotherapy and radiotherapy. The need of high level precision and accuracy on radiation dose are very important task. One of task is verification of Treatment Planning System (Tps) to the treatment of patients. The research has been done to verify Tps on beam exis of teletherapy Co-60. Result found that the different between Tps and measurements are about -2.682 % to 1.918% for simple geometry and homogeneous material, 5.278 % to 4.990 % for complex geometry, and -3.202 % to -2.090 % for more complex geometry. (author)

  13. Recovery of hypothalamo–pituitary–adrenal axis suppression during treatment with inhaled corticosteroids for childhood asthma

    Directory of Open Access Journals (Sweden)

    Gangadharan A

    2017-12-01

    in three (6%. Baseline tests results were normal in 42 patients, of whom six patients (14% were retested. Results remained normal in three (50%, were suboptimal in two (33%, and abnormal in one (17%. Basal and peak cortisol levels increased by >15% in 33/73 (45% and 42/73 (57% patients, respectively, and decreased by >15% in 14/73 (19% and 7/73 (10%, respectively. There was no significant change in height or BMI SDS.Conclusion: Recovery of adrenal function is common and occurs during continued ICS and cortisol replacement therapy. Keywords: HPA axis recovery, adrenal suppression, childhood asthma, inhaled steroids (ICS, LDSST

  14. The Hepatocyte Growth Factor (HGF/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

    Directory of Open Access Journals (Sweden)

    Marjorie Boissinot

    2014-08-01

    Full Text Available Met is the receptor of hepatocyte growth factor (HGF, a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML, and myeloproliferative neoplasms (MPNs. The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs.

  15. The Hepatocyte Growth Factor (HGF)/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

    Energy Technology Data Exchange (ETDEWEB)

    Boissinot, Marjorie [Translational Neuro-Oncology Group, Leeds Institute of Cancer and Pathology, University of Leeds, Level 5 Wellcome Trust Brenner Building, St James’s Hospital, Leeds LS9 7TF (United Kingdom); Vilaine, Mathias [Institute of Research on Cancer and Aging (IRCAN), CNRS-Inserm-UNS UMR 7284, U 1081, Centre A. Lacassagne, 33 Avenue Valombrose, Nice 06189 (France); Hermouet, Sylvie, E-mail: sylvie.hermouet@univ-nantes.fr [Centre Hospitalier Universitaire (CHU), Place Alexis Ricordeau, Nantes 44093 (France); Inserm UMR892, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 8 quai Moncousu, Nantes cedex 44007 (France)

    2014-08-12

    Met is the receptor of hepatocyte growth factor (HGF), a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML), and myeloproliferative neoplasms (MPNs). The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs)

  16. The insulin-like growth axis in patients with autoimmune thyrotoxicosis: effect of antithyroid drug treatment.

    Science.gov (United States)

    Zimmermann-Belsing, T; Juul, A; Juul Holst, J; Feldt-Rasmussen, U

    2004-06-01

    Hyperthyroidism is associated with altered growth hormone (GH) secretion. Many patients with thyroid dysfunction experience several poorly described complications such as symptoms and signs also seen in patients with growth hormone deficiency (GHD). We have therefore prospectively evaluated a possible relationship between the thyroid function, body composition, leptin levels and insulin-like growth factor (IGF) related peptides in patients with Graves' disease. DESIGN, PATIENTS, AND MEASUREMENTS: In a prospective group of 24 fasting female patients with Graves' disease (mean age (CI 95%): 40 years (33-47)), we measured serum thyroxine, triiodothyronine, thyrotropine (TSH), TSH receptor antibodies, anti-thyroid peroxidase, leptin, body composition, body mass index (BMI) and IGF-related peptides at diagnosis and after 12 months of treatment with thiamazol (ATD). In thyrotoxic patients IGF-I plus IGF-II correlated positively with IGFBP-3 at baseline (r = 0.90, p secretion during treatment of autoimmune thyroid disease influence IGF-related peptides leaving the patient in a state somewhat similar to partial GHD, but the mechanism behind these alterations remains unclear.

  17. Homeostatic Control of the Thyroid Pituitary Axis: Perspectives for Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    Rudolf eHoermann

    2015-11-01

    Full Text Available The long-held concept of a proportional negative feedback control between the thyroid and pituitary gland requires reconsideration in the light of more recent studies. Homeostatic equilibria depend on dynamic interrelationships between thyroid hormones and pituitary thyrotropin (TSH. They display a high degree of individuality, thyroid-state-related hierarchy and adaptive conditionality. Molecular mechanisms involve multiple feedback loops on several levels of organization, different time scales and varying conditions of their optimum operation, including a proposed feedforward motif. This supports the concept of a dampened response and multistep regulation, making the interactions between TSH, FT4 and FT3 situational and mathematically more complex. As a homeostatically integrated parameter, TSH becomes neither normatively fixed nor a precise marker of euthyroidism. This is exemplified by the therapeutic situation with L-thyroxine (L-T4 where TSH levels defined for optimum health may not apply equivalently during treatment. In particular, an FT3-FT4 dissociation, discernible FT3-TSH disjoint and conversion inefficiency have been recognised in L-T4-treated athyreotic patients. In addition to regulating T4 production, TSH appears to play an essential role in maintaining T3 homeostasis by directly controlling deiodinase activity. While still allowing for tissue-specific variation this questions the currently assumed independence of the local T3 supply. Rather it integrates peripheral and central elements into an overarching control system. On L-T4 treatment, altered equilibria have been shown to give rise to lower circulating FT3 concentrations in the presence of normal serum TSH. While data on T3 in tissues are largely lacking in humans, rodent models suggest that the disequilibria may reflect widespread T3 deficiencies at the tissue level in various organs.As a consequence, the use of TSH, valuable though it is in many situations, should be

  18. Homeostatic Control of the Thyroid–Pituitary Axis: Perspectives for Diagnosis and Treatment

    Science.gov (United States)

    Hoermann, Rudolf; Midgley, John E. M.; Larisch, Rolf; Dietrich, Johannes W.

    2015-01-01

    The long-held concept of a proportional negative feedback control between the thyroid and pituitary glands requires reconsideration in the light of more recent studies. Homeostatic equilibria depend on dynamic inter-relationships between thyroid hormones and pituitary thyrotropin (TSH). They display a high degree of individuality, thyroid-state-related hierarchy, and adaptive conditionality. Molecular mechanisms involve multiple feedback loops on several levels of organization, different time scales, and varying conditions of their optimum operation, including a proposed feedforward motif. This supports the concept of a dampened response and multistep regulation, making the interactions between TSH, FT4, and FT3 situational and mathematically more complex. As a homeostatically integrated parameter, TSH becomes neither normatively fixed nor a precise marker of euthyroidism. This is exemplified by the therapeutic situation with l-thyroxine (l-T4) where TSH levels defined for optimum health may not apply equivalently during treatment. In particular, an FT3–FT4 dissociation, discernible FT3–TSH disjoint, and conversion inefficiency have been recognized in l-T4-treated athyreotic patients. In addition to regulating T4 production, TSH appears to play an essential role in maintaining T3 homeostasis by directly controlling deiodinase activity. While still allowing for tissue-specific variation, this questions the currently assumed independence of the local T3 supply. Rather it integrates peripheral and central elements into an overarching control system. On l-T4 treatment, altered equilibria have been shown to give rise to lower circulating FT3 concentrations in the presence of normal serum TSH. While data on T3 in tissues are largely lacking in humans, rodent models suggest that the disequilibria may reflect widespread T3 deficiencies at the tissue level in various organs. As a consequence, the use of TSH, valuable though it is in many situations, should be scaled

  19. The insulin-like growth factor axis and collagen turnover during prednisolone treatment

    DEFF Research Database (Denmark)

    Wolthers, O D; Juul, A; Hansen, M

    1994-01-01

    Serum concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), the carboxyterminal propeptide of type I collagen (PICP), the carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), and the aminoterminal propeptide...... of type III procollagen (PIIINP) were studied in 10 prepubertal children with asthma (mean age 9.0 years). The children were treated with 2.5 and 5.0 mg/day prednisolone in a randomised double blind crossover trial with run in, treatment, and washout periods of two weeks. No statistically significant...... effects on serum concentrations of IGF-I and IGFBP-3 were found. Dose related reductions of PICP, ICTP, and PIIINP were observed: the mean (SEM) reduction in PICP was 33.4 (26.3) and 68.4 (20.6) micrograms/l, in ICTP 2.5 (0.5) and 2.9 (0.6) micrograms/l, and in PIIINP 2.1 (0.7) and 3.1 (1.8) micrograms...

  20. Inferior Pancreaticoduodenal Artery Aneurysms Associated with Occlusive Lesions of the Celiac Axis: Diagnosis, Treatment Options, Outcomes, and Review of the Literature

    International Nuclear Information System (INIS)

    Flood, Karen; Nicholson, Anthony A.

    2013-01-01

    Purpose. To describe the presentation, treatment, and outcomes for 14 patients with aneurysms of the inferior pancreaticoduodenal arteries associated with occlusive lesions of the celiac axis, and to review the literature for similar cases. Methods, Over a period of 12 years, 14 patients (10 women and 4 men) ranging in age from 26 to 50 (mean 46) years were demonstrated to have aneurysms of the inferior pancreaticoduodenal artery origin associated with stenosis or occlusion of the celiac axis. All patients were treated by a combination of surgery and interventional radiology. Results. Outcome data collected between 3 months and 4 years (mean 2 years) demonstrated that all aneurysms remained excluded, and all 14 patients were well. The 49 case reports in the literature confirm the findings of this cohort. Conclusion. In inferior pancreaticoduodenal artery aneurysm resulting from celiac occlusive disease, endovascular treatment is best achieved by stenting the celiac axis and/or embolizing the aneurysm when necessary.

  1. Inferior Pancreaticoduodenal Artery Aneurysms Associated with Occlusive Lesions of the Celiac Axis: Diagnosis, Treatment Options, Outcomes, and Review of the Literature

    Energy Technology Data Exchange (ETDEWEB)

    Flood, Karen, E-mail: karenrogers@doctors.org.uk; Nicholson, Anthony A. [Leeds Teaching Hospitals, Department of Radiology (United Kingdom)

    2013-06-15

    Purpose. To describe the presentation, treatment, and outcomes for 14 patients with aneurysms of the inferior pancreaticoduodenal arteries associated with occlusive lesions of the celiac axis, and to review the literature for similar cases. Methods, Over a period of 12 years, 14 patients (10 women and 4 men) ranging in age from 26 to 50 (mean 46) years were demonstrated to have aneurysms of the inferior pancreaticoduodenal artery origin associated with stenosis or occlusion of the celiac axis. All patients were treated by a combination of surgery and interventional radiology. Results. Outcome data collected between 3 months and 4 years (mean 2 years) demonstrated that all aneurysms remained excluded, and all 14 patients were well. The 49 case reports in the literature confirm the findings of this cohort. Conclusion. In inferior pancreaticoduodenal artery aneurysm resulting from celiac occlusive disease, endovascular treatment is best achieved by stenting the celiac axis and/or embolizing the aneurysm when necessary.

  2. Enhancement of Muscle T Regulatory Cells and Improvement of Muscular Dystrophic Process in mdx Mice by Blockade of Extracellular ATP/P2X Axis.

    Science.gov (United States)

    Gazzerro, Elisabetta; Baldassari, Simona; Assereto, Stefania; Fruscione, Floriana; Pistorio, Angela; Panicucci, Chiara; Volpi, Stefano; Perruzza, Lisa; Fiorillo, Chiara; Minetti, Carlo; Traggiai, Elisabetta; Grassi, Fabio; Bruno, Claudio

    2015-12-01

    Infiltration of immune cells and chronic inflammation substantially affect skeletal and cardiac muscle degeneration in Duchenne muscular dystrophy. In the immune system, extracellular adenosine triphosphate (ATP) released by dying cells is sensed as a danger associated molecular pattern through P2 purinergic receptors. Specifically, the P2X7 subtype has a prominent role in regulating immune system physiology and contributes to inflammasome activation also in muscle cells. Here, we show that in vivo blockade of the extracellular ATP/P2X purinergic signaling pathway by periodate-oxidized ATP delayed the progression of the dystrophic phenotype and dampened the local inflammatory response in mdx mice, a spontaneous mouse model of dystrophin deficiency. Reduced infiltration of leukocytes and macrophages and decreased expression of IL-6 were revealed in the muscles of periodate-oxidized ATP-treated mdx mice. Concomitantly, an increase in Foxp3(+) immunosuppressive regulatory T cells was observed and correlated with enhanced myofiber regeneration. Moreover, we detected reduced concentrations of profibrotic cytokines, including transforming growth factor-β and connective tissue growth factor, in muscles of periodate-oxidized ATP-treated mdx mice. The improvement of inflammatory features was associated with increased strength and reduced necrosis, thus suggesting that pharmacologic purinergic antagonism altering the adaptive immune component in the muscle infiltrates might represent a promising therapeutic approach in Duchenne muscular dystrophy. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. A Novel Regulatory Mechanism of Smooth Muscle α-Actin Expression by NRG-1/circACTA2/miR-548f-5p Axis.

    Science.gov (United States)

    Sun, Yan; Yang, Zhan; Zheng, Bin; Zhang, Xin-Hua; Zhang, Man-Li; Zhao, Xue-Shan; Zhao, Hong-Ye; Suzuki, Toru; Wen, Jin-Kun

    2017-09-01

    Neuregulin-1 (NRG-1) includes an extracellular epidermal growth factor-like domain and an intracellular domain (NRG-1-ICD). In response to transforming growth factor-β1, its cleavage by proteolytic enzymes releases a bioactive fragment, which suppresses the vascular smooth muscle cell (VSMC) proliferation by activating ErbB (erythroblastic leukemia viral oncogene homolog) receptor. However, NRG-1-ICD function in VSMCs remains unknown. Here, we characterize the function of NRG-1-ICD and underlying mechanisms in VSMCs. Immunofluorescence staining, Western blotting, and quantitative real-time polymerase chain reaction showed that NRG-1 was expressed in rat, mouse, and human VSMCs and was upregulated and cleaved in response to transforming growth factor-β1. In the cytoplasm of HASMCs (human aortic smooth muscle cells), the NRG-1-ICD participated in filamentous actin formation by interacting with α-SMA (smooth muscle α-actin). In the nucleus, the Nrg-1-ICD induced circular ACTA2 (alpha-actin-2; circACTA2) formation by recruitment of the zinc-finger transcription factor IKZF1 (IKAROS family zinc finger 1) to the first intron of α-SMA gene. We further confirmed that circACTA2, acting as a sponge binding microRNA (miR)-548f-5p, interacted with miR-548f-5p targeting 3' untranslated region of α-SMA mRNA, which in turn relieves miR-548f-5p repression of the α-SMA expression and thus upregulates α-SMA expression, thereby facilitating stress fiber formation and cell contraction in HASMCs. Accordingly, in vivo studies demonstrated that the localization of the interaction of circACTA2 with miR-548f-5p is significantly decreased in human intimal hyperplastic arteries compared with normal arteries, implicating that dysregulation of circACTA2 and miR-548f-5p expression is involved in intimal hyperplasia. These results suggest that circACTA2 mediates NRG-1-ICD regulation of α-SMA expression in HASMCs via the NRG-1-ICD/circACTA2/miR-548f-5p axis. Our data provide a molecular

  4. Pathogenesis and pharmacologic treatment of obesity: the role of energy regulatory mechanism.

    Science.gov (United States)

    Manulu, Mangatas S M; Sutanegara, I N Dwi

    2006-01-01

    Obesity has become a worldwide public health problem affecting millions of people. This is a chronic, stigmatized, and costly disease, rarely curable and is increasing in prevalence to a point today where we define obesity as an epidemic disease that not only in developed but also on developing countries. The pathogenesis of obesity is largely unknown, especially about energy regulatory mechanism that involved wide area of neuroendocrinology that is very interesting but very complex and makes internists "refuse" to learn. Obesity occurs through a longstanding imbalance between energy intake and energy expenditure, influenced by a complex biologic system that regulates appetite and adiposity. Obesity influences the pathogenesis of hypertension, type 2 diabetes, dyslipidemia, kidney, heart, and cerebrovascular disease. It is very wise for every internist to learn the pathogenesis and treatment of this worldwide diseases. Until now, the available treatments, including drugs, are palliative and are effective only while the treatment is being actively used; and besides so many side effects reported.

  5. Canadian uranium mines and mills evolution of regulatory expectations and requirements for effluent treatment

    International Nuclear Information System (INIS)

    LeClair, J.; Ashley, F.

    2006-01-01

    The regulation of uranium mining in Canada has changed over time as our understanding and concern for impacts on both human and non-human biota has evolved. Since the mid-1970s and early 1980s, new uranium mine and mill developments have been the subject of environmental assessments to assess and determine the significance of environmental effects throughout the project life cycle including the post-decommissioning phase. Water treatment systems have subsequently been improved to limit potential effects by reducing the concentration of radiological and non-radiological contaminants in the effluent discharge and the total loadings to the environment. This paper examines current regulatory requirements and expectations and how these impact uranium mining/milling practices. It also reviews current water management and effluent treatment practices and performance. Finally, it examines the issues and challenges for existing effluent treatment systems and identifies factors to be considered in optimizing current facilities and future facility designs. (author)

  6. Air Emissions Damages from Municipal Drinking Water Treatment Under Current and Proposed Regulatory Standards.

    Science.gov (United States)

    Gingerich, Daniel B; Mauter, Meagan S

    2017-09-19

    Water treatment processes present intersectoral and cross-media risk trade-offs that are not presently considered in Safe Drinking Water Act regulatory analyses. This paper develops a method for assessing the air emission implications of common municipal water treatment processes used to comply with recently promulgated and proposed regulatory standards, including concentration limits for, lead and copper, disinfection byproducts, chromium(VI), strontium, and PFOA/PFOS. Life-cycle models of electricity and chemical consumption for individual drinking water unit processes are used to estimate embedded NO x , SO 2 , PM 2.5 , and CO 2 emissions on a cubic meter basis. We estimate air emission damages from currently installed treatment processes at U.S. drinking water facilities to be on the order of $500 million USD annually. Fully complying with six promulgated and proposed rules would increase baseline air emission damages by approximately 50%, with three-quarters of these damages originating from chemical manufacturing. Despite the magnitude of these air emission damages, the net benefit of currently implemented rules remains positive. For some proposed rules, however, the promise of net benefits remains contingent on technology choice.

  7. Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection.

    Science.gov (United States)

    Arya, Vikram; Au, Stanley; Belew, Yodit; Miele, Peter; Struble, Kimberly

    2015-07-01

    To outline some of the regulatory challenges inherent to the development of long-acting antiretrovirals (ARVs) for the treatment or prevention of HIV infection. Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment. Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis (PrEP) have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately. Because of their pharmacokinetic properties, the development of long-acting ARVs can present novel regulatory challenges. Chief among them is determining the appropriate dosing regimen, the need for an oral lead-in, and whether existing data with an approved oral agent, if available, can be leveraged for a treatment or prevention indication. For PrEP, because validated biomarkers are lacking, additional nonclinical studies and evaluation of tissue concentrations in multiple compartments may be necessary to identify optimal dosages. Study design and choice of controls for registrational trials of new long-acting PrEP agents might also prove challenging following the availability of an oral PrEP drug.

  8. A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication.

    Science.gov (United States)

    Griffiths, Samantha J; Koegl, Manfred; Boutell, Chris; Zenner, Helen L; Crump, Colin M; Pica, Francesca; Gonzalez, Orland; Friedel, Caroline C; Barry, Gerald; Martin, Kim; Craigon, Marie H; Chen, Rui; Kaza, Lakshmi N; Fossum, Even; Fazakerley, John K; Efstathiou, Stacey; Volpi, Antonio; Zimmer, Ralf; Ghazal, Peter; Haas, Jürgen

    2013-01-01

    Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to

  9. A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication.

    Directory of Open Access Journals (Sweden)

    Samantha J Griffiths

    Full Text Available Herpes simplex virus type 1 (HSV-1 is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi screen with a druggable genome small interfering RNA (siRNA library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome

  10. Impact of alemtuzumab treatment on the survival and function of human regulatory T cells in vitro

    Science.gov (United States)

    Havari, Evis; Turner, Michael J; Campos-Rivera, Juanita; Shankara, Srinivas; Nguyen, Tri-Hung; Roberts, Bruce; Siders, William; Kaplan, Johanne M

    2014-01-01

    Alemtuzumab is a humanized monoclonal antibody specific for the CD52 protein present at high levels on the surface of B and T lymphocytes. In clinical trials, alemtuzumab has shown a clinical benefit superior to that of interferon-β in relapsing–remitting multiple sclerosis patients. Treatment with alemtuzumab leads to the depletion of circulating lymphocytes followed by a repopulation process characterized by alterations in the number, proportions and properties of lymphocyte subsets. Of particular interest, an increase in the percentage of T cells with a regulatory phenotype (Treg cells) has been observed in multiple sclerosis patients after alemtuzumab. Since Treg cells play an important role in the control of autoimmune responses, the effect of alemtuzumab on Treg cells was further studied in vitro. Alemtuzumab effectively mediated complement-dependent cytolysis of human T lymphocytes and the remaining population was enriched in T cells with a regulatory phenotype. The alemtuzumab-exposed T cells displayed functional regulatory characteristics including anergy to stimulation with allogeneic dendritic cells and ability to suppress the allogeneic response of autologous T cells. Consistent with the observed increase in Treg cell frequency, the CD25hi T-cell population was necessary for the suppressive activity of alemtuzumab-exposed T cells. The mechanism of this suppression was found to be dependent on both cell–cell contact and interleukin-2 consumption. These findings suggest that an alemtuzumab-mediated increase in the proportion of Treg cells may play a role in promoting the long-term efficacy of alemtuzumab in patients with multiple sclerosis. PMID:24116901

  11. Role of hepcidin-ferroportin axis in the pathophysiology, diagnosis, and treatment of anemia of chronic inflammation.

    Science.gov (United States)

    Langer, Arielle L; Ginzburg, Yelena Z

    2017-06-01

    Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis. The role of hepcidin-ferroportin axis in the pathophysiology of ACI is stimulating the development of new diagnostics and targeted therapies. In this review, we present an overview of and rationale for inflammation-, iron-, and erythropoiesis-related strategies currently in development. © 2017 International Society for Hemodialysis.

  12. Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Rodolfo Thomé

    Full Text Available BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg cells and suppressive Dendritic Cells (DCs, to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ, an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE, an experimental model for human Multiple Sclerosis, was investigated as well. METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55 peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of

  13. Outcome of long-axis percutaneous sacroplasty for the treatment of sacral insufficiency fractures with a radiofrequency-induced, high-viscosity bone cement

    Energy Technology Data Exchange (ETDEWEB)

    Eichler, Katrin [University of Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt (Germany); J. W. Goethe University of Frankfurt, Institute for Diagnostic and Interventional Radiology, Frankfurt (Germany); Zangos, Stephan; Vogl, Thomas J. [University of Frankfurt, Department of Diagnostic and Interventional Radiology, Frankfurt (Germany); Mack, Martin G. [Radiology Munich, Munich (Germany); Marzi, Ingo [University of Frankfurt, Department of Trauma, Hand and Reconstructive Surgery, Frankfurt (Germany)

    2014-04-15

    Our goal was to assess the technical results in patients who underwent long-axis sacroplasty for the treatment of sacral insufficiency fractures (SIF) by radiofrequency-induced high-viscosity bone cement augmentation. Twelve patients with bilateral sacral fractures were treated by augmentation with radiofrequency-activated, high-viscosity polymethylmethacrylate (PMMA) bone cement under local anesthesia. CT-guided sacroplasty was performed by using a long-axis approach through a single entry point. Thirty-six vertebrae were treated in 12 sessions under a combination of CT and fluoroscopic guidance using a bilateral access and a cavity-creating osteotome prior to remote-controlled, hydraulically driven cement injection. The visual analogue scale (VAS) score before sacroplasty and at 1 and 3 months after the treatment was obtained. PMMA leaks were evaluated retrospectively using the post-interventional CT. The mean amount of high-viscosity PMMA injected per patient was 7.8 ml. No major adverse events were observed. In the first 4 days after the procedure, the mean VAS score decreased from 8.1 ± 1.9 to mean 3.1 ± 1.2 and was followed by a gradual but continuous decrease throughout the rest of the follow-up period at 24 weeks (mean 2.2 ± 1.1) and 48 weeks (mean 2.1 ± 1.4). CT fluoroscopy-guided sacral augmentation was safe and effective in all 12 patients with osteoporotic SIF. (orig.)

  14. Integrating hinge axis approximation and the virtual facial simulation of prosthetic outcomes for treatment with CAD-CAM immediate dentures: A clinical report of a patient with microstomia.

    Science.gov (United States)

    Kuric, Katelyn M; Harris, Bryan T; Morton, Dean; Azevedo, Bruno; Lin, Wei-Shao

    2017-09-29

    This clinical report describes a digital workflow using extraoral digital photographs and volumetric datasets from cone beam computed tomography (CBCT) imaging to create a 3-dimensional (3D), virtual patient with photorealistic appearance. In a patient with microstomia, hinge axis approximation, diagnostic casts simulating postextraction alveolar ridge profile, and facial simulation of prosthetic treatment outcome were completed in a 3D, virtual environment. The approach facilitated the diagnosis, communication, and patient acceptance of the treatment of maxillary and mandibular computer-aided design and computer-aided manufacturing (CAD-CAM) of immediate dentures at increased occlusal vertical dimension. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  15. Treatment with Parkinsonia aculeata combats insulin resistance-induced oxidative stress through the increase in PPARγ/CuZn-SOD axis expression in diet-induced obesity mice.

    Science.gov (United States)

    Araújo, Tiago Gomes; Oliveira, Alexandre Gabarra; Vecina, Juliana Falcato; Marin, Rodrigo Miguel; Franco, Eryvelton Souza; Abdalla Saad, Mario J; de Sousa Maia, Maria Bernadete

    2016-08-01

    Parkinsonia aculeata L. (Caesalpiniaceae) is a traditional ethnomedicine and has been used for the empiric treatment of hyperglycemia, without scientific background. Mechanistic analyses at molecular level from the antioxidant mechanism observed by P. aculeata are required. Herein the effects of the treatment by hydroethanolic extract partitioned with ethyl acetate of P. aculeata aerial parts (HEPa/EtOAc) in mice fed a high-fat diet that share many obesity phenotypes with humans were evaluated. The animals were treated orally with HEPa/EtOAc (125 and 250 mg/kg/day) and pioglitazone (5 mg/kg/day), for 16 days. After the treatment, HEPa/EtOAc reduced fasting serum glucose and insulin levels, as well as homeostasis model assessment for insulin resistance. In addition, an improvement in glucose intolerance was also observed. Indeed, a reduction in the circulating levels of TNF-α and IL-6 was also observed. Furthermore, at molecular level, it was demonstrated that the HEPa/EtOAc treatment was able to improve these physiological parameters, through the activation of peroxisome proliferator-activated receptor γ (PPARγ) per si, as well as the enhancement of antioxidant mechanism by an increase in PPARγ/Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD) axis expression in liver and adipose tissue. In sum, P. aculeata is effective to improve insulin resistance in a mouse model of obesity and this effect seems to involve the antioxidant and anti-inflammatory mechanisms through the increase in PPARγ/CuZn-SOD axis expression.

  16. Prevalence and predictors of Axis I disorders in a large sample of treatment-seeking victims of sexual abuse and incest

    Directory of Open Access Journals (Sweden)

    Eoin McElroy

    2016-04-01

    Full Text Available Background: Childhood sexual abuse (CSA is a common occurrence and a robust, yet non-specific, predictor of adult psychopathology. While many demographic and abuse factors have been shown to impact this relationship, their common and specific effects remain poorly understood. Objective: This study sought to assess the prevalence of Axis I disorders in a large sample of help-seeking victims of sexual trauma, and to examine the common and specific effects of demographic and abuse characteristics across these different diagnoses. Method: The participants were attendees at four treatment centres in Denmark that provide psychological therapy for victims of CSA (N=434. Axis I disorders were assessed using the Millon Clinical Multiaxial Inventory-III (MCMI-III. Multivariate logistic regression analysis was used to examine the associations between CSA characteristics (age of onset, duration, number of abusers, number of abusive acts and 10 adult clinical syndromes. Results: There was significant variation in the prevalence of disorders and the abuse characteristics were differentially associated with the outcome variables. Having experienced sexual abuse from more than one perpetrator was the strongest predictor of psychopathology. Conclusions: The relationship between CSA and adult psychopathology is complex. Abuse characteristics have both unique and shared effects across different diagnoses.

  17. Comparison of changes in the transverse dental axis between patients with skeletal Class III malocclusion and facial asymmetry treated by orthognathic surgery with and without presurgical orthodontic treatment.

    Science.gov (United States)

    Song, Han-Sol; Choi, Sung-Hwan; Cha, Jung-Yul; Lee, Kee-Joon; Yu, Hyung-Seog

    2017-07-01

    To evaluate transverse skeletal and dental changes, including those in the buccolingual dental axis, between patients with skeletal Class III malocclusion and facial asymmetry after bilateral intraoral vertical ramus osteotomy with and without presurgical orthodontic treatment. This retrospective study included 29 patients with skeletal Class III malocclusion and facial asymmetry including menton deviation > 4 mm from the midsagittal plane. To evaluate changes in transverse skeletal and dental variables (i.e., buccolingual inclination of the upper and lower canines and first molars), the data for 16 patients who underwent conventional orthognathic surgery (CS) were compared with those for 13 patients who underwent preorthodontic orthognathic surgery (POGS), using three-dimensional computed tomography at initial examination, 1 month before surgery, and at 7 days and 1 year after surgery. The 1-year postsurgical examination revealed no significant changes in the postoperative transverse dental axis in the CS group. In the POGS group, the upper first molar inclined lingually on both sides (deviated side, -1.8° ± 2.8°, p = 0.044; nondeviated side, -3.7° ± 3.3°, p = 0.001) and the lower canine inclined lingually on the nondeviated side (4.0° ± 5.4°, p = 0.022) during postsurgical orthodontic treatment. There were no significant differences in the skeletal and dental variables between the two groups at 1 year after surgery. POGS may be a clinically acceptable alternative to CS as a treatment to achieve stable transverse axes of the dentition in both arches in patients with skeletal Class III malocclusion and facial asymmetry.

  18. Treatment of Radioactive Contaminated Soil and Concrete Wastes Using the Regulatory Clearance

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Il Sik; Ryu, W. S.; Kim, T. K.; Shon, J. S.; Ahn, S. J.; Lee, Y. H.; Bae, S. M.; Hong, D. S.; Ji, Y. Y.; Lee, B. C

    2008-11-15

    In the radioactive waste storage facilities at the Korea Atomic Energy Research Institute (KAERI) in Daejoen, there are thousands drums of radioactive contaminated soil and concrete wastes. The soil and concrete wastes were generated in 1988 during the decommissioning process of the research reactor and the attached radioactive waste treatment facility which were located in Seoul. The wastes were transported to Daejeon and have been stored since then. At the generation time, the radioactive contamination of the wastes was very low, and the radionuclides in the wastes was Co-60 and Cs-137. As the wastes have been stored for more than 20 years, the radioactivity concentration of the wastes has been decayed to become very extremely low. The wastes are needed to be treated because they take up large spaces at the storage facility. Also by treating the wastes, final disposal cost can be saved. So, the regulatory clearance was considered as a treatment method for the soil and concrete wastes with extremely low radioactivity concentration.

  19. Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals

    DEFF Research Database (Denmark)

    Tauriainen, Johanna; Scharf, Lydia; Frederiksen, Juliet

    2017-01-01

    HIV-specific CD8+ T cells demonstrate an exhausted phenotype associated with increased expression of inhibitory receptors, decreased functional capacity, and a skewed transcriptional profile, which are only partially restored by antiretroviral treatment (ART). Expression levels of the inhibitory...... and displayed a diminished expression of CD226. Furthermore, expression of PVR was increased on CD4+ T cells, especially T follicular helper (Tfh) cells, in HIV-infected lymph nodes. These results depict a skewing of the TIGIT/CD226 axis from CD226 co-stimulation towards TIGIT-mediated inhibition of CD8+ T...... increased over time despite early initiation of ART. HIV-specific CD8+ T cells were almost exclusively TIGIT+, had an inverse expression of the transcription factors T-bet and Eomes and co-expressed PD-1, CD160 and 2B4. HIV-specific TIGIThi cells were negatively correlated with polyfunctionality...

  20. Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia.

    Science.gov (United States)

    Weiss, Lukas; Melchardt, Thomas; Egle, Alexander; Grabmer, Christoph; Greil, Richard; Tinhofer, Inge

    2011-05-15

    Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression. T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data. The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028). Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia. 2010 American Cancer Society.

  1. Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

    Science.gov (United States)

    Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

    2013-11-01

    Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice. © 2013.

  2. The regulatory network of ThbZIP1 in response to abscisic acid treatment

    Directory of Open Access Journals (Sweden)

    Xiaoyu eJi

    2015-02-01

    Full Text Available Previously, a bZIP transcription factor from Tamarix hispida, ThbZIP1, was characterized: plants overexpressing ThbZIP1 displayed improved salt stress tolerance but were sensitive to abscisic acid (ABA. In the current study, we further characterized the regulatory network of ThbZIP1 and the mechanism of ABA sensitivity mediated by ThbZIP1. An ABF transcription factor from T. hispida, ThABF1, directly regulates the expression of ThbZIP1. Microarray analysis identified 1,662 and 1,609 genes that were respectively significantly upregulated or downregulated by ThbZIP1 when exposed to ABA. GO analysis showed that the processes including response to stimulus, catalytic activity, binding function, and metabolic process were highly altered in ThbZIP1 expressing plants exposed to ABA. The gene expression in ThbZIP1 transformed plants were compared between exposed to ABA and salt on the genome scale. Genes differentially regulated by both salt and ABA treatment only accounted for 9.75% of total differentially regulated genes. GO analysis showed that structural molecule activity, organelle part, membrane-enclosed lumen, reproduction and reproductive process are enhanced by ABA but inhibited by salt stress. Conversely, immune system and multi-organism process were improved by salt but inhibited by ABA. Transcription regulator activity, enzyme regulator activity and developmental process were significantly altered by ABA but were not affected by salt stress. Our study provides insights into how ThbZIP1 mediates ABA and salt stress response at the molecular level.

  3. HIT'91 (prospective, co-operative study for the treatment of malignant brain tumors in childhood): accuracy and acute toxicity of the irradiation of the craniospinal axis

    International Nuclear Information System (INIS)

    Kortmann, R.D.; Timmermann, B.; Bamberg, M.; Kuehl, J.; Willich, N.; Flentje, M.; Meisner, C.

    1999-01-01

    Background: It was the aim of the quality control program of the randomized trial HIT '91 (intensive chemotherapy before irradiation versus maintenance chemotherapy after irradiation) to assess prospectively the quality of neuroaxis irradiation with respect to the protocol guidelines and to evaluate acute toxicity with respect to treatment arm. Patients, Materials and Methods: Data of 134 patients undergoing irradiation of the craniospinal axis were available. Positioning aids, shielding techniques, treatment machines, choice of energy, total dose and fractionation were evaluated. A total of 651 simulation and verification films were analyzed to assess the coverage of the clinical target volume (whole brain, posterior fossa, sacral nerve roots) and deviations of field alignment between simulation and verification of first treatment. Field matching between whole brain and adjacent cranial spinal fields was analyzed with respect to site and width of junction. Acute maximal side effects were evaluated according to a modified WHO score for neurotoxicity, infections, skin, mucosa and myelotoxicity. Results: In 91.3% of patients contemporary positioning aids and individualized shielding techniques were used to assure a reproducible treatment. In 98 patients (73.1%) linear accelerators and in 36 patients (26.8%) 60 Cobalt machines were used. Single and total dose were administered according to the protocol guidelines in more than 90% of patients. In 20.2% of patients the cribriform plate, in 1.4% the middle cranial fossa and in 21.1% the posterior fossa and in 4.5% the 2nd sacral segment were incompletely encompassed by the treatment portals. Ninety-five percent of deviations of field alignment were less than 13.0 mm (whole brain) and 12 mm (cranial spinal field) with a random error between 4.9 and 7.6 mm (whole brain) and 6.9 mm and 9.9 mm (spinal canal), respectively. In 77.5% of patients the junctions between whole brain and cranial spinal fields were placed without a

  4. Possible evidence for re-regulation of HPA axis and brain reward systems over time in treatment in prescription opioid-dependent patients.

    Science.gov (United States)

    Bunce, Scott C; Harris, Jonathan D; Bixler, Edward O; Taylor, Megan; Muelly, Emilie; Deneke, Erin; Thompson, Kenneth W; Meyer, Roger E

    2015-01-01

    There is growing evidence for a neuroadaptive model underlying vulnerability to relapse in opioid dependence. The purpose of this study was to evaluate clinical measures hypothesized to mirror elements of allostatic dysregulation in patients dependent on prescription opioids at 2 time points after withdrawal, compared with healthy control participants. Recently withdrawn (n = 7) prescription opioid-dependent patients were compared with the patients in supervised residential care for 2 to 3 months (extended care; n = 7) and healthy controls (n = 7) using drug cue reactivity, affect-modulated startle response tasks, salivary cortisol, and 8 days of sleep actigraphy. Prefrontal cortex was monitored with functional near-infrared spectroscopy during the cue reactivity task. Startle response results indicated reduced hedonic response to natural rewards among patients recently withdrawn from opioids relative to extended care patients. The recently withdrawn patients showed increased activation to pill stimuli in right dorsolateral prefrontal cortex relative to extended care patients. Cortisol levels were elevated among recently withdrawn patients and intermediate for extended care relative to healthy controls. Actigraphy indicated disturbed sleep between recently withdrawn patients and extended care patients; extended care patients were similar to controls. Dorsolateral prefrontal cortex activation to drug and natural reward cues, startle responses to natural reward cues, day-time cortisol levels, time in bed, and total time spent sleeping were all correlated with the number of days since last drug use (ie, time in supervised residential treatment). These results suggest possible re-regulation of dysregulated hypothalamic-pituitary-adrenal axis and brain reward systems in prescription opioid-dependent patients over the drug-free period in residential treatment.

  5. Regulatory T-cells and immune tolerance in pregnancy : a new target for infertility treatment?

    NARCIS (Netherlands)

    Guerin, Leigh R.; Prins, Jelmer R.; Robertson, Sarah A.

    2009-01-01

    Adaptation of the maternal immune response to accommodate the semi-allogeneic fetus is necessary for pregnancy success, and disturbances in maternal tolerance are implicated in infertility and reproductive pathologies. T regulatory (Treg) cells are a recently discovered subset of T-lymphocytes with

  6. Small regulatory RNAs of the RNA interference (RNAi) pathway as a prophylactic treatment against fish pathogenic viruses

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Hajiabadi, Seyed Amir Hossein Jalali; Kristensen, Lasse Bøgelund Juel

    2011-01-01

    Small RNAs acting in the recently discovered gene regulatory mechanism called RNA interference has a potential as diagnostic signatures of disease and immunological state and when produced synthetically as prophylactic treatment of such diseases. In the RNAi mechanism the cell produces different....... The mechanism can be programmed with several types of small double stranded RNAs - the type of which defines the destiny of the target. One such class of regulatory RNAs called microRNAs are upregulated due to various physiological responses of the cell and they suppress many genes simultaneously believed...... small RNAs which inhibit gene expression through more or less specific interaction with messenger RNAs resulting in repression of translation to protein. In this way cells can turn of genes of specific pathways thereby leading to altered physiological stages of tissues and possibly of whole organisms...

  7. B7-H4-Ig treatment of normal mice changes lymphocyte homeostasis and increases the potential of regulatory T cells

    DEFF Research Database (Denmark)

    Kristensen, Nanna N; Schmidt, Esben G W; Rasmussen, Susanne

    2013-01-01

    Enteroantigens (eAgs) drive tolerogenic and inflammatory immune responses in the gut and are of importance for sustained immune homeostasis in colonic mucosa. Decline of regulatory activity in the gut mucosa might result in chronic colitis. B7-H4 is a co-inhibitory receptor expressed by professio......Enteroantigens (eAgs) drive tolerogenic and inflammatory immune responses in the gut and are of importance for sustained immune homeostasis in colonic mucosa. Decline of regulatory activity in the gut mucosa might result in chronic colitis. B7-H4 is a co-inhibitory receptor expressed...... of severe combined immune-deficient (SCID) mice undergoing T cell transfer colitis did not influence the course of disease probably reflecting the lack of Tregs in this model of chronic colitis. In conclusion, we show that treatment with B7-H4-Ig in vivo changes lymphocyte homeostasis and increases...

  8. The regulatory treatment of liquidity risk in South Africa / Johann R.G. Jacobs

    OpenAIRE

    Jacobs, Johann Renier Gabriel

    2008-01-01

    South Africa will be implementing Basel II on 1 January 2008. Basel II provides regulatory capital requirements for credit risk, market risk and operational risk. The purpose of capital requirements is to level the playing field for all internationally active banks and to protect consumers against these risks. Although there is an obvious threat of liquidity risk and it is important to correctly measure and manage liquidity risk, it is almost glaringly omitted from Basel II. The result of...

  9. Ratemaking treatment of decommissioning costs by the Federal Energy Regulatory Commission

    International Nuclear Information System (INIS)

    Lenart, R.J.

    1985-01-01

    The Nuclear Regulatory Commission (NRC) has the responsibility for the assurance of funds at the time of decommissioning. The Federal Energy Regulatory Commission (FERC), in conjunction with the State Public Utility Commissions, have the responsibilty to ensure that utilities have just and reasonable rates and an opportunity to collect an appropriate amount of dollars to decommission a nuclear reactor at the conclusion of its service life. Therefore, the Federal Energy Regulatory Commission allows utilities to include nuclear power plant decommissioning costs in rates based on the following ratemaking concepts: (1) that the methodology used by a utility equitably allocates costs between present and future ratepayers who receive service from a nuclear unit; (2) that, given the uncertainty and imprecision that are included in cost estimates for events that will transpire 20-40 years in the future, the FERC chose to err on the low side rather than run the risk of overcharging current customers for future decommissioning expense; and (3) that, as decommissioning experience accumulates, as decommissioning technology improves, and as decommissioning estimates become more refined, utilities would continue to seek revised decommissioning expense allowances from FERC in order to ensure that actual decommissioning costs are recovered over the useful life in which the plant provides service

  10. Evaluation of CD4+ CD25+ FoxP3+ regulatory T cells during treatment of patients with brucellosis.

    Science.gov (United States)

    Hasanjani Roushan, M R; Bayani, M; Soleimani Amiri, S; Mohammadnia-Afrouzi, M; Nouri, H R; Ebrahimpour, S

    2016-01-01

    Cell-mediated immunity (CMI) plays a critical role in the control of brucellosis. Regulatory T cells (Tregs) have a functional character in modulating the balance between host immune response and tolerance, which can eventually lead to chronic infection or relapse. The aim of this study was to assess the alteration of Tregs in cases of brucellosis before and after treatment. Thirty cases of acute brucellosis with the mean age of 41.03±15.15 years (case group) and 30 healthy persons with the mean age of 40.63±13.95 years (control group) were selected and assessed. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood of all individuals. We analyzed the alteration of Treg cell count using flow cytometry for CD4, CD25, and FoxP3 markers. The level of CD4+ CD25+ FoxP3+ Treg cells was increased in active patients compared with controls (2.5±0.99% vs 1.6±0.84%, p= 0.0004), but it had declined in the treated cases (1.83±0.73%, p=0.02). The level of Tregs was elevated in three relapsed cases. The frequency of Tregs and Treg/Teff (effector T cell) ratio was correlated with inverse serum agglutination test (SAT) and, 2-mercaptoethanol (2-ME) titers as markers of treatment in brucellosis. Based on our findings, we suggest that regulatory cells, such as CD4+ CD25+ FoxP3+ Treg cells, may contribute to the development of infection processes involving immune responses in brucellosis, and evaluation of regulatory T-cell levels may be a potential diagnostic strategy for the treatment outcome in chronic and relapsed cases of brucellosis.

  11. The regulatory treatment of adverse outcomes: Empirical evidence from the electric utility industry

    International Nuclear Information System (INIS)

    Ryan, N.E.

    1991-01-01

    This dissertation consists of two essays, both of them empirical studies using data from the US electric utility industry. Part I focuses on utilities' investment behavior, while Part II examines regulatory policy toward the industry. The first paper presents an analysis of utilities' decisions about whether to continue or cancel nuclear construction projects. During the seventies and eighties, changes in economic conditions and regulatory policy radically altered the costs and benefits of nuclear power. This study seeks to determine whether regulators pursued policies which induced utilities to employ socially efficient criteria in re-evaluating ongoing projects. The analysis also yields insights into regulators' distributional goals. Results based on data for 1978-84 are consistent with the capture theory hypothesis, which holds that regulators weigh industry interests more heavily than consumer interests. A test for structural change provides no support for the contention that the relative importance of consumer interests increased over this period. These empirical findings are inconsistent with a standard (and essential) assumption of theoretical principal-agent models of rate-of-return regulation, that regulators value consumers' payoffs more than utility profits. The second paper examines regulatory policy toward generating facilities that entered commercial service during the years 1983-88. In a significant departure from past practice, state public utility commissions often denied utilities full recovery of their investments in new plants. Although such ex post disallowances have an important efficiency rationale, they also provide a means for opportunistic regulators to effect transfers between utilities' ratepayers and shareholders. A probit model was used to assess the impact on the probability of a disallowance of firm and project characteristics as well as attributes of a state's political and institutional environment

  12. The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer

    International Nuclear Information System (INIS)

    Schwartz, J.L.; Shajahan, A.N.; Clarke, R.

    2011-01-01

    Resistance to endocrine therapy is common among breast cancer patients with estrogen receptor alpha-positive (ER+) tumors and limits the success of this therapeutic strategy. While the mechanisms that regulate endocrine responsiveness and cell fate are not fully understood, interferon regulatory factor-1 (IRF1) is strongly implicated as a key regulatory node in the underlying signaling network. IRF1 is a tumor suppressor that mediates cell fate by facilitating apoptosis and can do so with or without functional p53. Expression of IRF1 is down regulated in endocrine-resistant breast cancer cells, protecting these cells from IRF1-induced inhibition of proliferation and/or induction of cell death. Nonetheless, when IRF1 expression is induced following IFN treatment, antiestrogen sensitivity is restored by a process that includes the inhibition of pro survival BCL2 family members and caspase activation. These data suggest that a combination of endocrine therapy and compounds that effectively induce IRF1 expression may be useful for the treatment of many ER+ breast cancers. By understanding IRF1 signaling in the context of endocrine responsiveness, we may be able to develop novel therapeutic strategies and better predict how patients will respond to endocrine therapy

  13. K Basin spent fuel sludge treatment alternatives study. Volume 1, Regulatory options

    International Nuclear Information System (INIS)

    Beary, M.M.; Honekemp, J.R.; Winters, N.

    1995-01-01

    Approximately 2100 metric tons of irradiated N Reactor fuel are stored in the KE and KW Basins at the Hanford Site, Richland, Washington. Corrosion of the fuel has led to the formation of sludges, both within the storage canisters and on the basin floors. Concern about the degraded condition of the fuel and the potential for leakage from the basins in proximity to the Columbia River has resulted in DOE's commitment in the Tri-Party Agreement (TPA) to Milestone M-34-00-T08 to remove the fuel and sludges by a December 2002 target date. To support the planning for this expedited removal action, the implications of sludge management under various scenarios are examined. Volume 1 of this two-volume report describes the regulatory options for managing the sludges, including schedule and cost impacts, and assesses strategies for establishing a preferred path

  14. Pollutant emissions from vehicles with regenerating after-treatment systems in regulatory and real-world driving cycles.

    Science.gov (United States)

    Alvarez, Robert; Weilenmann, Martin; Novak, Philippe

    2008-07-15

    Regenerating exhaust after-treatment systems are increasingly employed in passenger cars in order to comply with regulatory emission standards. These systems include pollutant storage units that occasionally have to be regenerated. The regeneration strategy applied, the resultant emission levels and their share of the emission level during normal operation mode are key issues in determining realistic overall emission factors for these cars. In order to investigate these topics, test series with four cars featuring different types of such after-treatment systems were carried out. The emission performance in legislative and real-world cycles was monitored as well as at constant speeds. The extra emissions determined during regeneration stages are presented together with the methodology applied to calculate their impact on overall emissions. It can be concluded that exhaust after-treatment systems with storage units cause substantial overall extra emissions during regeneration mode and can appreciably affect the emission factors of cars equipped with such systems, depending on the frequency of regenerations. Considering that the fleet appearance of vehicles equipped with such after-treatment systems will increase due to the evolution of statutory pollutant emission levels, extra emissions originating from regenerations of pollutant storage units consequently need to be taken into account for fleet emission inventories. Accurately quantifying these extra emissions is achieved by either conducting sufficient repetitions of emission measurements with an individual car or by considerably increasing the size of the sample of cars with comparable after-treatment systems.

  15. HIT`91 (prospective, co-operative study for the treatment of malignant brain tumors in childhood): accuracy and acute toxicity of the irradiation of the craniospinal axis

    Energy Technology Data Exchange (ETDEWEB)

    Kortmann, R.D.; Timmermann, B.; Bamberg, M. [Tuebingen Univ. (Germany). Dept. of Radiotherapy; Kuehl, J. [Wuerzburg Univ. (Germany). Children`s Hospital; Willich, N. [Muenster Univ. (Germany). Dept. of Radiotherapy; Flentje, M. [Wuerzburg Univ. (Germany). Dept. of Radiotherapy; Meisner, C. [Tuebingen Univ. (Germany). Inst. for Medical Information Processing

    1999-04-01

    Background: It was the aim of the quality control program of the randomized trial HIT `91 (intensive chemotherapy before irradiation versus maintenance chemotherapy after irradiation) to assess prospectively the quality of neuroaxis irradiation with respect to the protocol guidelines and to evaluate acute toxicity with respect to treatment arm. Patients, Materials and Methods: Data of 134 patients undergoing irradiation of the craniospinal axis were available. Positioning aids, shielding techniques, treatment machines, choice of energy, total dose and fractionation were evaluated. A total of 651 simulation and verification films were analyzed to assess the coverage of the clinical target volume (whole brain, posterior fossa, sacral nerve roots) and deviations of field alignment between simulation and verification of first treatment. Field matching between whole brain and adjacent cranial spinal fields was analyzed with respect to site and width of junction. Acute maximal side effects were evaluated according to a modified WHO score for neurotoxicity, infections, skin, mucosa and myelotoxicity. Results: In 91.3% of patients contemporary positioning aids and individualized shielding techniques were used to assure a reproducible treatment. In 98 patients (73.1%) linear accelerators and in 36 patients (26.8%) {sup 60}Cobalt machines were used. Single and total dose were administered according to the protocol guidelines in more than 90% of patients. In 20.2% of patients the cribriform plate, in 1.4% the middle cranial fossa and in 21.1% the posterior fossa and in 4.5% the 2nd sacral segment were incompletely encompassed by the treatment portals. Ninety-five percent of deviations of field alignment were less than 13.0 mm (whole brain) and 12 mm (cranial spinal field) with a random error between 4.9 and 7.6 mm (whole brain) and 6.9 mm and 9.9 mm (spinal canal), respectively. In 77.5% of patients the junctions between whole brain and cranial spinal fields were placed

  16. Impact of hepatitis C virus polymorphisms on direct-acting antiviral treatment efficacy: Regulatory analyses and perspectives.

    Science.gov (United States)

    Harrington, Patrick R; Komatsu, Takashi E; Deming, Damon J; Donaldson, Eric F; O'Rear, Julian J; Naeger, Lisa K

    2018-06-01

    Several highly effective, interferon-free, direct-acting antiviral (DAA)-based regimens are available for the treatment of chronic hepatitis C virus (HCV) infection. Despite impressive efficacy overall, a small proportion of patients in registrational trials experienced treatment failure, which in some cases was associated with the detection of HCV resistance-associated substitutions (RASs) at baseline. In this article, we describe methods and key findings from independent regulatory analyses investigating the impact of baseline nonstructural (NS) 3 Q80K and NS5A RASs on the efficacy of current United States Food and Drug Administration (FDA)-approved regimens for patients with HCV genotype (GT) 1 or GT3 infection. These analyses focused on clinical trials that included patients who were previously naïve to the DAA class(es) in their investigational regimen and characterized the impact of baseline RASs that were enriched in the viral population as natural or transmitted polymorphisms (i.e., not drug-selected RASs). We used a consistent approach to optimize comparability of results across different DAA regimens and patient populations, including the use of a 15% sensitivity cutoff for next-generation sequencing results and standardized lists of NS5A RASs. These analyses confirmed that detection of NS3 Q80K or NS5A baseline RASs was associated with reduced treatment efficacy for multiple DAA regimens, but their impact was often minimized with the use of an intensified treatment regimen, such as a longer treatment duration and/or addition of ribavirin. We discuss the drug resistance-related considerations that contributed to pretreatment resistance testing and treatment recommendations in drug labeling for FDA-approved DAA regimens. Independent regulatory analyses confirmed that baseline HCV RASs can reduce the efficacy of certain DAA-based regimens in selected patient groups. However, highly effective treatment options are available for patients with or without

  17. The French regulatory experience and views on nickel-base alloy PWSCC prevention and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Turluer, G.; Cattiaux, G.; Monnot, B. [Institut de Radioprotection et de Surete Nucleaire, IRSN, 92 - Fontenay aux Roses (France); Emond, D.; Reuchet, J.; Chartier, Ph. [Direction Generale de la Surete Nucleaire et de la Radioprotection, 75 - Paris (France)

    2003-10-01

    This paper presents the experience feedback and views of the French Regulatory Authority (ASN) and of the technical support institute (IRSN) on PWSCC prevention since the initiation in 1989 of the 'Inconel Zones Review' requested by ASN to Electricite de France (EDF), the national operator of a fleet of 58 PWRs. This proactive requirement, launched before the discovery, in September 1991, of the only CRDM nozzle leak in France, on Bugey unit 3, was then triggered by the recurrence of many alloy 600 rapid degradations and leaks, world wide, and also in France in the late 1980's, particularly on steam generator tubes and on some pressurizer penetrations. Thus, the ASN requested that EDF, perform a comprehensive (generic) proactive assessment on all the nickel-base alloy components and parts of the main primary circuits, which of course included vessel head penetrations and bottom vessel head penetrations, and some other zones as a first priority. This proactive 'review' did, a minima, include the following tasks and actions: - Update and complete, by an extensive R and D program, the understanding and characterization of the Ni base alloys prone to PWSCC, - Analyze the various materials, metallurgical features, mechanical stresses, and physicochemical conditions of the parts exposed to primary water, in order to predict the occurrence of PWSCC initiation and propagation, - Provide a prioritization of the zones to be inspected, - Implement by improved NDE techniques a practical inspection program on the 58 PWRs, - Prepare and implement any needed mitigation actions as a result of the components conditions assessment. The present paper relates the main features of the French regulatory experience over more than 13 years and recalls the main principles of the assessment, which were applied by ASN. These principles, which are formalized in the current regulation rules revised in 1999, are briefly listed hereunder: - It is based on avoiding and

  18. The French regulatory experience and views on nickel-base alloy PWSCC prevention and treatment

    International Nuclear Information System (INIS)

    Turluer, G.; Cattiaux, G.; Monnot, B.; Emond, D.; Reuchet, J.; Chartier, Ph.

    2003-10-01

    This paper presents the experience feedback and views of the French Regulatory Authority (ASN) and of the technical support institute (IRSN) on PWSCC prevention since the initiation in 1989 of the 'Inconel Zones Review' requested by ASN to Electricite de France (EDF), the national operator of a fleet of 58 PWRs. This proactive requirement, launched before the discovery, in September 1991, of the only CRDM nozzle leak in France, on Bugey unit 3, was then triggered by the recurrence of many alloy 600 rapid degradations and leaks, world wide, and also in France in the late 1980's, particularly on steam generator tubes and on some pressurizer penetrations. Thus, the ASN requested that EDF, perform a comprehensive (generic) proactive assessment on all the nickel-base alloy components and parts of the main primary circuits, which of course included vessel head penetrations and bottom vessel head penetrations, and some other zones as a first priority. This proactive 'review' did, a minima, include the following tasks and actions: - Update and complete, by an extensive R and D program, the understanding and characterization of the Ni base alloys prone to PWSCC, - Analyze the various materials, metallurgical features, mechanical stresses, and physicochemical conditions of the parts exposed to primary water, in order to predict the occurrence of PWSCC initiation and propagation, - Provide a prioritization of the zones to be inspected, - Implement by improved NDE techniques a practical inspection program on the 58 PWRs, - Prepare and implement any needed mitigation actions as a result of the components conditions assessment. The present paper relates the main features of the French regulatory experience over more than 13 years and recalls the main principles of the assessment, which were applied by ASN. These principles, which are formalized in the current regulation rules revised in 1999, are briefly listed hereunder: - It is based on avoiding and preventing any leaking on

  19. Counter-regulatory hormone responses to spontaneous hypoglycaemia during treatment with insulin Aspart or human soluble insulin

    DEFF Research Database (Denmark)

    Brock Jacobsen, I; Vind, B F; Korsholm, Lars

    2011-01-01

    examined in a randomized, double-blinded cross-over study for two periods of 8 weeks. Sixteen patients with type 1 diabetes were subjected to three daily injections of human soluble insulin or Aspart in addition to Neutral Protamine Hagedorn (NPH) insulin twice daily. Each intervention period was followed......-regulatory responses regarding growth hormone, glucagon and ghrelin whereas no differences were found in relation to free fatty acid, cortisol, insulin-like growth factor (IGF)-I, IGF-II and IGF-binding proteins 1 and 2. Treatment with insulin Aspart resulted in well-defined peaks in serum insulin concentrations...... elicited a slightly different physiological response to spontaneous hypoglycaemia compared with human insulin. Keywords hypoglycaemia counter-regulation, insulin Aspart, type 1 diabetes....

  20. Do marketing and alcohol treatment/public health experts think televised alcohol advertisements abide by regulatory guidelines?

    Science.gov (United States)

    Lloyd, Kelly; Cameron, Elaine; Williams, Hannah; Banister, Emma; Donmall, Michael; Higgins, Alan; French, David P

    2018-04-01

    Televised alcohol advertisements in the United Kingdom must abide by the Broadcast Committee of Advertising Practice Code, which provides guidelines concerning advertisements not implying, condoning or encouraging immoderate, irresponsible or antisocial drinking. Previously, 75 per cent of 373 general public respondents were shown one of seven advertisements rated a breach of at least one guideline. This study assessed whether experts in marketing ( n = 25) and alcohol treatment/public health ( n = 25) perceived the same seven television alcohol advertisements as complying with the Broadcast Committee of Advertising Practice Code. Overall, 83 per cent of advertisements were rated as breaching at least one guideline. This provides further proof that self-regulatory alcohol guidelines are not fit for purpose.

  1. What characterizes substance abusers who commit suicide attempts? Factors related to Axis I disorders and patterns of substance use disorders. A study of treatment-seeking substance abusers in Norway.

    Science.gov (United States)

    Landheim, A S; Bakken, K; Vaglum, P

    2006-01-01

    The frequency of suicide attempts and clinical characteristics of attempters among poly-substance abusers and alcoholics were examined. A consecutive sample (n = 260) of in- and outpatients from two Norwegian counties were assessed by Composite International Diagnostic Interview (Axis I disorders), Millon's Clinical Multiaxial Inventory (Axis II disorders) and the Norwegian National Client Assessment Form. When analysing the association between suicide attempters and the range of predictor variables, logistic regression analysis was conducted. Almost half (47%) of the sample reported lifetime suicide attempts; significantly more frequently in poly-substance abusers (58%) than alcoholics (38%). A substance use disorder with duration of >or=15 years and an early onset (suicide attempter after controlling for Axis I disorders. In addition, eating disorders, agoraphobia and major depression were strongly and independently associated with being a suicide attempter. Attempts at preventing suicidal behaviour should not ignore the suicide risk among poly-substance abusers. In addition, prevention of suicidal behaviour demands a treatment programme focusing concomitantly on both addictive behaviour and comorbid psychiatric disorders. Copyright 2006 S. Karger AG, Basel.

  2. HLA-G regulatory haplotypes and implantation outcome in couples who underwent assisted reproduction treatment.

    Science.gov (United States)

    Costa, Cynthia Hernandes; Gelmini, Georgia Fernanda; Wowk, Pryscilla Fanini; Mattar, Sibelle Botogosque; Vargas, Rafael Gustavo; Roxo, Valéria Maria Munhoz Sperandio; Schuffner, Alessandro; Bicalho, Maria da Graça

    2012-09-01

    The role of HLA-G in several clinical conditions related to reproduction has been investigated. Important polymorphisms have been found within the 5'URR and 3'UTR regions of the HLA-G promoter. The aim of the present study was to investigate 16 SNPs in the 5'URR and 14-bp insertion/deletion (ins/del) polymorphism located in the 3'UTR region of the HLA-G gene and its possible association with the implantation outcome in couples who underwent assisted reproduction treatments (ART). The case group was composed of 25 ART couples. Ninety-four couples with two or more term pregnancies composed the control group. Polymorphism haplotype frequencies of the HLA-G were determined for both groups. The Haplotype 5, Haplotype 8 and Haplotype 11 were absolute absence in ART couples. The HLA-G*01:01:02a, HLA-G*01:01:02b alleles and the 14-bp ins polymorphism, Haplotype 2, showed an increased frequency in case women and similar distribution between case and control men. However, this susceptibility haplotype is significantly presented in case women and in couple with failure implantation after treatment, which led us to suggest a maternal effect, associated with this haplotype, once their presence in women is related to a higher number of couples who underwent ART. Copyright © 2012. Published by Elsevier Inc.

  3. Novel Concept of CD4-Mediated Activation of Regulatory T Cells for the Treatment of Graft-Versus-Host Disease

    Directory of Open Access Journals (Sweden)

    Janine Schlöder

    2017-11-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation is the only curative treatment option for several hematological malignancies and immune deficiency syndromes. Nevertheless, the development of a graft-versus-host disease (GvHD after transplantation is a high risk and a severe complication with high morbidity and mortality causing therapeutic challenges. Current pharmacological therapies of GvHD lead to generalized immunosuppression followed by severe adverse side effects including infections and relapse of leukemia. Several novel cell-based immunomodulatory strategies for treatment or prevention of GvHD have been developed. Herein, thymus-derived regulatory T cells (tTreg, essential for the maintenance of peripheral immunologic tolerance, are in the focus of investigation. However, due to the limited number of tTreg in the peripheral blood, a complex, time- and cost-intensive in vitro expansion protocol is necessary for the production of an efficient cellular therapeutic. We demonstrated that activation of tTreg using the CD4-binding human immunodeficiency virus-1 protein gp120 leads to a substantially increased suppressor activity of tTreg without the need for additional expansion. Gp120-activated tTreg prevent GvHD development in a preclinical humanized mouse model. In addition, gp120 is not only effective in prevention but also in therapy of GvHD by suppressing all clinical symptoms and improving survival of treated mice. These data indicate that tTreg activation by gp120 is a feasible and potent strategy for significant functional improvement of tTreg as cellular therapeutic for GvHD treatment without the need of complicated, time-intensive, and expensive in vitro expansion of isolated tTreg.

  4. Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment.

    Science.gov (United States)

    Molins, B; Mesquida, M; Lee, R W J; Llorenç, V; Pelegrín, L; Adán, A

    2015-03-01

    The aim of this study was to quantify the proportion of regulatory T cells (Treg ) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)(+) Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4(+) T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3(+) Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3(+) Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3(+) Treg cells. © 2014 British Society for Immunology.

  5. Non-pharmacological treatment effects on psychosomatic and immune regulatory mechanisms in patients with rheumatic arthritis

    Directory of Open Access Journals (Sweden)

    Zharikova I.P.

    2014-12-01

    Full Text Available Objective: comparative analysis of the influence of the methods of the lateral ophthalmotilapia and low-intensity magnetic therapy on the Central and peripheral nervous system and the immune status in patients with rheumatoid arthritis. Material and methods: a comparative analysis of the impact of the 44 patients with rheumatoid arthritis aged 18 to 65 years, of which 19 patients (43.2 percent — 1 group received low-frequency low-intensity magnetic therapy and 25 patients (56.8 per cent — group 2, the lateral ophthalmotilapia. Results. In group 1 significantly improved memory both short-term (from 69.2±9.0 to 81,7±12,7, p=0.003, and the reminiscence relating to medium-term characteristics of memory (57,3±22 to 79,0±14,5; p=0.004. In patients of the 2nd group in the course of treatment was observed more pronounced dynamics of improvement of parameters of higher nervous activity, namely short-term memory (79,4±17 to 88,2±12, p=0.003and reminiscences of memory (from 69.4±27 to 82.4±19,5, p=0,0016. Conclusion. Lateral ophthalmotilapia and low-frequency magnetotherapy for help expand the list of rehabilitation programs in rheumatoid arthritis, the disease having dual autoimmune and psychosomatic genesis.

  6. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2

    DEFF Research Database (Denmark)

    Bjoern, J; Brimnes, M K; Andersen, M H

    2011-01-01

    In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-α and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high......) , was prospectively analysed in fresh blood, and treatment-associated quantitative and qualitative changes were analysed. By the 4th vaccine, patients showed a marked increase in CD4+ CD25(high) T cell subset from 6% to 22% (P...

  7. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2

    DEFF Research Database (Denmark)

    Bjoern, J; Brimnes, M K; Andersen, M H

    2011-01-01

    In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-a and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high......) , was prospectively analysed in fresh blood, and treatment-associated quantitative and qualitative changes were analysed. By the 4th vaccine, patients showed a marked increase in CD4+ CD25(high) T cell subset from 6% to 22% (P...

  8. A European regulatory perspective on cystic fibrosis: current treatments, trends in drug development and translational challenges for CFTR modulators.

    Science.gov (United States)

    Ponzano, Stefano; Nigrelli, Giulia; Fregonese, Laura; Eichler, Irmgard; Bertozzi, Fabio; Bandiera, Tiziano; Galietta, Luis J V; Papaluca, Marisa

    2018-06-30

    In this article we analyse the current authorised treatments and trends in early drug development for cystic fibrosis (CF) in the European Union for the time period 2000-2016. The analysis indicates a significant improvement in the innovation and development of new potential medicines for CF, shifting from products that act on the symptoms of the disease towards new therapies targeting the cause of CF. However, within these new innovative medicines, results for CF transmembrane conductance regulator (CFTR) modulators indicate that one major challenge for turning a CF concept product into an actual medicine for the benefit of patients resides in the fact that, although pre-clinical models have shown good predictability for certain mutations, a good correlation to clinical end-points or biomarkers ( e.g. forced expiratory volume in 1 s and sweat chloride) for all mutations has not yet been achieved. In this respect, the use of alternative end-points and innovative nonclinical models could be helpful for the understanding of those translational discrepancies. Collaborative endeavours to promote further research and development in these areas as well as early dialogue with the regulatory bodies available at the European competent authorities are recommended. Copyright ©ERS 2018.

  9. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2008-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  10. Triple axis spectrometers

    International Nuclear Information System (INIS)

    Clausen, K.N.

    1997-01-01

    Conventional triple-axis neutron spectroscopy was developed by Brockhouse over thirty years ago' and remains today a versatile and powerful tool for probing the dynamics of condensed matter. The original design of the triple axis spectrometer is technically simple and probes momentum and energy space on a point-by-point basis. This ability to systematically probe the scattering function in a way which only requires a few angles to be moved under computer control and where the observed data in general can be analysed using a pencil and graph paper or a simple fitting routine, has been essential for the success of the method. These constraints were quite reasonable at the time the technique was developed. Advances in computer based data acquisition, neutron beam optics, and position sensitive area detectors have been gradually implemented on many triple axis spectrometer spectrometers, but the full potential of this has not been fully exploited yet. Further improvement in terms of efficiency (beyond point by point inspection) and increased sensitivity (use of focusing optics whenever the problem allows it) could easily be up to a factor of 10-20 over present instruments for many problems at a cost which is negligible compared to that of increasing the flux of the source. The real cost will be in complexity - finding the optimal set-up for a given scan and interpreting the data as the they are taken. On-line transformation of the data for an appropriate display in Q, ω space and analysis tools will be equally important for this task, and the success of these new ideas will crucially depend on how well we solve these problems. (author)

  11. Vertical axis wind turbines

    Science.gov (United States)

    Krivcov, Vladimir [Miass, RU; Krivospitski, Vladimir [Miass, RU; Maksimov, Vasili [Miass, RU; Halstead, Richard [Rohnert Park, CA; Grahov, Jurij [Miass, RU

    2011-03-08

    A vertical axis wind turbine is described. The wind turbine can include a top ring, a middle ring and a lower ring, wherein a plurality of vertical airfoils are disposed between the rings. For example, three vertical airfoils can be attached between the upper ring and the middle ring. In addition, three more vertical airfoils can be attached between the lower ring and the middle ring. When wind contacts the vertically arranged airfoils the rings begin to spin. By connecting the rings to a center pole which spins an alternator, electricity can be generated from wind.

  12. Vertical axis wind turbine

    International Nuclear Information System (INIS)

    Obretenov, V.; Tsalov, T.; Chakarov, T.

    2012-01-01

    In recent years, the interest in wind turbines with vertical axis noticeably increased. They have some important advantages: low cost, relatively simple structure, reliable packaging system of wind aggregate long period during which require no maintenance, low noise, independence of wind direction, etc.. The relatively low efficiency, however, makes them applicable mainly for small facilities. The work presents a methodology and software for approximately aerodynamic design of wind turbines of this type, and also analyzed the possibility of improving the efficiency of their workflow

  13. Regulation mechanisms of pituitary-thyroid axis in normal subjects and patients with Graves' disease

    International Nuclear Information System (INIS)

    Takagi, Shinko; Yamauchi, Kazuyuki; Mori, Yuichi

    1986-01-01

    The regulatory mechanism of the pituitary-thyroid axis in normal subjects and patients with Graves' disease was investigated using a highly sensitive TSH assay based on the immunoradiometric assay. All of the normal subjects had detectable TSH values within the range 0.35 to 6.0 μU/ml. No negative correlations between TSH and free thyroid hormones existed in normal subjects. Patients with thyroid carcinoma who seemed to have normal pituitary-thyroid function showed a rapid increase of TSH after total thyroidectomy. On the other hand, while untreated patients with Graves' disease all had undetectable TSH values, these patients took 1 to 3.5 months longer to normalize their TSH values than to normalize free thyroid hormones on antithyroid drug therapy. During the recovery phase by the treatment with decrease of antithyroid drug or supplement of T 4 from iatrogenic hypothyroid state after treatment for Graves' disease and thyroid carcinoma, normalization of TSH levels was delayed than that of free thyroid hormones. Patients with Graves' disease in remission showed an extremely positive correlation between basal and peak TSH levels in TRH test, and a negative correlation between basal TSH and FT 4 . In conclusion, an individual patient may have a different set point concerning the regulatory mechanism of the pituitary-thyroid axis, and the persistence of the hyperthyroid state would seem to have caused some reversible dysfunction of the pituitary gland. (author)

  14. Treg cell-IgA axis in maintenance of host immune homeostasis with microbiota

    OpenAIRE

    Feng, Ting; Elson, Charles O.; Cong, Yingzi

    2010-01-01

    The intestine is the home to a vast diversity of microbiota and a complex of mucosal immune system. Multiple regulatory mechanisms control host immune responses to microbiota and maintain intestinal immune homeostasis. This mini review will provide evidence indicating a Treg cell-IgA axis and such axis playing a major role in maintenance of intestinal homeostasis.

  15. Viimsi water treatment plant for Ra removal: NORM residue/waste generation, radiation safety issues, and regulatory response

    Energy Technology Data Exchange (ETDEWEB)

    Kiisk, M.; Suursoo, S.; Realo, E.; Jantsikene, A.; Lumiste, L.; Vaeaer, K.; Isakar, K.; Koch, R. [University of Tartu (Estonia)

    2014-07-01

    values established for these radionuclides. The design and construction of the plant have underestimated the importance of aspects related to NORM accumulation and their management. Therefore, the level of Ra accumulation, ingrowth of daughter radionuclides (Th-228, Pb-210) and generation of Rn-220 and Rn-222 may pose great difficulties for the operation of the plant, especially in the case when/if the filter material is classified as NORM residue/waste with elevated radiation hazard for plant workers, public and the environment. As the first large-scale water treatment plant of the kind, there are no routine legal experience or administrative practice established in Estonia. This paper presents an overview of the operation of Viimsi Vesi Ltd. water treatment plant. The legal aspects and issues associated with management of NORM waste/residues, including classification (residue vs. waste), potential management options, optimisation of the management and radiation safety of the workers are discussed. Views of both the operator and the regulatory authority will be considered. Document available in abstract form only. (authors)

  16. Comorbid substance use disorders with other Axis I and II mental disorders among treatment-seeking Asian Americans, Native Hawaiians/Pacific Islanders, and mixed-race people

    Science.gov (United States)

    Wu, Li-Tzy; Blazer, Dan G.; Gersing, Kenneth R.; Burchett, Bruce; Swartz, Marvin S.; Mannelli, Paolo

    2013-01-01

    Little is known about behavioral healthcare needs of Asian Americans (AAs), Native Hawaiians/Pacific Islanders (NHs/PIs), and mixed-race people (MRs)—the fastest growing segments of the U.S. population. We examined substance use disorder (SUD) prevalences and comorbidities among AAs, NHs/PIs, and MRs (N=4572) in a behavioral health electronic health record database. DSM-IV diagnoses among patients aged 1–90 years who accessed behavioral healthcare from 11 sites were systematically captured: SUD, anxiety, mood, personality, adjustment, childhood-onset, cognitive/dementia, dissociative, eating, factitious, impulse-control, psychotic/schizophrenic, sleep, and somatoform diagnoses. Of all patients, 15.0% had a SUD. Mood (60%), anxiety (31.2%), adjustment (30.9%), and disruptive (attention deficit-hyperactivity, conduct, oppositional defiant, disruptive behavior diagnosis, 22.7%) diagnoses were more common than others (psychotic 14.2%, personality 13.3%, other childhood-onset 11.4%, impulse-control 6.6%, cognitive 2.8%, eating 2.2%, somatoform 2.1%). Less than 1% of children aged sex, treatment setting, length of treatment, and number of comorbid diagnoses, NHs/PIs and MRs were about two times more likely than AAs to have ≥2 SUDs. Regardless of race/ethnicity, personality diagnosis was comorbid with SUD. NHs/PIs with a mood diagnosis had elevated odds of having SUD. Findings present the most comprehensive patterns of mental diagnoses available for treatment-seeking AAs, NHs/PIs, and MRs in the real-world medical setting. In-depth research is needed to elucidate intraracial and interracial differences in treatment needs. PMID:24060266

  17. Arsenic trioxide decreases the amount and inhibits the function of regulatory T cells, which may contribute to its efficacy in the treatment of acute promyelocytic leukemia.

    Science.gov (United States)

    Xu, Wen; Li, Xiaoxia; Quan, Lina; Yao, Jiying; Mu, Guannan; Guo, Jingjie; Wang, Yitong

    2018-03-01

    Arsenic trioxide (ATO) exhibits substantial clinical efficacy in the treatment of acute promyelocytic leukemia (APL). Here, we investigated whether ATO exerts its efficacy by affecting regulatory T (Treg) cells. We determined whether ATO treatment influenced the amount and function of purified Treg cells. We also examined the effect of ATO treatment on Treg cells from APL patients. ATO treatment induced apoptosis in purified Treg cells and dampened the inhibition of effector T (Teff) cells proliferation and the secretion of cytokine by Treg cells. Treg cell levels in the peripheral blood and serum IL-10 levels were dramatically decreased in APL patients after single ATO treatment. In summary, our results show that ATO decreases the amount and inhibits the function of Treg cells, thereby enhancing Teff cell function and overall anti-tumor immunity.

  18. Targeting the PD-1/PD-L1 Immune Evasion Axis With DNA Aptamers as a Novel Therapeutic Strategy for the Treatment of Disseminated Cancers.

    Science.gov (United States)

    Prodeus, Aaron; Abdul-Wahid, Aws; Fischer, Nicholas W; Huang, Eric H-B; Cydzik, Marzena; Gariépy, Jean

    2015-04-28

    Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a number of other tumor types as both a monotherapy and as part of combination regimens. Here, we report the development of DNA aptamers as synthetic, nonimmunogenic antibody mimics, which bind specifically to the murine extracellular domain of PD-1 and block the PD-1:PD-L1 interaction. One such aptamer, MP7, functionally inhibits the PD-L1-mediated suppression of IL-2 secretion in primary T-cells. A PEGylated form of MP7 retains the ability to block the PD-1:PD-L1 interaction, and significantly suppresses the growth of PD-L1+ colon carcinoma cells in vivo with a potency equivalent to an antagonistic anti-PD-1 antibody. Importantly, the anti-PD-1 DNA aptamer treatment was not associated with off-target TLR-9-related immune responses. Due to the inherent advantages of aptamers including their lack of immunogenicity, low cost, long shelf life, and ease of synthesis, PD-1 antagonistic aptamers may represent an attractive alternative over antibody-based anti PD-1 therapeutics.

  19. Targeting the PD-1/PD-L1 Immune Evasion Axis With DNA Aptamers as a Novel Therapeutic Strategy for the Treatment of Disseminated Cancers

    Directory of Open Access Journals (Sweden)

    Aaron Prodeus

    2015-01-01

    Full Text Available Blocking the immunoinhibitory PD-1:PD-L1 pathway using monoclonal antibodies has led to dramatic clinical responses by reversing tumor immune evasion and provoking robust and durable antitumor responses. Anti-PD-1 antibodies have now been approved for the treatment of melanoma, and are being clinically tested in a number of other tumor types as both a monotherapy and as part of combination regimens. Here, we report the development of DNA aptamers as synthetic, nonimmunogenic antibody mimics, which bind specifically to the murine extracellular domain of PD-1 and block the PD-1:PD-L1 interaction. One such aptamer, MP7, functionally inhibits the PD-L1-mediated suppression of IL-2 secretion in primary T-cells. A PEGylated form of MP7 retains the ability to block the PD-1:PD-L1 interaction, and significantly suppresses the growth of PD-L1+ colon carcinoma cells in vivo with a potency equivalent to an antagonistic anti-PD-1 antibody. Importantly, the anti-PD-1 DNA aptamer treatment was not associated with off-target TLR-9-related immune responses. Due to the inherent advantages of aptamers including their lack of immunogenicity, low cost, long shelf life, and ease of synthesis, PD-1 antagonistic aptamers may represent an attractive alternative over antibody-based anti PD-1 therapeutics.

  20. A Point Source of a Different Color: Identifying a Gap in United States Regulatory Policy for “Green” CSO Treatment Using Constructed Wetlands

    Directory of Open Access Journals (Sweden)

    Zeno F. Levy

    2014-04-01

    Full Text Available Up to 850 billion gallons of untreated combined sewer overflow (CSO is discharged into waters of the United States each year. Recent changes in CSO management policy support green infrastructure (GI technologies as “front of the pipe” approaches to discharge mitigation by detention/reduction of urban stormwater runoff. Constructed wetlands for CSO treatment have been considered among suites of GI solutions. However, these wetlands differ fundamentally from other GI technologies in that they are “end of the pipe” treatment systems that discharge from a point source, and are therefore regulated in the U.S. under the National Pollution Discharge Elimination System (NPDES. We use a comparative regulatory analysis to examine the U.S. policy framework for CSO treatment wetlands. We find in all cases that permitting authorities have used best professional judgment to determine effluent limits and compliance monitoring requirements, referencing technology and water quality-based standards originally developed for traditional “grey” treatment systems. A qualitative comparison with Europe shows less stringent regulatory requirements, perhaps due to institutionalized design parameters. We recommend that permitting authorities develop technical guidance documents for evaluation of “green” CSO treatment systems that account for their unique operational concerns and benefits with respect to sustainable development.

  1. Manipulation of the Growth Hormone-Insulin-Like Growth Factor (GH-IGF) Axis: A Treatment Strategy to Reverse the Effects of Early Life Developmental Programming.

    Science.gov (United States)

    Reynolds, Clare M; Perry, Jo K; Vickers, Mark H

    2017-08-08

    Evidence from human clinical, epidemiological, and experimental animal models has clearly highlighted a link between the early life environment and an increased risk for a range of cardiometabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and overnutrition, spanning exposure windows that cover the period from preconception through to early infancy, clearly highlight an increased risk for a range of disorders in offspring in later life. This process, preferentially termed "developmental programming" as part of the developmental origins of health and disease (DOHaD) framework, leads to phenotypic outcomes in offspring that closely resemble those of individuals with untreated growth hormone (GH) deficiency, including increased adiposity and cardiovascular disorders. As such, the use of GH as a potential intervention strategy to mitigate the effects of developmental malprogramming has received some attention in the DOHaD field. In particular, experimental animal models have shown that early GH treatment in the setting of poor maternal nutrition can partially rescue the programmed phenotype, albeit in a sex-specific manner. Although the mechanisms remain poorly defined, they include changes to endothelial function, an altered inflammasome, changes in adipogenesis and cardiovascular function, neuroendocrine effects, and changes in the epigenetic regulation of gene expression. Similarly, GH treatment to adult offspring, where an adverse metabolic phenotype is already manifest, has shown efficacy in reversing some of the metabolic disorders arising from a poor early life environment. Components of the GH-insulin-like growth factor (IGF)-IGF binding protein (GH-IGF-IGFBP) system, including insulin-like growth factor 1 (IGF-1), have also shown promise in ameliorating programmed metabolic disorders, potentially acting via epigenetic processes including changes in miRNA profiles and altered DNA methylation. However, as

  2. Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome

    DEFF Research Database (Denmark)

    Bueno, Héctor; de Graeff, Pieter; Richard-Lordereau, Isabelle

    2016-01-01

    syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic...... researchers, trialists, European and US regulators, and pharmaceutical industry researchers. Specific questions in four key areas were selected as priorities for changes in regulatory guidance: patient selection, endpoints, methodologic issues and issues related to the research for novel agents. Patients......Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary...

  3. Regulatory activities

    International Nuclear Information System (INIS)

    2001-01-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

  4. Regulatory and Technical Issues Concerning the Detection and Treatment of NDMA-Contaminated Groundwater at NASA WSTF

    Science.gov (United States)

    Wiebe, D. T.; Zigmond, M. J.; Tufts, C. A.

    2002-01-01

    The National Aeronautics and Space Administration (NASA) White Sands Test Facility (WSTF) was established in 1963 primarily to provide rocket engine testing services for several NASA programs. The groundwater underlying the site has been contaminated as a result of historical operations. Groundwater contaminants include several volatile organic compounds (VOCs) and two semi-volatile compounds: N-nitrosodimethylamine (NDMA) and N-nitrodimethylamine (DMN). This paper discusses some of the technical, analytical, regulatory, and health risk issues associated with the contaminant plume. The plume has moved approximately 2.5 miles downgradient of the facility industrial boundary, with evidence of continued migration. As a result, NASA has proposed a pump and treat system using air strippers and ultraviolet (UV) oxidation to stabilize future movement of the contaminant plume. The system has been designed to treat 1,076 gallons (4,073 liters) per minute, with provisions for future expansion. The UV oxidation process was selected to treat NDMA-contaminated groundwater based on successes at other NDMA-contaminated sites. Bench- and pilot-scale testing of WSTF groundwater confirmed the ability of UV oxidation to destroy NDMA and generated sufficient data to design the proposed full-scale treatment system. NDMA is acutely toxic and is a probable human carcinogen. EPA-recommended health risk criteria for the residential consumption of NDMA/DMN-contaminated groundwater was used to determine that a 1.0 x 10(exp -6) excess cancer risk corresponds to 1.7 parts per trillion (ppt). EPA analytical methods are unable to detect NDMA and DMN in the low ppt range. EPA's current Appendix IX analytical method used to screen for NDMA, Method 8270, can detect NDMA only at levels that are orders of magnitude greater than the recommended health risk level. Additionally, EPA Method 607, the most sensitive EPA approved method, has a detection limit of 150 ppt. This corresponds to an excess cancer

  5. Treating co-occurring Axis I disorders in recurrently suicidal women with borderline personality disorder: a 2-year randomized trial of dialectical behavior therapy versus community treatment by experts.

    Science.gov (United States)

    Harned, Melanie S; Chapman, Alexander L; Dexter-Mazza, Elizabeth T; Murray, Angela; Comtois, Katherine A; Linehan, Marsha M

    2008-12-01

    This study evaluated whether dialectical behavior therapy (DBT) was more efficacious than treatment by nonbehavioral psychotherapy experts in reducing co-occurring Axis I disorders among suicidal individuals with borderline personality disorder (BPD). Women with BPD and recent and repeated suicidal and/or self-injurious behavior (n = 101) were randomly assigned to 1 year of DBT or community treatment by experts (CTBE), plus 1 year of follow-up assessment. For substance dependence disorders (SDD), DBT patients were more likely to achieve full remission, spent more time in partial remission, spent less time meeting full criteria, and reported more drug- and alcohol-abstinent days than did CTBE patients. These findings suggest that improvements in co-occurring SDD among suicidal BPD patients are specific to DBT and cannot be attributed to general factors associated with nonbehavioral expert psychotherapy. Further, group differences in SDD remission were not explained by either psychotropic medication usage or changes in BPD criterion behaviors. DBT and CTBE did not significantly differ in the reduction of anxiety disorders, eating disorders, or major depressive disorder.

  6. Neurofibromin regulates somatic growth through the hypothalamic–pituitary axis

    Science.gov (United States)

    Hegedus, Balazs; Yeh, Tu-Hsueh; Lee, Da Yong; Emnett, Ryan J.; Li, Jia; Gutmann, David H.

    2008-01-01

    To study the role of the neurofibromatosis-1 (NF1) gene in mammalian brain development, we recently generated mice in which Nf1 gene inactivation occurs in neuroglial progenitor cells using the brain lipid binding protein (BLBP) promoter. We found that Nf1BLBPCKO mice exhibit significantly reduced body weights and anterior pituitary gland sizes. We further demonstrate that the small anterior pituitary size reflects loss of neurofibromin expression in the hypothalamus, leading to reduced growth hormone releasing hormone, pituitary growth hormone (GH) and liver insulin-like growth factor-1 (IGF1) production. Since neurofibromin both negatively regulates Ras activity and positively modulates cAMP levels, we examined the signaling pathway responsible for these abnormalities. While BLBP-mediated expression of an activated Ras molecule did not recapitulate the body weight and hypothalamic/pituitary defects, treatment of Nf1BLBPCKO mice with rolipram to increase cAMP levels resulted in a partial restoration of the body weight phenotype. Furthermore, conditional expression of the Ras regulatory GAP domain of neurofibromin also did not rescue the body weight or Igf1 mRNA defects in Nf1BLBPCKO mice. Collectively, these data demonstrate a critical role for neurofibromin in hypothalamic–pituitary axis function and provide further insights into the short stature and GH deficits seen in children with NF1. PMID:18614544

  7. Violacein Treatment Modulates Acute and Chronic Inflammation through the Suppression of Cytokine Production and Induction of Regulatory T Cells.

    Directory of Open Access Journals (Sweden)

    Liana Verinaud

    Full Text Available Inflammation is a necessary process to control infection. However, exacerbated inflammation, acute or chronic, promotes deleterious effects in the organism. Violacein (viola, a quorum sensing metabolite from the Gram-negative bacterium Chromobacterium violaceum, has been shown to protect mice from malaria and to have beneficial effects on tumors. However, it is not known whether this drug possesses anti-inflammatory activity. In this study, we investigated whether viola administration is able to reduce acute and chronic autoimmune inflammation. For that purpose, C57BL/6 mice were intraperitoneally injected with 1 μg of LPS and were treated with viola (3.5mg/kg via i.p. at the same time-point. Three hours later, the levels of inflammatory cytokines in the sera and phenotypical characterization of leukocytes were determined. Mice treated with viola presented a significant reduction in the production of inflammatory cytokines compared with untreated mice. Interestingly, although viola is a compound derived from bacteria, it did not induce inflammation upon administration to naïve mice. To test whether viola would protect mice from an autoimmune inflammation, Experimental Autoimmune Encephalomyelitis (EAE-inflicted mice were given viola i.p. at disease onset, at the 10th day from immunization. Viola-treated mice developed mild EAE disease in contrast with placebo-treated mice. The frequencies of dendritic cells and macrophages were unaltered in EAE mice treated with viola. However, the sole administration of viola augmented the levels of splenic regulatory T cells (CD4+Foxp3+. We also found that adoptive transfer of viola-elicited regulatory T cells significantly reduced EAE. Our study shows, for the first time, that violacein is able to modulate acute and chronic inflammation. Amelioration relied in suppression of cytokine production (in acute inflammation and stimulation of regulatory T cells (in chronic inflammation. New studies must be

  8. Gonadal Steroid Hormones and the Hypothalamo-Pituitary-Adrenal Axis

    OpenAIRE

    Handa, Robert J.; Weiser, Michael J.

    2013-01-01

    The hypothalamo-pituitary-adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, pr...

  9. Substantially Modified Ratios of Effector to Regulatory T Cells During Chemotherapy in Ovarian Cancer Patients Return to Pre-Treatment Levels at Completion: Implications for Immunotherapy

    International Nuclear Information System (INIS)

    Park, Anthony; Govindaraj, Chindu; Xiang, Sue D.; Halo, Julene; Quinn, Michael; Scalzo-Inguanti, Karen; Plebanski, Magdalena

    2012-01-01

    Ovarian cancer is the leading cause of death from gynaecological malignancy. Despite improved detection and treatment options, relapse rates remain high. Combining immunotherapy with the current standard treatments may provide an improved prognosis, however, little is known about how standard chemotherapy affects immune potential (particularly T cells) over time, and hence, when to optimally combine it with immunotherapy (e.g., vaccines). Herein, we assess the frequency and ratio of CD8+ central memory and effector T cells as well as CD4+ effector and regulatory T cells (Tregs) during the first 18 weeks of standard chemotherapy for ovarian cancer patients. In this pilot study, we observed increased levels of recently activated Tregs with tumor migrating ability (CD4+CD25 hi Foxp3+CD127−CCR4+CD38+ cells) in patients when compared to controls. Although frequency changes of Tregs as well as the ratio of effector T cells to Tregs were observed during treatment, the Tregs consistently returned to pre-chemotherapy levels at the end of treatment. These results indicate T cell subset distributions associated with recurrence may be largely resistant to being “re-set” to healthy control homeostatic levels following standard treatments. However, it may be possible to enhance T effector to Treg ratios transiently during chemotherapy. These results suggest personalized immune monitoring maybe beneficial when combining novel immuno-therapeutics with standard treatment for ovarian cancer patients

  10. Substantially Modified Ratios of Effector to Regulatory T Cells During Chemotherapy in Ovarian Cancer Patients Return to Pre-Treatment Levels at Completion: Implications for Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Park, Anthony; Govindaraj, Chindu; Xiang, Sue D., E-mail: Sue.Xiang@monash.edu [Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria 3004 (Australia); Halo, Julene; Quinn, Michael [Department of Oncology, Royal Women’s Hospital, Melbourne, Victoria 3052 (Australia); Scalzo-Inguanti, Karen; Plebanski, Magdalena, E-mail: Sue.Xiang@monash.edu [Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria 3004 (Australia)

    2012-06-18

    Ovarian cancer is the leading cause of death from gynaecological malignancy. Despite improved detection and treatment options, relapse rates remain high. Combining immunotherapy with the current standard treatments may provide an improved prognosis, however, little is known about how standard chemotherapy affects immune potential (particularly T cells) over time, and hence, when to optimally combine it with immunotherapy (e.g., vaccines). Herein, we assess the frequency and ratio of CD8+ central memory and effector T cells as well as CD4+ effector and regulatory T cells (Tregs) during the first 18 weeks of standard chemotherapy for ovarian cancer patients. In this pilot study, we observed increased levels of recently activated Tregs with tumor migrating ability (CD4+CD25{sup hi}Foxp3+CD127−CCR4+CD38+ cells) in patients when compared to controls. Although frequency changes of Tregs as well as the ratio of effector T cells to Tregs were observed during treatment, the Tregs consistently returned to pre-chemotherapy levels at the end of treatment. These results indicate T cell subset distributions associated with recurrence may be largely resistant to being “re-set” to healthy control homeostatic levels following standard treatments. However, it may be possible to enhance T effector to Treg ratios transiently during chemotherapy. These results suggest personalized immune monitoring maybe beneficial when combining novel immuno-therapeutics with standard treatment for ovarian cancer patients.

  11. Pharmacodynamic/Pharmacogenomic Modeling of Insulin Resistance Genes in Rat Muscle After Methylprednisolone Treatment: Exploring Regulatory Signaling Cascades

    Directory of Open Access Journals (Sweden)

    Zhenling Yao

    2008-01-01

    Full Text Available Corticosteroids (CS effects on insulin resistance related genes in rat skeletal muscle were studied. In our acute study, adrenalectomized (ADX rats were given single doses of 50 mg/kg methylprednisolone (MPL intravenously. In our chronic study, ADX rats were implanted with Alzet mini-pumps giving zero-order release rates of 0.3 mg/kg/h MPL and sacrificed at various times up to 7 days. Total RNA was extracted from gastrocnemius muscles and hybridized to Affymetrix GeneChips. Data mining and literature searches identified 6 insulin resistance related genes which exhibited complex regulatory pathways. Insulin receptor substrate-1 (IRS-1, uncoupling protein 3 (UCP3, pyruvate dehydrogenase kinase isoenzyme 4 (PDK4, fatty acid translocase (FAT and glycerol-3-phosphate acyltransferase (GPAT dynamic profiles were modeled with mutual effects by calculated nuclear drug-receptor complex (DR(N and transcription factors. The oscillatory feature of endothelin-1 (ET-1 expression was depicted by a negative feedback loop. These integrated models provide test- able quantitative hypotheses for these regulatory cascades.

  12. Low-level radioactive waste from commercial nuclear reactors. Volume 3. Bibliographic abstracts of significant source references. Part 2. Bibliography for treatment, storage, disposal and transportation regulatory constraints

    Energy Technology Data Exchange (ETDEWEB)

    Jolley, R.L.; Rodgers, B.R.

    1986-05-01

    The overall task of this program was to provide an assessment of currently available technology for treating commercial low-level radioactive waste (LLRW), to initiate development of a methodology for choosing one technology for a given application, and to identify research needed to improve current treatment techniques and decision methodology. The resulting report is issued in four volumes. Volume 3 of this series is a collection of abstracts of most of the reference documents used for this study. Because of the large volume of literature, the abstracts have been printed in two separate parts. Federal, state, and local regulations affect the decision process for selecting technology applications. Regulations may favor a particular technology and may prevent application of others. Volume 3, part 2 presents abstracts of the regulatory constraint documents that relate to all phases of LLRW management (e.g., treatment, packaging, storage, transportation, and disposal).

  13. To mitigate or not to mitigate: Regulatory treatment of emissions trading and its effect on marketplace incentives

    International Nuclear Information System (INIS)

    McDermott, K.A.

    1991-01-01

    The Clean Air Act Amendments of 1990 (hereafter CAAA) have created a market-based mechanism that is designed to employ a profit-oriented incentive to enable electric utilities to reduce SO 2 emissions at the least cost. One of the most important challenges facing state regulatory utility commissions in the next decade is the integration of this marker-based profit-incentive process into the traditional rate-base, rate-of-return, profit-control approach to regulation. How the struggle to meld two potentially contradictory control and incentive programs will be resolved remains to be seen. As of now, it is an open question. The purpose of this paper is to help clarify some of the issues that need to be addressed and to offer some policy recommendations that will allow regulators to employ the effectiveness of market forces while they still retain overall control of the evolution of the regulated electric supply market

  14. Gut Microbiota-brain Axis

    Institute of Scientific and Technical Information of China (English)

    Hong-Xing Wang; Yu-Ping Wang

    2016-01-01

    Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

  15. Vertical axis wind turbine airfoil

    Science.gov (United States)

    Krivcov, Vladimir; Krivospitski, Vladimir; Maksimov, Vasili; Halstead, Richard; Grahov, Jurij Vasiljevich

    2012-12-18

    A vertical axis wind turbine airfoil is described. The wind turbine airfoil can include a leading edge, a trailing edge, an upper curved surface, a lower curved surface, and a centerline running between the upper surface and the lower surface and from the leading edge to the trailing edge. The airfoil can be configured so that the distance between the centerline and the upper surface is the same as the distance between the centerline and the lower surface at all points along the length of the airfoil. A plurality of such airfoils can be included in a vertical axis wind turbine. These airfoils can be vertically disposed and can rotate about a vertical axis.

  16. Helical axis stellarator equilibrium model

    International Nuclear Information System (INIS)

    Koniges, A.E.; Johnson, J.L.

    1985-02-01

    An asymptotic model is developed to study MHD equilibria in toroidal systems with a helical magnetic axis. Using a characteristic coordinate system based on the vacuum field lines, the equilibrium problem is reduced to a two-dimensional generalized partial differential equation of the Grad-Shafranov type. A stellarator-expansion free-boundary equilibrium code is modified to solve the helical-axis equations. The expansion model is used to predict the equilibrium properties of Asperators NP-3 and NP-4. Numerically determined flux surfaces, magnetic well, transform, and shear are presented. The equilibria show a toroidal Shafranov shift

  17. An investigation of the differential effectiveness of bibliotherapy and self-regulatory treatments in individuals with panic attacks

    OpenAIRE

    Febbraro, Gregorio A. R.

    1997-01-01

    Several studies targeting individuals with panic disorder have demonstrated that Cognitive-behavioral treatment (CST) is the psychological treatment of choice. CST interventions that include exposure to panic symptoms, along with cognitive restructuring. breathing retraining, and relaxation training are more effective than any of these components administered alone. Past studies have demonstrated the efficacy of imparting the above CBT components in the form of bibliotherapy (BT) ...

  18. The Traumatic Brain Injury Endpoints Development (TED) Initiative: Progress on a Public-Private Regulatory Collaboration to Accelerate Diagnosis and Treatment of Traumatic Brain Injury.

    Science.gov (United States)

    Manley, Geoffrey T; MacDonald, Christine L; Markowitz, Amy; Stephenson, Diane; Robbins, Ann; Gardner, Raquel C; Winkler, Ethan A; Bodien, Yelena; Taylor, Sabrina; Yue, John K; Kannan, Lakshmi; Kumar, Allison; McCrea, Michael; Wang, Kevin K W

    2017-03-31

    The Traumatic Brain Injury Endpoints Development (TED) Initiative is a 5-year, Department of Defense (DoD) funded project that is working toward the ultimate goal of developing better designed clinical trials, leading to more precise diagnosis, and effective treatments for traumatic brain injury (TBI). TED is comprised of leading academic clinician-scientists, along with innovative industry leaders in biotechnology and imaging technology, patient advocacy organizations, and philanthropists, working collaboratively with regulatory authorities, specifically the US Food and Drug Administration (FDA). The goals of the TED Initiative are to gain consensus and validation of TBI clinical outcome assessment measures and biomarkers for endorsement by global regulatory agencies for use in drug and device development processes. This manuscript summarizes the Initiative's Stage 1 progress over the first 18 months, including intensive engagement with a number of FDA divisions responsible for review and validation of biomarkers and clinical outcome assessments, progression into the prequalification phase of FDA's Medical Device Development Tool program for a candidate set of neuroimaging biomarkers, and receipt of FDA's Recognition of Research Importance Letter regarding TBI. Other signal achievements relate to the creation of the TED Metadataset, harmonizing study measures across eight major TBI studies, and the leadership role played by TED investigators in the conversion of the NINDS TBI Common Data Elements (CDEs) to Clinical Data Interchange Standards Consortium (CDISC) standards. This paper frames both the near-term expectations and the Initiative's long-term vision to accelerate approval of treatments for patients affected by TBI in urgent need of effective therapies.

  19. Single or combined treatment with L-DOPA and quinpirole differentially modulate expression and phosphorylation of key regulatory kinases in neuroblastoma cells.

    Science.gov (United States)

    Fuzzati-Armentero, Marie Therese; Ghezzi, Cristina; Nisticò, Robert; Oda, Adriano; Blandini, Fabio

    2013-09-27

    In the past decades, the clinical use of dopamine agonists has expanded from adjunct therapy in patients with a deteriorating response to L-3,4-dihydroxyphenylalanine (L-DOPA) to monotherapy for the treatment of early PD. Dopamine agonists provide their antiparkinsonian benefit through stimulation of brain postsynaptic type 2 dopamine receptors that exert their effect through classical cAMP-dependent mechanisms, as well as cAMP-independent cellular signaling cascades, including the Akt/glycogen synthase kinase 3 (GSK3) pathway. Alterations of Akt/GSK3 have been observed and may contribute to the neurodegenerative processes and the development of L-DOPA-induced dyskinesia. The effects L-DOPA and quinpirole, a dopamine agonist, on the two key regulatory kinases, Akt and GSK3, were evaluated in neuroblastoma cell line. L-DOPA and dopamine agonist dose-dependently and differentially modulated Akt and GSK3 expression and phosphorylation when added alone or combined. The combined treatment inverted or potentiated the modulatory properties of the single compound. The drug- and concentration-dependent balance of dopamine receptor stimulation over auto-oxidation may distinctively modulate GSK3 isoforms and Akt. Our results indicate that particular attention must be given to drug concentration and combination when multiple therapies are applied for the clinical treatment of PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model.

    Science.gov (United States)

    Ardawi, Mohammed-Salleh M; Badawoud, Mohammed H; Hassan, Sherif M; Rouzi, Abdulrahim A; Ardawi, Jumanah M S; AlNosani, Nouf M; Qari, Mohammed H; Mousa, Shaker A

    2016-02-01

    Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n=264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2μg/kg body weight per day), for 12weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture. Copyright © 2015. Published by Elsevier Inc.

  1. Fel d 1-derived synthetic peptide immuno-regulatory epitopes show a long-term treatment effect in cat allergic subjects.

    Science.gov (United States)

    Couroux, P; Patel, D; Armstrong, K; Larché, M; Hafner, R P

    2015-05-01

    Cat-PAD, the first in a new class of synthetic peptide immuno-regulatory epitopes (SPIREs), was shown to significantly improve rhinoconjunctivitis symptoms in subjects with cat allergy up to 1 year after the start of a short course of treatment. To evaluate the long-term effects of Cat-PAD on rhinoconjunctivitis symptoms following standardized allergen challenge 2 years after treatment. In a randomized, double-blind, placebo-controlled, parallel group study, subjects were exposed to cat allergen in an environmental exposure chamber (EEC) before and after treatment with two regimens of Cat-PAD (either eight doses of 3 nmol or four doses of 6 nmol) given intradermally over a 3-month period. In this follow-up study, changes from baseline in rhinoconjunctivitis symptoms were reassessed 2 years after the start of treatment. The primary endpoint showed a mean reduction in total rhinoconjunctivitis symptom scores of 3.85 units in the 4 × 6 nmol Cat-PAD group compared to placebo 2 years after the start of treatment (P = 0.13), and this difference was statistically significant in the secondary endpoint at the end of day 4 when the cumulative allergen challenge was greatest (P = 0.02). Consistent reductions in nasal symptoms of between 2 and 3 units were observed for 4 × 6 nmol Cat-PAD compared to placebo between the 2 and 3 h time points on days 1-4 of EEC challenge at 2 years (P Cat-PAD. This study is the first to provide evidence of a long-term therapeutic effect with this new class of SPIREs. © 2015 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

  2. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  3. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

    Regulatory governance frameworks have become essential building blocks of world society. From supply chains to the regimes surrounding international organizations, extensive governance frameworks have emerged which structure and channel a variety of social exchanges, including economic, political...... by the International Transitional Administrations (ITAs) in Kosovo and Iraq as well as global supply chains and their impact on the garment industry in Bangladesh....

  4. Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment.

    Science.gov (United States)

    Soldevila, Berta; Alonso, Núria; Martínez-Arconada, Maria J; Granada, Maria L; Boada, Aram; Vallejos, Virginia; Fraile, Manuel; Fernández-Sanmartín, Marco A; Pujol-Borrell, Ricardo; Puig-Domingo, Manel; Sanmartí, Anna; Martínez-Cáceres, Eva M

    2013-04-01

    One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined. Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT. From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT). Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001). Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT. © 2012 Blackwell Publishing Ltd.

  5. The hypothalamic–pituitary–adrenal axis and sex hormones in chronic stress and obesity: pathophysiological and clinical aspects

    Science.gov (United States)

    Pasquali, Renato

    2012-01-01

    Obesity, particularly the abdominal phenotype, has been ascribed to an individual maladaptation to chronic environmental stress exposure mediated by a dysregulation of related neuroendocrine axes. Alterations in the control and action of the hypothalamic–pituitary–adrenal axis play a major role in this context, with the participation of the sympathetic nervous system. The ability to adapt to chronic stress may differ according to sex, with specific pathophysiological events leading to the development of stress-related chronic diseases. This seems to be influenced by the regulatory effects of sex hormones, particularly androgens. Stress may also disrupt the control of feeding, with some differences according to sex. Finally, the amount of experimental data in both animals and humans may help to shed more light on specific phenotypes of obesity, strictly related to the chronic exposure to stress. This challenge may potentially imply a different pathophysiological perspective and, possibly, a specific treatment. PMID:22612409

  6. Cognitive and Self-regulatory Mechanisms of Obesity Study (COSMOS): Study protocol for a randomized controlled weight loss trial examining change in biomarkers, cognition, and self-regulation across two behavioral treatments.

    Science.gov (United States)

    Hawkins, M A W; Colaizzi, Janna; Gunstad, John; Hughes, Joel W; Mullins, Larry L; Betts, Nancy; Smith, Caitlin E; Keirns, Natalie G; Vohs, Kathleen D; Moore, Shirley M; Forman, Evan M; Lovallo, William R

    2018-03-01

    Obesity is a global epidemic, yet successful interventions are rare. Up to 60% of people fail to achieve clinically meaningful, short-term weight loss (5-10% of start weight), whereas up to 72% are unsuccessful at achieving long-term weight loss (5-10% loss for ≥5years). Understanding how biological, cognitive, and self-regulatory factors work together to promote or to impede weight loss is clearly needed to optimize obesity treatment. This paper describes the methodology of the Cognitive and Self-regulatory Mechanisms of Obesity Study (the COSMOS trial). COSMOS is the first randomized controlled trial to investigate how changes in multiple biopsychosocial and cognitive factors relate to weight loss and one another across two weight loss treatments. The specific aims are to: 1) Confirm that baseline obesity-related physiological dysregulation is linked to cognitive deficits and poorer self-regulation, 2) Evaluate pre- to post-treatment change across time to assess individual differences in biomarkers, cognition, and self-regulation, and 3) Evaluate whether the acceptance-based treatment (ABT) group has greater improvements in outcomes (e.g., greater weight loss and less weight regain, improvements in biomarkers, cognition, and self-regulation), than the standard behavioral treatment group (SBT) from pre- to post-treatment and 1-year follow-up. The results of COSMOS will provide critical information about how dysregulation in biomarkers, cognition, and/or self-regulation is related to weight loss and whether weight loss treatments are differentially associated with these factors. This information will be used to identify promising treatment targets that are informed by biological, cognitive, and self-regulatory factors in order to advance obesity treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Role of Met Axis in Head and Neck Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yiru, E-mail: xuyiru@umich.edu; Fisher, Gary J., E-mail: xuyiru@umich.edu [Department of Dermatology, University of Michigan, Ann Arbor, MI 48109 (United States)

    2013-11-26

    Head and neck cancer is the sixth most common type of cancer worldwide. Despite advances in aggressive multidisciplinary treatments, the 5-year survival rate for this dreadful disease is only 50%, mostly due to high rate of recurrence and early involvement of regional lymph nodes and subsequent metastasis. Understanding the molecular mechanisms responsible for invasion and metastasis is one of the most pressing goals in the field of head and neck cancer. Met, also known as hepatocyte growth factor receptor (HGFR), is a member of the receptor protein tyrosine kinase (RPTK) family. There is compelling evidence that Met axis is dysregulated and plays important roles in tumorigenesis, progression, metastasis, angiogenesis, and drug resistance in head and neck cancer. We describe in this review current understanding of Met axis in head and neck cancer biology and development of therapeutic inhibitors targeting Met axis.

  8. A cytokine axis regulates elastin formation and degradation

    Science.gov (United States)

    Sproul, Erin P.; Argraves, W. Scott

    2013-01-01

    Underlying the dynamic regulation of tropoelastin expression and elastin formation in development and disease are transcriptional and post-transcriptional mechanisms that have been the focus of much research. Of particular importance is the cytokine–governed elastin regulatory axis in which the pro-elastogenic activities of transforming growth factor β-1 (TGFβ1) and insulin-like growth factor-I (IGF-I) are opposed by anti-elastogenic activities of basic fibroblast growth factor (bFGF/FGF-2), heparin-binding epidermal growth factor-like growth factor (HB-EGF), EGF, PDGF-BB, TGFα, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and noncanonical TGFβ1 signaling. A key mechanistic feature of the regulatory axis is that cytokines influence elastin formation through effects on the cell cycle involving control of cyclin–cyclin dependent kinase complexes and activation of the Ras/MEK/ERK signaling pathway. In this article we provide an overview of the major cytokines/growth factors that modulate elastogenesis and describe the underlying molecular mechanisms for their action on elastin production. PMID:23160093

  9. Anterior fixation of the axis.

    Science.gov (United States)

    Traynelis, Vincent C; Fontes, Ricardo B V

    2010-09-01

    Although anterior fixation of the axis is not commonly performed, plate fixation of C2 is an important technique for treating select upper cervical traumatic injuries and is also useful in the surgical management of spondylosis. To report the technique and outcomes of C2 anterior plate fixation for a series of patients in which the majority presented with symptomatic degenerative spondylosis. Forty-six consecutive patients underwent single or multilevel fusions over a 7-year period; 30 of these had advanced degenerative disease manifested by myelopathy or deformity. Exposure was achieved with rostral extension of the standard anterior cervical exposure via careful soft tissue dissection, mobilization of the superior thyroid artery, and the use of a table-mounted retractor. It was not necessary to remove the submandibular gland, section the digastric muscle, or make additional skin incisions. Screws were placed an average of 4.6 mm (+/- 2.3 mm) from the inferior C2 endplate with a mean sagittal trajectory of 15.7 degrees (+/- 7.6 degrees). Short- and long-term procedure-related mortality was 4.4%, and perioperative morbidity was 8.9%. Patients remained intubated an average of 2.5 days following surgery. Dysphagia was initially reported by 15.2% of patients but resolved by the 8th postoperative week in all patients. Arthrodesis was achieved in all patients available for long-term follow-up. Multilevel fusions were not associated with longer hospitalization or morbidity. Anterior plate fixation of the axis for degenerative disease can be accomplished with acceptable morbidity employing an extension of the standard anterolateral route.

  10. Autologous mesenchymal stem cell treatment increased T regulatory cells with no effect on disease activity in two systemic lupus erythematosus patients.

    Science.gov (United States)

    Carrion, F; Nova, E; Ruiz, C; Diaz, F; Inostroza, C; Rojo, D; Mönckeberg, G; Figueroa, F E

    2010-03-01

    Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the change in CD4+CD25+FoxP3+ T regulatory (Treg) cells in response to treatment. Two females (JQ and SA) of 19 and 25 years of age, fulfilling the 1997 American College of Rheumatology (ACR) criteria for SLE were infused with autologous BM-derived MSCs. Disease activity indexes and immunological parameters were assessed at baseline, 1, 2, 7 and 14 weeks. Peripheral blood lymphocyte (PBL) subsets and Treg cells were quantitated by flow cytometry, and MSCs tested for in-vitro suppression of activation and proliferation of normal PBLs. No adverse effects or change in disease activity indexes were noted during 14 weeks of follow-up, although circulating Treg cells increased markedly. Patient MSCs effectively suppressed in-vitro PBL function. However, JQ developed overt renal disease 4 months after infusion. MSC infusion was without adverse effects, but did not modify initial disease activity in spite of increasing CD4+CD25+FoxP3+ cell counts. One patient subsequently had a renal flare. We speculate that the suppressive effects of MSC-induced Treg cells might be dependent on a more inflammatory milieu, becoming clinically evident in patients with higher degrees of disease activity.

  11. Positive regulatory effects of perioperative probiotic treatment on postoperative liver complications after colorectal liver metastases surgery: a double-center and double-blind randomized clinical trial.

    Science.gov (United States)

    Liu, Zhihua; Li, Chao; Huang, Meijin; Tong, Chao; Zhang, Xingwei; Wang, Lei; Peng, Hui; Lan, Ping; Zhang, Peng; Huang, Nanqi; Peng, Junsheng; Wu, Xiaojian; Luo, Yanxing; Qin, Huanlong; Kang, Liang; Wang, Jianping

    2015-03-20

    Colorectal liver metastases (CLM) occur frequently and postoperative intestinal infection is a common complication. Our previous study showed that probiotics could decrease the rate of infectious complications after colectomy for colorectal cancer. To determine the effects of the perioperative administration of probiotics on serum zonulin levels which is a marker of intestinal permeability and the subsequent impact on postoperative infectious complications in patients with CLM. 150 patients with CLM were randomly divided into control group (n = 68) and probiotics group (n = 66). Probiotics and placebo were given orally for 6 days preoperatively and 10 days postoperatively to control group and probiotics group respectively. We used the local resection for metastatic tumor ,while for large tumor, the segmental hepatectomy. Postoperative outcome were recorded. Furthermore, complications in patients with normal intestinal barrier function and the relation with serum zonulin were analyzed to evaluate the impact on the liver barrier dysfunction. The incidence of infectious complications in the probiotics group was lower than control group. Analysis of CLM patients with normal postoperative intestinal barrier function paralleled with the serum zonulin level. And probiotics could also reduce the concentration of serum zonulin (P = 0.004) and plasma endotoxin (P zonulin level, the rate of postoperative septicemia and maintain the liver barrier in patients undergoing CLM surgery. we propose a new model about the regulation of probiotics to liver barrier via clinical regulatory pathway. We recommend the preoperative oral intake of probiotics combined with postoperative continued probiotics treatment in patients who undergo CLM surgery. ChiCTR-TRC- 12002841 . 2012/12/21.

  12. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  13. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of bench-marking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  14. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  15. Robustness and accuracy in sea urchin developmental gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Smadar eBen-Tabou De-Leon

    2016-02-01

    Full Text Available Developmental gene regulatory networks robustly control the timely activation of regulatory and differentiation genes. The structure of these networks underlies their capacity to buffer intrinsic and extrinsic noise and maintain embryonic morphology. Here I illustrate how the use of specific architectures by the sea urchin developmental regulatory networks enables the robust control of cell fate decisions. The Wnt-βcatenin signaling pathway patterns the primary embryonic axis while the BMP signaling pathway patterns the secondary embryonic axis in the sea urchin embryo and across bilateria. Interestingly, in the sea urchin in both cases, the signaling pathway that defines the axis controls directly the expression of a set of downstream regulatory genes. I propose that this direct activation of a set of regulatory genes enables a uniform regulatory response and a clear cut cell fate decision in the endoderm and in the dorsal ectoderm. The specification of the mesodermal pigment cell lineage is activated by Delta signaling that initiates a triple positive feedback loop that locks down the pigment specification state. I propose that the use of compound positive feedback circuitry provides the endodermal cells enough time to turn off mesodermal genes and ensures correct mesoderm vs. endoderm fate decision. Thus, I argue that understanding the control properties of repeatedly used regulatory architectures illuminates their role in embryogenesis and provides possible explanations to their resistance to evolutionary change.

  16. Modelling of the Hypothalamic-Pituitary-Adrenal Axis Perturbations by Externally Induced Cholesterol Pulses of Finite Duration and with Asymmetrically Distributed Concentration Profile

    Science.gov (United States)

    Stanojević, A.; Marković, V. M.; Čupić, Ž.; Vukojević, V.; Kolar-Anić, L.

    2017-12-01

    A model was developed that can be used to study the effect of gradual cholesterol intake by food on the HPA axis dynamics. Namely, well defined oscillatory dynamics of vital neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis has proven to be necessary for maintaining regular basal physiology and formulating appropriate stress response to various types of perturbations. Cholesterol, as a precursor of all steroid HPA axis hormones, can alter the dynamics of HPA axis. To analyse its particular influence on the HPA axis dynamics we used stoichiometric model of HPA axis activity, and simulate cholesterol perturbations in the form of finite duration pulses, with asymmetrically distributed concentration profile. Our numerical simulations showed that there is a complex, nonlinear dependence between the HPA axis responsiveness and different forms of applied cholesterol concentration pulses, indicating the significance of kinetic modelling, and dynamical systems theory for the understanding of large-scale self-regulatory, and homeostatic processes within this neuroendocrine system.

  17. Good Manufacturing Practice-Compliant Production and Lot-Release of Ex Vivo Expanded Regulatory T Cells As Basis for Treatment of Patients with Autoimmune and Inflammatory Disorders

    Directory of Open Access Journals (Sweden)

    Manuel Wiesinger

    2017-10-01

    Full Text Available In recent years, the exploration of regulatory T cell (Treg-based cellular therapy has become an attractive strategy to ameliorate inflammation and autoimmunity in various clinical settings. The main obstacle to the clinical application of Treg in human is their low number circulating in peripheral blood. Therefore, ex vivo expansion is inevitable. Moreover, isolation of Treg bears the risk of concurrent isolation of unwanted effector cells, which may trigger or deteriorate inflammation upon adoptive Treg transfer. Here, we present a protocol for the GMP-compliant production, lot-release and validation of ex vivo expanded Tregs for treatment of patients with autoimmune and inflammatory disorders. In the presented production protocol, large numbers of Treg, previously enriched from a leukapheresis product by using the CliniMACS® system, are ex vivo expanded in the presence of anti-CD3/anti-CD28 expander beads, exogenous IL-2 and rapamycin during 21 days. The expanded Treg drug product passed predefined lot-release criteria. These criteria include (i sterility testing, (ii assessment of Treg phenotype, (iii assessment of non-Treg cellular impurities, (iv confirmation of successful anti-CD3/anti-CD28 expander bead removal after expansion, and (v confirmation of the biological function of the Treg product. Furthermore, the Treg drug product was shown to retain its stability and suppressive function for at least 1 year after freezing and thawing. Also, dilution of the Treg drug product in 0.9% physiological saline did not affect Treg phenotype and Treg function for up to 90 min. These data indicate that these cells are ready to use in a clinical setting in which a cell infusion time of up to 90 min can be expected. The presented production process has recently undergone on site GMP-conform evaluation and received GMP certification from the Bavarian authorities in Germany. This protocol can now be used for Treg-based therapy of various

  18. Targeting the gut-liver axis in cirrhosis

    DEFF Research Database (Denmark)

    Madsen, Bjørn S; Havelund, Troels; Krag, Aleksander

    2013-01-01

    The gut-liver axis in cirrhosis and portal hypertension is gaining increasing attention as a key pathophysiological mechanism responsible for progression of liver failure and development of complications such as spontaneous infections and hepatocellular carcinoma. Antibiotics and non-selective β......-blockers (NSBB) intercept this axis and each drug has proven efficacy in clinical trials. A synergistic effect is a hitherto unproven possibility. There is an increasing body of evidence supporting improved outcome with expanded use of NSBB and antibiotic therapy beyond current indications. This review addresses...... the issue of pharmacological treatment of cirrhosis and portal hypertension with antibiotics and NSBB. We discuss their mechanism of action and suggest that combining the two treatment modalities could potentially reduce the risk of complications....

  19. Single and combination insecticides evaluated as regulatory immersion treatments to eliminate third-instar Japanese beetle (Coleoptera: Scarabaeidae) from small diameter field-grown and containerized nursery plants

    Science.gov (United States)

    Japanese beetles, Popillia japonica Newman, are a nursery regulatory pest. Immersion of field-grown plants harvested as balled and burlapped (B&B) or container plants grown in pine bark substrates in a solution of chlorpyrifos or bifenthrin is allowed for certification in the Domestic Japanese Beet...

  20. The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

    Science.gov (United States)

    McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

    2017-07-07

    The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis.

    Science.gov (United States)

    Li, Changfeng; Gao, Yongjian; Li, Yongchao; Ding, Dayong

    2017-09-16

    Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. Methotrexate (MTX) is one of the earliest cytotoxic drugs and serves as an anti-metabolite and anti-folate chemotherapy for various types of cancer. However, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the efficacy of MTX therapies in clinics. Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years. More and more evidences have shown that lncRNAs play regulatory roles in various biological activities and disease progression including drug resistance in cancer cells. Here, we observed lncRNA TUG1 was associated to the MTX resistant in colorectal cancer cells. Firstly, quantitative analysis indicated that TUG1 was significantly increased in tumors which were resistant to MTX treatment. TUG1 knockdown re-sensitized the MTX resistance in colorectal cancer cells, which were MTX-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-186 could directly bind to TUG1, suggesting TUG1 might worked as a ceRNA to sponge miR-186. Extensively, our study also showed that CPEB2 was the direct target of miR-186 in colorectal cancer cells. Taken together, our study suggests that lncRNA TUG1 mediates MTX resistance in colorectal cancer via miR-186/CPEB2 axis. Copyright © 2017. Published by Elsevier Inc.

  2. Activation of the HMGB1-RAGE axis upregulates TH expression in dopaminergic neurons via JNK phosphorylation.

    Science.gov (United States)

    Kim, Soo Jeong; Ryu, Min Jeong; Han, Jeongsu; Jang, Yunseon; Kim, Jungim; Lee, Min Joung; Ryu, Ilhwan; Ju, Xianshu; Oh, Eungseok; Chung, Woosuk; Kweon, Gi Ryang; Heo, Jun Young

    2017-11-04

    The derangement of tyrosine hydroxylase (TH) activity reduces dopamine synthesis and is implicated in the pathogenesis of Parkinson's disease. However, the extracellular modulator and intracellular regulatory mechanisms of TH have yet to be identified. Recently, high-mobility group box 1 (HMGB1) was reported to be actively secreted from glial cells and is regarded as a mediator of dopaminergic neuronal loss. However, the mechanism for how HMGB1 affects TH expression, particularly through the receptor for advanced glycation endproducts (RAGE), has not yet been investigated. We found that recombinant HMGB1 (rHMGB1) upregulates TH mRNA expression via simultaneous activation of JNK phosphorylation, and this induction of TH expression is blocked by inhibitors of RAGE and JNK. To investigate how TH expression levels change through the HMGB1-RAGE axis as a result of MPP + toxicity, we co-treated SN4741 dopaminergic cells with MPP + and rHMGB1. rHMGB1 blocked the reduction of TH mRNA following MPP + treatment without altering cell survival rates. Our results suggest that HMGB1 upregulates TH expression to maintain dopaminergic neuronal function via activating RAGE, which is dependent on JNK phosphorylation. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. From Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis

    Directory of Open Access Journals (Sweden)

    Jakob Triebel

    2017-12-01

    Full Text Available The prolactin/vasoinhibin axis defines an endocrine system, in which prolactin (PRL and vasoinhibins regulate blood vessel growth and function, the secretion of other hormones, inflammatory and immune processes, coagulation, and behavior. The core element of the PRL/vasoinhibin axis is the generation of vasoinhibins, which consists in the proteolytic cleavage of their precursor molecule PRL. Vasoinhibins can interact with multiple different partners to mediate their effects in various tissues and anatomical compartments, indicating their pleiotropic nature. Based on accumulating knowledge about the PRL/vasoinhibin axis, two clinical trials were initiated, in which vasoinhibin levels are the target of therapeutic interventions. One trial investigates the effect of levosulpiride, a selective dopamine D2-receptor antagonist, on retinal alterations in patients with diabetic macular edema and retinopathy. The rationale of this trial is that the levosulpiride-induced hyperprolactinemia resulting in increased retinal vasoinhibins could lead to beneficiary outcomes in terms of a vasoinhibin-mediated antagonization of diabetes-induced retinal alterations. Another trial investigated the effect of bromocriptine, a dopamine D2-receptor agonist, for the treatment of peripartum cardiomyopathy. The rationale of treatment with bromocriptine is the inhibition of vasoinhibin generation by substrate depletion to prevent detrimental effects on the myocardial microvascularization. The trial demonstrated that bromocriptine treatment was associated with a high rate of left ventricular recovery and low morbidity and mortality. Therapeutic interventions into the PRL/vasoinhibin axis bear the risk of side effects in the areas of blood coagulation, blood pressure, and alterations of the mental state.

  4. As to achieve regulatory action, regulatory approaches

    International Nuclear Information System (INIS)

    Cid, R.; Encinas, D.

    2014-01-01

    The achievement of the effectiveness in the performance of a nuclear regulatory body has been a permanent challenge in the recent history of nuclear regulation. In the post-Fukushima era this challenge is even more important. This article addresses the subject from two complementary points of view: the characteristics of an effective regulatory body and the regulatory approaches. This work is based on the most recent studies carried out by the Committee on Nuclear Regulatory Activities, CNRA (OECD/NEA), as well as on the experience of the Consejo de Seguridad Nuclear, CSN, the Spanish regulatory body. Rafael Cid is the representative of CSN in these project: Diego Encinas has participated in the study on regulatory approaches. (Author)

  5. Interplay between long noncoding RNA ZEB1-AS1 and miR-101/ZEB1 axis regulates proliferation and migration of colorectal cancer cells.

    Science.gov (United States)

    Xiong, Wan-Cheng; Han, Na; Wu, Nan; Zhao, Ke-Lei; Han, Chen; Wang, Hui-Xin; Ping, Guan-Fang; Zheng, Peng-Fei; Feng, Hailong; Qin, Lei; He, Peng

    2018-01-01

    Long noncoding RNAs (lncRNAs) are dysregulated in many diseases. MicroRNA-101 (miR-101) functions as a tumor suppressor by directly targeting ZEB1 in various cancers. However, the potential mechanism of lncRNA ZEB1-AS1 and miR-101/ZEB1 axis in CRC remains unknown. In this study, we further investigated the potential interplay between miR-101/ZEB1 axis and lncRNA ZEB1-AS1 in colorectal cancer (CRC). Results showed that ZEB1-AS1 was upregulated in CRC tissues and cells. MiR-101 was downregulated in CRC tissues and negatively correlated with ZEB1-AS1 and ZEB1 expression levels in CRC. Functional experiments showed that, consistent with ZEB1-AS1 depletion, miR-101 overexpression and ZEB1 depletion inhibited the proliferation and migration of CRC cells. Overexpression of miR-101 partially abolished the effects of ZEB1-AS1 on the proliferation and migration of these cells. Moreover, combined ZEB1-AS1 depletion and miR-101 overexpression significantly inhibited cell proliferation and migration of the CRC cells. Hence, ZEB1-AS1 functioned as a molecular sponge for miR-101 and relieved the inhibition of ZEB1 caused by miR-101. This study revealed a novel regulatory mechanism between ZEB1-AS1 and miR-101/ZEB1 axis. The interplay between ZEB1-AS1 and miR-101/ZEB1 axis contributed to the proliferation and migration of CRC cells, and targeting this interplay could be a promising strategy for CRC treatment.

  6. Increase of circulating CD4+CD25highFoxp3+ regulatory T cells in patients with metastatic renal cell carcinoma during treatment with dendritic cell vaccination and low-dose interleukin-2

    DEFF Research Database (Denmark)

    Berntsen, Annika; Brimnes, Marie Klinge; thor Straten, Per

    2010-01-01

    Regulatory T cells (Treg) play an important role in the maintenance of immune tolerance and may be one of the obstacles of successful tumor immunotherapy. In this study, we analyzed the impact of administration of dendritic cell (DC) vaccination in combination with low-dose interleukin (IL)-2...... in patients with metastatic renal cell carcinoma on the frequency of CD4+CD25highFoxp3+ Treg cells in peripheral blood. We found that the treatment increased the frequency of Treg cells more than 7-fold compared with pretreatment levels (P...

  7. UMAPRM: Uniformly sampling the medial axis

    KAUST Repository

    Yeh, Hsin-Yi Cindy

    2014-05-01

    © 2014 IEEE. Maintaining clearance, or distance from obstacles, is a vital component of successful motion planning algorithms. Maintaining high clearance often creates safer paths for robots. Contemporary sampling-based planning algorithms That utilize The medial axis, or The set of all points equidistant To Two or more obstacles, produce higher clearance paths. However, They are biased heavily Toward certain portions of The medial axis, sometimes ignoring parts critical To planning, e.g., specific Types of narrow passages. We introduce Uniform Medial Axis Probabilistic RoadMap (UMAPRM), a novel planning variant That generates samples uniformly on The medial axis of The free portion of Cspace. We Theoretically analyze The distribution generated by UMAPRM and show its uniformity. Our results show That UMAPRM\\'s distribution of samples along The medial axis is not only uniform but also preferable To other medial axis samplers in certain planning problems. We demonstrate That UMAPRM has negligible computational overhead over other sampling Techniques and can solve problems The others could not, e.g., a bug Trap. Finally, we demonstrate UMAPRM successfully generates higher clearance paths in The examples.

  8. Actuator assembly including a single axis of rotation locking member

    Science.gov (United States)

    Quitmeyer, James N.; Benson, Dwayne M.; Geck, Kellan P.

    2009-12-08

    An actuator assembly including an actuator housing assembly and a single axis of rotation locking member fixedly attached to a portion of the actuator housing assembly and an external mounting structure. The single axis of rotation locking member restricting rotational movement of the actuator housing assembly about at least one axis. The single axis of rotation locking member is coupled at a first end to the actuator housing assembly about a Y axis and at a 90.degree. angle to an X and Z axis providing rotation of the actuator housing assembly about the Y axis. The single axis of rotation locking member is coupled at a second end to a mounting structure, and more particularly a mounting pin, about an X axis and at a 90.degree. angle to a Y and Z axis providing rotation of the actuator housing assembly about the X axis. The actuator assembly is thereby restricted from rotation about the Z axis.

  9. Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal-axis (HPA-axis)

    OpenAIRE

    Lee, Richard; Sawa, Akira

    2014-01-01

    In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the hypothalamic-pituitary-adrenal axis (HPA)-axis function and behavior. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA-axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, duration, and intensity during di...

  10. Regulatory inspection of nuclear facilities and enforcement by the regulatory body. Safety guide

    International Nuclear Information System (INIS)

    2002-01-01

    The purpose of this Safety Guide is to provide recommendations for regulatory bodies on the inspection of nuclear facilities, regulatory enforcement and related matters. The objective is to provide the regulatory body with a high level of confidence that operators have the processes in place to ensure compliance and that they do comply with legal requirements, including meeting the safety objectives and requirements of the regulatory body. However, in the event of non-compliance, the regulatory body should take appropriate enforcement action. This Safety Guide covers regulatory inspection and enforcement in relation to nuclear facilities such as: enrichment and fuel manufacturing plants; nuclear power plants; other reactors such as research reactors and critical assemblies; spent fuel reprocessing plants; and facilities for radioactive waste management, such as treatment, storage and disposal facilities. This Safety Guide also covers issues relating to the decommissioning of nuclear facilities, the closure of waste disposal facilities and site rehabilitation. Section 2 sets out the objectives of regulatory inspection and enforcement. Section 3 covers the management of regulatory inspections. Section 4 covers the performance of regulatory inspections, including internal guidance, planning and preparation, methods of inspection and reports of inspections. Section 5 deals with regulatory enforcement actions. Section 6 covers the assessment of regulatory inspections and enforcement activities. The Appendix provides further details on inspection areas for nuclear facilities

  11. Professional and Regulatory Search

    Science.gov (United States)

    Professional and Regulatory search are designed for people who use EPA web resources to do their job. You will be searching collections where information that is not relevant to Environmental and Regulatory professionals.

  12. Nitric oxide in the stress axis.

    Science.gov (United States)

    López-Figueroa, M O; Day, H E; Akil, H; Watson, S J

    1998-10-01

    In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.

  13. Neutral axis as damage sensitive feature

    International Nuclear Information System (INIS)

    Sigurdardottir, D H; Glisic, B

    2013-01-01

    Structural health monitoring (SHM) is the process of continuously or periodically measuring structural parameters and the transformation of the collected data into information on real structural conditions. The centroid of stiffness is a universal parameter and its position in a cross-section can be evaluated for any load-carrying beam structure as the position of the neutral axis under conveniently chosen loads. Thus, a change in the position of the neutral axis within a cross-section can indicate a change in the position of the centroid of stiffness, i.e., unusual structural behaviors. This paper proposes a novel monitoring method based on deterministic and probabilistic determination of the position of the neutral axis under conveniently chosen conditions. Therefore, the method proposed in this paper is potentially applicable to a large variety of beam-like structures. Data from two existing structures were used to validate the method and assess its performance: Streicker Bridge at Princeton University and the US202/NJ23 highway overpass in Wayne, NJ. The results show that the neutral axis location is varying even when damage is not present. Reasons for this variation are determined and the accuracy in the evaluation assessed. This paper concludes that the position of the neutral axis can be evaluated with sufficient accuracy using static and dynamic strain measurements performed on appropriate time-scales and indicates its potential to be used as a damage sensitive feature. (paper)

  14. Neutral axis as damage sensitive feature

    Science.gov (United States)

    Sigurdardottir, D. H.; Glisic, B.

    2013-07-01

    Structural health monitoring (SHM) is the process of continuously or periodically measuring structural parameters and the transformation of the collected data into information on real structural conditions. The centroid of stiffness is a universal parameter and its position in a cross-section can be evaluated for any load-carrying beam structure as the position of the neutral axis under conveniently chosen loads. Thus, a change in the position of the neutral axis within a cross-section can indicate a change in the position of the centroid of stiffness, i.e., unusual structural behaviors. This paper proposes a novel monitoring method based on deterministic and probabilistic determination of the position of the neutral axis under conveniently chosen conditions. Therefore, the method proposed in this paper is potentially applicable to a large variety of beam-like structures. Data from two existing structures were used to validate the method and assess its performance: Streicker Bridge at Princeton University and the US202/NJ23 highway overpass in Wayne, NJ. The results show that the neutral axis location is varying even when damage is not present. Reasons for this variation are determined and the accuracy in the evaluation assessed. This paper concludes that the position of the neutral axis can be evaluated with sufficient accuracy using static and dynamic strain measurements performed on appropriate time-scales and indicates its potential to be used as a damage sensitive feature.

  15. Increase of Circulating CD4(+)CD25(high)Foxp3(+) Regulatory T Cells in Patients With Metastatic Renal Cell Carcinoma During Treatment With Dendritic Cell Vaccination and Low-Dose Interleukin-2

    DEFF Research Database (Denmark)

    Berntsen, Annika; Brimnes, M.K.; Straten, P.T.

    2010-01-01

    Regulatory T cells (Treg) play an important role in the maintenance of immune tolerance and may be one of the obstacles of successful tumor immunotherapy. In this study, we analyzed the impact of administration of dendritic cell (DC) vaccination in combination with low-dose interleukin (IL)-2...... in patients with metastatic renal cell carcinoma on the frequency of CD4(+) CD25(high)Foxp3(+) Treg cells in peripheral blood. We found that the treatment increased the frequency of Treg cells more than 7-fold compared with pretreatment levels (P cells decreased when patients...... had been off IL-2 treatment for only 8 days, but remained higher than pretreatment levels. A functional assay showed that isolated Treg cells were capable of inhibiting proliferation of responder cells. Also, in vitro studies showed that coculture of mature DCs, autologous T cells and IL-2 leads...

  16. Aeroelastically coupled blades for vertical axis wind turbines

    Science.gov (United States)

    Paquette, Joshua; Barone, Matthew F.

    2016-02-23

    Various technologies described herein pertain to a vertical axis wind turbine blade configured to rotate about a rotation axis. The vertical axis wind turbine blade includes at least an attachment segment, a rear swept segment, and optionally, a forward swept segment. The attachment segment is contiguous with the forward swept segment, and the forward swept segment is contiguous with the rear swept segment. The attachment segment includes a first portion of a centroid axis, the forward swept segment includes a second portion of the centroid axis, and the rear swept segment includes a third portion of the centroid axis. The second portion of the centroid axis is angularly displaced ahead of the first portion of the centroid axis and the third portion of the centroid axis is angularly displaced behind the first portion of the centroid axis in the direction of rotation about the rotation axis.

  17. Future nuclear regulatory challenges

    International Nuclear Information System (INIS)

    Royen, J.

    1998-01-01

    In December 1996, the NEA Committee on Nuclear Regulatory Activities concluded that changes resulting from economic deregulation and other recent developments affecting nuclear power programmes have consequences both for licensees and regulatory authorities. A number of potential problems and issues which will present a challenge to nuclear regulatory bodies over the next ten years have been identified in a report just released. (author)

  18. The Life and Death of Axis IV: Caught in the Quest for a Theory of Mental Disorder

    Science.gov (United States)

    Probst, Barbara

    2014-01-01

    Axis IV, one of the five dimensions of clinical description, has provided a way to report psychosocial and environmental problems that may affect the diagnosis, treatment, and/or prognosis of a psychiatric disorder. Originally conceived in DSM-III as a way to rate and rank the severity of particular environmental stressors, axis IV was simplified…

  19. Theoretical tool movement required to diamond turn an off-axis paraboloid on axis

    International Nuclear Information System (INIS)

    Thompson, D.C.

    1976-01-01

    Current techniques for manufacturing off-axis paraboloids are both expensive and insufficiently accurate. An alternative method, turning the workpiece about its axis on a diamond-turning machine, is presented, and the equations describing the necessary tool movement are derived. A discussion of a particular case suggests that the proposed technique is feasible

  20. New Urban Vertical Axis Wind Turbine Design

    Directory of Open Access Journals (Sweden)

    Alexandru-Mihai CISMILIANU

    2015-12-01

    Full Text Available This paper develops a different approach for enhancing the performance of Vertical Axis Wind Turbines for the use in the urban or rural environment and remote isolated residential areas. Recently the vertical axis wind turbines (VAWT have become more attractive due to the major advantages of this type of turbines in comparison to the horizontal axis wind turbines. We aim to enhance the overall performance of the VAWT by adding a second set of blades (3 x 2=6 blades following the rules of biplane airplanes. The model has been made to operate at a maximum power in the range of the TSR between 2 to 2.5. The performances of the VAWT were investigated numerically and experimentally and justify the new proposed design.

  1. RITA: The reinvented triple axis spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Mason, T.E. [Toronto Univ., ON (Canada). Dept. of Physics; Clausen, K.N.; Aeppli, G.; McMorrow, D.R.; Kjems, J.K. [Risoe National Lab., Roskilde (Denmark)

    1995-11-01

    Risoe National Laboratory was reported to be in the process of developing a new spectrometer design, RITA, based on the triple axis design. The spectrometer will attempt to incorporate more recent innovations such as multilayer supermirrors and microstrip proportional counters into a rethinking of the triple-axis spectrometer. By optimizing the beam optics, using supermirrors and extending the analyser to map regions of (Q, {omega}) space using an array of independently controllable pyrolytic graphite crystals focussed on an area detector, it was hoped that the efficiency of single-crystal inelastic experiments could be increased by as much as a factor of 20. 7 figs., 20 refs.

  2. Equilibrium studies of helical axis stellarators

    International Nuclear Information System (INIS)

    Hender, T.C.; Carreras, B.A.; Garcia, L.; Harris, J.H.; Rome, J.A.; Cantrell, J.L.; Lynch, V.E.

    1984-01-01

    The equilibrium properties of helical axis stellarators are studied with a 3-D equilibrium code and with an average method (2-D). The helical axis ATF is shown to have a toroidally dominated equilibrium shift and good equilibria up to at least 10% peak beta. Low aspect ratio heliacs, with relatively large toroidal shifts, are shown to have low equilibrium beta limits (approx. 5%). Increasing the aspect ratio and number of field periods proportionally is found to improve the equilibrium beta limit. Alternatively, increasing the number of field periods at fixed aspect ratio which raises and lowers the toroidal shift improves the equilibrium beta limit

  3. Regulatory activities; Actividades regulatorias

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information.

  4. Endothelial Activation: The Ang/Tie Axis in Sepsis

    Directory of Open Access Journals (Sweden)

    Aleksandra Leligdowicz

    2018-04-01

    Full Text Available Sepsis, a dysregulated host response to infection that causes life-threatening organ dysfunction, is a highly heterogeneous syndrome with no specific treatment. Although sepsis can be caused by a wide variety of pathogenic organisms, endothelial dysfunction leading to vascular leak is a common mechanism of injury that contributes to the morbidity and mortality associated with the syndrome. Perturbations to the angiopoietin (Ang/Tie2 axis cause endothelial cell activation and contribute to the pathogenesis of sepsis. In this review, we summarize how the Ang/Tie2 pathway is implicated in sepsis and describe its prognostic as well as therapeutic utility in life-threatening infections.

  5. Ancestral regulatory circuits governing ectoderm patterning downstream of Nodal and BMP2/4 revealed by gene regulatory network analysis in an echinoderm.

    Directory of Open Access Journals (Sweden)

    Alexandra Saudemont

    2010-12-01

    Full Text Available Echinoderms, which are phylogenetically related to vertebrates and produce large numbers of transparent embryos that can be experimentally manipulated, offer many advantages for the analysis of the gene regulatory networks (GRN regulating germ layer formation. During development of the sea urchin embryo, the ectoderm is the source of signals that pattern all three germ layers along the dorsal-ventral axis. How this signaling center controls patterning and morphogenesis of the embryo is not understood. Here, we report a large-scale analysis of the GRN deployed in response to the activity of this signaling center in the embryos of the Mediterranean sea urchin Paracentrotus lividus, in which studies with high spatial resolution are possible. By using a combination of in situ hybridization screening, overexpression of mRNA, recombinant ligand treatments, and morpholino-based loss-of-function studies, we identified a cohort of transcription factors and signaling molecules expressed in the ventral ectoderm, dorsal ectoderm, and interposed neurogenic ("ciliary band" region in response to the known key signaling molecules Nodal and BMP2/4 and defined the epistatic relationships between the most important genes. The resultant GRN showed a number of striking features. First, Nodal was found to be essential for the expression of all ventral and dorsal marker genes, and BMP2/4 for all dorsal genes. Second, goosecoid was identified as a central player in a regulatory sub-circuit controlling mouth formation, while tbx2/3 emerged as a critical factor for differentiation of the dorsal ectoderm. Finally, and unexpectedly, a neurogenic ectoderm regulatory circuit characterized by expression of "ciliary band" genes was triggered in the absence of TGF beta signaling. We propose a novel model for ectoderm regionalization, in which neural ectoderm is the default fate in the absence of TGF beta signaling, and suggest that the stomodeal and neural subcircuits that we

  6. Triple-axis spectrometer DruechaL

    International Nuclear Information System (INIS)

    Buehrer, W.; Keller, P.

    1996-01-01

    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs

  7. Vortex capturing vertical axis wind turbine

    International Nuclear Information System (INIS)

    Zannetti, L; Gallizio, F; Ottino, G

    2007-01-01

    An analytical-numerical study is presented for an innovative lift vertical axis turbine whose blades are designed with vortex trapping cavities that act as passive flow control devices. The unsteady flow field past one-bladed and two-bladed turbines is described by a combined analytical and numerical method based on conformal mapping and on a blob vortex method

  8. The Trading Axis in Irkutsk Downtown

    Directory of Open Access Journals (Sweden)

    Elena Grigoryeva

    2016-10-01

    Full Text Available The article reveals a linear concentration of the trading function in the historical center of Irkutsk. It features historical prerequisites and continuation of the tradition in the post-Soviet period, given the conversion of plants and factories. The article analyses the current state and prospects of modernization of the trading axis with its transformation into a modern public space.

  9. Triple-axis spectrometer DruechaL

    Energy Technology Data Exchange (ETDEWEB)

    Buehrer, W; Keller, P [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    DruechaL is a triple-axis spectrometer located at a cold guide. The characteristics of guide and instrument allow the use of a broad spectral range of neutrons. The resolution in momentum and energy transfer can be tuned to match the experimental requirements by using either collimators or focusing systems (monochromator, antitrumpet, analyser). (author) figs., tabs., refs.

  10. Lagrangian neoclassical transport theory applied to the region near the magnetic axis

    Energy Technology Data Exchange (ETDEWEB)

    Satake, Shinsuke [The Graduate Univ. for Advanced Studies, Dept. of Fusion Science, Toki, Gifu (Japan); Okamoto, Masao; Sugama, Hideo [National Inst. for Fusion Science, Toki, Gifu (Japan)

    2002-06-01

    Neoclassical transport theory around the magnetic axis of a tokamak is studied, in which relatively wide ''potato'' orbits play an important role in transport. Lagrangian formulation of transport theory, which has been investigated to reflect finiteness of guiding-center orbit widths to transport equations, is developed in order to analyze neoclassical transport near the axis for a low-collisionality plasma. The treatment of self-collision term in Lagrangian formulation is revised to retain momentum conservation property of it. With directly reflecting the orbital properties of all the types of orbits in calculation, the ion thermal conductivity around the axis is found to decrease than from that predicted by conventional neoclassical theory. This result supports recent numerical simulations which show the reduction of thermal conductivity near the magnetic axis. (author)

  11. Lagrangian neoclassical transport theory applied to the region near the magnetic axis

    International Nuclear Information System (INIS)

    Satake, Shinsuke; Okamoto, Masao; Sugama, Hideo

    2002-01-01

    Neoclassical transport theory around the magnetic axis of a tokamak is studied, in which relatively wide 'potato' orbits play an important role in transport. Lagrangian formulation of transport theory, which has been investigated to reflect finiteness of guiding-center orbit widths to transport equations, is developed in order to analyze neoclassical transport near the axis for a low-collisionality plasma. The treatment of self-collision term in Lagrangian formulation is revised to retain momentum conservation property of it. By directly reflecting the orbital properties of all the types of orbits in calculation, the ion thermal conductivity around the axis is found to decrease from that predicted by conventional neoclassical theory. This result supports recent numerical simulations which show the reduction of thermal conductivity near the magnetic axis

  12. Lagrangian neoclassical transport theory applied to the region near the magnetic axis

    International Nuclear Information System (INIS)

    Satake, Shinsuke; Okamoto, Masao; Sugama, Hideo

    2002-06-01

    Neoclassical transport theory around the magnetic axis of a tokamak is studied, in which relatively wide ''potato'' orbits play an important role in transport. Lagrangian formulation of transport theory, which has been investigated to reflect finiteness of guiding-center orbit widths to transport equations, is developed in order to analyze neoclassical transport near the axis for a low-collisionality plasma. The treatment of self-collision term in Lagrangian formulation is revised to retain momentum conservation property of it. With directly reflecting the orbital properties of all the types of orbits in calculation, the ion thermal conductivity around the axis is found to decrease than from that predicted by conventional neoclassical theory. This result supports recent numerical simulations which show the reduction of thermal conductivity near the magnetic axis. (author)

  13. Does the GH/IGF-1 axis contribute to skeletal sexual dimorphism? Evidence from mouse studies.

    Science.gov (United States)

    Liu, Zhongbo; Mohan, Subburaman; Yakar, Shoshana

    2016-04-01

    The contribution of the gonadotropic axis to skeletal sexual dimorphism (SSD) was clarified in recent years. Studies with animal models of estrogen receptor (ER) or androgen receptor (AR) null mice, as well as mice with bone cell-specific ablation of ER or AR, revealed that both hormones play major roles in skeletal acquisition, and that estrogen regulates skeletal accrual in both sexes. The growth hormone (GH) and its downstream effector, the insulin-like growth factor-1 (IGF-1) are also major determinants of peak bone mass during puberty and young adulthood, and play important roles in maintaining bone integrity during aging. A few studies in both humans and animal models suggest that in addition to the differences in sex steroid actions on bone, sex-specific effects of GH and IGF-1 play essential roles in SSD. However, the contributions of the somatotropic (GH/IGF-1) axis to SSD are controversial and data is difficult to interpret. GH/IGF-1 are pleotropic hormones that act in an endocrine and autocrine/paracrine fashion on multiple tissues, affecting body composition as well as metabolism. Thus, understanding the contribution of the somatotropic axis to SSD requires the use of mouse models that will differentiate between these two modes of action. Elucidation of the relative contribution of GH/IGF-1 axis to SSD is significant because GH is approved for the treatment of normal children with short stature and children with congenital growth disorders. Thus, if the GH/IGF-1 axis determines SSD, treatment with GH may be tailored according to sex. In the following review, we give an overview of the roles of sex steroids in determining SSD and how they may interact with the GH/IGF-1 axis in bone. We summarize several mouse models with impaired somatotropic axis and speculate on the possible contribution of that axis to SSD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Research and regulatory review

    International Nuclear Information System (INIS)

    Macleod, J.S.; Fryer, D.R.H.

    1979-01-01

    To enable the regulatory review to be effectively undertaken by the regulatory body, there is a need for it to have ready access to information generated by research activities. Certain advantages have been seen to be gained by the regulatory body itself directly allocating and controlling some portion of these activities. The princial reasons for reaching this conclusion are summarised and a brief description of the Inspectorates directly sponsored programme outlined. (author)

  15. Pituitary-Adrenal Axis in Prader Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Olivia S. Edgar

    2016-01-01

    Full Text Available Purpose: Prader Willi syndrome (PWS is a rare genetic condition that has concurrent endocrinological insufficiencies. The presence of growth hormone deficiency has been well documented, but adrenal insufficiency (AI is not widely reported. A review was conducted to investigate its prevalence and relevance in PWS in both adults and children. Methodology: A literature review was performed with the search terms “Prader-Willi syndrome” and “adrenal insufficiency”. Results: The review found studies disagree on the prevalence and method of investigation of AI in PWS. Case studies demonstrate that patients with PWS are at risk of premature death, often secondary to respiratory infections. The possibility that this may be the result of the inability to mount an effective cortisol response has been studied, with some evidence confirming AI in PWS patients. Most reports agreed AI is present in PWS, however, Farholt et al. showed no HPA axis dysfunction in adults, suggesting that perhaps it is rare in adults, and children should be the focus of further studies. Conclusion: AI is present in some patients with PWS. Further research is required to ensure optimal treatment can be implemented and to prevent premature deaths related to adrenal insufficiency. Clinicians should have a low threshold for testing the adrenal axis and considering treatment for adrenal insufficiency in PWS patients.

  16. UARS PEM Level 2 AXIS 2 V001 (UARPE2AXIS2) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 2 daily product contains the X-ray high-resolution spectral...

  17. UARS PEM Level 2 AXIS 1 V001 (UARPE2AXIS1) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 1 daily product contains the X-ray high-resolution spectral...

  18. Regulatory Commission of Alaska

    Science.gov (United States)

    Map Help Regulatory Commission of Alaska Login Forgot Password Arrow Image Forgot password? View Cart login Procedures for Requesting Login For Consumers General Information Telephone Electric Natural Gas

  19. Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

    Science.gov (United States)

    Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

    2017-01-01

    Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Executive function training with game elements for obese children: A novel treatment to enhance self-regulatory abilities for weight-control

    NARCIS (Netherlands)

    Verbeken, S.; Braet, C.; Goossens, L.; van der Oord, S.

    2013-01-01

    For obese children behavioral treatment results in only small changes in relative weight and frequent relapse. The current study investigated the effects of an Executive Functioning (EF) training with game-elements on weight loss maintenance in obese children, over and above the care as usual in an

  1. Resolution of a triple axis spectrometer

    DEFF Research Database (Denmark)

    Nielsen, Mourits; Bjerrum Møller, Hans

    1969-01-01

    A new method for obtaining the resolution function for a triple-axis neutron spectrometer is described, involving a combination of direct measurement and analytical calculation. All factors which contribute to the finite resolution of the instrument may be taken into account, and Gaussian...... or experimentally determined probability distributions may be used. The application to the study of the dispersion relation for excitations in a crystal is outlined...

  2. Interplay between tilted and principal axis rotation

    International Nuclear Information System (INIS)

    Datta, Pradip; Roy, Santosh; Chattopadhyay, S.

    2014-01-01

    At IUAC-INGA, our group has studied four neutron rich nuclei of mass-110 region, namely 109,110 Ag and 108,110 Cd. These nuclei provide the unique platform to study the interplay between Tilted and Principal axis rotation since these are moderately deformed and at the same time, shears structures are present at higher spins. The salient features of the high spin behaviors of these nuclei will be discussed which are the signatures of this interplay

  3. Interplay between tilted and principal axis rotation

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Pradip [Ananda Mohan College, 102/1 Raja Rammohan Sarani, Kolkata 700 009 (India); Roy, Santosh; Chattopadhyay, S. [Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata 700 064 (India)

    2014-08-14

    At IUAC-INGA, our group has studied four neutron rich nuclei of mass-110 region, namely {sup 109,110}Ag and {sup 108,110}Cd. These nuclei provide the unique platform to study the interplay between Tilted and Principal axis rotation since these are moderately deformed and at the same time, shears structures are present at higher spins. The salient features of the high spin behaviors of these nuclei will be discussed which are the signatures of this interplay.

  4. Path of a patient with a rare diagnosis: regulatory documents and organization of the process of treatment and diagnosis of an orphan disease in the Russian Federation

    OpenAIRE

    S. I. Kutsev

    2017-01-01

    The main legislative document of the organization of medical care in the Russian Federation “On fundamental healthcare principles in the Russian Federation” and points related to the rare (orphan) diseases are  discussed. The organization of care, rules for managing a federal  registry of orphan diseases and routing of patients with main orphan nosological forms for which treatment is known are presented.

  5. Path of a patient with a rare diagnosis: regulatory documents and organization of the process of treatment and diagnosis of an orphan disease in the Russian Federation

    Directory of Open Access Journals (Sweden)

    S. I. Kutsev

    2017-01-01

    Full Text Available The main legislative document of the organization of medical care in the Russian Federation “On fundamental healthcare principles in the Russian Federation” and points related to the rare (orphan diseases are  discussed. The organization of care, rules for managing a federal  registry of orphan diseases and routing of patients with main orphan nosological forms for which treatment is known are presented.

  6. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-10-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  7. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  8. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-01-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  9. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1991-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  10. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-08-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  11. Trust in regulatory regimes

    NARCIS (Netherlands)

    Six, Frédérique; Verhoest, Koen

    2017-01-01

    Within political and administrative sciences generally, trust as a concept is contested, especially in the field of regulatory governance. This groundbreaking book is the first to systematically explore the role and dynamics of trust within regulatory regimes. Conceptualizing, mapping and analyzing

  12. Nuclear Regulatory legislation

    International Nuclear Information System (INIS)

    1984-06-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 97th Congress, 2nd Session, has been prepared by the Office of the Executive Legal Director, U.S. Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document

  13. Stress axis regulation during social ascension in a group-living cichlid fish.

    Science.gov (United States)

    Culbert, Brett M; Gilmour, Kathleen M; Balshine, Sigal

    2018-06-19

    Animals living in groups often form social hierarchies, with characteristic behaviours and physiologies associated with rank. However, when social opportunities arise and a subordinate ascends into a dominant position, quick adjustments are necessary to secure this position. Such periods of social transition are typically associated with elevated glucocorticoid production, but the precise regulation of the stress axis during these occasions is not well understood. Using the group-living cichlid, Neolamprologus pulcher, the effects of social ascension on the stress axis were assessed. Ascenders rapidly filled experimentally created vacancies, adopting a dominant behavioural phenotype within 72 h-elevating aggression, activity, and workload, while receiving high rates of affiliative behaviours from their group members. Despite assuming behavioural dominance within their groups, ascenders displayed higher cortisol levels than dominants three days post-ascension. Additionally, compared to subordinates, ascenders had increased transcript abundance of steroidogenic acute regulatory protein (star) and cytochrome p450 side-chain cleavage enzyme (p450scc) in the head kidney, indicating activation of the stress axis. Cortisol levels were lowest in ascenders that displayed low rates of aggression, potentially reflecting the reestablishment of social stability in these groups. Increased transcript abundance of both glucocorticoid receptors (gr1 and gr2) in the brain's preoptic area (POA) of ascenders compared to dominants suggested an enhanced capacity for cortisol regulation via negative feedback. Our results reveal a regulatory cascade of behavioural and physiological interactions and highlight the importance of investigating the underlying mechanisms regulating the stress axis. Copyright © 2018. Published by Elsevier Inc.

  14. Improving nuclear regulatory effectiveness

    International Nuclear Information System (INIS)

    2001-01-01

    Ensuring that nuclear installations are operated and maintained in such a way that their impact on public health and safety is as low as reasonably practicable has been and will continue to be the cornerstone of nuclear regulation. In the past, nuclear incidents provided the main impetus for regulatory change. Today, economic factors, deregulation, technological advancements, government oversight and the general requirements for openness and accountability are leading regulatory bodies to review their effectiveness. In addition, seeking to enhance the present level of nuclear safety by continuously improving the effectiveness of regulatory bodies is seen as one of the ways to strengthen public confidence in the regulatory systems. This report covers the basic concepts underlying nuclear regulatory effectiveness, advances being made and future requirements. The intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

  15. Expression patterns of regulatory RNAs, including lncRNAs and tRNAs, during postnatal growth of normal and dystrophic (mdx) mouse muscles, and their response to taurine treatment.

    Science.gov (United States)

    Butchart, Lauren C; Terrill, Jessica R; Rossetti, Giulia; White, Robert; Filipovska, Aleksandra; Grounds, Miranda D

    2018-06-01

    Post-natal skeletal muscle growth in mice is very rapid and involves complex changes in many cells types over the first 6 weeks of life. The acute onset of dystropathology also occurs around 3 weeks of age in the mdx mouse model of the human disease Duchenne Muscular Dystrophy (DMD). This study investigated (i) alterations in expression patterns of regulatory non-coding RNAs (ncRNAs) in vivo, including miRNAs, lncRNAs and tRNAs, during early growth of skeletal muscles in normal control C57Bl/10Scsn (C57) compared with dystrophic mdx mice from 2 to 6 weeks of postnatal age, and revealed inherent differences in vivo for levels of 3 ncRNAs between C57 and mdx muscles before the onset of dystropathology. Since the amino acid taurine has many benefits and reduces disease severity in mdx mice, this study also (ii) determined the impact of taurine treatment on these expression patterns in mdx muscles at the onset of dystropathology (3 weeks) and after several bouts of myonecrosis and regeneration (6 weeks). Taurine treatment of mdx mice only altered ncRNA levels when administered from 18 days to 6 weeks of age, but a deficiency in tRNA levels was rectified earlier in mdx skeletal muscles treated from 14 days to 3 weeks. Myogenesis in tissue culture was also used to (iii) compare ncRNA expression patterns for both strains, and (iv) the response to taurine treatment. These analyses revealed intrinsic differences in ncRNA expression patterns during myogenesis between strains, as well as increased sensitivity of mdx ncRNA levels to taurine treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Reframing the Teenage Wasteland: Adolescent Microbiota-Gut-Brain Axis.

    Science.gov (United States)

    McVey Neufeld, Karen-Anne; Luczynski, Pauline; Dinan, Timothy G; Cryan, John F

    2016-04-01

    Human adolescence is arguably one of the most challenging periods of development. The young adult is exposed to a variety of stressors and environmental stimuli on a backdrop of significant physiological change and development, which is especially apparent in the brain. It is therefore unsurprising that many psychiatric disorders are first observable during this time. The human intestine is inhabited by trillions of microorganisms, and evidence from both preclinical and clinical research focusing on the established microbiota-gut-brain axis suggests that the etiology and pathophysiology of psychiatric disorders may be influenced by intestinal dysbiosis. Provocatively, many if not all of the challenges faced by the developing teen have a documented impact on these intestinal commensal microbiota. In this review, we briefly summarize what is known about the developing adolescent brain and intestinal microbiota, discuss recent research investigating the microbiota-gut-brain axis during puberty, and propose that pre- and probiotics may prove useful in both the prevention and treatment of psychiatric disorders specifically benefitting the young adult. © The Author(s) 2016.

  17. Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

    Science.gov (United States)

    Kennedy, Paul J; Cryan, John F; Dinan, Timothy G; Clarke, Gerard

    2014-01-01

    Irritable bowel syndrome (IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions. PMID:25339800

  18. Organization of co-occurring Axis II features in borderline personality disorder.

    Science.gov (United States)

    Critchfield, Kenneth L; Clarkin, John F; Levy, Kenneth N; Kernberg, Otto F

    2008-06-01

    Considerable heterogeneity exists in the comorbid Axis II features that frequently accompany borderline personality disorder (BPD). These features have potential to be meaningfully organized, relate to specific BPD presentation, and have implications for treatment process and outcome. The present study explored patterns of Axis II comorbidity in order to identify subtypes of BPD. A well-defined sample of 90 patients diagnosed with BPD was recruited as part of an RCT study. Participants were administered the International Personality Disorder Examination (Loranger, 1999) to diagnose BPD and assess comorbid Axis II features. Other measures were also administered to assess aspects of current work and relationship functioning, symptomatology, and self-concept. Q-factoring was used to develop subtypes based on commonly occurring Axis II profiles, identifying three: Cluster A (elevated paranoid and schizotypal features), Cluster B (elevated narcissistic and histrionic features), and Cluster C (elevated avoidant and obsessive-compulsive features). An additional factor analysis revealed two dimensions underlying the comorbid features identifiable as: extraversion versus introversion and antagonism versus constraint. Validity of these two maps of comorbidity was explored in terms of the BPD criteria themselves, as well as on work and relationship functioning, identity diffusion, views of self and others, positive and negative affect, behavioural dyscontrol, and symptomatic distress. Clinically meaningful subtypes can be identified for BPD based on co-occurring Axis II features. Further research is needed to replicate and further establish base-rates of these subtypes as well as their differential implications for treatment.

  19. Regulatory guidance document

    International Nuclear Information System (INIS)

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM's evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7

  20. Managing Regulatory Body Competence

    International Nuclear Information System (INIS)

    2013-01-01

    In 2001, the IAEA published TECDOC 1254, which examined the way in which the recognized functions of a regulatory body for nuclear facilities results in competence needs. Using the systematic approach to training (SAT), TECDOC 1254 provided a framework for regulatory bodies for managing training and developing and their maintaining their competence. It has been successfully used by many regulators. The IAEA has also introduced a methodology and an assessment tool - Guidelines for Systematic Assessment of Regulatory Competence Needs (SARCoN) - which provides practical guidance on analysing the training and development needs of a regulatory body and, through a gap analysis, guidance on establishing competence needs and how to meet them. In 2009, the IAEA established a steering committee (supported by a bureau) with the mission to advise the IAEA on how it could best assist Member States to develop suitable competence management systems for their regulatory bodies. The committee recommended the development of a safety report on managing staff competence as an integral part of a regulatory body's management system. This Safety Report was developed in response to this request. It supersedes TECDOC 1254, broadens its application to regulatory bodies for all facilities and activities, and builds upon the experience gained through the application of TECDOC 1254 and SARCoN and the feedback received from Member States. This Safety Report applies to the management of adequate competence as needs change, and as such is equally applicable to the needs of States 'embarking' on a nuclear power programme. It also deals with the special case of building up the competence of regulatory bodies as part of the overall process of establishing an 'embarking' State's regulatory system

  1. Theoretical tool movement required to diamond turn an off-axis paraboloid on axis

    International Nuclear Information System (INIS)

    Thompson, D.C.

    1975-01-01

    High-quality, off-axis parabolic reflectors, required by the CTR and laser-fusion programs at Lawrence Livermore Laboratory (LLL) and other ERDA laboratories, are currently manufactured by hand. There are several drawbacks to this method, including lead times of up to a year, costs in excess of dollars 75,000 for a small reflector, and unsatisfactory limits to the tolerances obtainable. This situation has led to a search for cheaper and more accurate methods of manufacturing off-axis paraboloids. An alternative method, turning the workpiece about its axis on a diamond-turning machine, is presented, and the equations describing the necessary tool movement are derived. A discussion of a particular case suggests that the proposed technique is feasible

  2. The Triple Axis and SPINS Spectrometers.

    Science.gov (United States)

    Trevino, S F

    1993-01-01

    In this paper are described the triple axis and spin polarized inelastic neutron scattering (SPINS) spectrometers which are installed at the NIST Cold Neutron Research Facility (CNRF). The general principle of operation of these two instruments is described in sufficient detail to allow the reader to make an informed decision as to their usefulness for his needs. However, it is the intention of the staff at the CNRF to provide the expert resources for their efficient use in any given situation. Thus, this work is not intended as a user manual but rather as a guide into the range of applicability of the two instruments.

  3. Equilibrium calculations for helical axis stellarators

    International Nuclear Information System (INIS)

    Hender, T.C.; Carreras, B.A.

    1984-04-01

    An average method based on a vacuum flux coordinate system is presented. This average method permits the study of helical axis stellarators with toroidally dominated shifts. An ordering is introduced, and to lowest order the toroidally averaged equilibrium equations are reduced to a Grad-Shafranov equation. Also, to lowest order, a Poisson-type equation is obtained for the toroidally varying corrections to the equilibium. By including these corrections, systems that are toroidally dominated, but with significant helical distortion to the equilibrium, may be studied. Numerical solutions of the average method equations are shown to agree well with three-dimensional calculations

  4. Three-axis asymmetric radiation detector system

    Science.gov (United States)

    Martini, Mario Pierangelo; Gedcke, Dale A.; Raudorf, Thomas W.; Sangsingkeow, Pat

    2000-01-01

    A three-axis radiation detection system whose inner and outer electrodes are shaped and positioned so that the shortest path between any point on the inner electrode and the outer electrode is a different length whereby the rise time of a pulse derived from a detected radiation event can uniquely define the azimuthal and radial position of that event, and the outer electrode is divided into a plurality of segments in the longitudinal axial direction for locating the axial location of a radiation detection event occurring in the diode.

  5. Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation.

    Science.gov (United States)

    Petra, Anastasia I; Panagiotidou, Smaro; Hatziagelaki, Erifili; Stewart, Julia M; Conti, Pio; Theoharides, Theoharis C

    2015-05-01

    Gut microbiota regulate intestinal function and health. However, mounting evidence indicates that they can also influence the immune and nervous systems and vice versa. This article reviews the bidirectional relationship between the gut microbiota and the brain, termed the microbiota-gut-brain (MGB) axis, and discusses how it contributes to the pathogenesis of certain disorders that may involve brain inflammation. Articles were identified with a search of Medline (starting in 1980) by using the key words anxiety, attention-deficit hypersensitivity disorder (ADHD), autism, cytokines, depression, gut, hypothalamic-pituitary-adrenal (HPA) axis, inflammation, immune system, microbiota, nervous system, neurologic, neurotransmitters, neuroimmune conditions, psychiatric, and stress. Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites all convey information to the central nervous system about the intestinal state. Conversely, the hypothalamic-pituitary-adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions seem to influence the pathogenesis of a number of disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity. Recognition of the relationship between the MGB axis and the neuroimmune systems provides a novel approach for better understanding and management of these disorders. Appropriate preventive measures early in life or corrective measures such as use of psychobiotics, fecal microbiota transplantation, and flavonoids are discussed. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  6. Multiple Sclerosis and the LIF/IL-6 Axis: Use of Nanotechnology to Harness the Tolerogenic and Reparative Properties of LIF

    Directory of Open Access Journals (Sweden)

    Su M. Metcalfe

    2015-05-01

    Full Text Available Leukaemia inhibitory factor (LIF plays a critical role in “stemness” versus “differentiation”, a property that underpins the core value of LIF as a therapeutic for both the treatment of autoimmune disease and for promoting tissue repair. This value can be realized using nano-engineering technology, where a new generation of tools can, with unprecedented ability, manipulate biological functions. One striking example is the treatment of multiple sclerosis (MS. The underpinning biology is the newly identified LIF/IL-6 axis in T lymphocytes, which can tilt the behaviour between immune tolerance versus immune attack. This LIF/IL-6 axis is ideally suited to nanotherapeutic manipulation, given its inherent mechanistic simplicity of two mutually opposing feed-forward loops that determine either tolerogenic (LIF or inflammatory (IL-6 immunity. Using LIF that is formulated in biodegradable nanoparticles (LIF-NP and targeted to CD4+ T cells, the axis is harnessed towards immune tolerance. This has implications for the treatment of autoimmune diseases, where the clinical burden is immense. It encompasses more than 100 diseases and, in the USA alone, costs more than $100 billion in direct health care costs annually. Other properties of LIF include the promotion of healthy neuro-glial interactions within the central nervous system (CNS, where, in addition to MS, LIF-NP therapy is relevant to inflammatory neurodegenerative diseases that represent a large and increasing need within aging populations. Thirdly, LIF is a reparative growth factor that can maintain genomic plasticity. LIF-NP supports the use of stem cell-based therapies in regenerative medicine plus augment therapeutic benefits within the patient. These core properties of LIF are greatly amplified in value by the advantage of being formulated as nanoparticles, namely (i targeted delivery, (ii exploitation of endogenous regulatory pathways and (iii creation of surrogate micro-stromal niches

  7. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-10-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  8. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-04-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  9. Through the regulatory hoop

    International Nuclear Information System (INIS)

    Kirner, N.P.

    1985-01-01

    There are many regulatory hoops through which waste generators, brokers, and disposal site operators must jump to dispose of waste safely. As the proposed exclusionary date of January 1, 1986, approaches, these regulatory hoops have the distinct possibility of multiplying or at least changing shape. The state of Washington, in its role as an Agreement State with the US Nuclear Regulatory Commission, licenses and inspects the commercial operator of the Northwest Compact's low-level radioactive waste disposal site on the Hanford Reservation. Washington has received as much as 53%, or 1.4 million cubic feet per year, of the nation's total volume of waste disposed. To control such a large volume of waste, a regulatory program involving six agencies has developed over the years in Washington

  10. Extracellular matrix dynamics during vertebrate axis formation.

    Science.gov (United States)

    Czirók, András; Rongish, Brenda J; Little, Charles D

    2004-04-01

    The first evidence for the dynamics of in vivo extracellular matrix (ECM) pattern formation during embryogenesis is presented below. Fibrillin 2 filaments were tracked for 12 h throughout the avian intraembryonic mesoderm using automated light microscopy and algorithms of our design. The data show that these ECM filaments have a reproducible morphogenic destiny that is characterized by directed transport. Fibrillin 2 particles initially deposited in the segmental plate mesoderm are translocated along an unexpected trajectory where they eventually polymerize into an intricate scaffold of cables parallel to the anterior-posterior axis. The cables coalesce near the midline before the appearance of the next-formed somite. Moreover, the ECM filaments define global tissue movements with high precision because the filaments act as passive motion tracers. Quantification of individual and collective filament "behaviors" establish fate maps, trajectories, and velocities. These data reveal a caudally propagating traveling wave pattern in the morphogenetic movements of early axis formation. We conjecture that within vertebrate embryos, long-range mechanical tension fields are coupled to both large-scale patterning and local organization of the ECM. Thus, physical forces or stress fields are essential requirements for executing an emergent developmental pattern-in this case, paraxial fibrillin cable assembly.

  11. VERITAS: Versatile Triple-Axis Spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Il

    2006-04-15

    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, {approx} 5 m Curved Guide, {approx} 26 m w/ R 1500 m Straight Guide before the Instrument, {approx} 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world.

  12. VERITAS: Versatile Triple-Axis Spectrometer

    International Nuclear Information System (INIS)

    Park, Sung Il

    2006-04-01

    Korea Atomic Energy Research Institute is planning to build a cold neutron triple-axis spectrometer at HANARO, the 30 MW research reactor. The spectrometer is expected to be completed in 2008 with the following configuration from the upstream to the downstream. Guide Supermirror m = 2, In-pile Straight Section, ∼ 5 m Curved Guide, ∼ 26 m w/ R 1500 m Straight Guide before the Instrument, ∼ 40 m Filters PG and Be Neutron Velocity Selector (Future) Monochromators Vertically Focusing Monochromators PG(002) and Heusler(111) Doubly Focusing Monochromators (Future) Monochromator-Sample Distance 2 m Collimation C1 Soller Collimators, 20', 40' 80'Beam Height at the Sample Table 1.5 m Sample-Analyzer Distance 1.0 m Collimation C2 Soller Collimators, 20', 40', 80' Radial Collimator Analyzers Horizontally Focusing Analyzers w/ Fixed Vertical Focusing PG(002) and Heusler(111) Analyzer-Detector Distance 0.5 m Detectors 5 cm Tube Detector 25 cm wide Position Sensitive Detector Once completed, the neutron flux at sample is expected to surpass that of SPINS at NCNR, making this instrument one of the most powerful 2nd generation cold neutron triple-axis spectrometers in the world

  13. Global Regulatory Differences for Gene- and Cell-Based Therapies

    DEFF Research Database (Denmark)

    Coppens, Delphi G M; De Bruin, Marie L; Leufkens, Hubert G M

    2017-01-01

    Gene- and cell-based therapies (GCTs) offer potential new treatment options for unmet medical needs. However, the use of conventional regulatory requirements for medicinal products to approve GCTs may impede patient access and therapeutic innovation. Furthermore, requirements differ between...... jurisdictions, complicating the global regulatory landscape. We provide a comparative overview of regulatory requirements for GCT approval in five jurisdictions and hypothesize on the consequences of the observed global differences on patient access and therapeutic innovation....

  14. Utilization of the bicipital groove axis for confirming alignment of the humerus with transepicondylar and ulnar shaft axes during intramedullary nailing.

    Science.gov (United States)

    Meriç, Gökhan; Zeybek, Gülşah; Kıray, Amaç; Atik, Aziz; Budeyri, Aydın; Koşay, Can

    2015-01-01

    Intramedullary nailing is the preferred surgical treatment of humerus shaft fractures. The purpose of this study was to investigate the relationship between the bicipital groove and specific anatomical landmarks in achieving correct alignment of the humerus during intramedullary nailing, and to describe these anatomical landmarks. Thirty (15 right; 15 left) total upper cadaver extremities were used in this study. After the anatomical landmarks were identified and marked, humeral head axis, transepicondylar axis, ulnar shaft axis, bicipital groove axis, and angular measurements of these were obtained. The mean angle between the bicipital groove axis and transepicondylar axis was 48.17°±12.35º (range: 20.10º to 74.6º). The mean angle between the bicipital groove axis and ulna diaphysis axis was 41.82º±11.56 º (range: 17.91º to 68.27º). The mean angle between the humeral head axis and bicipital groove axis was 20.53°±3.90º (range: 11.85º to 31.81º). The mean retroversion angle between the humeral head axis and transepicondylar axis was 27.52±11.37º (range: 4.26º to 49.36º). The mean angle between the humeral head axis and ulna diaphysis axis was 61.73º±12.08º (range: 33.97º to 86.37º). The mean torsion angle was 62.58º±11.28 º (range: 40.74º to 85.74º). Measurement and utilization of the relationship between the bicipital groove, ulna diaphysis and transepicondylar axes may be used for restoring humeral rotation.

  15. Irritable bowel syndrome, the microbiota and the gut-brain axis

    DEFF Research Database (Denmark)

    Raskov, Hans; Burcharth, Jakob; Pommergaard, Hans-Christian

    2016-01-01

    Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous...... nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review...... recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brain-axis, and possible treatment modalities on irritable bowel syndrome....

  16. Divergences between clinical and research methods for assessing personality disorders: implications for research and the evolution of axis II.

    Science.gov (United States)

    Westen, D

    1997-07-01

    The purpose of this study was to examine the extent to which instruments for assessing axis II diverge from clinical diagnostic processes. Subjects in the first study were 52 clinicians with experience in assessment and treatment of patients with personality disorders, who were surveyed about the methods they use in clinical practice to make diagnoses and other aspects of the diagnostic process. A second study replicated the major findings with a random national sample of 1,901 experienced psychiatrists and psychologists. Whereas current instruments rely primarily on direct questions derived from DSM-IV, clinicians of every theoretical persuasion found direct questions useful for assessing axis I disorders but only marginally so for axis II. They made axis II diagnoses, instead, by listening to patients describe interpersonal interactions and observing their behavior with the interviewer. In contrast to findings with current research instruments, most patients with personality disorders in clinical practice receive only one axis II diagnosis, and if they receive more than one, one is considered primary. Clinicians reported treating a substantial number of patients for enduring personality patterns that current axis II instruments do not assess, many of which meet neither axis I nor axis II criteria, notably problems with relatedness, work, self-esteem, and chronic subclinical depressive traits. Measurements of axis II were constructed by using a model derived from axis I instruments that diverges from clinical diagnostic procedures in a way that may be problematic for the assessment of personality disorders and the development of a more clinically and empirically sound taxonomy.

  17. Modulation of HPA axis response to social stress in schizophrenia by childhood trauma.

    Science.gov (United States)

    Lange, Claudia; Huber, Christian G; Fröhlich, Daniela; Borgwardt, Stefan; Lang, Undine E; Walter, Marc

    2017-08-01

    HPA axis functioning plays an important role in the etiology of schizophrenia spectrum disorders (SSD). However, only few studies have examined HPA axis responsivity to psychosocial stress in SSD, and results are heterogeneous. Furthermore, childhood trauma is known to influence psychopathology and treatment outcome in SSD, but studies on the influence of childhood trauma on stress related HPA axis activity are missing. The purpose of this study was to investigate cortisol response to a psychosocial stress challenge in SSD patients, and to examine its association with severity of childhood trauma. The present study included 25 subacutely ill patients with a current episode of a chronic SSD and 25 healthy controls. Participants underwent the modified Trier Social Stress Test, and salivary cortisol levels were assessed. The childhood trauma questionnaire was used to assess severity of adverse life events. Overall, cortisol response was blunted in the patient group compared to the control group (pchildhood trauma experience: responders had experienced more emotional abuse in their past (pchildhood trauma might influence stress-related HPA axis activity in SSD. Our data contribute to the hypothesis that severity of childhood trauma may be of pathophysiological relevance in schizophrenia. In addition, it may be an overlooked factor contributing to inconsistent findings regarding HPA axis response to psychosocial stress in SSD. Copyright © 2017. Published by Elsevier Ltd.

  18. Perceptions of regulatory approaches

    International Nuclear Information System (INIS)

    Halin, Magnus; Leinonen, Ruusaliisa

    2012-01-01

    Ms. Ruusaliisa Leinonen and Mr. Magnus Halin from Fortum gave a joint presentation on industry perceptions of regulatory oversight of LMfS/SC. It was concluded that an open culture of discussion exists between the regulator (STUK) and the licensee, based on the common goal of nuclear safety. An example was provided of on how regulatory interventions helped foster improvements to individual and collective dose rate trends, which had remained static. Regulatory interventions included discussions on the ALARA concept to reinforce the requirement to continuously strive for improvements in safety performance. Safety culture has also been built into regulatory inspections in recent years. Training days have also been organised by the regulatory body to help develop a shared understanding of safety culture between licensee and regulatory personnel. Fortum has also developed their own training for managers and supervisors. Training and ongoing discussion on LMfS/SC safety culture is considered particularly important because both Fortum and the regulatory body are experiencing an influx of new staff due to the demographic profile of their organisations. It was noted that further work is needed to reach a common understanding of safety culture on a practical level (e.g., for a mechanic setting to work), and in relation to the inspection criteria used by the regulator. The challenges associated with companies with a mix of energy types were also discussed. This can make it more difficult to understand responsibilities and decision making processes, including the role of the parent body organisation. It also makes communication more challenging due to increased complexity and a larger number of stakeholders

  19. Maternal control of the Drosophila dorsal–ventral body axis

    Science.gov (United States)

    Stein, David S.; Stevens, Leslie M.

    2016-01-01

    The pathway that generates the dorsal–ventral (DV) axis of the Drosophila embryo has been the subject of intense investigation over the previous three decades. The initial asymmetric signal originates during oogenesis by the movement of the oocyte nucleus to an anterior corner of the oocyte, which establishes DV polarity within the follicle through signaling between Gurken, the Drosophila Transforming Growth Factor (TGF)-α homologue secreted from the oocyte, and the Drosophila Epidermal Growth Factor Receptor (EGFR) that is expressed by the follicular epithelium cells that envelop the oocyte. Follicle cells that are not exposed to Gurken follow a ventral fate and express Pipe, a sulfotransferase that enzymatically modifies components of the inner vitelline membrane layer of the eggshell, thereby transferring DV spatial information from the follicle to the egg. These ventrally sulfated eggshell proteins comprise a localized cue that directs the ventrally restricted formation of the active Spätzle ligand within the perivitelline space between the eggshell and the embryonic membrane. Spätzle activates Toll, a transmembrane receptor in the embryonic membrane. Transmission of the Toll signal into the embryo leads to the formation of a ventral-to-dorsal gradient of the transcription factor Dorsal within the nuclei of the syncytial blastoderm stage embryo. Dorsal controls the spatially specific expression of a large constellation of zygotic target genes, the Dorsal gene regulatory network, along the embryonic DV circumference. This article reviews classic studies and integrates them with the details of more recent work that has advanced our understanding of the complex pathway that establishes Drosophila embryo DV polarity. PMID:25124754

  20. Do low-calorie drinks 'cheat' the enteral-brain axis?

    Science.gov (United States)

    Ferreira, Adaliene V M; Generoso, Simone Vasconcelos; Teixeira, Antônio Lúcio

    2014-09-01

    The consumption of low-calorie beverages has increased worldwide, mainly because of their combination of sweet taste without adding significant calories to the diet. However, some epidemiological studies have linked the higher consumption of low-calorie beverages with increased body weight gain. Although a matter of debate, this paradoxical association between low-calorie beverages and weight gain has been attributed to their effect on the enteral-brain axis. More specifically, artificial sweeteners present in low-calorie beverages could induce appetite increase, probably due to an ambiguous psychobiological signal (uncoupling sweet taste from calorie intake) that confounds the appetite's regulatory mechanisms, promoting overeating and, ultimately, leading to weight gain. However, many studies do not support this assumption, and the mechanisms underlying the interaction between low-calorie beverages and the enteral-brain axis remain to be defined. The understanding of the effects of low-calorie drinks on the enteral-brain axis still remains in its infancy and needs to be unveiled. The consumption of low-calorie beverages reduces the calories from that drink, but compensatory phenomena may increase energy intake, and if so must be recognized and avoided.

  1. Polarized triple-axis spectrometer TASP

    Energy Technology Data Exchange (ETDEWEB)

    Boeni, P; Keller, P [Lab. for Neutron Scattering ETH Zurich, Zurich (Switzerland) and Paul Scherrer Institute, Villigen (Switzerland)

    1996-11-01

    The polarized triple-axis spectrometer TASP at SINQ has been optimized for measuring magnetic cross sections in condensed matter. The neutrons are polarized or analyzed either by means of benders or Heusler monochromators. The beam divergence, i.e. the intensity, and the spectral range of the neutrons is rather large because of the supermirror coatings of the feeding neutron guide. The intensity can be further increased at the sample position by means of a focussing monochromator and a focussing anti-trumpet. The end position of TASP allows the tailoring of the neutron beam already before the monochromator and to scatter neutrons over very wide ranges of angles. (author) 6 figs., 1 tab., 8 refs.

  2. A Portable Single Axis Magnetic Gradiometer

    DEFF Research Database (Denmark)

    Merayo, José M.G.; Petersen, Jan Raagaard; Nielsen, Otto V

    2001-01-01

    not provide vector information about the magnetic field. Secondly, one of the sensors measures the ambient magnetic field and is used to compensate for the main field at both sensors. Several methods have been developed for characterization of the 2 gradiometer, and the calibration of the gradient......The single axis magnetic gradiometer based on two compact detector compensation (CDC) fluxgate ringcore sensors separated 20 cm is described. Despite its high stability and precision better than 1 nT, the calibration procedures are not straightforward. Firstly, the mono-axial measurement does...... measurements is achieved by using a magnetic dipole of strength 2 mAm(2). In a coil facility, the gradient can be determined with an accuracy of 0.3 nT/m(RMS)....

  3. RITA-type triple axis spectrometers

    International Nuclear Information System (INIS)

    Roennow, H.M.

    2001-01-01

    The RITA spectrometer at Risoe National Laboratory was the first to incorporate a complete re-thinking of the neutron-path from source, through detector to analysis. Since then, other RITA-type spectrometers such as SPINS at NIST, RITA-II at PSI have been built, and several new spectrometers around the world are adapting the same philosophy. The main novelty of RITA was the introduction of a single back-end tank featuring both an analyser block with multiple individually turnable analyser blades and a 2D position sensitive detector. Several new triple-axis spectrometers are presently being built at existing and future sources, and almost all of them have learnt from the experience with RITA. (R.P.)

  4. Combined fracture of atlas and axis with infrequent

    International Nuclear Information System (INIS)

    Mosquera Betancourt, Dra. C. Gretel; Hernández González, MSc. Erick Héctor; Guevara Oré, Dr. Erick; Sulca Cedeño, Dr. Xavier; Téllez Isla, Dr. Rogers; Ramírez Reyes, Dra. Elizabet

    2016-01-01

    Background: combined lesions of atlas and axis are the most common cervical spine traumas in elderly people, with an incidence of about 70 %. The diagnosis demands the use of advance radiologic procedures and the treatment options runs through conservative to complex surgical interventions to restore the stability of the occipito-cervical region. Objective: to present a combined lesion of the first and second cervical vertebra as a less frequent shape of odontoid fracture. Clinical case: a 79-year-old patient who suffered a posterior cranial trauma followed by bilateral crevice brachialgia and paraesthesias after a horse fall. At physical exploration no signs of radicular or cordonal compression were demonstrated. Computarized axial tomography with tridimentional reconstructions showed a bilateral and symmetrical fracture of the posterior arch of the atlas, associated with longitudinal and oblique fracture of odontoid next to the isthmus. No dislocation was observed that is why the upper cervical spine stability was preserved. Conservative treatment was achieved by an external orthesis with a favourable evolution. Conclusions: for atlantoaxial traumatic lesions diagnosis, the use of computerized axial tomography is important associated or not with nuclear magnetic resonance. The stability of this region in correspondence with neurological status are the most important factors to select the best treatment choice. (author)

  5. Usefulness of Non-coplanar Helical Tomotherapy Using Variable Axis Baseplate

    International Nuclear Information System (INIS)

    Ha, Jin Sook; Chung, Yoon Sun; Lee, Ik Jae; Shin, Dong Bong; Kim, Jong Dae; Kim, Sei Joon; Jeon, Mi Jin; Chok, Yoon Jin; Kim, Ki Kwang; Lee, Seul Bee

    2011-01-01

    Helical Tomotherapy allows only coplanar beam delivery because it does not allow couch rotation. We investigated a method to introduce non-coplanar beam by tilting a patient's head for Tomotherapy. The aim of this study was to compare intrafractional movement during Tomotherapy between coplanar and non-coplanar patient's setup. Helical Tomotherapy was used for treating eight patients with intracranial tumor. The subjects were divided into three groups: one group (coplanar) of 2 patients who lay on S-plate with supine position and wore thermoplastic mask for immobilizing the head, second group (non-coplanar) of 3 patients who lay on S-plate with supine position and whose head was tilted with Variable Axis Baseplate and wore thermoplastic mask, and third group (non-coplanar plus mouthpiece) of 3 patients whose head was tilted and wore a mouthpiece immobilization device and thermoplastic mask. The patients were treated with Tomotherapy after treatment planning with Tomotherapy Planning System. Megavoltage computed tomography (MVCT) was performed before and after treatment, and the intrafractional error was measured with lateral(X), longitudinal(Y), vertical(Z) direction movements and vector (√x 2 +√y 2 +√z 2 ) value for assessing overall movement. Intrafractional error was compared among three groups by taking the error of MVCT taken after the treatment. As the correction values (X, Y, Z) between MVCT image taken after treatment and CT-simulation image are close to zero, the patient movement is small. When the mean values of movement of each direction for non-coplanar setup were compared with coplanar setup group, X-axis movement was decreased by 13%, but Y-axis and Z-axis movement were increased by 109% and 88%, respectively. Movements of Y-axis and Z-axis with non-coplanar setup were relatively greater than that of X-axis since a tilted head tended to slip down. The mean of X-axis movement of the group who used a mouthpiece was greater by 9.4% than the group

  6. Nuclear regulatory decision making

    International Nuclear Information System (INIS)

    Wieland, Patricia; Almeida, Ivan Pedro Salati de

    2011-01-01

    The scientific considerations upon which the nuclear regulations are based provide objective criteria for decisions on nuclear safety matters. However, the decisions that a regulatory agency takes go far beyond granting or not an operating license based on assessment of compliance. It may involve decisions about hiring experts or research, appeals, responses to other government agencies, international agreements, etc.. In all cases, top management of the regulatory agency should hear and decide the best balance between the benefits of regulatory action and undue risks and other associated impacts that may arise, including issues of credibility and reputation. The establishment of a decision framework based on well established principles and criteria ensures performance stability and consistency, preventing individual subjectivity. This article analyzes the challenges to the decision-making by regulatory agencies to ensure coherence and consistency in decisions, even in situations where there is uncertainty, lack of reliable information and even divergence of opinions among experts. The article explores the basic elements for a framework for regulatory decision-making. (author)

  7. Nuclear regulatory decision making

    International Nuclear Information System (INIS)

    2005-01-01

    The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear utilities operate their plants at all times in an acceptably safe manner. In meeting this objective, the regulatory body should strive to ensure that its regulatory decisions are technically sound, consistent from case to case, and timely. In addition, the regulator must be aware that its decisions and the circumstances surrounding those decisions can affect how its stakeholders, such as government policy makers, the industry it regulates, and the public, view it as an effective and credible regulator. In order to maintain the confidence of those stakeholders, the regulator should make sure that its decisions are transparent, have a clear basis in law and regulations, and are seen by impartial observers to be fair to all parties. Based on the work of a Nuclear Energy Agency (NEA) expert group, this report discusses some of the basic principles and criteria that a regulatory body should consider in making decisions and describes the elements of an integrated framework for regulatory decision making. (author)

  8. Model-based therapeutic correction of hypothalamic-pituitary-adrenal axis dysfunction.

    Directory of Open Access Journals (Sweden)

    Amos Ben-Zvi

    2009-01-01

    Full Text Available The hypothalamic-pituitary-adrenal (HPA axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS. At present these dynamics are not formally considered in the development of treatment strategies. Here we use model-based predictive control (MPC methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels. Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning.

  9. Nuclear Regulatory Legislation

    International Nuclear Information System (INIS)

    1989-08-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 100th Congress, 2nd Session, has been prepared by the Office of the General Counsel, US Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document. Persons using this document are placed on notice that it may not be used as an authoritative citation in lieu of the primary legislative sources. Furthermore, while every effort has been made to ensure the completeness and accuracy of this material, neither the United States Government, the Nuclear Regulatory Commission, nor any of their employees makes any expressed or implied warranty or assumes liability for the accuracy or completeness of the material presented in this compilation

  10. Regulatory and licensee surveys

    International Nuclear Information System (INIS)

    2009-01-01

    Prior to the workshop two CSNI/WGHOF surveys were distributed. One survey was directed at regulatory bodies and the other was directed at plant licensees. The surveys were: 1 - Regulatory Expectations of Licensees' Arrangements to Ensure Suitable Organisational Structure, Resources and Competencies to Manage Safety (sent to WGHOF regulatory members). The survey requested that the respondents provide a brief overview of the situation related to plant organisations in their country, their regulatory expectations and their formal requirements. The survey addressed three subjects: the demonstration and documentation of organisational structures, resources and competencies, organisational changes, issues for improvement (for both current and new plants). Responses were received from eleven regulatory bodies. 2 - Approaches to Justify Organisational Suitability (sent to selected licensees). The purpose of the survey to was to gain an understanding of how licensees ensure organisational suitability, resources and competencies. This information was used to assist in the development of the issues and subjects that were addressed at the group discussion sessions. Responses were received from over fifteen licensees from nine countries. The survey requested that the licensees provide information on how they ensure effective organisational structures at their plants. The survey grouped the questions into the following four categories: organisational safety functions, resource and competence, decision-making and communication, good examples and improvement needs. The findings from these surveys were used in conjunction with other factors to identify the key issues for the workshop discussion sessions. The responses from these two surveys are discussed briefly in Sections 4 and 5 of this report. More extensive reviews of the regulatory and licensee responses are provided in Appendix 1

  11. Excessive crying in infants with regulatory disorders.

    Science.gov (United States)

    Maldonado-Duran, M; Sauceda-Garcia, J M

    1996-01-01

    The authors point out a correlation between regulatory disorders in infants and the problem of excessive crying. The literature describes other behavioral problems involving excessive crying in very young children, but with little emphasis on this association. The recognition and diagnosis of regulatory disorders in infants who cry excessively can help practitioners design appropriate treatment interventions. Understanding these conditions can also help parents tailor their caretaking style, so that they provide appropriate soothing and stimulation to their child. In so doing, they will be better able to develop and preserve a satisfactory parent-child relationship, as well as to maintain their own sense of competence and self-esteem as parents.

  12. Prediction of regulatory elements

    DEFF Research Database (Denmark)

    Sandelin, Albin

    2008-01-01

    Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet......-lab methods are time consuming and expensive, it is not realistic to identify TFBS for all uncharacterized genes in the genome by purely experimental means. Computational methods aimed at predicting potential regulatory regions can increase the efficiency of wet-lab experiments significantly. Here, methods...

  13. Rationales for regulatory activity

    Energy Technology Data Exchange (ETDEWEB)

    Perhac, R.M. [Univ. of Tennessee, Knoxville, TN (United States)

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  14. Analysis and design of a vertical axis wind turbine

    OpenAIRE

    Goyena Iriso, Joseba

    2011-01-01

    The main objective of this project is to design a new vertical axis wind turbine, specifically one Giromill wind turbine. The project development requires performing a previous study of the vertical axis wind turbines currently development. This study has to be performed before starting to design the wind turbine. Other very important aim is the development of a new vertical axis wind turbine. The after analyses that will result in the final design of the wind turbine will b...

  15. Self-starting aerodynamics analysis of vertical axis wind turbine

    OpenAIRE

    Jianyang Zhu; Hailin Huang; Hao Shen

    2015-01-01

    Vertical axis wind turbine is a special type of wind-force electric generator which is capable of working in the complicated wind environment. The self-starting aerodynamics is one of the most important considerations for this kind of turbine. This article aims at providing a systematic synthesis on the self-starting aerodynamic characteristics of vertical axis wind turbine based on the numerical analysis approach. First, the physical model of vertical axis wind turbine and its parameter defi...

  16. Early life stress, HPA axis adaptation and mechanisms contributing to later health outcomes

    Directory of Open Access Journals (Sweden)

    Jayanthi eManiam

    2014-05-01

    Full Text Available Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early life stress can impact on later health but less is known about how early life stress impairs HPA axis activity, contributing to maladaptation of the stress response system. Early life stress exposure (either prenatally or in the early postnatal period can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical and experimental studies have demonstrated that early life stress produces long-term hyper responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviours. Recently, evidence has emerged on early life stress induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1. We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early life stress induced maladaptation of the HPA axis, and its subsequent effects on energy utilisation and expenditure. The effects of positive later environments as a means of ameliorating early life stress induced health deficits, and proposed mechanisms underpinning the interaction between early life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early life stress and later health outcomes will also

  17. Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

    Science.gov (United States)

    Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

    2014-01-01

    Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be

  18. Concept of a Programmable Fixture for 3-Axis CNC

    Directory of Open Access Journals (Sweden)

    Ahmad Dalloul

    2017-09-01

    Full Text Available CNC machine is the one of the major reasons for industrial advancement in recent decades for its ability of producing accurate parts. The most commen CNC machines are of 3-axis and adopted widely in the industrial sector. However, for producing more complicated parts 5-axis CNC machines are required. Although the introduction of the 5-axis machine came after the 3-axis CNC machine has established itself and many manufacturers did not make the move toward the newer model and its high pricing compared to the 3-axis model did not help either. In this time the development of a fixture or a platform to help transfer the 3-axis to a 5-axis to some degree. This paper discusses the concept of a programmable fixture that gives 3-axis CNC machine the freedom to act in similar manner as the 5-axis. The paper describes the mechanism with some initial results of the testing. Result showed that the platform moves in translation manner with an average error of 5.58 % and 7.303% average error for rotation movement.

  19. Suicidal behavior on Axis VI: clinical data supporting a sixth Axis for DSM-V.

    Science.gov (United States)

    Van Orden, Kimberly A; Witte, Tracy K; Holm-Denoma, Jill; Gordon, Kathryn H; Joiner, Thomas E

    2011-01-01

    Oquendo and colleagues (Oquendo, Baca-García, Mann, & Giner, 2008; Oquendo & Currier, 2009) recommend that DSM-V emphasize suicide risk assessment on a sixth axis, thereby increasing regularity of suicide risk assessments. We propose that evidence of nonredundancy with Axis V - Global Assessment of Functioning (GAF) is one piece of data that can serve as a starting point for a line of research establishing incremental predictive utility for a separate suicide risk assessment in the DSM framework. A standardized suicide risk assessment protocol, measures of depressive, anxious, and eating disordered symptomatology, as well as an index of comorbidity were administered to a sample of 412 adult outpatients. Our data indicate that data from standardized suicide risk assessments are associated with indices of symptomatology severity as well as comorbidity, controlling for GAF. These results support the nonredundancy of the assessments and suggest the utility of longitudinal investigations of the predictive utility of a sixth DSM axis in the assessment of suicide risk.

  20. Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function.

    Science.gov (United States)

    Perakakis, Nikolaos; Upadhyay, Jagriti; Ghaly, Wael; Chen, Joyce; Chrysafi, Pavlina; Anastasilakis, Athanasios D; Mantzoros, Christos S

    2018-05-09

    We have previously demonstrated that the adipose tissue derived hormone leptin controls reproductive function by regulating the hypothalamic-pituitary-gonadal axis in response to energy deficiency. Here, we evaluate the activins-follistatins-inhibins (AFI) axis during acute (short-term fasting in healthy people) and chronic energy deficiency (women with hypothalamic amenorrhea due to strenuous exercise [HA]) and investigate their relation to leptin and reproductive function in healthy subjects and subjects with HA. The AFI axis was investigated in: a) A double-blinded study in healthy subjects having three randomly assigned admissions, each time for four days: in the isocaloric fed state, complete fasting with placebo treatment, complete fasting with leptin replacement, b) A case-control study comparing women with HA vs healthy controls, c) An open-label interventional study investigating leptin treatment in women with HA over a period of up to three months, d) A randomized interventional trial investigating leptin treatment vs placebo in women with HA for nine months. The circulating levels of activin A, activin B, follistatin and follistatin-like 3 change robustly in response to acute and chronic energy deficiency. Leptin replacement in acute energy deprivation does not affect the levels of these hormones suggesting an independent regulation by these two hormonal pathways. In chronic energy deficiency, leptin replacement restores only activin B levels, which are in turn associated with an increase in the number of dominant follicles. We demonstrate for the first time that the AFI axis is affected both by acute and chronic energy deficiency. Partial restoration of a component of the axis, i.e. activin B only, through leptin replacement is associated with improved reproductive function in women with HA. Copyright © 2018. Published by Elsevier Inc.

  1. FORECAST: Regulatory effects cost analysis software annual

    International Nuclear Information System (INIS)

    Lopez, B.; Sciacca, F.W.

    1991-11-01

    Over the past several years the NRC has developed a generic cost methodology for the quantification of cost/economic impacts associated with a wide range of new or revised regulatory requirements. This methodology has been developed to aid the NRC in preparing Regulatory Impact Analyses (RIAs). These generic costing methods can be useful in quantifying impacts both to industry and to the NRC. The FORECAST program was developed to facilitate the use of the generic costing methodology. This PC program integrates the major cost considerations that may be required because of a regulatory change. FORECAST automates much of the calculations typically needed in an RIA and thus reduces the time and labor required to perform these analysis. More importantly, its integrated and consistent treatment of the different cost elements should help assure comprehensiveness, uniformity, and accuracy in the preparation of needed cost estimates

  2. Recommendations for an update of the 2010 European regulatory guideline on clinical investigation of medicinal products used in the treatment of osteoarthritis and reflections about related clinically relevant outcomes: expert consensus statement.

    Science.gov (United States)

    Reginster, J-Y; Reiter-Niesert, S; Bruyère, O; Berenbaum, F; Brandi, M-L; Branco, J; Devogelaer, J-P; Herrero-Beaumont, G; Kanis, J; Maggi, S; Maheu, E; Richette, P; Rizzoli, R; Cooper, C

    2015-12-01

    The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA). Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process. It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs - i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter - in the timing of assessments. Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing). This working document might be considered by the European regulatory authorities in a future update of the guideline for the registration of drugs in OA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Essence of "Shen (Kidney) Controlling Bones": Conceptual Analysis Based on Hypothalamic-Pituitary-Adrenal-Osteo-Related Cells Axis.

    Science.gov (United States)

    Xu, Tao-Tao; Jin, Hong-Ting; Tong, Pei-Jian

    2018-04-12

    As a traditional concept of Chinese medicine (CM), the theory of "Shen (Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen defifi ciency as a pathological condition has a negative effect on the skeleton of body, specififi cally the disorder of bone homeostasis. Present studies indicate that Shen defifi ciency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal (HPA) axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis: cells that comprise bone tissue (osteo-related cells) are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.

  4. Developing regulatory approaches

    International Nuclear Information System (INIS)

    Axelsson, Lars

    2012-01-01

    Lars Axelsson presented SSM progress on oversight of LMfS/SC since the Chester 1 Workshop in 2007. Current SSM approaches for safety culture oversight include targeted safety management and safety culture inspections, compliance inspections which cover aspects of safety management/safety culture and multi-disciplinary team inspections. Examples of themes for targeted inspections include management of ambiguous operational situations or other weak signals, understanding of and attitudes to Human Performance tools, the Safety Department's role and authority and Leadership for safety. All regulatory activities provide inputs for the SSM yearly safety evaluation of each licensee. A form has been developed to capture safety culture observations from inspections and other interactions with licensees. Analysis will be performed to identify patterns and provide information to support planning of specific Safety Culture activities. Training has been developed for regulatory staff to enhance the quality of regulatory interventions on safety culture. This includes a half-day seminar to provide an overview of safety culture, and a workshop which provides more in-depth discussion on cultural issues and how to capture those during regulatory activities. Future plans include guidance for inspectors, and informal seminars on safety culture with licensees

  5. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1992-07-01

    This document compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rule making which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  6. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-02-01

    This document is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considered action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  7. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1989-07-01

    This document is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  8. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1992-11-01

    This document provides a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  9. Comments on regulatory reform

    International Nuclear Information System (INIS)

    Hendrie, J.M.

    1982-01-01

    Nuclear regulatory reform is divided into two parts. The first part contains all those matters for which new legislation is required. The second part concerns all those matters that are within the power of the Commission under existing statutes. Recommendations are presented

  10. Comments on regulatory reform

    Energy Technology Data Exchange (ETDEWEB)

    Hendrie, J.M.

    1982-01-01

    Nuclear regulatory reform is divided into two parts. The first part contains all those matters for which new legislation is required. The second part concerns all those matters that are within the power of the Commission under existing statutes. Recommendations are presented.

  11. 3 CFR - Regulatory Review

    Science.gov (United States)

    2010-01-01

    ... as a means of promoting regulatory goals. The fundamental principles and structures governing... review. In this time of fundamental transformation, that process—and the principles governing regulation... the Office of Management and Budget (OMB) has reviewed Federal regulations. The purposes of such...

  12. Effective solidity in vertical axis wind turbines

    Science.gov (United States)

    Parker, Colin M.; Leftwich, Megan C.

    2016-11-01

    The flow surrounding vertical axis wind turbines (VAWTs) is investigated using particle imaging velocimetry (PIV). This is done in a low-speed wind tunnel with a scale model that closely matches geometric and dynamic properties tip-speed ratio and Reynolds number of a full size turbine. Previous results have shown a strong dependance on the tip-speed ratio on the wake structure of the spinning turbine. However, it is not clear whether this is a speed or solidity effect. To determine this, we have measured the wakes of three turbines with different chord-to-diameter ratios, and a solid cylinder. The flow is visualized at the horizontal mid-plane as well as the vertical mid-plane behind the turbine. The results are both ensemble averaged and phase averaged by syncing the PIV system with the rotation of the turbine. By keeping the Reynolds number constant with both chord and diameter, we can determine how each effects the wake structure. As these parameters are varied there are distinct changes in the mean flow of the wake. Additionally, by looking at the vorticity in the phase averaged profiles we can see structural changes to the overall wake pattern.

  13. Mitochondrial–Lysosomal Axis in Acetaminophen Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Anna Moles

    2018-05-01

    Full Text Available Acetaminophen (APAP toxicity is the most common cause of acute liver failure and a major indication for liver transplantion in the United States and Europe. Although significant progress has been made in understanding the molecular mechanisms underlying APAP hepatotoxicity, there is still an urgent need to find novel and effective therapies against APAP-induced acute liver failure. Hepatic APAP metabolism results in the production of the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI, which under physiological conditions is cleared by its conjugation with glutathione (GSH to prevent its targeting to mitochondria. APAP overdose or GSH limitation leads to mitochondrial NAPQI-protein adducts formation, resulting in oxidative stress, mitochondrial dysfunction, and necrotic cell death. As mitochondria are a major target of APAP hepatotoxicity, mitochondrial quality control and clearance of dysfunctional mitochondria through mitophagy, emerges as an important strategy to limit oxidative stress and the engagement of molecular events leading to cell death. Recent evidence has indicated a lysosomal–mitochondrial cross-talk that regulates APAP hepatotoxicity. Moreover, as lysosomal function is essential for mitophagy, impairment in the fusion of lysosomes with autophagosomes-containing mitochondria may compromise the clearance of dysfunctional mitochondria, resulting in exacerbated APAP hepatotoxicity. This review centers on the role of mitochondria in APAP hepatotoxicity and how the mitochondrial/lysosomal axis can influence APAP-induced liver failure.

  14. Yaw dynamics of horizontal axis wind turbines

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, A.C. (Utah Univ., Salt Lake City, UT (United States))

    1992-05-01

    Designers of a horizontal axis wind turbine yaw mechanism are faced with a difficult decision. They know that if they elect to use a yaw- controlled rotor then the system will suffer increased initial cost and increased inherent maintenance and reliability problems. On the other hand, if they elect to allow the rotor to freely yaw they known they will have to account for unknown and random, though bounded, yaw rates. They will have a higher-risk design to trade-off against the potential for cost savings and reliability improvement. The risk of a yaw-free system could be minimized if methods were available for analyzing and understanding yaw behavior. The complexity of yaw behavior has, until recently, discouraged engineers from developing a complete yaw analysis method. The objectives of this work are to (1) provide a fundamental understanding of free-yaw mechanics and the design concepts most effective at eliminating yaw problems, and (2) provide tested design tools and guidelines for use by free-yaw wind systems manufacturers. The emphasis is on developing practical and sufficiently accurate design methods.

  15. Six axis force feedback input device

    Science.gov (United States)

    Ohm, Timothy (Inventor)

    1998-01-01

    The present invention is a low friction, low inertia, six-axis force feedback input device comprising an arm with double-jointed, tendon-driven revolute joints, a decoupled tendon-driven wrist, and a base with encoders and motors. The input device functions as a master robot manipulator of a microsurgical teleoperated robot system including a slave robot manipulator coupled to an amplifier chassis, which is coupled to a control chassis, which is coupled to a workstation with a graphical user interface. The amplifier chassis is coupled to the motors of the master robot manipulator and the control chassis is coupled to the encoders of the master robot manipulator. A force feedback can be applied to the input device and can be generated from the slave robot to enable a user to operate the slave robot via the input device without physically viewing the slave robot. Also, the force feedback can be generated from the workstation to represent fictitious forces to constrain the input device's control of the slave robot to be within imaginary predetermined boundaries.

  16. Creating a Multi-axis Machining Postprocessor

    Directory of Open Access Journals (Sweden)

    Petr Vavruška

    2012-01-01

    Full Text Available This paper focuses on the postprocessor creation process. When using standard commercially available postprocessors it is often very difficult to modify its internal source code, and it is a very complex process, in many cases even impossible, to implement the newly-developed functions. It is therefore very important to have a method for creating a postprocessor for any CAM system, which allows CL data (Cutter Location data to be generated to a separate text file. The goal of our work is to verify the proposed method for creating a postprocessor. Postprocessor functions for multi-axis machiningare dealt with in this work. A file with CL data must be translated by the postprocessor into an NC program that has been customized for a specific production machine and its control system. The postprocessor is therefore verified by applications for machining free-form surfaces of complex parts, and by executing the NC programs that are generated on real machine tools. This is also presented here.

  17. Pollution prevention: A regulatory update

    International Nuclear Information System (INIS)

    Walzer, A.E.; Maynard, J.W.

    1993-01-01

    Pollution prevention is the emphasis of the 1990s environmental philosophy. This new environmental era was ushered in when President Bush signed the Pollution Prevention Act in October 1990. This law, with its accompanying philosophy, was in response to the realization that end-of-the-pipe treatment, which frequently changed the media in which a pollutant or waste was discharged, was inadequate to protect the environment and human health. Pollution prevention advocates source reduction, where material substitutions and engineering solutions are sought to reduce the volume and toxicity of waste and pollutants. This proactive approach reduces environmental impacts such as those of former waste sites which have produced environmental legacies that will cost billions of dollars and take decades to remediate. This paper describes pollution prevention philosophy and summarizes regulatory pollution prevention requirements. It describes current regulatory trends in the area of pollution prevention, including voluntary programs and enforcement actions. The Pollution Prevention Act of 1990 is described, and pollution prevention initiatives embodied in other laws, including the Clean Air Act, the Clean Water Act, the Emergency Planning and Community Right-To-Know Act, the Resource Conservation and Recovery Act, and the Toxic Substances Control Act, are discussed. A historical overview of waste minimization initiatives within the Department of Energy is given, and other pollution prevention initiatives that affect federal facilities, such as Executive Order 12780, which mandates recycling and the procurement of recycled materials, are also outlined

  18. Regulatory Issues Surrounding Merchant Interconnection

    International Nuclear Information System (INIS)

    Kuijlaars, Kees-Jan; Zwart, Gijsbert

    2003-11-01

    We discussed various issues concerning the regulatory perspective on private investment in interconnectors. One might claim that leaving investment in transmission infrastructure to competing market parties is more efficient than relying on regulated investment only (especially in the case of long (DC) lines connecting previously unconnected parts of the grids, so that externalities from e.g. loop flows do not play a significant role). We considered that some aspects of interconnection might reduce these market benefits. In particular, the large fixed costs of interconnection construction may lead to significant under investment (due to both first mover monopoly power and the fact that part of generation cost efficiencies realised by interconnection are not captured by the investor itself, and remain external to the investment decision). Second, merchant ownership restricts future opportunities for adaptation of regulation, as would be required e.g. for introduction of potentially more sophisticated methods of congestion management or market splitting. Some of the disadvantages of merchant investment may be mitigated however by a suitable regulatory framework, and we discussed some views in this direction. The issues we discussed are not intended to give a complete framework, and detailed regulation will certainly involve many more specific requirements. Areas we did not touch upon include e.g. the treatment of deep connection costs, rules for operation and maintenance of the line, and impact on availability of capacity on other interconnections

  19. Regulatory Issues Surrounding Merchant Interconnection

    Energy Technology Data Exchange (ETDEWEB)

    Kuijlaars, Kees-Jan; Zwart, Gijsbert [Office for Energy Regulation (DTe), The Hague (Netherlands)

    2003-11-01

    We discussed various issues concerning the regulatory perspective on private investment in interconnectors. One might claim that leaving investment in transmission infrastructure to competing market parties is more efficient than relying on regulated investment only (especially in the case of long (DC) lines connecting previously unconnected parts of the grids, so that externalities from e.g. loop flows do not play a significant role). We considered that some aspects of interconnection might reduce these market benefits. In particular, the large fixed costs of interconnection construction may lead to significant under investment (due to both first mover monopoly power and the fact that part of generation cost efficiencies realised by interconnection are not captured by the investor itself, and remain external to the investment decision). Second, merchant ownership restricts future opportunities for adaptation of regulation, as would be required e.g. for introduction of potentially more sophisticated methods of congestion management or market splitting. Some of the disadvantages of merchant investment may be mitigated however by a suitable regulatory framework, and we discussed some views in this direction. The issues we discussed are not intended to give a complete framework, and detailed regulation will certainly involve many more specific requirements. Areas we did not touch upon include e.g. the treatment of deep connection costs, rules for operation and maintenance of the line, and impact on availability of capacity on other interconnections.

  20. Treatment

    Directory of Open Access Journals (Sweden)

    Safaa M. Raghab

    2013-08-01

    The main goal of this study is to utilize a natural low cost material “as an accelerator additive to enhance the chemical treatment process using Alum coagulant and the accelerator substances were Perlite and Bentonite. The performance of the chemical treatment was enhanced using the accelerator substances with 90 mg/l Alum as a constant dose. Perlite gave better performance than the Bentonite effluent. The removal ratio for conductivity, turbidity, BOD and COD for Perlite was 86.7%, 87.4%, 89.9% and 92.8% respectively, and for Bentonite was 83.5%, 85.0%, 86.5% and 85.0% respectively at the same concentration of 40 mg/l for each.

  1. Binge-pattern alcohol exposure during puberty induces long-term changes in HPA axis reactivity.

    Directory of Open Access Journals (Sweden)

    Magdalena M Przybycien-Szymanska

    2011-04-01

    Full Text Available Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA axis, as manifested by alterations in corticotrophin-releasing hormone (CRH, arginine vasopressin (AVP, and corticosterone (CORT during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

  2. Distortion definition and correction in off-axis systems

    Science.gov (United States)

    Da Deppo, Vania; Simioni, Emanuele; Naletto, Giampiero; Cremonese, Gabriele

    2015-09-01

    Off-axis optical configurations are becoming more and more used in a variety of applications, in particular they are the most preferred solution for cameras devoted to Solar System planets and small bodies (i.e. asteroids and comets) study. Off-axis designs, being devoid of central obstruction, are able to guarantee better PSF and MTF performance, and thus higher contrast imaging capabilities with respect to classical on-axis designs. In particular they are suitable for observing extended targets with intrinsic low contrast features, or scenes where a high dynamical signal range is present. Classical distortion theory is able to well describe the performance of the on-axis systems, but it has to be adapted for the off-axis case. A proper way to deal with off-axis distortion definition is thus needed together with dedicated techniques to accurately measure and hence remove the distortion effects present in the acquired images. In this paper, a review of the distortion definition for off-axis systems will be given. In particular the method adopted by the authors to deal with the distortion related issues (definition, measure, removal) in some off-axis instruments will be described in detail.

  3. A psychology of the human brain-gut-microbiome axis.

    Science.gov (United States)

    Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

    2017-04-01

    In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

  4. Late Presentation of a Type III Axis Fracture with Spondyloptosis

    Science.gov (United States)

    Jayakumar, Prakash; Choi, David; Casey, Adrian

    2008-01-01

    A 58-year-old man presented with an undiagnosed Effendi type III classification fracture and spondyloptosis of the axis with remarkably normal neurology. We discuss his surgery 4 years since the initial injury, and the presentation, features and management of fractures of the axis. PMID:18430325

  5. Axis: Generating Explanations at Scale with Learnersourcing and Machine Learning

    Science.gov (United States)

    Williams, Joseph Jay; Kim, Juho; Rafferty, Anna; Heffernan, Neil; Maldonado, Samuel; Gajos, Krzysztof Z.; Lasecki, Walter S.; Heffernan, Neil

    2016-01-01

    While explanations may help people learn by providing information about why an answer is correct, many problems on online platforms lack high-quality explanations. This paper presents AXIS (Adaptive eXplanation Improvement System), a system for obtaining explanations. AXIS asks learners to generate, revise, and evaluate explanations as they solve…

  6. Angular momentum projection of tilted axis rotating states

    Energy Technology Data Exchange (ETDEWEB)

    Oi, M; Onishi, N; Tajima, N [Tokyo Univ. (Japan); Horibata, T

    1998-03-01

    We applied an exact angular momentum projection to three dimensional cranked HFB (3d-CHFB) states. Tilted axis rotating states (TAR) and principal axis rotating states (PAR) are compared. It is shown that TAR is more adequate than PAR for description of the back bending phenomena driven by tilted rotation or wobbling motion. (author)

  7. A psychology of the human brain–gut–microbiome axis

    Science.gov (United States)

    Allen, Andrew P.; Dinan, Timothy G.; Clarke, Gerard

    2017-01-01

    Abstract In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain–gut–microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress‐related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain–gut–microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain–gut–microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain–gut–microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain–gut–microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology. PMID:28804508

  8. The Performance Characteristics of a Closed Loop, One Axis ...

    African Journals Online (AJOL)

    This paper presents a closed loop one axis solar tracking device of the polar axis type, which achieves an accurate tracking of the sun with a steady state error of less, than 2%. This prototype uses a photo-sensing system to generate an error signal. This error signal switches on a relay, which actuates an electromechanical ...

  9. Regulatory aspects of sludge management

    International Nuclear Information System (INIS)

    Sharples, F.E.

    1992-01-01

    The paper presents an overview of radioactive waste land disposal restrictions by discussing the following topics: highlights of Resource Conservation and Recovery Act history; purposes of land disposal restrictions; regulatory definition of land disposal; US Environmental Protection Agency (EPA) implementation of land disposal restrictions; schedules for implementing land disposal restrictions; solvent and dioxin wastes; classification of liquid hazardous and radioactive wastes; generator and treatment, storage, and disposal responsibilities; variances and extensions; and options for mixed waste management. Land disposal restrictions take into account the long-term uncertainties associated with land disposal, the need to manage waste right the first time they are disposed, and the persistence toxicity, mobility, propensity to bioaccumulate, and volume. In the Department of Energy system land disposal restrictions affect mixed waste management and site remedial action programs

  10. Nuclear Regulatory Commission information digest

    International Nuclear Information System (INIS)

    1990-03-01

    The Nuclear Regulatory Commission information digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the commission. This is an annual publication for the general use of the NRC Staff and is available to the public. The digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide

  11. The hypothalamo-pituitary-adrenal axis in major affective disorder

    DEFF Research Database (Denmark)

    Christensen, M V; Kessing, L V

    2001-01-01

    disorder. The HPA axis is a complex neuroendocrine network with multiple integrated levels of control, and it is likely that the dysregulation involves abnormalities at several sites within the axis. At present, it is not clear whether the abnormalities are related to the affective episodes only......This paper reviews studies of the hypothalamo-pituitary-adrenal (HPA)-axis activity in patients with affective disorders. It is concluded that, despite methodological drawbacks in most studies, dysregulation of the HPA axis seems to be a consistent finding in a proportion of patients with affective...... or to the disorder itself. There is a need for prospective studies of larger samples of patients to be followed during successive affective episodes with a combination of measurements of the HPA-axis activity and brain imaging....

  12. Shot H3837: Darht's First Dual-Axis Explosive Experiment

    Science.gov (United States)

    Mendez, Jacob; McNeil, Wendy Vogan; Harsh, James; Hull, Lawrence

    2011-06-01

    Test H3837 was the first explosive shot performed in front of both flash x-ray axes at the Los Alamos Dual Axis Radiographic HydroTest (DARHT) facility. Executed in November 2009, the shot was an explosively-driven metal flyer plate in a series of experiments designed to explore equation-of-state properties of shocked materials. Imaging the initial shock wave traveling through the flyer plate, DARHT Axis II captured the range of motion from the shock front emergence in the flyer to breakout at the free surface; the Axis I pulse provided a perpendicular perspective of the shot at a time coinciding with the third pulse of Axis II. Since the days of the Manhattan Project, penetrating radiography with multiple frames from different viewing angles has remained a high-profile goal at the Laboratory. H3837 is merely the beginning of a bright future for two-axis penetrating radiography.

  13. Three-Axis Ground Reaction Force Distribution during Straight Walking.

    Science.gov (United States)

    Hori, Masataka; Nakai, Akihito; Shimoyama, Isao

    2017-10-24

    We measured the three-axis ground reaction force (GRF) distribution during straight walking. Small three-axis force sensors composed of rubber and sensor chips were fabricated and calibrated. After sensor calibration, 16 force sensors were attached to the left shoe. The three-axis force distribution during straight walking was measured, and the local features of the three-axis force under the sole of the shoe were analyzed. The heel area played a role in receiving the braking force, the base area of the fourth and fifth toes applied little vertical or shear force, the base area of the second and third toes generated a portion of the propulsive force and received a large vertical force, and the base area of the big toe helped move the body's center of mass to the other foot. The results demonstrate that measuring the three-axis GRF distribution is useful for a detailed analysis of bipedal locomotion.

  14. The Hypothalamic-Pituitary-Thyroid Axis in Infants and Children: Protection from Radioiodines

    Directory of Open Access Journals (Sweden)

    Jeffrey Fisher

    2014-01-01

    Full Text Available Potassium iodide (KI is recommended as an emergency treatment for exposure to radioiodines, most commonly associated with nuclear detonation or mishaps at nuclear power plants. Protecting the thyroid gland of infants and children remains a priority because of increased incidence of thyroid cancer in the young exposed to radioiodines (such as 131I and 133I. There is a lack of clinical studies for KI and radioiodines in children or infants to draw definitive conclusions about the effectiveness and safety of KI administration in the young. In this paper, we compare functional aspects of the hypothalamic-pituitary-thyroid (HPT axis in the young and adults and review the limited studies of KI in children. The HPT axis in the infant and child is hyperactive and therefore will respond less effectively to KI treatment compared to adults. Research on the safety and efficacy of KI in infants and children is needed.

  15. Theoretical performance of cross-wind axis turbines with results for a catenary vertical axis configuration

    Science.gov (United States)

    Muraca, R. J.; Stephens, M. V.; Dagenhart, J. R.

    1975-01-01

    A general analysis capable of predicting performance characteristics of cross-wind axis turbines was developed, including the effects of airfoil geometry, support struts, blade aspect ratio, windmill solidity, blade interference and curved flow. The results were compared with available wind tunnel results for a catenary blade shape. A theoretical performance curve for an aerodynamically efficient straight blade configuration was also presented. In addition, a linearized analytical solution applicable for straight configurations was developed. A listing of the computer program developed for numerical solutions of the general performance equations is included in the appendix.

  16. Brain angiotensin-(1-7)/Mas axis: A new target to reduce the cardiovascular risk to emotional stress.

    Science.gov (United States)

    Fontes, Marco Antônio Peliky; Martins Lima, Augusto; Santos, Robson Augusto Souza dos

    2016-04-01

    Emotional stress is now considered a risk factor for several diseases including cardiac arrhythmias and hypertension. It is well known that the activation of neuroendocrine and autonomic mechanisms features the response to emotional stress. However, its link to cardiovascular diseases and the regulatory mechanisms involved remain to be further comprehended. The renin-angiotensin system (RAS) plays an important role in homeostasis on all body systems. Specifically in the brain, the RAS regulates a number of physiological aspects. Recent data indicate that the activation of angiotensin-converting enzyme/angiotensin II/AT1 receptor axis facilitates the emotional stress responses. On the other hand, growing evidence indicates that its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/(Ang)iotensin-(1-7)/Mas axis, reduces anxiety and attenuates the physiological responses to emotional stress. The present review focuses on angiotensin-(1-7)/Mas axis as a promising target to attenuate the physiological response to emotional stress reducing the risk of cardiovascular diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Investigating the effect of acute sleep deprivation on hypothalamic-pituitary-adrenal-axis response to a psychosocial stressor.

    Science.gov (United States)

    Vargas, Ivan; Lopez-Duran, Nestor

    2017-05-01

    The hypothalamic-pituitary-adrenal (HPA) axis has been previously identified as one potential mechanism that may explain the link between sleep deprivation and negative health outcomes. However, few studies have examined the direct association between sleep deprivation and HPA-axis functioning, particularly in the context of stress. Therefore, the aim of the current study was to investigate the relationship between acute sleep deprivation and HPA-axis reactivity to a psychosocial stressor. Participants included 40 healthy, young adults between the ages of 18-29. The current protocol included spending two nights in the laboratory. After an adaptation night (night 1), participants were randomized into either a sleep deprivation condition (29 consecutive hours awake) or a control condition (night 2). Following the second night, all participants completed the Trier Social Stress Test (TSST). Salivary cortisol was collected before, during, and after the TSST. Results indicated that there were significant group differences in cortisol stress reactivity. Specifically, compared to participants in the control condition, participants in the sleep deprivation condition had greater baseline (i.e., pre-stress) cortisol, yet a blunted cortisol response to the TSST. Taken together, a combination of elevated baseline cortisol (and its subsequent effect on HPA-axis regulatory processes) and a relative 'ceiling' on the amount of cortisol a laboratory stressor can produce may explain why participants in the sleep deprivation condition demonstrated blunted cortisol responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Characteristics of regulatory regimes

    Directory of Open Access Journals (Sweden)

    Noralv Veggeland

    2013-03-01

    Full Text Available The overarching theme of this paper is institutional analysis of basic characteristics of regulatory regimes. The concepts of path dependence and administrative traditions are used throughout. Self-reinforcing or positive feedback processes in political systems represent a basic framework. The empirical point of departure is the EU public procurement directive linked to OECD data concerning use of outsourcing among member states. The question is asked: What has caused the Nordic countries, traditionally not belonging to the Anglo-Saxon market-centred administrative tradition, to be placed so high on the ranking as users of the Market-Type Mechanism (MTM of outsourcing in the public sector vs. in-house provision of services? A thesis is that the reason may be complex, but might be found in an innovative Scandinavian regulatory approach rooted in the Nordic model.

  19. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-07-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter. The rules on which final action has been taken since March 31, 1993 are: Repeal of NRC standards of conduct; Fitness-for-duty requirements for licensees who possess, use, or transport Category I material; Training and qualification of nuclear power plant personnel; Monitoring the effectiveness of maintenance at nuclear power plants; Licensing requirements for land disposal of radioactive wastes; and Licensees' announcements of safeguards inspections

  20. An augmented reality C-arm for intraoperative assessment of the mechanical axis: a preclinical study.

    Science.gov (United States)

    Fallavollita, Pascal; Brand, Alexander; Wang, Lejing; Euler, Ekkehard; Thaller, Peter; Navab, Nassir; Weidert, Simon

    2016-11-01

    Determination of lower limb alignment is a prerequisite for successful orthopedic surgical treatment. Traditional methods include the electrocautery cord, alignment rod, or axis board which rely solely on C-arm fluoroscopy navigation and are radiation intensive. To assess a new augmented reality technology in determining lower limb alignment. A camera-augmented mobile C-arm (CamC) technology was used to create a panorama image consisting of hip, knee, and ankle X-rays. Twenty-five human cadaver legs were used for validation with random varus or valgus deformations. Five clinicians performed experiments that consisted in achieving acceptable mechanical axis deviation. The applicability of the CamC technology was assessed with direct comparison to ground-truth CT. A t test, Pearson's correlation, and ANOVA were used to determine statistical significance. The value of Pearson's correlation coefficient R was 0.979 which demonstrates a strong positive correlation between the CamC and ground-truth CT data. The analysis of variance produced a p value equal to 0.911 signifying that clinician expertise differences were not significant with regard to the type of system used to assess mechanical axis deviation. All described measurements demonstrated valid measurement of lower limb alignment. With minimal effort, clinicians required only 3 X-ray image acquisitions using the augmented reality technology to achieve reliable mechanical axis deviation.

  1. [The hypothalamic-pituitary-adrenal axis and depressive disorder: recent progress].

    Science.gov (United States)

    Kunugi, Hiroshi; Hori, Hiroaki; Numakawa, Tadahiro; Ota, Miho

    2012-08-01

    Depression is a stress-induced disorder and there is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in the disease. Chronic hyperactivity of the HPA axis and resultant excessive glucocorticoid (hypercortisolism) may be causal to depression. We demonstrated that the dexamethasone (DEX)/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities. Restoration from HPA axis abnormalities occurs with clinical responses to treatment. Brain-derived neurotrophic factor (BDNF) has also been implicated in depression. We found that glucocorticoid (DEX) suppresses BDNF-induced dendrite outgrowth and synaptic formation via blocking the MAPK pathway in early-developing cultured hippocampal neurons. Furthermore, we demonstrated that glucocorticoid receptor (GR) and TrkB (a specific receptor of BDNF) interact and that DEX acutely suppresses BDNF-induced glutamate release by affecting the PLC-gamma pathway in cultured cortical neurons, indicating a mechanism underlying the effect of excessive glucocorticoid on BDNF function and resultant damage in cortical neurons. In a macroscopic view using magnetic resonance imaging (MRI), we found that individuals with hypercortisolism detected by the DEX/CRH test demonstrated volume loss in gray matter and reduced neural network assessed with diffusion tensor imaging in several brain regions. Finally, we observed that individuals with hypocortisolism detected by the DEX/CRH test tend to present more distress symptoms, maladaptive coping styles, and schizotypal personality traits than their counterparts, which points to the important role of hypocortisolism as well as hypercortisolism in depression spectrum disorders.

  2. Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity

    Directory of Open Access Journals (Sweden)

    Marcella Balbo

    2010-01-01

    Full Text Available The daily rhythm of cortisol secretion is relatively stable and primarily under the influence of the circadian clock. Nevertheless, several other factors affect hypothalamo-pituitary-adrenal (HPA axis activity. Sleep has modest but clearly detectable modulatory effects on HPA axis activity. Sleep onset exerts an inhibitory effect on cortisol secretion while awakenings and sleep offset are accompanied by cortisol stimulation. During waking, an association between cortisol secretory bursts and indices of central arousal has also been detected. Abrupt shifts of the sleep period induce a profound disruption in the daily cortisol rhythm, while sleep deprivation and/or reduced sleep quality seem to result in a modest but functionally important activation of the axis. HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders and could be involved in the well-documented associations between sleep disturbances and the risk of obesity, diabetes and cognitive dysfunction. Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments. Further research to delineate the functional links between sleep and HPA axis activity is needed to fully understand the pathophysiology of these syndromes and to develop adequate strategies of prevention and treatment.

  3. Effective shunt impedance comparison between s-band standing wave accelerators with on-axis and off-axis couplers

    International Nuclear Information System (INIS)

    Schriber, S.O.; Funk, L.W.; Hutcheon, R.M.

    1976-01-01

    The effective shunt impedances of a side-coupled S-band standing wave accelerating structure and a structure employing on-axis couplers have been compared by measuring the energy of accelerated electrons. Criteria for choosing an on-axis coupled structure compared to side-coupled and ''disk and washer'' accelerating structures are given. (author)

  4. A flexible regulatory framework

    International Nuclear Information System (INIS)

    Silvennoinen, T.

    2000-01-01

    Regulatory reform of the Finnish electricity market meant opening up potentially competitive parts of the electricity sector to competition and eliminating all unnecessary forms of regulation covering generation, wholesale supply, retail supply, and foreign trade in electricity. New types of control and regulatory mechanisms and institutions were set up for those parts of the electricity industry that were excluded from competition, such as network operations. Network activities now have to be licensed, whereas no licence is needed for generation or supply. A new sector-specific regulatory authority was established in 1995 to coincide with the implementation of the Electricity Market Act, known as the Electricity Market Authority. This is responsible for regulating network activities and retail supply to captive customers. The core function of the authority, which employs some 14 people, is to promote the smooth operation of the Finnish electricity market and to oversee the implementation of the Electricity Market Act and its provisions. Its most important duties are linked to overseeing the process by which network companies price their electricity. As price regulation no longer exists, all the companies in the electricity sector set their tariffs independently, even network companies. The job of controlling the pricing of network services is handed by the Electricity Market Authority, following the principles of competition control. Pricing control takes place ex post - after a pricing system has been adopted by a company and concentrates on individual cases and companies. There is no ex ante system of setting or approving prices and tariffs by the regulator. The tariffs and pricing of network services can be evaluated, however, by both the Electricity Market Authority and the Finnish Competition Authority, which have overlapping powers as regards the pricing of network activities. The Finnish regulatory framework can be described as a system of light

  5. The changing regulatory environment

    International Nuclear Information System (INIS)

    Caron, G.

    1999-01-01

    The role and value of regulation in the energy sector was discussed, demonstrating how, despite common perception, regulation is an essential part of Canada's strategy to find and develop new opportunities. The future vision of regulation for industry participants was presented with particular focus on issues related to streamlining the regulatory process. As far as pipelines are concerned, regulatory actions are necessary to facilitate capacity increases and to ensure the line's integrity, safety and environmental record. Furthermore, regulation provides economic solutions where market forces cannot provide them, as for example where business has elements of monopoly. It arbitrates interests of landowners, business, consumers, and environmental groups. It looks for ways to ensure conditions under which competition can flourish. It acts as the guardian of citizens' rights in a democratic society by providing citizens with an opportunity to be heard on the building or expansion of pipelines and associated facilities. As citizens become more and more concerned about their property and the land that surrounds them, citizen involvement in decision making about how industry activity affects their quality of life will become correspondingly more important. Regulatory agencies are committed to facilitate this engagement by flexible hearing procedures and by making use of evolving communication and information technology

  6. Regulatory aspects of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Kristensen, K.

    1985-01-01

    Regulatory systems in the field of radiopharmaceuticals have two main purposes: efficacy and safety. Efficacy expresses the quality of the diagnostic and therapeutic process for the patient. Safety involves the patient, the staff, and the environment. The world situation regarding regulations for radiopharmaceuticals is reviewed on the basis of a survey in WHO Member States. The main content of such regulations is discussed. The special properties of radiopharmaceuticals compared with ordinary drugs may call for modified regulations. Several countries are preparing such regulations. Close co-operation and good understanding among scientists working in hospital research, industry and regulatory bodies will be of great importance for the fast and safe introduction of new radiopharmaceuticals for the benefit of the patient. Before introducing new legislation in this field, a radiopharmaceutical expert should analyse the situation in the country and the relationship to the existing regulations. It is expected that the most important factor in promoting the fast introduction of new, safe and effective radiopharmaceuticals will be the training of people working within the regulatory bodies. It is foreseen that the IAEA and WHO will have an important role to play by providing expert advice and training in this area. (author)

  7. The NAD+/PARP1/SIRT1 Axis in Aging.

    Science.gov (United States)

    Mendelsohn, Andrew R; Larrick, James W

    2017-06-01

    NAD+ levels decline with age in diverse animals from Caenorhabditis elegans to mice. Raising NAD+ levels by dietary supplementation with NAD+ precursors, nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), improves mitochondrial function and muscle and neural and melanocyte stem cell function in mice, as well as increases murine life span. Decreased NAD+ levels with age reduce SIRT1 function and reduce the mitochondrial unfolded protein response, which can be overcome by NR supplementation. Decreased NAD+ levels cause NAD+-binding protein DBC1 to form a complex with PARP1, inhibiting poly(adenosine diphosphate-ribose) polymerase (PARP) catalytic activity. Old mice have increased amounts of DBC1-PARP1 complexes, lower PARP activity, increased DNA damage, and reduced nonhomologous end joining and homologous recombination repair. DBC1-PARP1 complexes in old mice can be broken by increasing NAD+ levels through treatment with NMN, reducing DNA damage and restoring PARP activity to youthful levels. The mechanism of declining NAD+ levels and its fundamental importance to aging are yet to be elucidated. There is a correlation of PARP activity with mammalian life span that suggests that NAD+/SIRT1/PARP1 may be more significant than the modest effects on life span observed for NR supplementation in old mice. The NAD+/PARP1/SIRT1 axis may link NAD+ levels and DNA damage with the apparent epigenomic DNA methylation clocks that have been described.

  8. Propagation of angular errors in two-axis rotation systems

    Science.gov (United States)

    Torrington, Geoffrey K.

    2003-10-01

    Two-Axis Rotation Systems, or "goniometers," are used in diverse applications including telescope pointing, automotive headlamp testing, and display testing. There are three basic configurations in which a goniometer can be built depending on the orientation and order of the stages. Each configuration has a governing set of equations which convert motion between the system "native" coordinates to other base systems, such as direction cosines, optical field angles, or spherical-polar coordinates. In their simplest form, these equations neglect errors present in real systems. In this paper, a statistical treatment of error source propagation is developed which uses only tolerance data, such as can be obtained from the system mechanical drawings prior to fabrication. It is shown that certain error sources are fully correctable, partially correctable, or uncorrectable, depending upon the goniometer configuration and zeroing technique. The system error budget can be described by a root-sum-of-squares technique with weighting factors describing the sensitivity of each error source. This paper tabulates weighting factors at 67% (k=1) and 95% (k=2) confidence for various levels of maximum travel for each goniometer configuration. As a practical example, this paper works through an error budget used for the procurement of a system at Sandia National Laboratories.

  9. Perspectives on Regulatory T Cell Therapies

    OpenAIRE

    Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S.P.; Buer, Jan

    2009-01-01

    Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (Treg) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, Treg cell therapies and development of drugs that specifically enhance Treg cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human Treg cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 ...

  10. Thoughts on the so-called 'radius-capitellum axis'

    International Nuclear Information System (INIS)

    Schild, H.; Mueller, H.A.; Wagner, H.; Baetz, W.; Mainz Univ.

    1982-01-01

    We have studied 438 patients radiologically in order to observe the so-called 'radius-capitellum axis'. In about a quarter of people with normal elbows the axis passes lateral to the middle portion of the capitellum, so that even when there is marked deviation, there is no certainty that the humero-radial joint is abnormal. Deviation of the axis can be caused by changes in the shape of the capitellum or of the radius, or by distension of the capsule of the elbow joint, or by various changes in muscular pull. (orig.) [de

  11. Thoughts on the so-called radius-capitellum axis

    Energy Technology Data Exchange (ETDEWEB)

    Schild, H; Mueller, H A; Wagner, H; Baetz, W

    1982-02-01

    We have studied 438 patients radiologically in order to observe the so-called 'radius-capitellum axis'. In about a quarter of people with normal elbows the axis passes lateral to the middle portion of the capitellum, so that even when there is marked deviation, there is no certainty that the humero-radial joint is abnormal. Deviation of the axis can be caused by changes in the shape of the capitellum or of the radius, or by distension of the capsule of the elbow joint, or by various changes in muscular pull.

  12. [Localization and registration of the hinge axis in black Africans].

    Science.gov (United States)

    Assi, K D; N'Guessan, K S; N'Dindin, C; Bamba, A

    2003-06-01

    The study of the cinematic method using "SAM" and "Quick Axis of FAG" added to mandibular condyle palpation for the hinge axis limited points, show that the Black Africans mandibular condyle rotation axis position is higher (3.5 mm) and backer (2 mm) than the Caucasians. The axial points are located to between 11 and 12 mm in front of the tragus and between 7 and 8 mm below on the perpendicular line to the furrow defining the tragus superior side to the Ectocanthus.

  13. Radiation and the hypothalamic-pituitary axis

    International Nuclear Information System (INIS)

    Littley, M.D.; Shalet, S.M.; Beardwell, C.G.

    1991-01-01

    This paper reports on radiation therapy which is an essential treatment in the management of many conditions. It is important to appreciate the high incidence of subsequent endocrine morbidity, however, if the hypothalamic pituitary region is within the radiation fields. This is very much more common with external radiation therapy than with other forms of radiation treatment. The dose and fractional of administered radiation are important determinants of the endocrine deficits, their time on onset, and severity. Irradiation of large volumes of brain and hypothalamus may increase the risk of hormonal abnormalities as may preceding surgery in the treatment of pituitary disease. The phenomena observed in children and adults illustrate that there may be damage to pituitary, hypothalamus, and higher centers. In patients who have received a significant radiation dose to the hypothalamic-pituitary region, regular follow-up is mandatory. In adults, surveillance will include pituitary function testing on an annual basis for at least 10 years. In children careful monitoring of growth and pubertal development and early treatment of radiation-induced GH deficiency are vital

  14. Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis.

    Science.gov (United States)

    Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Nakamura, Yumi; Koyama, Hidekazu

    2015-01-01

    Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD), which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1), which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2), which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX), an 11HSD inhibitor, on the healthy dog's pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH), and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing's disease.

  15. Insulin-like factor 3 (INSL3 and the HPG axis in the male

    Directory of Open Access Journals (Sweden)

    Richard eIvell

    2014-01-01

    Full Text Available The HPG (hypothalamo-pituitary-gonadal axis comprises pulsatile GnRH from the hypothalamus impacting on the anterior pituitary to induce expression and release of both LH and FSH into the circulation. These in turn stimulate receptors on testicular Leydig and Sertoli cells, respectively, to promote steroidogenesis and spermatogenesis. Both Leydig and Sertoli cells exhibit negative feedback to the pituitary and/or hypothalamus via their products testosterone and inhibin B, respectively, thereby allowing tight regulation of the HPG axis. In particular, LH exerts both acute control on Leydig cells by influencing steroidogenic enzyme activity, as well as chronic control by impacting on Leydig cell differentiation and gene expression. Insulin-like peptide 3 (INSL3 represents an additional and different endpoint of the HPG axis. This Leydig cell hormone interacts with specific receptors, called RXFP2, on Leydig cells themselves to modulate steroidogenesis, and on male germ cells, probably to synergize with androgen-dependent Sertoli cell products to support spermatogenesis. Unlike testosterone, INSL3 is not acutely regulated by the HPG axis, but is a constitutive product of Leydig cells, which reflects their number and/or differentiation status and their ability therefore to produce various factors including steroids, together this is referred to as Leydig cell functional capacity. Because INSL3 is not subject to the acute episodic fluctuations inherent in the HPG axis itself, it serves as an excellent marker for Leydig cell differentiation and functional capacity, as in puberty, or in monitoring the treatment of hypogonadal patients, and at the same time buffering the HPG output.

  16. T-regulatory cells in chronic rejection versus stable grafts.

    Science.gov (United States)

    Al-Wedaie, Fatima; Farid, Eman; Tabbara, Khaled; El-Agroudy, Amgad E; Al-Ghareeb, Sumaya M

    2015-04-01

    Studying regulatory T cells in kidney allograft acceptance versus chronic rejection may help in the understanding of more mechanisms of immune tolerance and, in the future, may enable clinicians to induce immune tolerance and decrease the use of immunosuppressive drugs. The aim of the current study was to evaluate regulatory T cells in kidney transplant patients with stable graft versus transplant with biopsy-proven chronic rejection. The 3 groups that were studied included: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); and healthy age-matched nontransplanted individuals as controls (n = 42).The percentage of regulatory T cells (CD4+CD25+Foxp3+) in blood was determined by flow cytometry. The regulatory T cell percentage was significantly lower in chronic rejection patients than control or stable graft groups. No significant difference was observed in regulatory T cell percentage between the stable graft and control groups. In the stable graft group, patients on rapamycin had a significantly higher regulatory T cell percentage than patients on cyclosporine. No effect of donor type, infection, or duration after transplant was observed on regulatory T cell percentage. The results of the current study are consistent with previous studies addressing the function of regulatory T cells in inducing immunotolerance after kidney transplant. Considering the established role of regulatory T cells in graft maintenance and our observation of high regulatory T cell percentage in patients receiving rapamycin than cyclosporine, we recommend including rapamycin when possible in immunosuppressive protocols. The findings from the current study on the chronic rejection group support ongoing research of having treatment with regulatory T cells, which may constitute a novel, efficient antirejection therapy in the future.

  17. Brain-gut axis and mucosal immunity: a perspective on mucosal psychoneuroimmunology.

    LENUS (Irish Health Repository)

    Shanahan, F

    2012-02-03

    The role of the brain-gut axis has traditionally been investigated in relation to intestinal motility, secretion, and vascularity. More recently, the concept of brain-gut dialogue has extended to the relationship between the nervous system and mucosal immune function. There is compelling evidence for a reciprocal or bi-directional communication between the immune system and the neuroendocrine system. This is mediated, in part, by shared ligands (chemical messengers) and receptors that are common to the immune and nervous systems. Although the concept of psychoneuroimmunology and neuroimmune cross-talk has been studied primarily in the context of the systemic immune system, it is likely to have special significance in the gut. The mucosal immune system is anatomically, functionally, and operationally distinct from the systemic immune system and is subject to independent regulatory signals. Furthermore, the intestinal mucosal immune system operates in a local milieu that depends on a dense innervation for its integrity, with juxtaposition of neuroendocrine cells and mucosal immune cells. An overview of evidence for the biologic plausibility of a brain-gut-immune axis is presented and its potential relevance to mucosal inflammatory disorders is discussed.

  18. Maternal co-ordinate gene regulation and axis polarity in the scuttle fly Megaselia abdita.

    Science.gov (United States)

    Wotton, Karl R; Jiménez-Guri, Eva; Jaeger, Johannes

    2015-03-01

    Axis specification and segment determination in dipteran insects are an excellent model system for comparative analyses of gene network evolution. Antero-posterior polarity of the embryo is established through systems of maternal morphogen gradients. In Drosophila melanogaster, the anterior system acts through opposing gradients of Bicoid (Bcd) and Caudal (Cad), while the posterior system involves Nanos (Nos) and Hunchback (Hb) protein. These systems act redundantly. Both Bcd and Hb need to be eliminated to cause a complete loss of polarity resulting in mirror-duplicated abdomens, so-called bicaudal phenotypes. In contrast, knock-down of bcd alone is sufficient to induce double abdomens in non-drosophilid cyclorrhaphan dipterans such as the hoverfly Episyrphus balteatus or the scuttle fly Megaselia abdita. We investigate conserved and divergent aspects of axis specification in the cyclorrhaphan lineage through a detailed study of the establishment and regulatory effect of maternal gradients in M. abdita. Our results show that the function of the anterior maternal system is highly conserved in this species, despite the loss of maternal cad expression. In contrast, hb does not activate gap genes in this species. The absence of this activatory role provides a precise genetic explanation for the loss of polarity upon bcd knock-down in M. abdita, and suggests a general scenario in which the posterior maternal system is increasingly replaced by the anterior one during the evolution of the cyclorrhaphan dipteran lineage.

  19. Maternal co-ordinate gene regulation and axis polarity in the scuttle fly Megaselia abdita.

    Directory of Open Access Journals (Sweden)

    Karl R Wotton

    2015-03-01

    Full Text Available Axis specification and segment determination in dipteran insects are an excellent model system for comparative analyses of gene network evolution. Antero-posterior polarity of the embryo is established through systems of maternal morphogen gradients. In Drosophila melanogaster, the anterior system acts through opposing gradients of Bicoid (Bcd and Caudal (Cad, while the posterior system involves Nanos (Nos and Hunchback (Hb protein. These systems act redundantly. Both Bcd and Hb need to be eliminated to cause a complete loss of polarity resulting in mirror-duplicated abdomens, so-called bicaudal phenotypes. In contrast, knock-down of bcd alone is sufficient to induce double abdomens in non-drosophilid cyclorrhaphan dipterans such as the hoverfly Episyrphus balteatus or the scuttle fly Megaselia abdita. We investigate conserved and divergent aspects of axis specification in the cyclorrhaphan lineage through a detailed study of the establishment and regulatory effect of maternal gradients in M. abdita. Our results show that the function of the anterior maternal system is highly conserved in this species, despite the loss of maternal cad expression. In contrast, hb does not activate gap genes in this species. The absence of this activatory role provides a precise genetic explanation for the loss of polarity upon bcd knock-down in M. abdita, and suggests a general scenario in which the posterior maternal system is increasingly replaced by the anterior one during the evolution of the cyclorrhaphan dipteran lineage.

  20. Schedules for Regulatory Regimes

    International Nuclear Information System (INIS)

    Austvik, Ole Gunnar

    2003-01-01

    The idea of regulating transporters' terms of operations is that if the market itself does not produce optimal outcomes, then it can be mimicked to do so through regulatory and other public instruments. The first-best solution could be a subsidized (publicly owned) enterprise that sets tariffs according to marginal costs. This has been the tradition in many European countries in the aftermath of WW2. Due to lack of innovative pressure on and x-inefficiency in these companies, this solution is today viewed as inferior to the system of regulating independent (privately owned) firms. When the European gas market becomes liberalized, part of the process in many countries is to (partially) privatise the transport utilities. Privatised or not, in a liberalized market, the transport utilities should face an independent authority that overviews their operations not only in technical, but also in economic terms. Under regulation, a ''visible hand'' is introduced to correct the imperfect market's ''invisible hand''. By regulating the framework and conditions for how firms may operate, public authorities seek to achieve what is considered optimal for the society. The incentives and disincentives given for pricing and production should create mechanisms leading to an efficient allocation of resources and ''acceptable'' distribution of income. As part of intervening into firms' behavior, regulation may be introduced to direct the firm to behave in certain ways. The framework and regulatory mechanisms for the market must then be constructed in a way that companies voluntarily produce an amount at a price that gives maximal profits and simultaneously satisfies social goals. The regulations should lead to consistency between the company's desire to maximize profits and the society's desire for maximizing welfare, as in a perfectly competitive market. This is the core of regulatory economics

  1. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    In this last part is reviewed international regulatory activities and bilateral agreements including two parts: concerning European atomic energy community with European commission proposal for a council directive setting up a community framework for nuclear safety, update of the nuclear illustrative programme in the context of the second strategic energy review, european commission recommendation on criteria for the export of radioactive waste and spent fuel to third countries and a communication on nuclear non-proliferation and the second part in relation with international atomic energy agency with a joint convention on the safety of spent fuel management and on safety of radioactive waste management (third review meeting). (N.C.)

  2. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

    Different international regulatory activities are presented: recommendation on the protection of the public against exposure to radon in drinking water supplies, amendment to the legislation implementing the regulation on imports of agricultural products originating in third countries following the Chernobyl accident, resolution on the commission green paper towards a European strategy for the security of energy supply, declaration of mandatory nature of the international code for the safe carriage of packaged irradiated nuclear fuel, plutonium and high level radioactive wastes on board ships, adoption of action plan against nuclear terrorism. (N.C.)

  3. The core to regulatory reform

    International Nuclear Information System (INIS)

    Partridge, J.W. Jr.

    1993-01-01

    Federal Energy Regulatory Commission (FERC) Orders 436, 500, and 636, the Clean Air Act Amendments of 1990, Public Utility Holding Company Act reform, and the 1992 Energy Policy Act all can have significant effects on an LDC's operations. Such changes in an LDC's environments must be balanced by changes within the utility, its marketplace, and its state regulatory environment. The question is where to start. For Columbia Gas Distribution Cos., based in Columbus, OH, the new operating foundation begins with each employee. Internal strength is critical in designing initiatives that meet the needs of the marketplace and are well-received by regulators. Employees must understand not only the regulatory environment in which the LDC operates, but also how their work contributes to a positive regulatory relationship. To achieve this, Columbia initiated the COntinuing Regulatory Education program, or CORE, in 1991. CORE is a regulatory-focused, information-initiative program coordinated by Columbia's Regulatory Policy, Planning, and Government Affairs Department. The CORE programs can take many forms, such as emerging issue discussions, dialogues with regulators and key parties, updates on regulatory fillings, regulatory policy meetings, and formal training classes. The speakers and discussion facilitators can range from human resource department trainers to senior officers, from regulatory department staff members to external experts, or from state commissioners to executives from other LDCs. The goals of CORE initiatives are to: Support a professional level of regulatory expertise through employee participation in well-developed regulatory programs presented by credible experts. Encourage a constructive state regulatory environment founded on communication and cooperation. CORE achieves these goals via five program levels: introductory basics, advanced learning, professional expertise, crossfunctional dialogues, and external idea exchanges

  4. Regulatory T-cells and autoimmunity.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh

    2012-02-03

    Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.

  5. Regulatory Challenges for Cartilage Repair Technologies.

    Science.gov (United States)

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

  6. Politically Induced Regulatory Risk and Independent Regulatory Agencies

    OpenAIRE

    Strausz, Roland

    2015-01-01

    Uncertainty in election outcomes generates politically induced regulatory risk. Political parties' risk attitudes towards such risk depend on a fluctuation effect that hurts both parties and an output--expansion effect that benefits at least one party. Notwithstanding the parties' risk attitudes, political parties have incentives to negotiate away all regulatory risk by pre-electoral bargaining. Efficient pre-electoral bargaining outcomes fully eliminate politically induced regulatory risk. P...

  7. Regulatory networks, legal federalism, and multi-level regulatory systems

    OpenAIRE

    Kerber, Wolfgang; Wendel, Julia

    2016-01-01

    Transnational regulatory networks play important roles in multi-level regulatory regimes, as e.g, the European Union. In this paper we analyze the role of regulatory networks from the perspective of the economic theory of legal federalism. Often sophisticated intermediate institutional solutions between pure centralisation and pure decentralisation can help to solve complex tradeoff problems between the benefits and problems of centralised and decentralised solutions. Drawing upon the insight...

  8. A Method for Modeling of Floating Vertical Axis Wind Turbine

    DEFF Research Database (Denmark)

    Wang, Kai; Hansen, Martin Otto Laver; Moan, Torgeir

    2013-01-01

    It is of interest to investigate the potential advantages of floating vertical axis wind turbine (FVAWT) due to its economical installation and maintenance. A novel 5MW vertical axis wind turbine concept with a Darrieus rotor mounted on a semi-submersible support structure is proposed in this paper....... In order to assess the technical and economic feasibility of this novel concept, a comprehensive simulation tool for modeling of the floating vertical axis wind turbine is needed. This work presents the development of a coupled method for modeling of the dynamics of a floating vertical axis wind turbine....... This integrated dynamic model takes into account the wind inflow, aerodynamics, hydrodynamics, structural dynamics (wind turbine, floating platform and the mooring lines) and a generator control. This approach calculates dynamic equilibrium at each time step and takes account of the interaction between the rotor...

  9. design and implementation of a microcontroller based dual axis

    African Journals Online (AJOL)

    user

    In this paper, an efficient microcontroller-based dual axis solar radiation tracker which can be used to align a single photovoltaic (PV) ... replaced them with wind turbine generating stations. ... tracker which has both horizontal and vertical axle.

  10. The effects of lateral head tilt on ocular astigmatic axis

    Directory of Open Access Journals (Sweden)

    Hamid Fesharaki

    2014-01-01

    Conclusion: Any minimal angle of head tilt may cause erroneous measurement of astigmatic axis and should be avoided during refraction. One cannot rely on the compensatory function of ocular counter-torsion during the refraction.

  11. Particle orbit analysis for LHD helical axis configurations

    International Nuclear Information System (INIS)

    Guasp, J.; Yamazaki, K.; Motojima, O.

    1993-04-01

    Fast ion orbits for helical magnetic axis configurations in LHD (Large Helical Device) are analyzed and compared with the standard circular axis case. Boundaries between passing and helically trapped particle regions show clear differences: in the non-planar axis case the helically trapped region spreads, near the magnetic axis, over a much wider band across the 90deg pitch angle value and shows a very marked asymmetry. The locally trapped particle region is also wider than in the standard case. The differences in the loss cone boundaries of the two cases are rather small, however, the effects of re-entering criteria are very important in both cases. On the contrary, effects of finite coil size are not significant. (author)

  12. Space/Flight Operable Miniature Six Axis Transducer, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — FUTEK will fully design and manufacture a sensor capable of measuring forces in and about each axis. The unit will measure forces up to 300 Newton's in the principle...

  13. Off-axis vortex breakdown in a shallow whirlpool.

    Science.gov (United States)

    Herrada, Miguel A; Shtern, Vladimir N; López-Herrera, José María

    2013-06-01

    The off-axis emergence of vortex breakdown (VB) is revealed. The steady axisymmetric flow in a vertical sealed cylinder, which is partially filled with water and the rest is filled with air, is driven by the rotating bottom disk. The numerical simulations show that VB can emerge away from the rotation axis, interface, and walls. As the rotation intensifies, VB first develops in the water region. If the water height is less (larger) than nearly one half of the cylinder radius, VB emerges off (on) the axis. As the rotation further increases, the off-axis VB ring touches the interface and then a thin countercirculation layer develops in the air flow above the water VB domain. This two-fluid VB ring shrinks (it even disappears in a very shallow whirlpool) as the interface approaches the bottom disk.

  14. Helical-axis stellarators with noninterlocking planar coils

    International Nuclear Information System (INIS)

    Reiman, A.; Boozer, A.

    1983-08-01

    The properties of helical axis stellarator fields generated by unlinked, planar coils are described. It is shown that such fields can have a magnetic well and large rotational transform, implying large equilibrium and stability beta limits

  15. Helical-axis stellarators with noninterlocking planar coils

    Energy Technology Data Exchange (ETDEWEB)

    Reiman, A.; Boozer, A.

    1983-08-01

    The properties of helical axis stellarator fields generated by unlinked, planar coils are described. It is shown that such fields can have a magnetic well and large rotational transform, implying large equilibrium and stability beta limits.

  16. Design of a Three-Axis Machine Tool Module

    National Research Council Canada - National Science Library

    Childers, Marshal

    2003-01-01

    This report documents the design improvement process of the components in a tool module for a three-axis machine tool, which occurred during the period of March-April 2002 in support of a critical U.S...

  17. Proper time axis of a closed relativistic system

    International Nuclear Information System (INIS)

    Chernikov, N.A.; Fadeev, N.G.; Shavokhina, N.S.

    1997-01-01

    The definition of a proper time axis of a closed relativistic system of colliding particles is given. The solution of the proper time axis problem is presented. If the light velocity c equals the imaginary unit i, then in the case of a plane motion of the system the problem about the proper time axis turns out to be equivalent to the known in engineering mechanics problem about the reduction of any system of forces, applied to a rigid body, to the dynamic screw. In the general case, when c=i, the problem about the proper time axis turns out to be equivalent to the problem about the reduction to the dynamic screw of a system of forces, applied to a rigid body in a four-dimensional Euclidean space

  18. UARS PEM Level 2 AXIS 1 V001

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 1 daily product contains the X-ray high-resolution spectral...

  19. UARS PEM Level 2 AXIS 2 V001

    Data.gov (United States)

    National Aeronautics and Space Administration — The UARS Particle Environment Monitor (PEM) level 2 Atmosphere X-Ray Imaging Spectrometer (AXIS) unit 2 daily product contains the X-ray high-resolution spectral...

  20. Dual Axis Controller for Extreme Environments, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The Dual Axis Controller for Extreme Environments (DACEE) addresses a critical need of NASA's future exploration plans to investigate extreme environments within our...

  1. Three-Axis Gasless Sounding Rocket Payload Attitude Control

    Data.gov (United States)

    National Aeronautics and Space Administration — Gas released by current sounding rocket payload attitude control systems (ACS) has the potential to interfere with some types of science instruments. A single-axis...

  2. Assessment of regulatory effectiveness. Peer discussions on regulatory practices

    International Nuclear Information System (INIS)

    1999-09-01

    This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

  3. Microbiota-gut-brain axis and the central nervous system

    OpenAIRE

    Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

    2017-01-01

    The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated ...

  4. Selection for growth rate and body size have altered the expression profiles of somatotropic axis genes in chickens

    Science.gov (United States)

    Liu, Yong; Xu, Zhiqiang; Duan, Xiaohua; Li, Qihua; Dou, Tengfei; Gu, Dahai; Rong, Hua; Wang, Kun; Li, Zhengtian; Talpur, Mir Zulqarnain; Huang, Ying; Wang, Shanrong; Yan, Shixiong; Tong, Huiquan; Zhao, Sumei; Zhao, Guiping; Su, Zhengchang; Ge, Changrong

    2018-01-01

    The growth hormone / insulin-like growth factor-1 (GH/IGF-1) pathway of the somatotropic axis is the major controller for growth rate and body size in vertebrates, but the effect of selection on the expression of GH/IGF-1 somatotropic axis genes and their association with body size and growth performance in farm animals is not fully understood. We analyzed a time series of expression profiles of GH/IGF-1 somatotropic axis genes in two chicken breeds, the Daweishan mini chickens and Wuding chickens, and the commercial Avian broilers hybrid exhibiting markedly different body sizes and growth rates. We found that growth rate and feed conversion efficiency in Daweishan mini chickens were significantly lower than those in Wuding chickens and Avian broilers. The Wuding and Daweishan mini chickens showed higher levels of plasma GH, pituitary GH mRNA but lower levels of hepatic growth hormone receptor (GHR) mRNA than in Avian broilers. Daweishan mini chickens showed significantly lower levels of plasma IGF-1, thigh muscle and hepatic IGF-1 mRNA than did Avian broilers and Wuding chickens. These results suggest that the GH part of the somatotropic axis is the main regulator of growth rate, while IGF-1 may regulate both growth rate and body weight. Selection for growth performance and body size have altered the expression profiles of somatotropic axis genes in a breed-, age-, and tissue-specific manner, and manner, and alteration of regulatory mechanisms of these genes might play an important role in the developmental characteristics of chickens. PMID:29630644

  5. Visions of regulatory renewal

    International Nuclear Information System (INIS)

    Edgeworth, A.

    1998-01-01

    The economic contribution of the CEPA (Canadian Energy Pipeline Association) member companies to Canada's trade balance was discussed. CEPA member companies transport 95 per cent of the crude oil and natural gas produced in Canada to domestic and export markets. This represents a total of 5.6 Tcf of gas annually. Half of Canada's natural gas and oil production is exported to U.S. markets. All of these exports are transported by pipeline. CEPA member companies operate 90,000 km of pipeline from British Columbia to Quebec. Expansions are needed as a result of a significant increase in demand for natural gas and crude oil since 1990. Several issues exist for regulatory renewal. They include the need to create a level playing field, the overseeing of tolls and contract renewal terms, changing risk/reward trade-offs, the right to confidentiality of information and price discovery mechanism. The drivers for regulatory reform at Westcoast Energy are the need for pricing flexibility, customers desire for toll certainty, decontracting and opposition to rolled-in expansions for gathering and processing. An overview of Westcoast Energy's negotiated toll settlement, its implications, and the components of Westcoast Energy's 'light handed regulation' (LHR) was presented

  6. The regulatory dynamic

    International Nuclear Information System (INIS)

    Dybwad, C.

    2001-01-01

    An outline of the activities and efforts expanded by the National Energy Board to adjust to the changing natural gas market was provided in this presentation. The author began by defining the role of the National Energy Board in energy markets. It must ensure the adoption of rules and procedures that result in a more competitive and efficient market. Light-handed regulatory techniques are the norm, and the National Energy Board is now committed to facilitating the availability and flow of information so that all parties know where opportunities exist, the terms offered to buy or sell goods and services, their quality and costs. It will specialize in providing new participants with information on the workings of the market, who the players are, the regulatory processes in place, and how, when and where the market can be accessed. The manner in which the Board deals with information was reviewed, providing examples along the way to clarify some points. Some of the documents produced by the National Energy Board are being reviewed with the intent of making them easier to read and understand. Audio streaming over the Internet is another avenue being pursued to ensure individuals can listen in real time to hearings without having to be present in the room. The National Energy Board is also exploring alternative dispute resolution techniques. Consultation with energy market participants represents another facet of these efforts to be more accessible and responsive

  7. Self-starting aerodynamics analysis of vertical axis wind turbine

    Directory of Open Access Journals (Sweden)

    Jianyang Zhu

    2015-12-01

    Full Text Available Vertical axis wind turbine is a special type of wind-force electric generator which is capable of working in the complicated wind environment. The self-starting aerodynamics is one of the most important considerations for this kind of turbine. This article aims at providing a systematic synthesis on the self-starting aerodynamic characteristics of vertical axis wind turbine based on the numerical analysis approach. First, the physical model of vertical axis wind turbine and its parameter definitions are presented. Secondary, the interaction model between the vertical axis wind turbine and fluid is developed by using the weak coupling approach; the numerical data of this model are then compared with the wind tunnel experimental data to show its feasibility. Third, the effects of solidity and fixed pitch angle on the self-starting aerodynamic characteristics of the vertical axis wind turbine are analyzed systematically. Finally, the quantification effects of the solidity and fixed pitch angle on the self-starting performance of the turbine can be obtained. The analysis in this study will provide straightforward physical insight into the self-starting aerodynamic characteristics of vertical axis wind turbine.

  8. Energy Efficient Hybrid Dual Axis Solar Tracking System

    Directory of Open Access Journals (Sweden)

    Rashid Ahammed Ferdaus

    2014-01-01

    Full Text Available This paper describes the design and implementation of an energy efficient solar tracking system from a normal mechanical single axis to a hybrid dual axis. For optimizing the solar tracking mechanism electromechanical systems were evolved through implementation of different evolutional algorithms and methodologies. To present the tracker, a hybrid dual-axis solar tracking system is designed, built, and tested based on both the solar map and light sensor based continuous tracking mechanism. These light sensors also compare the darkness and cloudy and sunny conditions assisting daily tracking. The designed tracker can track sun’s apparent position at different months and seasons; thereby the electrical controlling device requires a real time clock device for guiding the tracking system in seeking solar position for the seasonal motion. So the combination of both of these tracking mechanisms made the designed tracker a hybrid one. The power gain and system power consumption are compared with a static and continuous dual axis solar tracking system. It is found that power gain of hybrid dual axis solar tracking system is almost equal to continuous dual axis solar tracking system, whereas the power saved in system operation by the hybrid tracker is 44.44% compared to the continuous tracking system.

  9. Design and optimize of 3-axis filament winding machine

    Science.gov (United States)

    Quanjin, Ma; Rejab, M. R. M.; Idris, M. S.; Bachtiar, B.; Siregar, J. P.; Harith, M. N.

    2017-10-01

    Filament winding technique is developed as the primary process for composite cylindrical structures fabrication at low cost. Fibres are wound on a rotating mandrel by a filament winding machine where resin impregnated fibres pass through a pay-out eye. This paper aims to develop and optimize a 3-axis, lightweight, practical, efficient, portable filament winding machine to satisfy the customer demand, which can fabricate pipes and round shape cylinders with resins. There are 3 main units on the 3-axis filament winding machine, which are the rotary unit, the delivery unit and control system unit. Comparison with previous existing filament winding machines in the factory, it has 3 degrees of freedom and can fabricate more complex shape specimens based on the mandrel shape and particular control system. The machine has been designed and fabricated on 3 axes movements with control system. The x-axis is for movement of the carriage, the y-axis is the rotation of mandrel and the z-axis is the movement of the pay-out eye. Cylindrical specimens with different dimensions and winding angles were produced. 3-axis automated filament winding machine has been successfully designed with simple control system.

  10. Major and minor axis kinematics of 22 ellipticals

    International Nuclear Information System (INIS)

    Franx, M.; Illingworth, G.; Heckman, T.

    1989-01-01

    Rotation curves and velocity dispersion profiles have been determined for the major and the minor axes of 22 elliptical galaxies. Rotation was detected in all but one galaxy, even though the sample was biased toward round ellipticals. Minor axis rotation larger than major axis rotation was measured in two galaxies, NGC 4406 and NGC 7507. Roughly 10 percent of ellipticals may show large minor axis velocities relative to those on the major axis. A simple model is used to derive a rotational axis from the observed minor and major axis velocities to a typical accuracy of 6 deg. The rotational and photometric minor axes aligned to better than 10 deg for 60 percent of the sample, implying that the direction of the angular momentum is related to the orientation of the figure of the galaxy. IC 1459 has a kinematically distinct core with its angular momentum opposite to the angular momentum of the outer parts, and NGC 4406 has a core with its angular momentum perpendicular to that of the outer parts. 46 refs

  11. Optic axis-driven new horizons for hyperbolic metamaterials

    Directory of Open Access Journals (Sweden)

    Boardman Allan D.

    2015-01-01

    Full Text Available The broad assertion here is that the current hyperbolic metamaterial world is only partially served by investigations that incorporate only some limited version of anisotropy. Even modest deviations of the optic axis from the main propagation axis lead to new phase shifts, which not only compete with those created by absorption but end up dominating them. Some progress has been attempted in the literature by introducing the terms “asymmetric hyperbolic media”, but it appears that this kind of asymmetry only involves an optic axis at an angle to the interface of a uniaxial crystal. From a device point of view, many new prospects should appear and the outcomes of the investigations presented here yield a new general theory. It is emphasised that the orientation of the optic axis is a significant determinant in the resulting optical properties. Whereas for conventional anisotropic waveguides homogeneous propagating waves occur over a limited range of angular dispositions of the optic axis it is shown that for a hyperbolic guide a critical angular setting exists, above which the guided waves are always homogeneous. This has significant implications for metawaveguide designs. The resulting structures are more tolerant to optic axis misalignment.

  12. Predictors of incidence, remission and relapse of Axis I mental disorders in young women: A transdiagnostic approach

    NARCIS (Netherlands)

    Lukat, J.; Becker, E.S.; Lavallee, K.L.; Veld, W.M. van der; Margraf, J.

    2017-01-01

    An understanding of etiological and maintaining factors of mental disorders is essential for the treatment of mental disorders, as well as mental health promotion and protection. The present study examines predictors of the incidence, remission and relapse of a wide range of Axis I mental disorders,

  13. No damaging effect of chemotherapy in addition to radiotherapy on the thyroid axis in young adult survivors of childhood cancer

    NARCIS (Netherlands)

    van Santen, Hanneke M.; Vulsma, Thomas; Dijkgraaf, Marcel G.; Blumer, Regje M. E.; Heinen, Richard; Jaspers, Monique W. M.; Geenen, Maud M.; Offringa, Martin O.; de Vijlder, Jan J. M.; van den Bos, Cor

    2003-01-01

    Late effects of treatment for childhood cancer on the thyroid axis are ascribed predominantly to radiotherapy. Whether chemotherapy has an additional detrimental effect is still unclear. Our aim was to evaluate this effect in young adult survivors of a broad spectrum of childhood cancers. The

  14. Circadian Clocks and the Interaction between Stress Axis and Adipose Function

    Directory of Open Access Journals (Sweden)

    Isa Kolbe

    2015-01-01

    Full Text Available Many physiological processes and most endocrine functions show fluctuations over the course of the day. These so-called circadian rhythms are governed by an endogenous network of cellular clocks and serve as an adaptation to daily and, thus, predictable changes in the organism’s environment. Circadian clocks have been described in several tissues of the stress axis and in adipose cells where they regulate the rhythmic and stimulated release of stress hormones, such as glucocorticoids, and various adipokine factors. Recent work suggests that both adipose and stress axis clock systems reciprocally influence each other and adrenal-adipose rhythms may be key players in the development and therapy of metabolic disorders. In this review, we summarize our current understanding of adrenal and adipose tissue rhythms and clocks and how they might interact to regulate energy homoeostasis and stress responses under physiological conditions. Potential chronotherapeutic strategies for the treatment of metabolic and stress disorders are discussed.

  15. Spinal axis irradiation with electrons: Measurements of attenuation by the spinal processes

    International Nuclear Information System (INIS)

    Muller-Runkel, R.; Vijayakumar, S.

    1986-01-01

    Electrons may be used beneficially for spinal axis irradiation in medulloblastoma children to avoid some of the long-term sequelae induced by megavoltage photons. However, the attenuation by the intervening bone ought to be considered. Three-dimensional computer treatment planning with inhomogeneity correction for electron beams is not yet generally available, and alternate methods are needed to evaluate the attenuation by the complex bony structure of the spine. Here, we present our experimental data showing the alteration in the electron isodoses due to the intervening spinous processes. Film dosimetric measurements were made in the vertebral columns obtained from autopsies of a goat, a dog, and a child. Our results show that electron beam therapy for the spinal axis is a viable option

  16. Regulatory inspection of BARC facilities

    International Nuclear Information System (INIS)

    Rajdeep; Jayarajan, K.

    2017-01-01

    Nuclear and radiation facilities are sited, constructed, commissioned, operated and decommissioned, in conformity with the current safety standards and codes. Regulatory bodies follow different means to ensure compliance of the standards for the safety of the personnel, the public and the environment. Regulatory Inspection (RI) is one of the important measures employed by regulatory bodies to obtain the safety status of a facility or project and to verify the fulfilment of the conditions stipulated in the consent

  17. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2012-01-01

    This section gathers the following national legislative and regulatory activities sorted by country: Bulgaria: General legislation; Czech Republic: General legislation; France: General legislation, Regulatory infrastructure and activity; Germany: General legislation; India: Liability and compensation, Organisation and structure; Ireland: Radiation protection, General legislation; Korea (Republic of): Organisation and structure; Lithuania: Regulatory infrastructure and activity, Radioactive waste management, Radiation protection, international cooperation, Nuclear safety; Poland: General legislation; Romania: Environmental protection; Russian Federation: Radioactive waste management; Slovenia: Nuclear safety; Spain: Liability and compensation, Nuclear security; Sweden: Nuclear safety; Turkey: Radiation protection, Regulatory infrastructure and activity, Nuclear safety, Liability and compensation; United States: General legislation

  18. 77 FR 9273 - WORKSHOP Sponsored by the Nuclear Regulatory Commission and the Electric Power Research Institute...

    Science.gov (United States)

    2012-02-16

    ... Commission and the Electric Power Research Institute on the Treatment of Probabilistic Risk Assessment.... SUMMARY: The U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research (RES), in cooperation with the Electric Power Research Institute (EPRI), will hold a joint workshop on the Treatment of...

  19. Design Of Single-Axis And Dual-Axis Solar Tracking Systems Protected Against High Wind Speeds

    Directory of Open Access Journals (Sweden)

    Mai Salaheldin Elsherbiny

    2017-09-01

    Full Text Available Solar energy is rapidly gaining ground as an important mean of expanding renewable energy use. Solar tracking is employed in order to maximize collected solar radiation by a photovoltaic panel. In this paper we present a prototype for Automatic solar tracker that is designed using Arduino UNO with Wind sensor to Cease Wind effect on panels if wind speed exceeds certain threshold. The Proposed solar tracker tracks the location of the sun anywhere in any time by calculating the position of the sun. For producing the maximum amount of solar energy a solar panel must always be perpendicular to the source of light. Because the sun motion plane varies daily and during the day it moves from east to west one needs two axis tracking to follow the suns position. Maximum possible power is collected when two axis tracking is done. However two axis tracking is relatively costly and complex. A compromise between maximum power collection and system simplicity is obtained by single axis tracking where the plane North south axis is fixed while the east west motion is accomplished. This work deals with the design of both single and two axis tracking systems. Automatic trackers is also compared to Fixed one in terms of Energy generated Efficiency Cost and System reliability.

  20. Regulatory audit to the Argentine teletherapy units

    International Nuclear Information System (INIS)

    Kay, J.M.

    1995-01-01

    As a consequence of an erroneous calibration of the ionization chamber dosimeter of a new licensed 6 Mev electron lineal accelerator that caused accidental overexposures in the first patients under treatment, the Regulatory Board decided to perform an audit to every teletherapy unit (accelerator and telegammatherapy units) in Argentina. The audit was carried out at the en of 1994 in 27 accelerators and 107 telegammatherapy units. The objectives of the audit were the control of the mechanical and optical aspects of the each accelerator and telegammatherapy unit and the control of the calibration of their radiation beams. The last action was undertaken to detect as soon as possible, any eventual accidental overexposure or underexposure of patients under treatment. The audit was conducted by the author and performed for a team of 22 inspectors who worked in groups of 2 to 3 people and completed the inspection of the teletherapy units of the whole country in 3 months. As a result of the audit, the Regulatory Board had in a short period a clear panorama of the performance of each teletherapy unit of the country and also confirmed that no accidental situation had happened. The audit revealed the necessity of imposing urgent regulatory requirements not related to the calibration of the radiation beam in 5% of the cases, as well as non-urgent requirements of different importance in approximately other 60% of the cases. (author)

  1. Regulatory dendritic cells in autoimmunity: A comprehensive review.

    Science.gov (United States)

    Liu, Juan; Cao, Xuetao

    2015-09-01

    Dendritic cells (DCs) are professional antigen-presenting cells (APC) with significant phenotypic heterogeneity and functional plasticity. DCs play crucial roles in initiating effective adaptive immune responses for elimination of invading pathogens and also in inducing immune tolerance toward harmless components to maintain immune homeostasis. The regulatory capacity of DCs depends on their immature state and distinct subsets, yet not restricted to the immature state and one specialized subset. The tolerogenicity of DC is controlled by a complex network of environmental signals and cellular intrinsic mechanisms. Regulatory DCs play an important role in the maintenance of immunological tolerance via the induction of T cell unresponsiveness or apoptosis, and generation of regulatory T cells. DCs play essential roles in driving autoimmunity via promoting the activation of effector T cells such as T helper 1 and T helper 17 cells, and/or suppressing the generation of regulatory T cells. Besides, a breakdown of DCs-mediated tolerance due to abnormal environmental signals or breakdown of intrinsic regulatory mechanisms is closely linked with the pathogenesis of autoimmune diseases. Novel immunotherapy taking advantage of the tolerogenic potential of regulatory DCs is being developed for treatment of autoimmune diseases. In this review, we will describe the current understanding on the generation of regulatory DC and the role of regulatory DCs in promoting tolerogenic immune responses and suppressing autoimmune responses. The emerging roles of DCs dysfunction in the pathogenesis of autoimmune diseases and the potential application of regulatory DCs in the treatment of autoimmune diseases will also be discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Postnatal development of the atlas and axis: CT study

    International Nuclear Information System (INIS)

    Byun, Sung Su; Kim, Hyung Jin; Lim, Myung Kwan; Kim, Won Hong; Jeon, Yong Sun; Kim, Jeong Ho; Kim, Sung Tae

    2003-01-01

    To evaluate normal postnatal development of the atlas and axis by means of CT scanning. We prospectively analyzed CT scans of the developing atlas and axis of 200 normal children aged less than 14, investigating the CT appearance of these regions with particular attenuation to two synchondroses related to the atlas and four synchondroses and one ossification center related to the axis. Fusion varying was categorized as either low (grade1-5) or high (grade4-5), according to the varying degrees of fusion at each synchondrosis of ossification center. Neurocentral synchondrosis of the atlas was low grade in all children less than five, and high grade in all aged nine or more, while posterior synchondrosis of the atlas was low grade in 97% of children less than three and high grade in 99% aged three or more. As for the axis, neurocentral synchondrosis was low grade in all children less than three, and high grade in 97% of children aged five or more. PS of the axis was low grade in both children less than 6 months, and high grade in all aged two years or more. Dentocentral synchondrosis of the axis was low grade in 93% of children less than three and high grade in 96% of those aged at least five. Intradental axial synchondrosis was high grade in all children. Fusion of the terminal ossicle with the remainder of the dens was low in all children less than five and high in 97% of those aged nine of more. CT can help determine the parameters of normal postnatal development of the atlas and axis. A knowledge of normal ossification patterns of these regions may help provide an understanding of developmental anomalies and also help prevent confusion with fractures

  3. Regulatory actions post - Fukushima

    International Nuclear Information System (INIS)

    Ciurea Ercau, C.

    2013-01-01

    The paper presents the results of the safety reviews performed in Romania after the Fukushima accident and the resulting actions for improving the safety. The actions taken by the National Commission for Nuclear Activities Control (CNCAN) to improve the regulatory framework include the development of new regulations and the enhancement of inspection practices, taking account of the lessons learned from the Fukushima accident. A regulation on the response to transients, accidents and emergency situations at nuclear power plants has been developed, which includes requirements on transient and accident scenarios that have to be covered by the Emergency Operating Procedures (EOPs), accident scenarios to be covered by the Severe Accident Management Guidelines (SAMGs), emergency situations to be covered by the on-site emergency response plan and emergency response procedures. (authors)

  4. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2010-01-01

    Concerning International regulatory activities, we find for the european atomic energy community an entry into force of the lisbon treaty (2009), it amends the treaty on European union and replaces the treaty establishing the European Community by the new treaty on the functioning of the European Union; more, an amendment to council regulation on the conditions governing imports of agricultural products originating in third countries following the accident at the Chernobyl nuclear power station (2009). About International atomic energy agency is reported an open-ended meeting of technical and legal experts for sharing of information on states implementation of the code of conduct on the safety and security of radioactive sources and its supplementary guidance on the import and export of radioactive sources (2010). (N.C.)

  5. Regulatory mark; Marco regulatorio

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter is based on a work performed in distinct phases. The first phase consisted in of the analysis regulatory legislation existent in Brazil for the sugar-alcohol sector since the beginning of the X X century. This analysis allowed the identification of non existent points and legal devices related to the studied aspects, and that were considered as problematic for the sector expansion. In the second phase, related treaties and international agreements was studied and possible obstacles for the brazilian bio ethanol exportation for the international market. Initiatives were examined at European Union, United States of America, Caribbean and countries of the sub-Saharan Africa. In this phase, policies were identified related to the incentives and adoption of use of bio fuels added to the gasoline in countries or group of countries considered as key for the consolidation of bio ethanol as a world commodity.

  6. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2003-01-01

    Among international regulatory activities we find resolutions adopted by the IAEA general conference (2003), through European Union we find proposals for directives on nuclear safety and radioactive waste management, new regulation on the application of EURATOM safeguards, control of high activity sealed radioactive sources, recommendation on the protection and information of the public with regard to the continued contamination of certain wild food products following the Chernobyl accident, proposals for decisions authorizing the Member states to sign and ratify the Protocol to amend the Paris convention, p)proposals for a directive on environment liability with regard to the prevention and remedying of environmental damage, proposal of a regulation on the law applicable to non-contractual obligation. (N.C.)

  7. Nuclear Regulatory Commission Issuances

    International Nuclear Information System (INIS)

    1992-01-01

    This is the thirty-sixth volume of issuances (1-396) of the Nuclear Regulatory Commission and its Atomic Safety and Licensing Boards, Administrative Law Judges, and Office Directors. It covers the period from July 1, 1992-December 31, 1992. Atomic Safety and Licensing Boards are authorized by Section 191 of the Atomic Energy Act of 1954. These Boards, comprised of three members conduct adjudicatory hearings on applications to construct and operate nuclear power plants and related facilities and issue initial decisions which, subject to internal review and appellate procedures, become the final Commission action with respect to those applications. Boards are drawn from the Atomic Safety and Licensing Board Panel, comprised of lawyers, nuclear physicists and engineers, environmentalists, chemists, and economists. The Atomic Energy Commission first established Licensing Boards in 1962 and the Panel in 1967

  8. Mechanical impedance of the sitting human body in single-axis compared to multi-axis whole-body vibration exposure.

    Science.gov (United States)

    Holmlund, P; Lundström, R

    2001-01-01

    The study was aimed to investigate the mechanical impedance of the sitting human body and to compare data obtained in laboratory single-axis investigations with multi-axis data from in vehicle measurements. The experiments were performed in a laboratory for single-axis measurements. The multi-axis exposure was generated with an eight-seat minibus where the rear seats had been replaced with a rigid one. The subjects in the multi-axis experiment all participated in the single-axis experiments. There are quite a few investigations in the literature describing the human response to single-axis exposure. The response from the human body can be expected to be affected by multi-axis input in a different way than from a single-axis exposure. The present knowledge of the effect of multiple axis exposure is very limited. The measurements were performed using a specially designed force and accelerometer plate. This plate was placed between the subject and the hard seat. Outcome shows a clear difference between mechanical impedance for multi-axis exposure compared to single-axis. This is especially clear in the x-direction where the difference is very large. The conclusion is that it seems unlikely that single-axis mechanical impedance data can be directly transferred to a multi-axis environment. This is due to the force cross-talk between different directions.

  9. Craniospinal axis irradiation: an improved electron technique for irradiation of the spinal axis

    International Nuclear Information System (INIS)

    Chun Li; Vijayakumar, S.; Myrianthopoulos, L.C.; Kuchnir, F.T.; Muller-Runkel, R.

    1994-01-01

    The authors review dosimetric features of craniospinal axis irradiation in the areas of matching cranial and spinal fields, with reference to normal structures within the spinal field. The implications of the use of photon or electron modalities for the spinal port were evaluated. A novel method of matching the cranial photon and the spinal electron fields involving a computer-aided junction design is presented, involving moving the photon beam in three steps to degrade its penumbra to match that of the electron field. Thermoluminescent dosimetry in a Rando phantom and computed tomography-based dose-volume histogram study for an illustrative paediatric case were used to compare dose to normal structures within the spinal field. Results show that the use of electrons for the spinal field leads to better sparing of deep seated normal structures. For bone marrow, the use of a customized bolus for the spinal field results in an improved dose distribution, making electrons potentially superior to photons for radiobiological reasons. (author)

  10. Sympatho-renal axis in chronic disease.

    Science.gov (United States)

    Sobotka, Paul A; Mahfoud, Felix; Schlaich, Markus P; Hoppe, Uta C; Böhm, Michael; Krum, Henry

    2011-12-01

    Essential hypertension, insulin resistance, heart failure, congestion, diuretic resistance, and functional renal disease are all characterized by excessive central sympathetic drive. The contribution of the kidney's somatic afferent nerves, as an underlying cause of elevated central sympathetic drive, and the consequences of excessive efferent sympathetic signals to the kidney itself, as well as other organs, identify the renal sympathetic nerves as a uniquely logical therapeutic target for diseases linked by excessive central sympathetic drive. Clinical studies of renal denervation in patients with resistant hypertension using an endovascular radiofrequency ablation methodology have exposed the sympathetic link between these conditions. Renal denervation could be expected to simultaneously affect blood pressure, insulin resistance, sleep disorders, congestion in heart failure, cardiorenal syndrome and diuretic resistance. The striking epidemiologic evidence for coexistence of these disorders suggests common causal pathways. Chronic activation of the sympathetic nervous system has been associated with components of the metabolic syndrome, such as blood pressure elevation, obesity, dyslipidemia, and impaired fasting glucose with hyperinsulinemia. Over 50% of patients with essential hypertension are hyperinsulinemic, regardless of whether they are untreated or in a stable program of treatment. Insulin resistance is related to sympathetic drive via a bidirectional mechanism. In this manuscript, we review the data that suggests that selective impairment of renal somatic afferent and sympathetic efferent nerves in patients with resistant hypertension both reduces markers of central sympathetic drive and favorably impacts diseases linked through central sympathetics-insulin resistance, heart failure, congestion, diuretic resistance, and cardiorenal disorders.

  11. Regulatory focus in groupt contexts

    NARCIS (Netherlands)

    Faddegon, Krispijn Johannes

    2009-01-01

    The thesis examines the influence of group processes on the regulatory focus of individual group members. It is demonstrated that the group situation can affect group members' regulatory focus both in a top-down fashion (via the identitiy of the group) and in a bottom-up fashion (emerging from the

  12. Disclosure as a regulatory tool

    DEFF Research Database (Denmark)

    Sørensen, Karsten Engsig

    2006-01-01

    The chapter analyses how disclure can be used as a regulatory tool and analyses how it has been applied so far in the area of financial market law and consumer law.......The chapter analyses how disclure can be used as a regulatory tool and analyses how it has been applied so far in the area of financial market law and consumer law....

  13. Identification of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis.

    Directory of Open Access Journals (Sweden)

    Itaru Kato

    Full Text Available In acute lymphoblastic leukemia (ALL patients, the bone marrow niche is widely known to be an important element of treatment response and relapse. Furthermore, a characteristic liver pathology observed in ALL patients implies that the hepatic microenvironment provides an extramedullary niche for leukemic cells. However, it remains unclear whether the liver actually provides a specific niche. The mechanism underlying this pathology is also poorly understood. Here, to answer these questions, we reconstituted the histopathology of leukemic liver by using patients-derived primary ALL cells into NOD/SCID/Yc (null mice. The liver pathology in this model was similar to that observed in the patients. By using this model, we clearly demonstrated that bile duct epithelial cells form a hepatic niche that supports infiltration and proliferation of ALL cells in the liver. Furthermore, we showed that functions of the niche are maintained by the SDF-1/CXCR4 axis, proposing a novel therapeutic approach targeting the extramedullary niche by inhibition of the SDF-1/CXCR4 axis. In conclusion, we demonstrated that the liver dissemination of leukemia is not due to nonselective infiltration, but rather systematic invasion and proliferation of leukemic cells in hepatic niche. Although the contribution of SDF-1/CXCR4 axis is reported in some cancer cells or leukemic niches such as bone marrow, we demonstrated that this axis works even in the extramedullary niche of leukemic cells. Our findings form the basis for therapeutic approaches that target the extramedullary niche by inhibiting the SDF-1/CXCR4 axis.

  14. Measurement Axis Searching Model for Terrestrial Laser Scans Registration

    Directory of Open Access Journals (Sweden)

    Shaoxing Hu

    2016-01-01

    Full Text Available Nowadays, terrestrial Lidar scans can cover rather a large area; the point densities are strongly varied because of the line-of-sight measurement principle in potential overlaps with scans taken from different viewpoints. Most of the traditional methods focus on registration algorithm and ignore searching model. Sometimes the traditional methods are directly used to align two point clouds; a large critically unsolved problem of the large biases will be created in areas distant from the overlaps while the local overlaps are often aligned well. So a novel measurement axis searching model (MASM has been proposed in this paper. The method includes four steps: (1 the principal axis fitting, (2 the measurement axis generation, (3 low-high-precision search, and (4 result generation. The principal axis gives an orientation to the point cloud; the search scope is limited by the measurement axis. The point cloud orientation can be adjusted gradually until the achievement of the global optimum using low- and high-precision search. We perform some experiments with simulated point clouds and real terrestrial laser scans. The results of simulated point clouds have shown the processing steps of our method, and the results of real terrestrial laser scans have shown the sensitivity of the approach with respect to the indoor and outdoor scenes.

  15. Ankle-foot orthosis bending axis influences running mechanics.

    Science.gov (United States)

    Russell Esposito, Elizabeth; Ranz, Ellyn C; Schmidtbauer, Kelly A; Neptune, Richard R; Wilken, Jason M

    2017-07-01

    Passive-dynamic ankle-foot orthoses (AFOs) are commonly prescribed to improve locomotion for people with lower limb musculoskeletal weakness. The clinical prescription and design process are typically qualitative and based on observational assessment and experience. Prior work examining the effect of AFO design characteristics generally excludes higher impact activities such as running, providing clinicians and researchers limited information to guide the development of objective prescription guidelines. The proximal location of the bending axis may directly influence energy storage and return and resulting running mechanics. The purpose of this study was to determine if the location of an AFO's bending axis influences running mechanics. Marker and force data were recorded as 12 participants with lower extremity weakness ran overground while wearing a passive-dynamic AFO with posterior struts manufactured with central (middle) and off-centered (high and low) bending axes. Lower extremity joint angles, moments, powers, and ground reaction forces were calculated and compared between limbs and across bending axis conditions. Bending axis produced relatively small but significant changes. Ankle range of motion increased as the bending axis shifted distally (pbenefits during running, although individual preference and physical ability should also be considered. Published by Elsevier B.V.

  16. 75 FR 7526 - Withdrawal of Regulatory Guide

    Science.gov (United States)

    2010-02-19

    ...'s Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2010-0052] Withdrawal of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 1.56, ``Maintenance of Water Purity in Boiling...

  17. 12 CFR 562.2 - Regulatory reports.

    Science.gov (United States)

    2010-01-01

    ... § 562.2 Regulatory reports. (a) Definition and scope. This section applies to all regulatory reports, as... (TFR) are examples of regulatory reports. Regulatory reports are regulatory documents, not accounting... limited to, the accounting instructions provided in the TFR, guidance contained in OTS regulations...

  18. Virginia Power's regulatory reduction program

    International Nuclear Information System (INIS)

    Miller, G.D.

    1996-01-01

    Virginia Power has two nuclear plants, North Anna and Surry Power Stations, which have two units each for a total of four nuclear units. In 1992, the Nuclear Regulatory Commission solicited comments from the nuclear industry to obtain their ideas for reducing the regulatory burden on nuclear facilities. Pursuant to the new regulatory climate, Virginia Power developed an internal program to evaluate and assess the regulatory and self-imposed requirements to which they were committed, and to pursue regulatory relief or internal changes where possible and appropriate. The criteria were that public safety must be maintained, and savings must be significant. Up to the date of the conference, over US$22 million of one-time saving had been effected, and US$2.75 million in annual savings

  19. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune...... reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells......Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...

  20. The hypothalamic-pituitary-thyroid axis and biological rhythms: The discovery of TSH's unexpected role using animal models.

    Science.gov (United States)

    Ikegami, Keisuke; Yoshimura, Takashi

    2017-10-01

    Thyroid hormones (TH) are important for development, growth, and metabolism. It is also clear that the synthesis and secretion of TH are regulated by the hypothalamic-pituitary-thyroid (HPT) axis. Animal models have helped advance our understanding of the roles and regulatory mechanisms of TH. The animals' bodies develop through coordinated timing of cell division and differentiation. Studies of frog metamorphosis led to the discovery of TH and their role in development. However, to adapt to rhythmic environmental changes, animals also developed various endocrine rhythms. Studies of rodents clarified the neural and molecular mechanisms underlying the circadian regulation of the HPT axis. Moreover, birds have a sophisticated seasonal adaptation mechanism, and recent studies of quail revealed unexpected roles for thyroid-stimulating hormone (TSH) and TH in the seasonal regulation of reproduction. Interestingly, this mechanism is conserved in mammals. Thus, we review how animal studies have shaped our general understanding of the HPT axis in relation to biological rhythms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Maternal Cortisol Mediates Hypothalamus-Pituitary-Interrenal Axis Development in Zebrafish

    Science.gov (United States)

    Nesan, Dinushan; Vijayan, Mathilakath M.

    2016-01-01

    In zebrafish (Danio rerio), de novo synthesis of cortisol in response to stressor exposure commences only after hatch. Maternally deposited cortisol is present during embryogenesis, but a role for this steroid in early development is unclear. We tested the hypothesis that maternal cortisol is essential for the proper development of hypothalamus-pituitary-interrenal (HPI) axis activity and the onset of the stressor-induced cortisol response in larval zebrafish. In this study, zygotic cortisol content was manipulated by microinjecting antibody to sequester this steroid, thereby making it unavailable during embryogenesis. This was compared with embryos containing excess cortisol by microinjection of exogenous steroid. The resulting larval phenotypes revealed distinct treatment effects, including deformed mesoderm structures when maternal cortisol was unavailable and cardiac edema after excess cortisol. Maternal cortisol unavailability heightened the cortisol stress response in post-hatch larvae, whereas excess cortisol abolished the stressor-mediated cortisol elevation. This contrasting hormonal response corresponded with altered expression of key HPI axis genes, including crf, 11B hydroxylase, pomca, and star, which were upregulated in response to reduced cortisol availability and downregulated when embryos had excess cortisol. These findings for the first time underscore a critical role for maternally deposited cortisol in programming HPI axis development and function in zebrafish. PMID:26940285

  2. P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer.

    Science.gov (United States)

    Sharma, Shivani; Nagpal, Neha; Ghosh, Prahlad C; Kulshreshtha, Ritu

    2017-08-01

    miRNAs have emerged as key participants of p53 signaling pathways because they regulate or are regulated by p53. Here, we provide the first study demonstrating direct regulation of an oncogenic miRNA, miR-191-5p, by p53 and existence of a regulatory feedback loop. Using a combination of qRT-PCR, promoter-luciferase, and chromatin-immunoprecipitation assays, we show that p53 brings about down-regulation of miR-191-5p in breast cancer. miR-191-5p overexpression brought about inhibition of apoptosis in breast cancer cell lines (MCF7 and ZR-75) as demonstrated by reduction in annexin-V stained cells and caspase 3/7 activity, whereas miR-191-5p down-regulation showed the opposite. We further unveiled that SOX4 was a direct target of miR-191-5p. SOX4 overexpression was shown to increase p53 protein levels in MCF7 cells. miR-191-5p overexpression brought about down-regulation of SOX4 and thus p53 levels, suggesting the existence of a regulatory feedback loop. Breast cancer treatment by doxorubicin, an anti-cancer drug, involves induction of apoptosis by p53; we thus wanted to check whether miR-191-5p affects doxorubicin sensitivity. Interestingly, Anti-miR-191 treatment significantly decreased the IC50 of the doxorubicin drug and thus sensitized breast cancer cells to doxorubicin treatment by promoting apoptosis. Overall, this work highlights the importance of the p53-miR-191- SOX4 axis in the regulation of apoptosis and drug resistance in breast cancer and offers a preclinical proof-of-concept for use of an Anti-miR-191 and doxorubicin combination as a rational approach to pursue for better breast cancer treatment. © 2017 Sharma et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  3. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2001-01-01

    These columns treat of the legislative and regulatory activities of different OECD countries: Australia (environment protection and biodiversity conservation act and regulations, 1999-2000); Bulgaria (basic standards for radiation protection, 2000); France (decree on the standard tax charged on polluting activities due from operators of installations classified for environmental protection purposes, 2000; amendment of the orders on the transport of dangerous goods by road and by rail, 2000); Georgia (law on nuclear and radiation safety, 1998); Germany (amendments to nuclear legislation implementing EURATOM directives, 2000; amendment to the nuclear third party liability provisions of the atomic energy act, 2001; amendment to the foreign trade ordinance, 2000; ordinance on the treatment of foodstuffs with radiation, 2000; general administrative regulations on radioactivity limits in food and feeds); Ireland (European communities regulations on foodstuffs treated with ionizing radiations, 2000); Japan (law for nuclear sitting area development, 2000; Republic of Korea (amendments to the act on compensation for nuclear damage, 2001); Latvia (act on radiation safety and nuclear safety, 2000); Lithuania (resolution approving the decommissioning program for Unit 1, Ignalina NPP, 2001); Luxembourg (grand-ducal regulations on the protection of the public against the risks resulting from ionizing radiation, 2000; grand-ducal regulations relating to foods and food ingredients treated with ionizing radiation, 2000); Mexico (norm regarding selection, qualification and training requirements for staff of a NPP, 2000; norm regarding solid residue as radioactive waste, 2000); Mongolia (law on nuclear weapons free status and its implementing resolution, 2000); Netherlands (amendment to the nuclear energy act, 2000); Norway (act on radiation and use of radiation, 2000); Pakistan (nuclear authority ordinance, 2001); Poland (atomic energy act, 2000); Spain (royal decree on activities

  4. Subquadratic medial-axis approximation in $\\mathbb{R}^3$

    Directory of Open Access Journals (Sweden)

    Christian Scheffer

    2015-09-01

    Full Text Available We present an algorithm that approximates the medial axis of a smooth manifold in $\\mathbb{R}^3$ which is given by a sufficiently dense point sample. The resulting, non-discrete approximation is shown to converge to the medial axis as the sampling density approaches infinity. While all previous algorithms guaranteeing convergence have a running time quadratic in the size $n$ of the point sample, we achieve a running time of at most $\\mathcal{O}(n\\log^3 n$. While there is no subquadratic upper bound on the output complexity of previous algorithms for non-discrete medial axis approximation, the output of our algorithm is guaranteed to be of linear size.

  5. Small Vertical Axis Wind Turbines: aerodynamics and starting behavior

    Directory of Open Access Journals (Sweden)

    Horia DUMITRESCU

    2013-12-01

    Full Text Available In urban areas the wind is very turbulent and unstable with fast changes in direction andvelocity. In these environments, the use of small vertical axis wind turbines (VAWT becomesincreasingly attractive due to several advantages over horizontal axis wind turbines (HAWT.However, such designs have received much less attention than the more common propeller-typedesigns and the understanding of same aspects of their operation remains, to this day, incomplete.This is particularly true of their starting characteristics. Indeed, same authors heuristically maintainthat they cannot start without external assistance. This paper reviews the cause of the inability of thelow solidity fixed pitch vertical axis wind turbines to self-start, and investigates the way ofovercoming this draw back.

  6. Off-axis and inline electron holography: Experimental comparison

    International Nuclear Information System (INIS)

    Latychevskaia, Tatiana; Formanek, Petr; Koch, C.T.; Lubk, Axel

    2010-01-01

    Electron holography is a very powerful technique for mapping static electric and magnetic potentials down to atomic resolution. While electron holography is commonly considered synonymous with its off-axis variant in the high energy electron microscopy community, inline electron holography is widely applied in low-energy electron microscopy, where the realization of the off-axis setup is still an experimental challenge. This paper demonstrates that both inline and off-axis holography may be used to recover amplitude and phase shift of the very same object, in our example latex spheres of 90 and 200 nm in diameter, producing very similar results, provided the object does not charge under the electron beam.

  7. Vertical axis wind turbines: a survey and bibliography

    Energy Technology Data Exchange (ETDEWEB)

    Abramovich, H

    1987-01-01

    The stimulus for the development of modern, big wind turbines has been the world-wide oil crisis during the seventies. Although the horizontal axis wind turbines (HAWT) was the most popular type of wind turbine the Darrieus vertical axis wind turbine (VAWT) has been recognized as a machine with competitive economic potential. The state of the art of the VAWT is reviewed. The wind turbine carrying the name of Darrieus was first proposed by the French inventor in 1925. His original patent covered a range of vertical-axis configurations but the term 'Darrieus' is now generally associated with the curved-blade geometry. In 1966 two researchers at the Canadian NRC again raised the idea of both the straight and curved-blade versions of the Darrieus VAWT.

  8. Calibration of three-axis magnetometers with differential evolution algorithm

    International Nuclear Information System (INIS)

    Pang, Hongfeng; Zhang, Qi; Wang, Wei; Wang, Junya; Li, Ji; Luo, Shitu; Wan, Chengbiao; Chen, Dixiang; Pan, Mengchun; Luo, Feilu

    2013-01-01

    The accuracy of three-axis magnetometers is influenced by different scale and bias of each axis and nonorthogonality between axes. One limitation of traditional iteration methods is that initial parameters influence the calibration, thus leading to the local optimal or wrong results. In this paper, a new method is proposed to calibrate three-axis magnetometers. To employ this method, a nonmagnetic rotation platform, a proton magnetometer, a DM-050 three-axis magnetometer and the differential evolution (DE) algorithm are used. The performance of this calibration method is analyzed with simulation and experiment. In simulation, the calibration results of DE, unscented Kalman filter (UKF), recursive least squares (RLS) and genetic algorithm (GA) are compared. RMS error using DE is least, which is reduced from 81.233 nT to 1.567 nT. Experimental results show that comparing with UKF, RLS and GA, the DE algorithm has not only the least calibration error but also the best robustness. After calibration, RMS error is reduced from 68.914 nT to 2.919 nT. In addition, the DE algorithm is not sensitive to initial parameters, which is an important advantage compared with traditional iteration algorithms. The proposed algorithm can avoid the troublesome procedure to select suitable initial parameters, thus it can improve the calibration performance of three-axis magnetometers. - Highlights: • The calibration results and robustness of UKF, GA, RLS and DE algorithm are analyzed. • Calibration error of DE is the least in simulation and experiment. • Comparing with traditional calibration algorithms, DE is not sensitive to initial parameters. • It can improve the calibration performance of three-axis magnetometers

  9. Research on Parameter Design of Multi - axis Hydrostatic Transmission Vehicle

    Directory of Open Access Journals (Sweden)

    Zhao Liang

    2017-01-01

    Full Text Available In order to obtain reasonable parameters in the design of driving system of multi-axis hydrostatic transmission vehicle, the working principle of single-side drive of hydrostatic transmission vehicle is introduced. The matching and control of engine and hydraulic pump are analyzed. According to the driving equation of vehicle, The driving force required for driving system is determined, and the parameters of hydraulic motor, hydraulic pump, system working pressure and braking system are designed and calculated, which provides the parameter design for driving system of multi-axis hydrostatic transmission Reliable theoretical basis.

  10. Microbiota-gut-brain axis and the central nervous system.

    Science.gov (United States)

    Zhu, Xiqun; Han, Yong; Du, Jing; Liu, Renzhong; Jin, Ketao; Yi, Wei

    2017-08-08

    The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseases.

  11. Three axis vector atomic magnetometer utilizing polarimetric technique

    Energy Technology Data Exchange (ETDEWEB)

    Pradhan, Swarupananda, E-mail: spradhan@barc.gov.in, E-mail: pradhans75@gmail.com [Laser and Plasma Technology Division, Bhabha Atomic Research Centre, Mumbai 400085, India and Homi Bhabha National Institute, Department of Atomic Energy, Mumbai 400094 (India)

    2016-09-15

    The three axis vector magnetic field measurement based on the interaction of a single elliptically polarized light beam with an atomic system is described. The magnetic field direction dependent atomic responses are extracted by the polarimetric detection in combination with laser frequency modulation and magnetic field modulation techniques. The magnetometer geometry offers additional critical requirements like compact size and large dynamic range for space application. Further, the three axis magnetic field is measured using only the reflected signal (one polarization component) from the polarimeter and thus can be easily expanded to make spatial array of detectors and/or high sensitivity field gradient measurement as required for biomedical application.

  12. Interpretation and quality of the tilted axis cranking approximation

    International Nuclear Information System (INIS)

    Frauendorf, S.; Meng, J.

    1996-06-01

    Comparing with the exact solutions of the model system of one and two particles coupled to an axial rotor, the quality of the semi classical tilted axis cranking approximation is investigated. Extensive comparisons of the energies and M1 and E2 transition probabilities are carried out for the lowest bands. Very good agreement is found, except near band crossings. Various recipes to take into account finite K within the frame of the usual principal axis cranking are included into the comparison. A set of rules is suggested that permits to construct the excited bands from the cranking configurations, avoiding spurious states. (orig.)

  13. Optical Three-Axis Tactile Sensor for Robotic Fingers

    OpenAIRE

    Ohka, Masahiro; Takata, Jumpei; Kobayashi, Hiroaki; Suzuki, Hirofumi; Morisawa, Nobuyuki; Yussof, Hanafiah Bin

    2008-01-01

    A new three-axis tactile sensor to be mounted on multi-fingered hands is developed based on the principle of an optical waveguide-type tactile sensor comprised of an acrylic hemispherical dome, a light source, an array of rubber sensing elements, and a CCD camera. The sensing element of the present tactile sensor includes one columnar feeler and eight conical feelers. A three-axis force applied to the tip of the sensing element is detected by the contact areas of the conical feelers, which ma...

  14. 75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

    Science.gov (United States)

    2010-03-10

    ... the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission March 2, 2010. The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold...

  15. Ontario regulatory update

    International Nuclear Information System (INIS)

    Thompson, P.

    1998-01-01

    This paper provides a summary of recent events which when combined add up to a gradual but unmistakable movement of the energy sector in Ontario towards a fully competitive market. Some of the events precipitating this movement towards competition include the passing of the Energy Competition Act of 1998 (Bill 35), electricity deregulation, regulatory reform of the natural gas sector, and changes to the consumer protection legislation. The role of the Ontario Energy Board was also updated to bring it in line with the demands of the competitive marketplace. Among the new roles that the Board will assume are to facilitate competition, to maintain fair and reasonable rates, and to facilitate rational expansion. Another objective is to provide opportunities for including energy efficiency in government policies. Implications of the changes in the OEB's mandate for market participants were also discussed, including (1) regulated gas sales and delivery mechanisms, (2) transactional services, (3) contract restructuring, (4) consumer protection, (5) supervision of competitive market participants, and (6) market surveillance

  16. Regulatory risk coherence

    International Nuclear Information System (INIS)

    Remick, F.J.

    1992-01-01

    As one of the most progressive users of risk assessment in decision making, the US Nuclear Regulatory Commission (NRC) is in a position to play an important role in influencing the development of standard government wide policies for the application of risk assessment in decision making. The NRC, with the support of the nuclear industry, should use the opportunity provided by its experience with risk assessment to actively encourage the adoption of standard national and international health-based safety goals and at the same time accelerate its own efforts to implement the safety goals it has already developed for itself. There are signs of increased recognition of the need for consistency and coherence in the application of risk assessment in government decision making. The NRC and the nuclear industry have recently taken a great step toward establishing a consistant and coherent risk assessment-based culture in the US nuclear industry. As a result of Generic Letter 88-20, which asks each commercial nuclear power plant licensee to perform an individual plant examination by September 1992, for the first time a risk assessment characterizing initiating events in each plant will exist

  17. Strengthening Regulatory Competence in Pakistan

    International Nuclear Information System (INIS)

    Sadiq, M.

    2016-01-01

    Capacity building of Pakistan Nuclear Regulatory Authority is considered an essential element in pursuit of its vision to become a world class regulatory body. Since its inception in 2001, PNRA has continuously endeavoured to invest in its people, develop training infrastructure and impart sound knowledge and professional skills with the aim to improve its regulatory effectiveness. The use of nuclear and radioactive material in Pakistan has increased manifold in recent years, thus induction of more manpower was needed for regulatory oversight. PNRA adopted two pronged approach for meeting the manpower demand (a) employment of university graduates through fast track recruitment drive and (b) induction of graduates by offering fellowships for Master degree programs. Although, the newly employed staff was selected on the basis of their excellent academic qualifications in basic and applied sciences, but they required rigorous knowledge and skills in regulatory perspectives. In order to implement a structured training program, PNRA conducted Training Needs Assessment (TNA) and identified competency gaps of the regulatory staff in legal, technical, regulatory practice and behavioural domains. PNRA took several initiatives for capacity building which included establishment of a training centre for sustainability of trainings, initiation of a fellowship scheme for Master program, attachment of staff at local institutes for on-the-job training and placement at foreign regulatory bodies and organizations for technical development with the assistance of IAEA. The above strategies have been very beneficial in competence building of the PNRA staff to perform all regulatory activities indigenously for nuclear power plants, research reactors and radiation facilities. Provision of vibrant technical support to IAEA and Member States in various programs by PNRA is a landmark of these competence development efforts. This paper summarizes PNRA initiatives and the International Atomic

  18. Perspectives on Regulatory T Cell Therapies.

    Science.gov (United States)

    Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S P; Buer, Jan

    2009-01-01

    Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (T(reg)) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, T(reg) cell therapies and development of drugs that specifically enhance T(reg) cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human T(reg) cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 at different levels, hampered such an approach. Recent identification of the orphan receptor glycoprotein-A repetitions predominant (GARP or LRRC32) as T(reg) cell-specific key molecule that dominantly controls FOXP3 via a positive feedback loop opens up new perspectives for molecular and cellular therapies. This brief review focuses on the role of GARP as a safeguard of a complex regulatory network of human T(reg) cells and its implications for regulatory T cell therapies in autoimmunity and graft-versus-host disease.

  19. Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression.

    Science.gov (United States)

    Kunugi, Hiroshi; Hori, Hiroaki; Adachi, Naoki; Numakawa, Tadahiro

    2010-10-01

    Although the pathophysiology of depressive disorder remains elusive, two hypothetical frameworks seem to be promising: the involvement of hypothalamic pituitary-adrenal (HPA) axis abnormalities and brain-derived neurotrophic factor (BDNF) in the pathogenesis and in the mechanism of action of antidepressant treatments. In this review, we focused on research based on these two frameworks in relation to depression and related conditions and tried to formulate an integrated theory of the disorder. Hormonal challenge tests, such as the dexamethasone/corticotropin-releasing hormone test, have revealed elevated HPA activity (hypercortisolism) in at least a portion of patients with depression, although growing evidence has suggested that abnormally low HPA axis (hypocortisolism) has also been implicated in a variety of stress-related conditions. Several lines of evidence from postmortem studies, animal studies, blood levels, and genetic studies have suggested that BDNF is involved in the pathogenesis of depression and in the mechanism of action of biological treatments for depression. Considerable evidence has suggested that stress reduces the expression of BDNF and that antidepressant treatments increase it. Moreover, the glucocorticoid receptor interacts with the specific receptor of BDNF, TrkB, and excessive glucocorticoid interferes with BDNF signaling. Altered BDNF function is involved in the structural changes and possibly impaired neurogenesis in the brain of depressed patients. Based on these findings, an integrated schema of the pathological and recovery processes of depression is illustrated. © 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.

  20. The Danish Regulatory Reform of Telecommunications

    DEFF Research Database (Denmark)

    Skouby, Knud Erik

    1998-01-01

    An overview of the liberalisation process and regulatory reform of telecommunications in Denmark......An overview of the liberalisation process and regulatory reform of telecommunications in Denmark...

  1. Strengthening Regulatory Competence in a Changing Nuclear Regulatory Environment

    International Nuclear Information System (INIS)

    Illizastigui, P.F.

    2016-01-01

    The paper addresses the approach followed by the Cuban National Center for Nuclear Safety for the management of current and new competences of its regulatory staff with the aim of allowing those staff to effectively fulfill their core regulatory functions. The approach is realized through an Integrated System for Competence Building, which is based on the IAEA recommendations, shown to be effective in ensuring the necessary competence in the relevant areas. In the author’s opinion, competence of the regulatory staff in the area of human and organizational factors is of paramount importance and needs to be further strengthened in order to be able to assess safety performance at the facilities and detect early signs of deteriorating safety performance. The former is defined by the author as the core regulatory function “Analysis” which covers the entire spectrum of assessment tasks carried out by the regulatory staff to: a) detect declining safety performance, b) diagnose latent weaknesses (root causes) and c) make effective safety culture interventions. The author suggests that competence associated with the fulfillment of the analysis function is distinctly identified and dealt with separately in the current system of managing regulatory competence. (author)

  2. Regulatory Immunotherapy in Bone Marrow Transplantation

    Directory of Open Access Journals (Sweden)

    Vanessa Morales-Tirado

    2011-01-01

    Full Text Available Every year individuals receive hematopoietic stem cell transplantation (HSCT to eradicate malignant and nonmalignant disease. The immunobiology of allotransplantation is an area of ongoing discovery, from the recipient's conditioning treatment prior to the transplant to the donor cell populations responsible for engraftment, graft-versus-host disease, and graft-versus-tumor effect. In this review, we focus on donor-type immunoregulatory T cells, namely, natural killer T cells (NKT and regulatory T cells (Treg, and their current and potential roles in tolerance induction after allogeneic HSCT.

  3. 1992 Nuclear Regulatory Commission Annual Report

    International Nuclear Information System (INIS)

    1993-01-01

    This is the 18th annual report of the US Nuclear Regulatory Commission (NRC), covering events and activities occurring in fiscal year 1992 (the year ending September 30, 1992), with some treatment of events from the last quarter of calendar year 1992. The NRC was created by enactment in the Congress of the Energy Reorganization Act of 1974. It is an independent agency of the Federal Government. The five NRC Commissioners are nominated by the President and confirmed by the United States Senate. The Chairman of the Commission is appointed by the President from among the Commissioners confirmed

  4. Facing regulatory challenges of on-line hemodiafiltration.

    Science.gov (United States)

    Kümmerle, Wolfgang

    2011-01-01

    On-line hemodiafiltration (on-line HDF) is the result of a vision that triggered multifarious changes in very different areas. Driven by the idea to offer better medical treatment for renal patients, technological innovations were developed and established that also constituted new challenges in the field of regulatory affairs. The existing regulations predominantly addressed the quality and safety of those products needed to perform dialysis treatment which were supplied by industrial manufacturers. However, the complexity of treatment system required for the provision of on-line fluids demanded a holistic approach encompassing all components involved. Hence, focus was placed not only on single products, but much more on their interfacing, and the clinical infrastructure, in particular, had to undergo substantial changes. The overall understanding of the interaction between such factors, quite different in their nature, was crucial to overcome the arising regulatory obstacles. This essay describes the evolution of the on-line HDF procedure from the regulatory point of view. A simplified diagram demonstrates the path taken from the former regulatory understanding to the realization of necessary changes. That achievement was only possible through 'management of preview' and consequent promotion of technical and medical innovations as well as regulatory re-evaluations. Copyright © 2011 S. Karger AG, Basel.

  5. Neurovascular-neuroenergetic coupling axis in the brain: master regulation by nitric oxide and consequences in aging and neurodegeneration.

    Science.gov (United States)

    Lourenço, Cátia F; Ledo, Ana; Barbosa, Rui M; Laranjinha, João

    2017-07-01

    The strict energetic demands of the brain require that nutrient supply and usage be fine-tuned in accordance with the specific temporal and spatial patterns of ever-changing levels of neuronal activity. This is achieved by adjusting local cerebral blood flow (CBF) as a function of activity level - neurovascular coupling - and by changing how energy substrates are metabolized and shuttled amongst astrocytes and neurons - neuroenergetic coupling. Both activity-dependent increase of CBF and O 2 and glucose utilization by active neural cells are inextricably linked, establishing a functional metabolic axis in the brain, the neurovascular-neuroenergetic coupling axis. This axis incorporates and links previously independent processes that need to be coordinated in the normal brain. We here review evidence supporting the role of neuronal-derived nitric oxide ( • NO) as the master regulator of this axis. Nitric oxide is produced in tight association with glutamatergic activation and, diffusing several cell diameters, may interact with different molecular targets within each cell type. Hemeproteins such as soluble guanylate cyclase, cytochrome c oxidase and hemoglobin, with which • NO reacts at relatively fast rates, are but a few of the key in determinants of the regulatory role of • NO in the neurovascular-neuroenergetic coupling axis. Accordingly, critical literature supporting this concept is discussed. Moreover, in view of the controversy regarding the regulation of catabolism of different neural cells, we further discuss key aspects of the pathways through which • NO specifically up-regulates glycolysis in astrocytes, supporting lactate shuttling to neurons for oxidative breakdown. From a biomedical viewpoint, derailment of neurovascular-neuroenergetic axis is precociously linked to aberrant brain aging, cognitive impairment and neurodegeneration. Thus, we summarize current knowledge of how both neurovascular and neuroenergetic coupling are compromised in

  6. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2004-01-01

    The 48. session of the IAEA general conference was held in Vienna from 20 to 24 september 2004 with the participation of delegates from 125 members states and representatives of various international organisations. A number of resolutions were adopted by the conference in the following fields: nuclear safety, radiation, transport and waste safety. The general conference also adopted a resolution on measures to protect against nuclear terrorism. The Director General decided in 2003 to appoint a group of experts to explore and advise on issues related to nuclear liability. This group called the International Expert Group on Nuclear Liability (I.N.L.E.X.) consists of 20 experts members from nuclear power and non nuclear power countries and from shipping and non shipping states. It serves three major functions: to create a forum of expertise to explore and advise on issues related to nuclear liability; to enhance global adherence by nuclear and non nuclear states to an effective nuclear liability regime, inter alia, on the basis of the convention on supplementary compensation for nuclear damage and the annex thereto, the Vienna convention on civil liability for nuclear damage, the Paris convention on third party liability in the field of nuclear energy, the joint protocol relating to the application of the vienna convention and the paris convention and the amendments thereto; and to assist in the development and strengthening of the national nuclear liability legal frameworks in IAEA members states to protect the public and the environment and to enhance nuclear safety. The second part of international regulatory concerns a directive on public access to environmental information made by the European Parliament. (N.C.)

  7. Experimental characterization of individual pitch controlled vertical axis wind turbine

    NARCIS (Netherlands)

    Leblanc, B.P.; Simao Ferreira, C.

    2017-01-01

    Research into the Vertical Axis Wind Turbine (VAWT) has been progressing over the last few years due to
    the large shift in design constraints for large floating offshore wind turbines by leveraging tools and experience
    from research beginning in the 1970s and lasting until the HAWT

  8. Comparison of aerodynamic models for Vertical Axis Wind Turbines

    DEFF Research Database (Denmark)

    Ferreira, C. Simão; Aagaard Madsen, Helge; Barone, M.

    2014-01-01

    Multi-megawatt Vertical Axis Wind Turbines (VAWTs) are experiencing an increased interest for floating offshore applications. However, VAWT development is hindered by the lack of fast, accurate and validated simulation models. This work compares six different numerical models for VAWTS: a multiple...

  9. Local charge measurement using off-axis electron holography

    DEFF Research Database (Denmark)

    Beleggia, Marco; Gontard, L.C.; Dunin-Borkowski, R.0E.

    2016-01-01

    A model-independent approach based on Gauss’ theorem for measuring the local charge in a specimen from an electron-optical phase image recorded using off-axis electron holography was recently proposed. Here, we show that such a charge measurement is reliable when it is applied to determine the to...

  10. Tilted axis rotation in odd-odd {sup 164}Tm

    Energy Technology Data Exchange (ETDEWEB)

    Reviol, W.; Riedinger, L.L.; Wang, X.Z.; Zhang, J.Y. [Univ. of Tennessee, Knoxville, TN (United States)] [and others

    1996-12-31

    Ten band structures are observed in {sup 164}Tm, among them sets of parallel and anti-parallel couplings of the proton and neutron spins. The Tilted Axis Cranking scheme is applied for the first time to an odd-odd nucleus in a prominent region of nuclear deformation.

  11. An improved computer controlled triple-axis neutron spectrometer

    International Nuclear Information System (INIS)

    Cooper, M.J.; Hall, J.W.; Hutchings, M.T.

    1975-07-01

    A description is given of the computer-controlled triple-axis neutron spectrometer installed at the PLUTO reactor at Harwell. The reasons for an nature of recent major improvements are discussed. Following a general description of the spectrometer, details are then given of the new computerised control system, including the functions of the various programs which are now available to the user. (author)

  12. The GH/IGF-1 axis in ageing and longevity

    Science.gov (United States)

    List, Edward O.; Berryman, Darlene E.; Murrey, John W.

    2014-01-01

    Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals aged ≥60 years. This phenomenon, which is known as the ‘somatopause’, has led to recombinant human GH being widely promoted and abused as an antiageing drug, despite lack of evidence of efficacy. By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice. In humans, corresponding or similar mutations have been identified, but whether these mutations alter longevity has yet to be established. The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay ageing. Moreover, mice as well as humans with reduced activity of the GH/IGF-1 axis are protected from cancer and diabetes mellitus, two major ageing-related morbidities. Here, we review data on mouse strains with alterations in the GH/IGF-1 axis and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits and risks of medical disruption of the GH/IGF-1 axis in humans. PMID:23591370

  13. Lake Malawi cichlid evolution along a benthic/limnetic axis.

    Science.gov (United States)

    Hulsey, C D; Roberts, R J; Loh, Y-H E; Rupp, M F; Streelman, J T

    2013-07-01

    Divergence along a benthic to limnetic habitat axis is ubiquitous in aquatic systems. However, this type of habitat divergence has largely been examined in low diversity, high latitude lake systems. In this study, we examined the importance of benthic and limnetic divergence within the incredibly species-rich radiation of Lake Malawi cichlid fishes. Using novel phylogenetic reconstructions, we provided a series of hypotheses regarding the evolutionary relationships among 24 benthic and limnetic species that suggests divergence along this axis has occurred multiple times within Lake Malawi cichlids. Because pectoral fin morphology is often associated with divergence along this habitat axis in other fish groups, we investigated divergence in pectoral fin muscles in these benthic and limnetic cichlid species. We showed that the eight pectoral fin muscles and fin area generally tended to evolve in a tightly correlated manner in the Lake Malawi cichlids. Additionally, we found that larger pectoral fin muscles are strongly associated with the independent evolution of the benthic feeding habit across this group of fish. Evolutionary specialization along a benthic/limnetic axis has occurred multiple times within this tropical lake radiation and has produced repeated convergent matching between exploitation of water column habitats and locomotory morphology.

  14. The somatotropic axis: Effects on brain and cognitive functions

    NARCIS (Netherlands)

    Quik, E.H.

    2012-01-01

    Both hormones of the somatotropic axis, insulin-like growth factor-1 (IGF-1) and growth hormone (GH) can cross the blood-brain barrier and bind to their receptors in neurons and glia throughout the brain. Features of aging resemble those of GHD and aging is also associated with a decline in the

  15. Locating an axis-parallel rectangle on a Manhattan plane

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Körner, Mark-Christoph

    2014-01-01

    In this paper we consider the problem of locating an axis-parallel rectangle in the plane such that the sum of distances between the rectangle and a finite point set is minimized, where the distance is measured by the Manhattan norm 1. In this way we solve an extension of the Weber problem...

  16. Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Hay-Schmidt, Anders; Kiss, Alexander

    2004-01-01

    Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma corticosterone levels, and it is likely that these recept...

  17. Off-axis electron holography of ferromagnetic multilayer nanowires

    DEFF Research Database (Denmark)

    Akhtari-Zavareh, Azadeh; Carignan, L. P.; Yelon, A.

    2014-01-01

    with respect to the axis of the wires. In thinner Cu/CoFeB ((multilayer, magnetic field vortices were detected, associated with opposing magnetization in neighbouring layers. The measured crystallinity, compositions, and layer thicknesses of individual NWs were found to be significantly different...

  18. Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

    Science.gov (United States)

    Quigley, Eamonn M M

    2017-10-17

    The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.

  19. On the Turbulent Mixing in Horizontal Axis Wind Turbine Wakes

    NARCIS (Netherlands)

    Lignarolo, L.E.M.

    2016-01-01

    The wake flow of a horizontal axis wind turbine is characterised by lower wind speed and higher turbulence than the free-stream conditions. When clustered in large wind farms, wind turbines regularly operate inside the wake of one or more upstream machines. This is a major cause of energy production

  20. Phytochemicals for taming agitated immune-endocrine-neural axis.

    Science.gov (United States)

    Patel, Seema

    2017-07-01

    Homeostasis of immune-endocrine-neural axis is paramount for human health. If this axis gets agitated due to age, genetic variations, environmental exposures or lifestyle assaults, a cascade of adverse reactions occurs in human body. Cytokines, hormones and neurotransmitters, the effector molecules of this axis behave erratically, leading to a gamut of neural, endocrine, autoimmune, and metabolic diseases. Current panel of drugs can tackle some of them but not in a sustainable, benign way as a myriad of side effects, causal of them have been documented. In this context, phytochemicals, the secondary metabolites of plants seem beneficial. These bioactive constituents encompassing polyphenols, alkaloids, flavonoids, terpenoids, tannins, lignans, stilbenoids (resveratrol), saponins, polysaccharides, glycosides, and lectins etc. have been proven to exert antioxidant, anti-inflammatory, hypolipidemic, hypotensive, antidiabetic, anticancer, immunomodulatory, anti-allergic, analgesic, hepatoprotective, neuroprotective, dermatoprotective, and antimicrobial properties, among a litany of other biological effects. This review presents a holistic perspective of common afflictions resultant of immune-endocrine-neural axis disruption, and the phytochemicals capable of restoring their normalcy and mitigating the ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. A four-axis hand controller for helicopter flight control

    Science.gov (United States)

    Demaio, Joe

    1993-01-01

    A proof-of-concept hand controller for controlling lateral and longitudinal cyclic pitch, collective pitch and tail rotor thrust was developed. The purpose of the work was to address problems of operator fatigue, poor proprioceptive feedback and cross-coupling of axes associated with many four-axis controller designs. The present design is an attempt to reduce cross-coupling to a level that can be controlled with breakout force, rather than to eliminate it entirely. The cascaded design placed lateral and longitudinal cyclic in their normal configuration. Tail rotor thrust was placed atop the cyclic controller. A left/right twisting motion with the wrist made the control input. The axis of rotation was canted outboard (clockwise) to minimize cross-coupling with the cyclic pitch axis. The collective control was a twist grip, like a motorcycle throttle. Measurement of the amount of cross-coupling involved in pure, single-axis inputs showed cross coupling under 10 percent of full deflection for all axes. This small amount of cross-coupling could be further reduced with better damping and force gradient control. Fatigue was not found to be a problem, and proprioceptive feedback was adequate for all flight tasks executed.

  2. 78 FR 1634 - Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ... amendments include updates to organizational information, use of the term ``disability'' in lieu of the term.../00/13 Regulatory Flexibility Analysis Required: No. Agency Contact: Robert W. Cosgrove, External...

  3. 78 FR 44329 - Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... amendments include updates to organizational information, use of the term ``disability'' in lieu of the term.../00/13 Regulatory Flexibility Analysis Required: No. Agency Contact: Robert W. Cosgrove, External...

  4. 78 FR 44279 - Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... Vol. 78 Tuesday, No. 141 July 23, 2013 Part XI Department of Justice Semiannual Regulatory Agenda #0;#0;Federal Register / Vol. 78 , No. 141 / Tuesday, July 23, 2013 / Unified Agenda#0;#0; [[Page 44280

  5. Recent regulatory issues in Finland

    International Nuclear Information System (INIS)

    Laaksonen, J.; Tiipana, P.

    2001-01-01

    This paper presents general regulatory issues from Finland since the last WWER Regulators Forum meeting in Odessa 11-13 October 2000. More specific issues concerning Loviisa NPP are described in the Annex of this paper. (author)

  6. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2016-01-01

    This section treats of the following National legislative and regulatory activities: 1 - France: General legislation, regulations and instruments; Nuclear trade (including non-proliferation); International co-operation; 2 - India: Licensing and regulatory infrastructure; Liability and compensation; 3 - Ireland: Nuclear safety and radiological protection (including nuclear emergency planning); Transport of radioactive material; Nuclear trade (including non-proliferation); 4 - Lithuania: Licensing and regulatory infrastructure; Nuclear safety and radiological protection (including nuclear emergency planning); Radioactive waste management; 5 - Luxembourg: Nuclear safety and radiological protection (including nuclear emergency planning); 6 - Slovak Republic: International co-operation; General legislation, regulations and instruments; 7 - Spain: Radioactive materials (including physical protection); Radioactive waste management; 8 - United States: Licensing and regulatory infrastructure

  7. Quality assurance within regulatory bodies

    International Nuclear Information System (INIS)

    1999-06-01

    The IAEA directed extensive efforts during the years 1991 to 1995 to the integral revision of all NUSS quality assurance publications, which were approved and issued as Safety Series No.50-C/SG-Q, Quality Assurance for Safety in Nuclear Power Plants and other Nuclear Installations (1996). When these quality assurance publications were developed, their prime focus was on requirements against which work performed by the licensees could be measured and assessed by the regulatory bodies. In this way, they only helped to facilitate the functions of regulators. No requirements or recommendations were provided on how the regulators should ensure the effective implementation of their own activities. The present publication is a first attempt to collect, integrate and offer available experience to directly support performance of regulatory activities. It presents a comprehensive compilation on the application of quality assurance principles and methods by regulatory bodies to their activities. The aim is consistent good performance of regulatory activities through a systematic approach

  8. State/Federal Regulatory Considerations

    Science.gov (United States)

    This page contains presentations from the Brown to Green: Make the Connection to Renewable Energy workshop held in Santa Fe, New Mexico, during December 10-11, 2008, regarding State/Federal Regulatory Considerations.

  9. The role of sex and autonomy-connectedness in internalizing and externalizing personality pathology, coping and axis-I pathology: among psychiatric and healthy elderly.

    Science.gov (United States)

    Bachrach, Nathan; Croon, Marcel; Bekker, Marrie

    2017-06-01

    In the current study we investigated the relationship of sex and autonomy-connectedness with internalizing and externalizing personality disorder symptoms (PDS), coping and axis-I pathology in older age. A path model was tested which was based on neo-analytical object relation, attachment- and primary-personality theory, among 100 clinical and 106 non-clinical elderly. In line with our model, autonomy-connectedness (self-awareness and capacity of managing new situations) was strongly associated to internalizing PDS in both groups. In both groups, neither sex nor autonomy-connectedness predicted externalizing PDS. Sex, internalizing as well as externalizing PDS and reactive defensive coping were associated to axis-I psychopathology. We conclude that sex and autonomy-connectedness were, similarly as in adult populations, associated to internalizing PDS and axis-I pathology. Treatment of elderly with internalizing PDS and axis-I psychopathology should therefore focus on enhancing autonomy-connectedness.

  10. The manufacturing and metrology of off-axis mirrors

    Science.gov (United States)

    Penzkofer, Karlheinz; Rascher, Rolf; Küpper, Lutz; Liebl, Johannes

    2015-10-01

    Especially in the area of the large mirror manufacturing only a few manufacturers are capable to produce optical surfaces of high quality. Therefore a deterministic process should be developed in the project IFasO. In the field of telescope optics off-axis optical systems are becoming increasingly important. These systems try to avoid an obstructing of the incoming light by moving the secondary mirror out of the primary mirror's optical axis. This advantage leads to an increasing market for this type of optical surface. Until now off-axis mirrors were difficult or almost impossible to produce. With the processes developed in IFasO, high quality mirrors become possible. For this reason, this paper describes the manufacturing of off-axis surfaces and its problems. The mirror production used in the project IFasO is based on the specific design of the CNC center developed by the company Optotech. This center UPG2000 is capable of grinding, polishing, sagitta measurement and interferometric measurement in one mounting of the specimen. Usually a large optics has to be transported during their manufacturing after every individual process step. There is always a risk of damage of the specimen. The exact orientation of the surface relatively to the tool position is also required. This takes a huge amount of time and makes up most of the production time. In this presentation the use of UPG2000 and the next steps within the process development are described. In the current status the manufacturing of large off-axis elements with a PV < λ/10 rms is reproducible.

  11. GRB 170817A: a short GRB seen off-axis

    Science.gov (United States)

    He, Xin-Bo; Tam, Pak-Hin Thomas; Shen, Rong-Feng

    2018-04-01

    The angular distribution of gamma-ray burst (GRB) jets is not yet clear. The observed luminosity of GRB 170817A is the lowest among all known short GRBs, which is best explained by the fact that our line of sight is outside of the jet opening angle, θ obs > θ j , where θ obs is the angle between our line of sight and the jet axis. As inferred by gravitational wave observations, as well as radio and X-ray afterglow modeling of GRB 170817A, it is likely that θ obs ∼ 20° – 28°. In this work, we quantitatively consider two scenarios of angular energy distribution of GRB ejecta: a top-hat jet and a structured jet with a power law index s. For the top-hat jet model, we get a large θ j (e.g., θ j > 10°), a rather high local (i.e., z 7.5 × 104, keV (∼500, keV for a typical short GRB). For the structured jet model, we use θ obs to give limits on s and θj for typical on-axis luminosity of a short GRB (e.g., 1049 erg s‑1 ∼ 1051 erg s‑1), and a low on-axis luminosity case (e.g., 1049 erg s‑1) gives more reasonable values of s. The structured jet model is more feasible for GRB 170817A than the top-hat jet model due to the rather high local short GRB rate, and the extremely high on-axis E peak,0 almost rules out the top-hat jet model. GRB 170817A is likely a low on-axis luminosity GRB (1049 erg s‑1) with a structured jet.

  12. Analytical Aerodynamic Simulation Tools for Vertical Axis Wind Turbines

    International Nuclear Information System (INIS)

    Deglaire, Paul

    2010-01-01

    Wind power is a renewable energy source that is today the fastest growing solution to reduce CO 2 emissions in the electric energy mix. Upwind horizontal axis wind turbine with three blades has been the preferred technical choice for more than two decades. This horizontal axis concept is today widely leading the market. The current PhD thesis will cover an alternative type of wind turbine with straight blades and rotating along the vertical axis. A brief overview of the main differences between the horizontal and vertical axis concept has been made. However the main focus of this thesis is the aerodynamics of the wind turbine blades. Making aerodynamically efficient turbines starts with efficient blades. Making efficient blades requires a good understanding of the physical phenomena and effective simulations tools to model them. The specific aerodynamics for straight bladed vertical axis turbine flow are reviewed together with the standard aerodynamic simulations tools that have been used in the past by blade and rotor designer. A reasonably fast (regarding computer power) and accurate (regarding comparison with experimental results) simulation method was still lacking in the field prior to the current work. This thesis aims at designing such a method. Analytical methods can be used to model complex flow if the geometry is simple. Therefore, a conformal mapping method is derived to transform any set of section into a set of standard circles. Then analytical procedures are generalized to simulate moving multibody sections in the complex vertical flows and forces experienced by the blades. Finally the fast semi analytical aerodynamic algorithm boosted by fast multipole methods to handle high number of vortices is coupled with a simple structural model of the rotor to investigate potential aeroelastic instabilities. Together with these advanced simulation tools, a standard double multiple streamtube model has been developed and used to design several straight bladed

  13. DARHT Axis-I Diode Simulations II: Geometrical Scaling

    Energy Technology Data Exchange (ETDEWEB)

    Ekdahl, Carl A. Jr. [Los Alamos National Laboratory

    2012-06-14

    Flash radiography of large hydrodynamic experiments driven by high explosives is a venerable diagnostic technique in use at many laboratories. Many of the largest hydrodynamic experiments study mockups of nuclear weapons, and are often called hydrotests for short. The dual-axis radiography for hydrodynamic testing (DARHT) facility uses two electron linear-induction accelerators (LIA) to produce the radiographic source spots for perpendicular views of a hydrotest. The first of these LIAs produces a single pulse, with a fixed {approx}60-ns pulsewidth. The second axis LIA produces as many as four pulses within 1.6-{micro}s, with variable pulsewidths and separation. There are a wide variety of hydrotest geometries, each with a unique radiographic requirement, so there is a need to adjust the radiographic dose for the best images. This can be accomplished on the second axis by simply adjusting the pulsewidths, but is more problematic on the first axis. Changing the beam energy or introducing radiation attenuation also changes the spectrum, which is undesirable. Moreover, using radiation attenuation introduces significant blur, increasing the effective spot size. The dose can also be adjusted by changing the beam kinetic energy. This is a very sensitive method, because the dose scales as the {approx}2.8 power of the energy, but it would require retuning the accelerator. This leaves manipulating the beam current as the best means for adjusting the dose, and one way to do this is to change the size of the cathode. This method has been proposed, and is being tested. This article describes simulations undertaken to develop scaling laws for use as design tools in changing the Axis-1 beam current by changing the cathode size.

  14. Velocity measurement of model vertical axis wind turbines

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, D.A.; McWilliam, M. [Waterloo Univ., ON (Canada). Dept. of Mechanical Engineering

    2006-07-01

    An increasingly popular solution to future energy demand is wind energy. Wind turbine designs can be grouped according to their axis of rotation, either horizontal or vertical. Horizontal axis wind turbines have higher power output in a good wind regime than vertical axis turbines and are used in most commercial class designs. Vertical axis Savonius-based wind turbine designs are still widely used in some applications because of their simplistic design and low wind speed performance. There are many design variables that must be considered in order to optimize the power output in a given wind regime in a typical wind turbine design. Using particle image velocimetry, a study of the air flow around five different model vertical axis wind turbines was conducted in a closed loop wind tunnel. A standard Savonius design with two semi-circular blades overlapping, and two variations of this design, a deep blade and a shallow blade design were among the turbine models included in this study. It also evaluated alternate designs that attempt to increase the performance of the standard design by allowing compound blade curvature. Measurements were collected at a constant phase angle and also at random rotor orientations. It was found that evaluation of the flow patterns and measured velocities revealed consistent and stable flow patterns at any given phase angle. Large scale flow structures are evident in all designs such as vortices shed from blade surfaces. An important performance parameter was considered to be the ability of the flow to remain attached to the forward blade and redirect and reorient the flow to the following blade. 6 refs., 18 figs.

  15. Regulatory competition in partnership law.

    OpenAIRE

    Siems, Mathias

    2009-01-01

    Regulatory competition in company law has been extensively debated in the last few decades, but it has rarely been discussed whether there could also be regulatory competition in partnership law. This article fills this gap. It addresses the partnership law of the US, the UK, Germany, and France, and presents empirical data on the different types of partnerships and companies established in these jurisdictions. The main focus is on the use of a limited liability partnership (LLP) outside its ...

  16. Nuclear regulatory developments in Canada

    International Nuclear Information System (INIS)

    Binder, M.

    2012-01-01

    This paper from CNSC discusses nuclear regulatory developments in Canada. It starts with the Fukushima accident and the effect on the nuclear sector. It summarises what CNSC has done, what it has learned and their plans going forward. It has made recommendations to IAEA for international enhancements to regulatory procedures. It outline the activities of Canada's nuclear power plants, Canada's uranium projects, deep geological repository and waste management as well as nuclear research in Canada.

  17. Regulatory facility guide for Ohio

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, S.S.; Bock, R.E.; Francis, M.W.; Gove, R.M.; Johnson, P.E.; Kovac, F.M.; Mynatt, J.O. [Oak Ridge National Lab., TN (United States); Rymer, A.C. [Transportation Consulting Services, Knoxville, TN (United States)

    1994-02-28

    The Regulatory Facility Guide (RFG) has been developed for the DOE and contractor facilities located in the state of Ohio. It provides detailed compilations of international, federal, and state transportation-related regulations applicable to shipments originating at destined to Ohio facilities. This RFG was developed as an additional resource tool for use both by traffic managers who must ensure that transportation operations are in full compliance with all applicable regulatory requirements and by oversight personnel who must verify compliance activities.

  18. Challenges in orphan drug development and regulatory policy in China.

    Science.gov (United States)

    Cheng, Alice; Xie, Zhi

    2017-01-18

    While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.

  19. Metabolic syndrome, activity of the hypothalamic-pituitary-adrenal axis and inflammatory mediators in depressive disorder.

    Science.gov (United States)

    Martinac, Marko; Pehar, Davor; Karlović, Dalibor; Babić, Dragan; Marcinko, Darko; Jakovljević, Miro

    2014-03-01

    Depression has been associated with various cardiovascular risk factors such as hypertension, obesity, atherogenic dyslipidemia and hyperglycemia. In depressive disorder, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and changes in the immune system have been observed. On the other hand, somatic diseases such as obesity, hyperlipidemia, hypertension and diabetes mellitus type 2 are now perceived as important comorbid conditions in patients with depression. The pathogenesis of the metabolic syndrome and depression is complex and poorly researched; however, it is considered that the interaction of chronic stress, psychotrauma, hypercotisolism and disturbed immune functions contribute to the development of these disorders. The aim of the study was to investigate the relationship between depression and metabolic syndrome regarding the HPA axis dysfunction and altered inflammatory processes. Literature search in Medline and other databases included articles written in English published between 1985 and 2012. Analysis of the literature was conducted using a systematic approach with the search terms such as depression, metabolic syndrome, inflammation, cytokines, glucocorticoids, cortisol, and HPA axis. In conclusion, the relationship between depression and metabolic syndrome is still a subject of controversy. Further prospective studies are required to clarify the possible causal relationship between depression and metabolic syndrome and its components. Furthermore, it is important to explore the possibility of a common biologic mechanism in the pathogenesis of these two disorders, in which special attention should be paid to the immune system function, especially the possible specific mechanisms by which cytokines can induce and maintain depressive symptoms and metabolic disorders. The data presented here emphasize the importance of recognition and treatment of depressive disorders with consequent reduction in the incidence of metabolic syndrome, but

  20. Experimental hyperthyroidism and central mediators of stress axis and thyroid axis activity in common carp (Cyprinus carpio L.).

    Science.gov (United States)

    Geven, Edwin J W; Verkaar, Folkert; Flik, Gert; Klaren, Peter H M

    2006-12-01

    The effect of experimental hyperthyroidism, realized by T(4) injection, on central mediators of the hypothalamo-pituitary-interrenal axis (HPI-axis) in common carp (Cyprinus carpio L.) was studied. Our results show that hyperthyroidism evokes a marked 3.2-fold reduction in basal plasma cortisol levels. Corticotropin-releasing hormone-binding protein (CRH-BP) mRNA levels in the hypothalamus, measured by real-time quantitative PCR, were significantly elevated by 40%, but CRH, urotensin-I, prepro-TRH, prohormone convertase-1 (PC1), and POMC mRNA levels were unchanged. In the pituitary pars distalis, PC1, CRH receptor-1, and POMC mRNA levels were unaffected, as was ACTH content. Plasma alpha-MSH concentrations were significantly elevated by 30% in hyperthyroid fish, and this was reflected in PC1 and POMC mRNA levels in pituitary pars intermedia that were increased 1.5- and 2.4-fold respectively. The alpha-MSH content of the pars intermedia was unchanged. Hyperthyroidism has profound effects on the basal levels of a central mediator, i.e., CRH-BP, of HPI-axis function in unstressed carp in vivo, and we conclude that HPI- and hypothalamo-pituitary-thyroid-axis functions are strongly interrelated. We suggest that the changes in plasma cortisol, thyroid hormone, and alpha-MSH levels reflect their concerted actions on energy metabolism.

  1. DOE regulatory reform initiative vitrified mixed waste

    International Nuclear Information System (INIS)

    Carroll, S.J.; Holtzscheiter, E.W.

    1997-01-01

    The US Department of Energy (DOE) is charged with responsibly managing the largest volume of mixed waste in the United States. This responsibility includes managing waste in compliance with all applicable Federal and State laws and regulations, and in a cost-effective, environmentally responsible manner. Managing certain treated mixed wastes in Resource Conservation and Recovery Act (RCRA) permitted storage and disposal units (specifically those mixed wastes that pose low risks from the hazardous component) is unlikely to provide additional protection to human health and the environment beyond that afforded by managing these wastes in storage and disposal units subject to requirements for radiological control. In October, 1995, the DOE submitted a regulatory reform proposal to the Environmental Protection Agency (EPA) relating to vitrified mixed waste forms. The technical proposal supports a regulatory strategy that would allow vitrified mixed waste forms treated through a permit or other environmental compliance mechanism to be granted an exemption from RCRA hazardous waste regulation, after treatment, based upon the inherent destruction and immobilization capabilities of vitrification technology. The vitrified waste form will meet, or exceed the performance criteria of the Environmental Assessment (EA) glass that has been accepted as an international standard for immobilizing radioactive waste components and the LDR treatment standards for inorganics and metals for controlling hazardous constituents. The proposal further provides that vitrified mixed waste would be responsibly managed under the Atomic Energy Act (AEA) while reducing overall costs. Full regulatory authority by the EPA or a State would be maintained until an acceptable vitrified mixed waste form, protective of human health and the environment, is produced

  2. Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis

    Science.gov (United States)

    Tsang, S.W.; Auyeung, K.K.W.; Bian, Z.X.; Ko, J.K.S.

    2016-01-01

    Background Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Methods Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. Results When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. Conclusion Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients. PMID:27009115

  3. Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tome, Wolfgang A. [Department of Human Oncology, University of Wisconsin-Madison, WI, 53792 (United States); Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, VIC 3002 (Australia) and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Department of Human Oncology, University of Wisconsin-Madison, WI 53792 (United States); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia) and Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Einstein Institute of Oncophysics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461 (United States) and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

    2012-08-15

    Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

  4. Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

    International Nuclear Information System (INIS)

    Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tomé, Wolfgang A.

    2012-01-01

    Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed “Super Sampling” involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

  5. 75 FR 22868 - Withdrawal of Regulatory Guide

    Science.gov (United States)

    2010-04-30

    ...'s public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are also available for inspection at the NRC's... NUCLEAR REGULATORY COMMISSION [NRC-2010-0167] Withdrawal of Regulatory Guide AGENCY: Nuclear...

  6. The medical dictionary for regulatory activities (MedDRA).

    Science.gov (United States)

    Brown, E G; Wood, L; Wood, S

    1999-02-01

    The International Conference on Harmonisation has agreed upon the structure and content of the Medical Dictionary for Regulatory Activities (MedDRA) version 2.0 which should become available in the early part of 1999. This medical terminology is intended for use in the pre- and postmarketing phases of the medicines regulatory process, covering diagnoses, symptoms and signs, adverse drug reactions and therapeutic indications, the names and qualitative results of investigations, surgical and medical procedures, and medical/social history. It can be used for recording adverse events and medical history in clinical trials, in the analysis and tabulations of data from these trials and in the expedited submission of safety data to government regulatory authorities, as well as in constructing standard product information and documentation for applications for marketing authorisation. After licensing of a medicine, it may be used in pharmacovigilance and is expected to be the preferred terminology for international electronic regulatory communication. MedDRA is a hierarchical terminology with 5 levels and is multiaxial: terms may exist in more than 1 vertical axis, providing specificity of terms for data entry and flexibility in data retrieval. Terms in MedDRA were derived from several sources including the WHO's adverse reaction terminology (WHO-ART), Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART), International Classification of Diseases (ICD) 9 and ICD9-CM. It will be maintained, further developed and distributed by a Maintenance Support Services Organisation (MSSO). It is anticipated that using MedDRA will improve the quality of data captured on databases, support effective analysis by providing clinically relevant groupings of terms and facilitate electronic communication of data, although as a new tool, users will need to invest time in gaining expertise in its use.

  7. The joint power of sex and stress to modulate brain-gut-microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome.

    Science.gov (United States)

    Pigrau, M; Rodiño-Janeiro, B K; Casado-Bedmar, M; Lobo, B; Vicario, M; Santos, J; Alonso-Cotoner, C

    2016-04-01

    Intestinal homeostasis is a dynamic process that takes place at the interface between the lumen and the mucosa of the gastrointestinal tract, where a constant scrutiny for antigens and toxins derived from food and microorganisms is carried out by the vast gut-associated immune system. Intestinal homeostasis is preserved by the ability of the mucus layer and the mucosal barrier to keep the passage of small-sized and antigenic molecules across the epithelium highly selective. When combined and preserved, immune surveillance and barrier's selective permeability, the host capacity of preventing the development of intestinal inflammation is optimized, and viceversa. In addition, the brain-gut-microbiome axis, a multidirectional communication system that integrates distant and local regulatory networks through neural, immunological, metabolic, and hormonal signaling pathways, also regulates intestinal function. Dysfunction of the brain-gut-microbiome axis may induce the loss of gut mucosal homeostasis, leading to uncontrolled permeation of toxins and immunogenic particles, increasing the risk of appearance of intestinal inflammation, mucosal damage, and gut disorders. Irritable bowel syndrome is prevalent stress-sensitive gastrointestinal disorder that shows a female predominance. Interestingly, the role of stress, sex and gonadal hormones in the regulation of intestinal mucosal and the brain-gut-microbiome axis functioning is being increasingly recognized. We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain-gut-microbiome axis dysfunction and the implications for irritable bowel syndrome. © 2015 John Wiley & Sons Ltd.

  8. Effect of feed restriction and subsequent re-alimentation on hormones and genes of the somatotropic axis in cattle.

    Science.gov (United States)

    Keogh, Kate; Waters, Sinéad M; Kelly, Alan K; Wylie, Alastair R G; Kenny, David A

    2015-07-01

    The objective of this study was to characterize the effect of feed restriction and compensatory growth during re-alimentation on the functionality of the somatotropic axis. We blocked 60 bulls into one of two groups: 1) restricted feed allowance for 125 days (period 1) (RES, n = 30) followed by ad libitum feeding for 55 days (period 2) or 2) ad libitum access to feed throughout (ADLIB, n = 30). A growth hormone releasing hormone (GHRH) challenge was performed during each period. At the end of each period, 15 animals from each treatment were slaughtered and hepatic tissue collected. Hepatic expression of 13 genes of the somatotropic axis was measured by qRT-PCR. RES displayed a lower growth rate during period 1 (0.6 vs. 1.9 kg/day; P 0.05); however, resultant plasma IGF-1 was lower in period 1 and greater in period 2 in RES animals (P 0.05). Collectively, the results of this study are consistent with uncoupling of the somatotropic axis following feed restriction. However, there is no evidence from this study that the somatotropic axis per se is a significant contributor to compensatory growth. Copyright © 2015 the American Physiological Society.

  9. CXCR4/CXCL12/CXCR7 axis is functional in neuroendocrine tumors and signals on mTOR.

    Science.gov (United States)

    Circelli, Luisa; Sciammarella, Concetta; Guadagno, Elia; Tafuto, Salvatore; del Basso de Caro, Marialaura; Botti, Giovanni; Pezzullo, Luciano; Aria, Massimo; Ramundo, Valeria; Tatangelo, Fabiana; Losito, Nunzia Simona; Ieranò, Caterina; D'Alterio, Crescenzo; Izzo, Francesco; Ciliberto, Gennaro; Colao, Annamaria; Faggiano, Antongiulio; Scala, Stefania

    2016-04-05

    To evaluate the possible crosstalk between C-X-C chemokine receptor 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12)/C-X-C chemokine receptor 7 (CXCR7) axis with the mammalian target of rapamycin (mTOR) pathway in neuroendocrine tumors (NETs). Sixty-one human NETs were included into the study. CXCR4/CXCL12/CXCR7 axis and mTOR pathway were assessed by qRT-PCR and immunohistochemistry (IHC). The effect of mTOR inhibitor, RAD001, was evaluated on CXCR4 pathway through proliferation and p-Erk and p-AKT induction. CXCR4/CXCL12/CXCR7 axis and p-mTOR were found to be active and correlated with grading, Ki67 index and tumor stage. mTOR pathway activation significantly correlated with poor prognosis. In human NET cells, CXCL12 induced mTOR signalling while AMD3100 (CXCR4-antagonist) impaired it. The mTOR-antagonist, RAD001, impaired the CXCL12-dependent induction of CXCR4 downstream effectors. Combination of AMD3100 and RAD001 potentiate cell growth inhibition. CXCR4/CXCL12/CXCR7 axis is active in NETs and signals on mTOR. CXCR4 might be considered a prognostic factor in NETs. Combined treatment with AMD3100 and RAD001 may provide clinical benefits in NET patients with drug-resistant.

  10. Development of triple axis neutron spectrometer (Paper No. 24)

    International Nuclear Information System (INIS)

    Pal, B.C.; Wadhwa, N.R.; Goveas, S.H.

    1987-02-01

    The triple axis neutron spectrometers are the basic instruments intended for use with neutron beams from reactors. Various types of spectrometers, each devoted to different kinds of measurement can be designed and manufactured, once a prototype having all the attributes of a versatile instrument is designed and developed. With the view to achieving self reliance in this field, Central Workshops of Bhabha Atomic Research Centre (BARC), Bombay designed and developed a prototype of triple axis spectrometer meeting the specifications prepared by Nuclear Physics Division of BARC . This spectrometer, with a moving wedge system was successfully manufactured and installed at 'DHRUVA'. Another version of this spectrometer, called the 'Polarised Neutron Spectrometer' was also built and exported to South Korea and installed at Korea Advanced Energy Research Institute, Seoul. This paper deals with basic concept, development of design, engineering of mechanical assemblies, the manufacturing approach and problems encountered during manufacture. (author). 3 figs

  11. Self-assembly of orthogonal three-axis sensors

    International Nuclear Information System (INIS)

    Cho, J. H.; Hu, S.; Gracias, D. H.

    2008-01-01

    Conventional planar microfabrication is widely utilized to construct sensors for the measurement of physical or chemical properties. However, in these devices, the information component measured is typically restricted to only one vectorial axis. Here, we describe a self-assembling strategy that can be utilized to construct three dimensional (3D) cubic devices that facilitate measurement along three axes. This 3D measurement is achieved by arranging sensing elements orthogonally; any sensing element that can be lithographically patterned can be utilized. The 3D arrangement of sensors allows for the measurement of angular and orientation parameters. As an example, we describe a three-axis cantilever based sensor and demonstrate measurement of an evaporated analyte using resonant frequency shifts of cantilevers in each of the x, y, and z axes

  12. Dynamic Compensation for Two-Axis Robot Wrist Force Sensors

    Directory of Open Access Journals (Sweden)

    Junqing Ma

    2013-01-01

    Full Text Available To improve the dynamic characteristic of two-axis force sensors, a dynamic compensation method is proposed. The two-axis force sensor system is assumed to be a first-order system. The operation frequency of the system is expanded by a digital filter with backward difference network. To filter high-frequency noises, a low-pass filter is added after the dynamic compensation network. To avoid overcompensation, parameters of the proposed dynamic compensation method are defined by trial and error. Step response methods are utilized in dynamic calibration experiments. Compared to experiment data without compensation, the response time of the dynamic compensated data is reduced by 30%~40%. Experiments results demonstrate the effectiveness of our method.

  13. Efficiency of the DOMUS 750 vertical-axis wind turbine

    Science.gov (United States)

    Hallock, Kyle; Rasch, Tyler; Ju, Guoqiang; Alonso-Marroquin, Fernando

    2017-06-01

    The aim of this paper is to present some preliminary results on the efficiency of a wind turbine for an off-grid housing unit. To generate power, the unit uses a photovoltaic solar array and a vertical-axis wind turbine (VAWT). The existing VAWT was analysed to improve efficiency and increase power generation. There were found to be two main sources of inefficiency: 1. the 750W DC epicyclic generator performed poorly in low winds, and 2. the turbine blades wobbled, allowing for energy loss due to off-axis rotation. A 12V DC permanent magnet alternator was chosen that met the power requirements of the housing unit and would generate power at lower wind speeds. A support bracket was designed to prevent the turbine blades from wobbling.

  14. Design optimization and analysis of vertical axis wind turbine blade

    International Nuclear Information System (INIS)

    Jarral, A.; Ali, M.; Sahir, M.H.

    2013-01-01

    Wind energy is clean and renwable source of energy and is also the world's fastest growing energy resource. Keeping in view power shortages and growing cost of energy, the low cost wind energy has become a primary solution. It is imperative that economies and individuals begin to conserve energy and focus on the production of energy from renewable sources. Present study describes a wind turbine blade designed with enhanced aerodynamic properties. Vertical axis turbine is chosen because of its easy installment, less noisy and having environmental friendly characteristics. Vertical axis wind turbines are thought to be ideal for installations where wind conditions are not consistent. The presented turbine blade is best suitable for roadsides where the rated speed due to vehicles is most /sup -1/ often 8 ms .To get an optimal shape design symmetrical profile NACA0025 has been considered which is then analyzed for stability and aerodynamic characteristics at optimal conditions using analysis tools ANSYS and CFD tools. (author)

  15. A new vertical axis wind turbine design for urban areas

    Science.gov (United States)

    Frunzulica, Florin; Cismilianu, Alexandru; Boros, Alexandru; Dumitrache, Alexandru; Suatean, Bogdan

    2016-06-01

    In this paper we aim at developing the model of a Vertical Axis Wind Turbine (VAWT) with the short-term goal of physically realising this turbine to operate at a maximmum power of 5 kW. The turbine is designed for household users in the urban or rural areas and remote or isolated residential areas (hardly accsessible). The proposed model has a biplane configuration on each arm of the VAWT (3 × 2 = 6 blades), allowing for increased performance of the turbine at TSR between 2 and 2.5 (urban area operation) compared to the classic vertical axis turbines. Results that validate the proposed configuration as well as passive control methods to increase the performance of the classic VAWTs are presented.

  16. Tuning the DARHT Axis-II linear induction accelerator focusing

    Energy Technology Data Exchange (ETDEWEB)

    Ekdahl, Carl A. [Los Alamos National Laboratory

    2012-04-24

    Flash radiography of large hydrodynamic experiments driven by high explosives is a well-known diagnostic technique in use at many laboratories, and the Dual-Axis Radiography for Hydrodynamic Testing (DARHT) facility at Los Alamos produces flash radiographs of large hydrodynamic experiments. Two linear induction accelerators (LIAs) make the bremsstrahlung radiographic source spots for orthogonal views of each test. The 2-kA, 20-MeV Axis-I LIA creates a single 60-ns radiography pulse. The 1.7-kA, 16.5-MeV Axis-II LIA creates up to four radiography pulses by kicking them out of a longer pulse that has a 1.6-{mu}s flattop. The Axis-II injector, LIA, kicker, and downstream transport (DST) to the bremsstrahlung converter are described. Adjusting the magnetic focusing and steering elements to optimize the electron-beam transport through an LIA is often called 'tuning.' As in all high-current LIAs, the focusing field is designed to be as close to that of the ideal continuous solenoid as physically possible. In ideal continuous solenoidal transport a smoothly varying beam size can easily be found for which radial forces balance, and the beam is said to be 'matched' to the focusing field. A 'mismatched' beam exhibits unwanted oscillations in size, which are a source of free energy that contributes to emittance growth. This is undesirable, because in the absence of beam-target effects, the radiographic spot size is proportional to the emittance. Tuning the Axis-II LIA is done in two steps. First, the solenoidal focusing elements are set to values designed to provide a matched beam with little or no envelope oscillations, and little or no beam-breakup (BBU) instability growth. Then, steering elements are adjusted to minimize the motion of the centroid of a well-centered beam at the LIA exit. This article only describes the design of the tune for the focusing solenoids. The DARHT Axis-II LIA was required to be re-tuned after installing an

  17. Ground Vibration Attenuation Measurement using Triaxial and Single Axis Accelerometers

    Science.gov (United States)

    Mohammad, A. H.; Yusoff, N. A.; Madun, A.; Tajudin, S. A. A.; Zahari, M. N. H.; Chik, T. N. T.; Rahman, N. A.; Annuar, Y. M. N.

    2018-04-01

    Peak Particle Velocity is one of the important term to show the level of the vibration amplitude especially traveling wave by distance. Vibration measurement using triaxial accelerometer is needed to obtain accurate value of PPV however limited by the size and the available channel of the data acquisition module for detailed measurement. In this paper, an attempt to estimate accurate PPV has been made by using only a triaxial accelerometer together with multiple single axis accelerometer for the ground vibration measurement. A field test was conducted on soft ground using nine single axis accelerometers and a triaxial accelerometer installed at nine receiver location R1 to R9. Based from the obtained result, the method shows convincing similarity between actual PPV with the calculated PPV with error ratio 0.97. With the design method, vibration measurement equipment size can be reduced with fewer channel required.

  18. Vertical-axis turbine/propeller for ship propulsion

    Energy Technology Data Exchange (ETDEWEB)

    Barkla, H.M.

    1984-01-01

    There are so many variables in the design and operating conditions of a vertical-axis turbine/propeller for the propulsion of a ship by wind that a preliminary study is offered, based on two simplified models. Study of a linear motion of blades in air and water shows optimum conditions for blade-speed and blade-incidence. Analysis of the second, cyclical model is simplified by the assumption of constant angles of incidence. While the logical superiority of the vertical-axis system, with its low transmission loss, may not alone give it the advantage over all other systems in upwind and downwind sailing, there are indications that in the beam wind it is in a class of its own; the Voith-Schneider-Type propeller then produces a thrust with a major component to windward, so that the combined unit leaves little or no athwartships force.

  19. APS-U LATTICE DESIGN FOR OFF-AXIS ACCUMULATION

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yipeng; Borland, M.; Lindberg, R.; Sajaev, V.

    2017-06-25

    A 67-pm hybrid-seven-bend achromat (H7BA) lattice is being proposed for a future Advanced Photon Source (APS) multi-bend-achromat (MBA) upgrade project. This lattice design pushes for smaller emittance and requires use of a swap-out (on-axis) injection scheme due to limited dynamic acceptance. Alternate lattice design work has also been performed for the APS upgrade to achieve better beam dynamics performance than the nominal APS MBA lattice, in order to allow off-axis accumulation. Two such alternate H7BA lattice designs, which target a still-low emittance of 90 pm, are discussed in detail in this paper. Although the single-particle-dynamics performance is good, simulations of collective effects indicate that surprising difficulty would be expected accumulating high single-bunch charge in this lattice. The brightness of the 90-pm lattice is also a factor of two lower than the 67-pm H7BA lattice.

  20. Axis-switching of a micro-jet

    Science.gov (United States)

    Cabaleiro, Juan Martin; Aider, Jean-Luc

    2014-03-01

    In this study, it is shown that free microjets can undergo complex transitions similar to large-scale free jets despite relatively low Reynolds numbers. Using an original experimental method allowing for the 3D reconstruction of the instantaneous spatial organization of the microjet, the axis-switching of a micro-jet is observed for the first time. This is the first experimental evidence of such complex phenomena for free micro-jets. Combining these experimental results with Direct Numerical Simulations it is shown that the mechanism responsible for the axis-switching is the deformation of a micro-vortex ring due to induction by the corner vortices, as it occurs in large scale non-circular jets.

  1. Averaging scheme for atomic resolution off-axis electron holograms.

    Science.gov (United States)

    Niermann, T; Lehmann, M

    2014-08-01

    All micrographs are limited by shot-noise, which is intrinsic to the detection process of electrons. For beam insensitive specimen this limitation can in principle easily be circumvented by prolonged exposure times. However, in the high-resolution regime several instrumental instabilities limit the applicable exposure time. Particularly in the case of off-axis holography the holograms are highly sensitive to the position and voltage of the electron-optical biprism. We present a novel reconstruction algorithm to average series of off-axis holograms while compensating for specimen drift, biprism drift, drift of biprism voltage, and drift of defocus, which all might cause problematic changes from exposure to exposure. We show an application of the algorithm utilizing also the possibilities of double biprism holography, which results in a high quality exit-wave reconstruction with 75 pm resolution at a very high signal-to-noise ratio. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Development of a Single-Axis Edge Detection System

    Energy Technology Data Exchange (ETDEWEB)

    Hanshaw, R.A.

    2000-02-18

    A SIP (Societe Genevoise d'Instruments de Physique) Trioptic coordinate measuring machine was modified for calibration of high quality single-axis glass standards to an uncertainty of {+-}0.000020 inch. The modification was accomplished through the addition of a frame grabber board, vision software, a high-resolution camera, stepper motors, a two-axis motor controller, and an HP-IB interface card. An existing temperature system (hygrometer, barometer, laser interferometer system, and optics) was retained as part of the system. An existing Hewlett Packard computer was replaced with a personal computer to accommodate the frame grabber board. Each component was integrated into the existing system using Visual Basic. The system was automated for unattended measurements by creating a machine programming language, which is recognized within the main program.

  3. Development of the adrenal axis in the neonatal rat

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, Ronnie [Univ. of Rochester, NY (United States)

    1977-01-01

    Plasma corticosterone and ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, under a variety of experimental conditions, to obtain more information on the postnatal development of the rat hypothalamo-adrenal (HHA) axis. The results indicate that: (1) there is a diminution followed by an increase in responsiveness of the adrenal gland, but the pituitary response to direct hormonal stimulation is unchanged during the first three postnatal weeks; (2) continued stimulation of the adrenal by ACTH or of the central nervous system (CNS) or hypothalamus by corticosterone is necessary during early postnatal development to allow normal maturation of the HHA axis; and (3) feedback inhibition is operative by birth, at least to a moderate degree. Taken together, the studies suggest that both the adrenal and pituitary glands are potentially functional at birth, but that the hypothalamic and CNS mediators of the stress response are not mature until at least the second or third postnatal week. (ERB)

  4. Application of one-axis sun tracking system

    Energy Technology Data Exchange (ETDEWEB)

    Sefa, Ibrahim; Demirtas, Mehmet; Colak, Ilhami [Gazi University, Faculty of Technical Education, Department of Electrical Education, GEMEC-Gazi Electric Machines and Control Group, Ankara (Turkey)

    2009-11-15

    This paper introduces design and application of a novel one-axis sun tracking system which follows the position of the sun and allows investigating effects of one-axis tracking system on the solar energy in Turkey. The tracking system includes a serial communication interface based on RS 485 to monitor whole processes on a computer screen and to plot data as graphic. In addition, system parameters such as the current, the voltage and the panel position have been observed by means of a microcontroller. The energy collected is measured and compared with a fixed solar system for the same solar panel. The results show that the solar energy collected on the tracking system is considerably much efficient than the fixed system. The tracking system developed in this study provides easy installation, simple mechanism and less maintenance. (author)

  5. Summary of tower designs for large horizontal axis wind turbines

    Science.gov (United States)

    Frederick, G. R.; Savino, J. M.

    1986-01-01

    Towers for large horizontal axis wind turbines, machines with a rotor axis height above 30 meters and rated at more than 500 kW, have varied in configuration, materials of construction, type of construction, height, and stiffness. For example, the U.S. large HAWTs have utilized steel truss type towers and free-standing steel cylindrical towers. In Europe, the trend has been to use only free-standing and guyed cylindrical towers, but both steel and reinforced concrete have been used as materials of construction. These variations in materials of construction and type of construction reflect different engineering approaches to the design of cost effective towers for large HAWTs. Tower designs are the NASA/DOE Mod-5B presently being fabricated. Design goals and requirements that influence tower configuration, height and materials are discussed. In particular, experiences with United States large wind turbine towers are elucidated. Finally, current trends in tower designs for large HAWTs are highlighted.

  6. Application of one-axis sun tracking system

    International Nuclear Information System (INIS)

    Sefa, Ibrahim; Demirtas, Mehmet; Colak, Ilhami

    2009-01-01

    This paper introduces design and application of a novel one-axis sun tracking system which follows the position of the sun and allows investigating effects of one-axis tracking system on the solar energy in Turkey. The tracking system includes a serial communication interface based on RS 485 to monitor whole processes on a computer screen and to plot data as graphic. In addition, system parameters such as the current, the voltage and the panel position have been observed by means of a microcontroller. The energy collected is measured and compared with a fixed solar system for the same solar panel. The results show that the solar energy collected on the tracking system is considerably much efficient than the fixed system. The tracking system developed in this study provides easy installation, simple mechanism and less maintenance.

  7. Regulatory Expectations for Safety Culture

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-05-15

    The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

  8. Radioactive waste below regulatory concern

    International Nuclear Information System (INIS)

    Neuder, S.M.

    1987-01-01

    The U.S. Nuclear Regulatory Commission (NRC) published two notices in the Federal Register concerning radioactive waste below regulatory concern. The first, a Commission Policy Statement and Implementation Plan published August 29, 1986, concerns petition to exempt specific radioactive waste streams from the regulations. The second, an Advanced Notice of Proposed Rulemaking published Decemger 2, 1986, addresses the concept of generic rulemaking by the NRC on radioactive wastes that are below regulatory concern. Radioactive waste determined to be below regulatory concern would not be subject to regulatory control and would not need to go to a licensed low-level radioactive waste disposal site. The Policy Statement and Implementation Plan describe (1) the information a petitioner should file in support of a petition to exempt a specific waste stream, (2) the decision criteria the Commission intends to use for judging the petition, and (3) the internal administrative procedures to use be followed in order to permit the Commission to act upon the petition in an expedited manner

  9. The Regulatory Independence of FANR

    International Nuclear Information System (INIS)

    ALNuaimi, Fatema; Choi, Kwang Shik

    2012-01-01

    Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

  10. Regulatory Expectations for Safety Culture

    International Nuclear Information System (INIS)

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung

    2014-01-01

    The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety

  11. The Regulatory Independence of FANR

    Energy Technology Data Exchange (ETDEWEB)

    ALNuaimi, Fatema; Choi, Kwang Shik [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2012-05-15

    Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

  12. Device for passive flow control around vertical axis marine turbine

    Science.gov (United States)

    Coşoiu, C. I.; Georgescu, A. M.; Degeratu, M.; Haşegan, L.; Hlevca, D.

    2012-11-01

    The power supplied by a turbine with the rotor placed in a free stream flow may be increased by augmenting the velocity in the rotor area. The energy of the free flow is dispersed and it may be concentrated by placing a profiled structure around the bare turbine in order to concentrate more energy in the rotor zone. At the Aerodynamic and Wind Engineering Laboratory (LAIV) of the Technical University of Civil Engineering of Bucharest (UTCB) it was developed a concentrating housing to be used for hydro or aeolian horizontal axis wind turbines, in order to increase the available energy in the active section of turbine rotor. The shape of the concentrating housing results by superposing several aero/hydro dynamic effects, the most important being the one generated by the passive flow control devices that were included in the housing structure. Those concentrating housings may be also adapted for hydro or aeolian turbines with vertical axis. The present paper details the numerical research effectuated at the LAIV to determine the performances of a vertical axis marine turbine equipped with such a concentrating device, in order to increase the energy quantity extracted from the main flow. The turbine is a Darrieus type one with three vertical straight blades, symmetric with respect to the axis of rotation, generated using a NACA4518 airfoil. The global performances of the turbine equipped with the concentrating housing were compared to the same characteristics of the bare turbine. In order to validate the numerical approach used in this paper, test cases from the literature resulting from experimental and numerical simulations for similar situations, were used.

  13. Device for passive flow control around vertical axis marine turbine

    International Nuclear Information System (INIS)

    Coşoiu, C I; Georgescu, A M; Degeratu, M; Haşegan, L; Hlevca, D

    2012-01-01

    The power supplied by a turbine with the rotor placed in a free stream flow may be increased by augmenting the velocity in the rotor area. The energy of the free flow is dispersed and it may be concentrated by placing a profiled structure around the bare turbine in order to concentrate more energy in the rotor zone. At the Aerodynamic and Wind Engineering Laboratory (LAIV) of the Technical University of Civil Engineering of Bucharest (UTCB) it was developed a concentrating housing to be used for hydro or aeolian horizontal axis wind turbines, in order to increase the available energy in the active section of turbine rotor. The shape of the concentrating housing results by superposing several aero/hydro dynamic effects, the most important being the one generated by the passive flow control devices that were included in the housing structure. Those concentrating housings may be also adapted for hydro or aeolian turbines with vertical axis. The present paper details the numerical research effectuated at the LAIV to determine the performances of a vertical axis marine turbine equipped with such a concentrating device, in order to increase the energy quantity extracted from the main flow. The turbine is a Darrieus type one with three vertical straight blades, symmetric with respect to the axis of rotation, generated using a NACA4518 airfoil. The global performances of the turbine equipped with the concentrating housing were compared to the same characteristics of the bare turbine. In order to validate the numerical approach used in this paper, test cases from the literature resulting from experimental and numerical simulations for similar situations, were used.

  14. Small-Scale vertical axis wind turbine design

    OpenAIRE

    Castillo Tudela, Javier

    2011-01-01

    The thesis focuses on the design of a small vertical axis wind turbine rotor with solid wood as a construction material. The aerodynamic analysis is performed implementing a momentum based model on a mathematical computer program. A three bladed wind turbine is proposed as candidate for further prototype testing after evaluating the effect of several parameters in turbine efficiency, torque and acceleration. The results obtained indicate that wood is a suitable material for rotor cons...

  15. Classification of threespine stickleback along the benthic-limnetic axis

    OpenAIRE

    Willacker, James J.; von Hippel, Frank A.; Wilton, Peter R.; Walton, Kelly M.

    2010-01-01

    Many species of fish display morphological divergence between individuals feeding on macroinvertebrates associated with littoral habitats (benthic morphotypes) and individuals feeding on zooplankton in the limnetic zone (limnetic morphotypes). Threespine stickleback (Gasterosteus aculeatus L.) have diverged along the benthic-limnetic axis into allopatric morphotypes in thousands of populations and into sympatric species pairs in several lakes. However, only a few well known populations have b...

  16. Roll-Axis Hydrofluidic Stability Augmentation System Development

    Science.gov (United States)

    1975-09-01

    lifi .1035 SW 30 left for znro time delay - r Ight for other. 17 Preceding page Hank Recordings of the simulated aircraft performance to...DESIGN The analytical effort defined the gains and shaping networks required for the roll-axis damper system for the OH-58A helicopter, and the...Shaping Networks Usually a combination of resistors and capacitors (bellows) is designed to provide the following functions: a) b) 3.1.4 1 Lag

  17. Three-axis orthogonal transceiver coil for eddy current sounding

    Science.gov (United States)

    Sukhanov, D.; Zavyalova, K.; Goncharik, M.

    2017-08-01

    We propose the new structure of three-axis transceiver magnetic-induction coil for eddy current probing. Due to the orientation of the coils, the direct signal from the transmitting coil to the receiving coil is minimized, which provided a high dynamic range. Sensitivity in all directions is provided by combining coils of different orientations. Numerical simulation and experimental studies of such a system have been carried out and confirmed the applicability of the proposed method and the mathematical model.

  18. Inelastic scattering using the three-axis spectrometer technique

    International Nuclear Information System (INIS)

    Currat, R.

    1999-01-01

    The three-axis technique is a basic neutron scattering technique for inelastic work on single-crystal specimens. There is, at the moment, a fair degree of complementarity between TAS instruments on steady-state sources and TOF instruments on steady-state or pulsed sources. The technique is described, the issue of TAS versus TOF method is discussed, and investigations relating to the resolution functions are presented. (K.A.)

  19. Estimation of power in low velocity vertical axis wind turbine

    Science.gov (United States)

    Sampath, S. S.; Shetty, Sawan; Chithirai Pon Selvan, M.

    2015-06-01

    The present work involves in the construction of a vertical axis wind turbine and the determination of power. Various different types of turbine blades are considered and the optimum blade is selected. Mechanical components of the entire setup are built to obtain maximum rotation per minute. The mechanical energy is converted into the electrical energy by coupling coaxially between the shaft and the generator. This setup produces sufficient power for consumption of household purposes which is economic and easily available.

  20. MARRT: Medial Axis biased rapidly-exploring random trees

    KAUST Repository

    Denny, Jory

    2014-05-01

    © 2014 IEEE. Motion planning is a difficult and widely studied problem in robotics. Current research aims not only to find feasible paths, but to ensure paths have certain properties, e.g., shortest or safest paths. This is difficult for current state-of-the-art sampling-based techniques as they typically focus on simply finding any path. Despite this difficulty, sampling-based techniques have shown great success in planning for a wide range of applications. Among such planners, Rapidly-Exploring Random Trees (RRTs) search the planning space by biasing exploration toward unexplored regions. This paper introduces a novel RRT variant, Medial Axis RRT (MARRT), which biases tree exploration to the medial axis of free space by pushing all configurations from expansion steps towards the medial axis. We prove that this biasing increases the tree\\'s clearance from obstacles. Improving obstacle clearance is useful where path safety is important, e.g., path planning for robots performing tasks in close proximity to the elderly. Finally, we experimentally analyze MARRT, emphasizing its ability to effectively map difficult passages while increasing obstacle clearance, and compare it to contemporary RRT techniques.

  1. A New, Adaptable, Optical High-Resolution 3-Axis Sensor

    Directory of Open Access Journals (Sweden)

    Niels Buchhold

    2017-01-01

    Full Text Available This article presents a new optical, multi-functional, high-resolution 3-axis sensor which serves to navigate and can, for example, replace standard joysticks in medical devices such as electric wheelchairs, surgical robots or medical diagnosis devices. A light source, e.g., a laser diode, is affixed to a movable axis and projects a random geometric shape on an image sensor (CMOS or CCD. The downstream microcontroller’s software identifies the geometric shape’s center, distortion and size, and then calculates x, y, and z coordinates, which can be processed in attached devices. Depending on the image sensor in use (e.g., 6.41 megapixels, the 3-axis sensor features a resolution of 1544 digits from right to left and 1038 digits up and down. Through interpolation, these values rise by a factor of 100. A unique feature is the exact reproducibility (deflection to coordinates and its precise ability to return to its neutral position. Moreover, optical signal processing provides a high level of protection against electromagnetic and radio frequency interference. The sensor is adaptive and adjustable to fit a user’s range of motion (stroke and force. This recommendation aims to optimize sensor systems such as joysticks in medical devices in terms of safety, ease of use, and adaptability.

  2. Blade pitch optimization methods for vertical-axis wind turbines

    Science.gov (United States)

    Kozak, Peter

    Vertical-axis wind turbines (VAWTs) offer an inherently simpler design than horizontal-axis machines, while their lower blade speed mitigates safety and noise concerns, potentially allowing for installation closer to populated and ecologically sensitive areas. While VAWTs do offer significant operational advantages, development has been hampered by the difficulty of modeling the aerodynamics involved, further complicated by their rotating geometry. This thesis presents results from a simulation of a baseline VAWT computed using Star-CCM+, a commercial finite-volume (FVM) code. VAWT aerodynamics are shown to be dominated at low tip-speed ratios by dynamic stall phenomena and at high tip-speed ratios by wake-blade interactions. Several optimization techniques have been developed for the adjustment of blade pitch based on finite-volume simulations and streamtube models. The effectiveness of the optimization procedure is evaluated and the basic architecture for a feedback control system is proposed. Implementation of variable blade pitch is shown to increase a baseline turbine's power output between 40%-100%, depending on the optimization technique, improving the turbine's competitiveness when compared with a commercially-available horizontal-axis turbine.

  3. A procedure for denoising dual-axis swallowing accelerometry signals

    International Nuclear Information System (INIS)

    Sejdić, Ervin; Chau, Tom; Steele, Catriona M

    2010-01-01

    Dual-axis swallowing accelerometry is an emerging tool for the assessment of dysphagia (swallowing difficulties). These signals however can be very noisy as a result of physiological and motion artifacts. In this note, we propose a novel scheme for denoising those signals, i.e. a computationally efficient search for the optimal denoising threshold within a reduced wavelet subspace. To determine a viable subspace, the algorithm relies on the minimum value of the estimated upper bound for the reconstruction error. A numerical analysis of the proposed scheme using synthetic test signals demonstrated that the proposed scheme is computationally more efficient than minimum noiseless description length (MNDL)-based denoising. It also yields smaller reconstruction errors than MNDL, SURE and Donoho denoising methods. When applied to dual-axis swallowing accelerometry signals, the proposed scheme exhibits improved performance for dry, wet and wet chin tuck swallows. These results are important for the further development of medical devices based on dual-axis swallowing accelerometry signals. (note)

  4. l=1 helical axis heliotron device in Kyoto university

    International Nuclear Information System (INIS)

    Nagasaki, K.; Sano, F.; Mizuuchi, T.; Hanatani, K.; Okada, H.; Obiki, T.

    1999-01-01

    Helical systems are an attractive candidate for magnetic fusion reactor. Recently, there has been great progress in theoretical research of three dimensional magnetic field structures, resulting in several kinds of confinement optimization being proposed for toroidal magnetic confinement system. For example, some sophisticated ideas have appeared on stage such as quasi-helical symmetry and quasi-isodynamic system. To find experimentally which way is the best Optimisation, a new helical axis heliotron device, so called 'Heliotron J', is under construction in the Institute of Advanced Energy, Kyoto University, Japan. In this conference, the basic concept and the present status will be presented. In the conventional plane axis helical system, it was difficult to have both good particle confinement and good MHD stability simultaneously. The goal of Heliotron J project is to clarify their compatibility in the spatial axis toroidal device. The best way for Optimising the helical magnetic field configuration will be explored by investigating the plasma response to the change in the field components. The main subjects for plasma experiment are: demonstration of the existence of good magnetic flux surfaces, reduction of neoclassical transport in collisionless regime, MHD Stabilisation in high β plasma, controllability of bootstrap current, good confinement of high energy particles

  5. Three-Axis Attitude Estimation Using Rate-Integrating Gyroscopes

    Science.gov (United States)

    Crassidis, John L.; Markley, F. Landis

    2016-01-01

    Traditionally, attitude estimation has been performed using a combination of external attitude sensors and internal three-axis gyroscopes. There are many studies of three-axis attitude estimation using gyros that read angular rates. Rate-integrating gyros measure integrated rates or angular displacements, but three-axis attitude estimation using these types of gyros has not been as fully investigated. This paper derives a Kalman filtering framework for attitude estimation using attitude sensors coupled with rate- integrating gyroscopes. In order to account for correlations introduced by using these gyros, the state vector must be augmented, compared with filters using traditional gyros that read angular rates. Two filters are derived in this paper. The first uses an augmented state-vector form that estimates attitude, gyro biases, and gyro angular displacements. The second ignores correlations, leading to a filter that estimates attitude and gyro biases only. Simulation comparisons are shown for both filters. The work presented in this paper focuses only on attitude estimation using rate-integrating gyros, but it can easily be extended to other applications such as inertial navigation, which estimates attitude and position.

  6. Regulatory authority information system RAIS

    International Nuclear Information System (INIS)

    Ortiz, P.; Mrabit, K.; Miaw, S.

    2000-01-01

    In this lecture the principles of the regulatory authority information system (RAIS) are presented. RAIS is a tool currently being developed by the IAEA for the Regulatory Authorities. It is a part of a set of supporting actions designed to assist member states in achieving the objectives of the Model project on radiation and waste safety infrastructure. RAIS is a tool that provides the management of the Regulatory Authority with the key information needed for the planning and implementation of activities and to ensure confidence that resources are optimally used. The RAIS contains five modules: Inventory of installations and radiation sources; Authorization process; Inspection and follow-up actions; Information on personal dosimetry; Assessment of effectiveness by means of performance indicators

  7. Transparency of nuclear regulatory activities

    International Nuclear Information System (INIS)

    2007-01-01

    One of the main missions of nuclear regulators is to protect the public, and this cannot be completely achieved without public confidence. The more a regulatory process is transparent, the more such confidence will grow. Despite important cultural differences across countries, a number of common features characterise media and public expectations regarding any activity with an associated risk. A common understanding of transparency and main stakeholders' expectations in the field of nuclear safety were identified during this workshop, together with a number of conditions and practices aimed at improving the transparency of nuclear regulatory activities. These conditions and practices are described herein, and will be of particular interest to all those working in the nuclear regulatory field. Their implementation may, however, differ from one country to another depending on national context. (authors)

  8. Measurements of isocenter path characteristics of the gantry rotation axis with a smartphone application

    International Nuclear Information System (INIS)

    Schiefer, H.; Peters, S.; Plasswilm, L.; Ingulfsen, N.; Kluckert, J.

    2015-01-01

    Purpose: For stereotactic radiosurgery, the AAPM Report No. 54 [AAPM Task Group 42 (AAPM, 1995)] requires the overall stability of the isocenter (couch, gantry, and collimator) to be within a 1 mm radius. In reality, a rotating system has no rigid axis and thus no isocenter point which is fixed in space. As a consequence, the isocenter concept is reviewed here. It is the aim to develop a measurement method following the revised definitions. Methods: The mechanical isocenter is defined here by the point which rotates on the shortest path in the room coordinate system. The path is labeled as “isocenter path.” Its center of gravity is assumed to be the mechanical isocenter. Following this definition, an image-based and radiation-free measurement method was developed. Multiple marker pairs in a plane perpendicular to the assumed gantry rotation axis of a linear accelerator are imaged with a smartphone application from several rotation angles. Each marker pair represents an independent measuring system. The room coordinates of the isocenter path and the mechanical isocenter are calculated based on the marker coordinates. The presented measurement method is by this means strictly focused on the mechanical isocenter. Results: The measurement result is available virtually immediately following completion of measurement. When 12 independent measurement systems are evaluated, the standard deviations of the isocenter path points and mechanical isocenter coordinates are 0.02 and 0.002 mm, respectively. Conclusions: The measurement is highly accurate, time efficient, and simple to adapt. It is therefore suitable for regular checks of the mechanical isocenter characteristics of the gantry and collimator rotation axis. When the isocenter path is reproducible and its extent is in the range of the needed geometrical accuracy, it should be taken into account in the planning process. This is especially true for stereotactic treatments and radiosurgery

  9. Measurements of isocenter path characteristics of the gantry rotation axis with a smartphone application

    Energy Technology Data Exchange (ETDEWEB)

    Schiefer, H., E-mail: johann.schiefer@kssg.ch; Peters, S.; Plasswilm, L. [Klinik für Radio-Onkologie, Kantonsspital St.Gallen, Rorschacherstrasse 107, St.Gallen CH-9007 (Switzerland); Ingulfsen, N.; Kluckert, J. [Kantonsschule am Burggraben St.Gallen, Burggraben 21, St.Gallen CH-9000 (Switzerland)

    2015-03-15

    Purpose: For stereotactic radiosurgery, the AAPM Report No. 54 [AAPM Task Group 42 (AAPM, 1995)] requires the overall stability of the isocenter (couch, gantry, and collimator) to be within a 1 mm radius. In reality, a rotating system has no rigid axis and thus no isocenter point which is fixed in space. As a consequence, the isocenter concept is reviewed here. It is the aim to develop a measurement method following the revised definitions. Methods: The mechanical isocenter is defined here by the point which rotates on the shortest path in the room coordinate system. The path is labeled as “isocenter path.” Its center of gravity is assumed to be the mechanical isocenter. Following this definition, an image-based and radiation-free measurement method was developed. Multiple marker pairs in a plane perpendicular to the assumed gantry rotation axis of a linear accelerator are imaged with a smartphone application from several rotation angles. Each marker pair represents an independent measuring system. The room coordinates of the isocenter path and the mechanical isocenter are calculated based on the marker coordinates. The presented measurement method is by this means strictly focused on the mechanical isocenter. Results: The measurement result is available virtually immediately following completion of measurement. When 12 independent measurement systems are evaluated, the standard deviations of the isocenter path points and mechanical isocenter coordinates are 0.02 and 0.002 mm, respectively. Conclusions: The measurement is highly accurate, time efficient, and simple to adapt. It is therefore suitable for regular checks of the mechanical isocenter characteristics of the gantry and collimator rotation axis. When the isocenter path is reproducible and its extent is in the range of the needed geometrical accuracy, it should be taken into account in the planning process. This is especially true for stereotactic treatments and radiosurgery.

  10. Regulatory authority infrastructure for Namibia

    International Nuclear Information System (INIS)

    Shangula, K.

    2001-01-01

    The Republic of Namibia is participating in the International Atomic Energy Agency's Model Project for the Improvement of National Regulatory Authority Infrastructures in Member States. The paper illustrates our experience in solving problems and difficulties confronted in establishing an effective regulatory authority operating within the existing national infrastructure that should be supported by the Government. An effective regulatory authority is seen as part of the wider administrative scope of our Government through ministerial mandates given by the State from time to time, guaranteeing its independence when implementing legal provisions under statutes. Sections of the report illustrate our experience in the following areas: 1. National radiation protection policy 2. Structure of our national regulatory authority 3. Laws and regulations 4. Provisions for notification, authorization and registration 5. In-depth security measures for radiation sources and radioactive material 6. Systems for the inspection of radiation sources, radioactive materials, enforcement of legal provisions 7. Extent of the applications of radiation sources and radioactive materials in the country. The paper provides information regarding existing Government policy on radiation protection; structure and legal aspects of the national regulatory, including statutes and regulations; the extent of application and uses of radiation sources and security of radioactive materials; human resources: strengths and constraints; management practices and financing of regulatory authority; and plans for emergency recovery of orphan sources. National plans for management of disused sources, recovery of orphan sources, abnormal emergencies, communication of information to affected persons on exposure effects, and the safety training of persons using these applications are discussed. the paper provides a summary and some suggestions of the way forward for Namibia. (author)

  11. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section treats of the following activities sorted by country: 1 - Belarus: International cooperation, Organisation and structure, Licensing and regulatory infrastructure, Nuclear safety and radiological protection; 2 - France: Nuclear safety and radiological protection, Radioactive waste management, Environmental protection, Liability and compensation, International co-operation; 3 - Hungary: General legislation, Radioactive waste management, Nuclear security; 4 - Ireland: Nuclear safety and radiological protection (including emergency planning); 5 - Lithuania: Licensing and regulatory infrastructure; 6 - Moldova: Nuclear safety and radiological protection; 7 - Portugal: Radioactive waste management, Nuclear safety and radiological protection; 8 - Slovak Republic: Radioactive waste management, Liability and compensation; 9 - Spain: Radioactive waste management; 10 - Ukraine: Radioactive waste management; 11 - United Kingdom: Organisation and structure

  12. Glycoconjugate Vaccines: The Regulatory Framework.

    Science.gov (United States)

    Jones, Christopher

    2015-01-01

    Most vaccines, including the currently available glycoconjugate vaccines, are administered to healthy infants, to prevent future disease. The safety of a prospective vaccine is a key prerequisite for approval. Undesired side effects would not only have the potential to damage the individual infant but also lead to a loss of confidence in the respective vaccine-or vaccines in general-on a population level. Thus, regulatory requirements, particularly with regard to safety, are extremely rigorous. This chapter highlights regulatory aspects on carbohydrate-based vaccines with an emphasis on analytical approaches to ensure the consistent quality of successive manufacturing lots.

  13. Regulatory frameworks for decentralised energy

    International Nuclear Information System (INIS)

    Woodman, Bridget; Baker, Philip

    2008-01-01

    This paper considers aspects of the current regulatory frameworks for markets and infrastructure which can inhibit the deployment of decentralised energy. The government has stated that decentralised energy can make a positive contribution to reducing the UK's carbon emissions, but recognises that at the moment the technologies face market and regulatory barriers. If it is to become a viable alternative to centralised generation, energy market design and the regulation of energy infrastructure will have to evolve to ensure that decentralised options are no longer locked out. (author)

  14. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section of the Bulletin presents a summary of the recent national legislative and regulatory activities sorted by country and topic: - Algeria: Nuclear security. - France: Radioactive waste management; Nuclear safety and radiological protection; General legislation; International co-operation. - Germany: International trade. - Indonesia: Nuclear security, General legislation. - Ireland: Nuclear safety and radiological protection; General legislation. - Lithuania: Nuclear security; Nuclear safety and radiological protection. - Slovak Republic: International co-operation; Liability and compensation; Environmental protection. - Switzerland: Radioactive waste management. - United Arab Emirates: Liability and compensation. - United States: Radioactive waste management; Licensing and regulatory infrastructure

  15. Croatian energy regulatory council - independent Croatian regulatory body

    International Nuclear Information System (INIS)

    Klepo, M.

    2002-01-01

    By means of approving five energy laws, the Republic of Croatia established an appropriate legislative framework for energy sector regulation. A series of sub-law acts is presently being elaborated as well as some additional documents in order to bring about transparent and non-discriminatory provisions for the establishment of electric energy, gas, oil/oil derivatives and thermal energy markets, i.e. for the introduction and management of market activities and public services. A considerable share of these activities relates to the definition of transparent regulatory mechanisms that would guarantee the implementation of regulation rules based on the law, and be carried out by the independent regulatory body - Croatian Energy Regulatory Council. The Council's rights and obligations include firm executive functions, which present obligations to every energy entity. A dissatisfied party may set in motion a settlement of dispute, if it maintains that the decisions are not based on the law or reveal a flaw in the procedure. Therefore, it is the Council's priority to always make careful and law-abiding decisions. This paper gives insight into the regulatory framework elements based on the laws including the Council's organisational structure and non-profit entities that will prepare act proposals for the Council and perform other professional activities. (author)

  16. The Hypothalamic-Pituitary-Adrenal Axis, Obesity, and Chronic Stress Exposure: Sleep and the HPA Axis in Obesity

    OpenAIRE

    Lucassen, Eliane A.; Cizza, Giovanni

    2012-01-01

    Obesity, exposure to stress and inadequate sleep are prevalent phenomena in modern society. In this review we focus on their relationships and critically evaluate causality. In obese individuals, one of the main stress systems, the hypothalamic-pituitary-adrenal axis, is altered, and concentrations of cortisol are elevated in adipose tissue due to elevated local activity of 11β-hydroxysteroid dehydrogenase (HSD) type 1. Short sleep and decreased sleep quality are also associated with obesity....

  17. 76 FR 20759 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-04-13

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

  18. 76 FR 40412 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-07-08

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... a more limited application by their terms. For more information about the rulebook consolidation...

  19. 75 FR 60157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-09-29

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

  20. 75 FR 71164 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-11-22

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

  1. 76 FR 12380 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-03-07

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Amendment No. 1..., the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

  2. 76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-10-26

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... 31, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of... consolidation process, see Information Notice, March 12, 2008 (Rulebook Consolidation Process). For convenience...

  3. 75 FR 17456 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-04-06

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... terms. For more information about the rulebook consolidation process, see Information Notice, March 12...

  4. Regulatory Control of Radiation Sources. Safety Guide

    International Nuclear Information System (INIS)

    2009-01-01

    This Safety Guide is intended to assist States in implementing the requirements established in Safety Standards Series No. GS-R-1, Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, for a national regulatory infrastructure to regulate any practice involving radiation sources in medicine, industry, research, agriculture and education. The Safety Guide provides advice on the legislative basis for establishing regulatory bodies, including the effective independence of the regulatory body. It also provides guidance on implementing the functions and activities of regulatory bodies: the development of regulations and guides on radiation safety; implementation of a system for notification and authorization; carrying out regulatory inspections; taking necessary enforcement actions; and investigating accidents and circumstances potentially giving rise to accidents. The various aspects relating to the regulatory control of consumer products are explained, including justification, optimization of exposure, safety assessment and authorization. Guidance is also provided on the organization and staffing of regulatory bodies. Contents: 1. Introduction; 2. Legal framework for a regulatory infrastructure; 3. Principal functions and activities of the regulatory body; 4. Regulatory control of the supply of consumer products; 5. Functions of the regulatory body shared with other governmental agencies; 6. Organization and staffing of the regulatory body; 7. Documentation of the functions and activities of the regulatory body; 8. Support services; 9. Quality management for the regulatory system.

  5. Regulatory decision making by decision analyses

    International Nuclear Information System (INIS)

    Holmberg, J.; Pulkkinen, U.

    1993-11-01

    The Technical Research Centre of Finland (VTT) has studied with the Finnish Centre for Radiation and Nuclear Safety (STUK) the applicability of decision analytic approach to the treatment of nuclear safety related problems at the regulatory body. The role of probabilistic safety assessment (PSA) in decision making has also been discussed. In the study, inspectors from STUK exercised with a decision analytic approach by reoperationalizing two occurred and solved problems. The research scientist from VTT acted as systems analysts guiding the analysis process. The first case was related to a common cause failure phenomenon in solenoid valves controlling pneumatic valves important to safety of the plant. The problem of the regulatory body was to judge whether to allow continued operation or to require more detailed inspections and in which time chedule the inspections should be done. The latter problem was to evaluate design changes of external electrical grid connections after a fire incident had revealed weakness in the separation of electrical system. In both cases, the decision analysis was carried out several sessions in which decision makers, technical experts as well as experts of decision analysis participated. A multi-attribute value function was applied as a decision model so that attributes had to be defined to quantify the levels of achievements of the objectives. The attributes included both indicators related to the level of operational safety of the plant such as core damage frequency given by PSA, and indicators related to the safety culture, i.e., how well the chosen option fits on the regulatory policy. (24 refs., 6 figs., 9 tabs.)

  6. Wearing red for signaling: the heme-bach axis in heme metabolism, oxidative stress response and iron immunology.

    Science.gov (United States)

    Igarashi, Kazuhiko; Watanabe-Matsui, Miki

    2014-04-01

    The connection between gene regulation and metabolism is an old issue that warrants revisiting in order to understand both normal as well as pathogenic processes in higher eukaryotes. Metabolites affect the gene expression by either binding to transcription factors or serving as donors for post-translational modification, such as that involving acetylation and methylation. The focus of this review is heme, a prosthetic group of proteins that includes hemoglobin and cytochromes. Heme has been shown to bind to several transcription factors, including Bach1 and Bach2, in higher eukaryotes. Heme inhibits the transcriptional repressor activity of Bach1, resulting in the derepression of its target genes, such as globin in erythroid cells and heme oxygenase-1 in diverse cell types. Since Bach2 is important for class switch recombination and somatic hypermutation of immunoglobulin genes as well as regulatory and effector T cell differentiation and the macrophage function, the heme-Bach2 axis may regulate the immune response as a signaling cascade. We discuss future issues regarding the topic of the iron/heme-gene regulation network based on current understanding of the heme-Bach axis, including the concept of "iron immunology" as the synthesis of the iron metabolism and the immune response.

  7. Pre-treatment cortisol awakening response predicts symptom reduction in posttraumatic stress disorder after treatment

    NARCIS (Netherlands)

    Rapcencu, A.E.; Gorter, R.; Kennis, Mitzy; van Rooij, S.J.H.; Geuze, E.

    2017-01-01

    Dysfunction of the HPA-axis has frequently been found in the aftermath of trauma exposure with or without PTSD. Decreasing HPA-axis reactivity to different stress cues has been reported during PTSD treatment. The cortisol awakening response (CARi) is a well-validated, standardized measure of

  8. Pre-treatment cortisol awakening response predicts symptom reduction in posttraumatic stress disorder after treatment

    NARCIS (Netherlands)

    Rapcencu, A E; Gorter, R; Kennis, M; van Rooij, S J H; Geuze, E

    Dysfunction of the HPA-axis has frequently been found in the aftermath of trauma exposure with or without PTSD. Decreasing HPA-axis reactivity to different stress cues has been reported during PTSD treatment. The cortisol awakening response (CARi) is a well-validated, standardized measure of

  9. Automated Slicing for a Multi-Axis Metal Deposition System (Preprint)

    Science.gov (United States)

    2006-09-01

    experimented with different materials like H13 tool steel to build the part. Following the same slicing and scanning toolpath result, there is a geometric...and analysis tool -centroidal axis. Similar to medial axis, it contains geometry and topological information but is significantly computationally...geometry reasoning and analysis tool -centroidal axis. Similar to medial axis, it contains geometry and topological information but is significantly

  10. Differences in IGF-axis protein expression and survival among multiethnic breast cancer patients

    International Nuclear Information System (INIS)

    Hernandez, Brenda Y; Wilkens, Lynne R; Le Marchand, Loïc; Horio, David; Chong, Clayton D; Loo, Lenora W M

    2015-01-01

    There is limited knowledge about the biological basis of racial/ethnic disparities in breast cancer outcomes. Aberrations in IGF signaling induced by obesity and other factors may contribute to these disparities. This study examines the expression profiles of the insulin-like growth factor (IGF)-axis proteins and the association with breast cancer survival across a multiethnic population. We examined the expression profiles of the IGF1, IGF1R, IGFBP2 (IGF-binding proteins), and IGFBP3 proteins in breast tumor tissue and their relationships with all-cause and breast cancer-specific survival up to 17 years postdiagnosis in a multiethnic series of 358 patients in Hawaii, USA. Native Hawaiians, Caucasians, and Japanese were compared. Covariates included demographic and clinical factors and ER/PR/HER2 (estrogen receptor/progesterone receptor/human epidermal growth factor receptor-2) status. In Native Hawaiian patients, IGFBP2 and IGFBP3 expression were each independently associated with overall and breast cancer mortality (IGFB2: HR mort = 10.96, 95% CI: 2.18–55.19 and HR mort = 35.75, 95% CI: 3.64–350.95, respectively; IGFBP3: HR mort = 5.16, 95% CI: 1.27–20.94 and HR mort = 8.60, 95% CI: 1.84–40.15, respectively). IGF1R expression was also positively associated with all-cause mortality in Native Hawaiians. No association of IGF-axis protein expression and survival was observed in Japanese or Caucasian patients. The interaction of race/ethnicity and IGFBP3 expression on mortality risk was significant. IGF-axis proteins may have variable influence on breast cancer progression across different racial/ethnic groups. Expression of binding proteins and receptors in breast tumors may influence survival in breast cancer patients by inducing aberrations in IGF signaling and/or through IGF-independent mechanisms. Additional studies to evaluate the role of the IGF-axis in breast cancer are critical to improve targeted breast cancer treatment strategies

  11. FAMILY HISTORY STUDY OF THE FAMILIAL COAGGREGATION OF BORDERLINE PERSONALITY DISORDER WITH AXIS I AND NON-BORDERLINE DRAMATIC CLUSTER AXIS II DISORDERS

    OpenAIRE

    Zanarini, Mary C.; Barison, Leah K.; Frankenburg, Frances R.; Reich, D. Bradford; Hudson, James I.

    2009-01-01

    The purpose of this study was to assess the familial coaggregation of borderline personality disorder (BPD) with a full array of axis I disorders and four axis II disorders (antisocial personality disorder, histrionic personality disorder, narcissistic personality disorder, and sadistic personality disorder) in the first-degree relatives of borderline probands and axis II comparison subjects. Four hundred and forty-five inpatients were interviewed about familial psychopathology using the Revi...

  12. Cranial electrotherapy stimulation affects mood state but not levels of peripheral neurotrophic factors or hypothalamic- pituitary-adrenal axis regulation.

    Science.gov (United States)

    Roh, Hee-Tae; So, Wi-Young

    2017-01-01

    Cranial electrotherapy stimulation (CES) is reported to aid in relieving symptoms of depression and anxiety, though the mechanism underlying this effect remains unclear. Therefore, the present study aimed to evaluate changes in the hypothalamic-pituitary-adrenal (HPA) axis response and levels of neurotrophic factors, as well as changes in mood state, in patients undergoing CES therapy. Fifty healthy postmenopausal women were randomly assigned to either a Sham CES group (n = 25) or an Active CES group (n = 25). CES treatment was conducted in 20-minute sessions, three times per week for 8 weeks, using a micro current cranial electrotherapy stimulator. Blood samples were collected prior to and following the 8-week treatment period for measurement of cortisol, adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) levels. Changes in mood state were also examined at the time of blood collection using the Profile of Mood States (POMS). No significant differences in cortisol, ACTH, BDNF, or NGF were observed between the two participant groups (p > 0.05) following the treatment period. However, those in the Active CES group exhibited significantly decreased Tension-Anxiety and Depression-Dejection scores on the POMS relative to pre-treatment scores (p 0.05). These results suggest that 8 weeks of CES treatment does not induce changes in blood levels of neurotrophic factors or HPA-axis-related hormones, though such treatment may be effective in treating symptoms of anxiety and depression.

  13. The effect of source-axis distance on integral dose: implications for IMRT

    International Nuclear Information System (INIS)

    Keall, P.

    2001-01-01

    The source-axis distance (SAD) is a treatment machine design parameter that affects integral dose, dose rate and patient clearance. The aim of this work was to investigate the effect of source-axis distance on integral dose for conformal arc therapy. This work is part of a larger project to determine the ideal characteristics of a dedicated IMRT machine. The sensitivity of SAD to beam energy, PTV size, body size and PTV position were determined for conformal arc therapy. For the calculations performed here it was assumed that dose equals terma. The integral dose ratio (IDR) was used to quantify the calculation results. It was found that the IDR increases as both SAD and photon energy increase, though the dependence of IDR on SAD decreases as energy increases. The PTV size was found to have a negligible effect on the relationship between the SAD and IDR, however the body size does affect the relationship between the SAD and IDR. The position of the PTV within the body also affects the IDR. From dosimetric considerations alone, the larger the SAD, the better the possible dose distribution. The IDR for a very large SAD is increased by approximately 5% when compared with the IDR for 100 cm SAD. Similarly, the IDR for 100 cm SAD is approximately 5% higher than the IDR at 50 cm SAD. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

  14. Effects of global warming on fish reproductive endocrine axis, with special emphasis in pejerrey Odontesthes bonariensis.

    Science.gov (United States)

    Miranda, Leandro Andrés; Chalde, Tomás; Elisio, Mariano; Strüssmann, Carlos Augusto

    2013-10-01

    The ongoing of global warming trend has led to an increase in temperature of several water bodies. Reproduction in fish, compared with other physiological processes, only occurs in a bounded temperature range; therefore, small changes in water temperature could significantly affect this process. This review provides evidence that fish reproduction may be directly affected by further global warming and that abnormal high water temperature impairs the expression of important genes throughout the brain-pituitary-gonad axis. In all fishes studied, gonads seem to be the organ more readily damaged by heat treatments through the inhibition of the gene expression and subsequent synthesis of different gonadal steroidogenic enzymes. In view of the feedback role of sex steroids upon the synthesis and release of GnRH and GtHs in fish, it is possible that the inhibition observed at brain and pituitary levels in treated fish is consequence of the sharp decrease in plasma steroids levels. Results of in vitro studies on the inhibition of pejerrey gonad aromatase expression by high temperature corroborate that ovary functions are directly disrupted by high temperature independently of the brain-pituitary axis. For the reproductive responses obtained in laboratory fish studies, it is plausible to predict changes in the timing and magnitude of reproductive activity or even the total failure of spawning season may occur in warm years, reducing annual reproductive output and affecting future populations. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Derivation of electron and photon energy spectra from electron beam central axis depth dose curves

    Energy Technology Data Exchange (ETDEWEB)

    Deng Jun [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305 (United States)]. E-mail: jun@reyes.stanford.edu; Jiang, Steve B.; Pawlicki, Todd; Li Jinsheng; Ma, C.M. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305 (United States)

    2001-05-01

    A method for deriving the electron and photon energy spectra from electron beam central axis percentage depth dose (PDD) curves has been investigated. The PDD curves of 6, 12 and 20 MeV electron beams obtained from the Monte Carlo full phase space simulations of the Varian linear accelerator treatment head have been used to test the method. We have employed a 'random creep' algorithm to determine the energy spectra of electrons and photons in a clinical electron beam. The fitted electron and photon energy spectra have been compared with the corresponding spectra obtained from the Monte Carlo full phase space simulations. Our fitted energy spectra are in good agreement with the Monte Carlo simulated spectra in terms of peak location, peak width, amplitude and smoothness of the spectrum. In addition, the derived depth dose curves of head-generated photons agree well in both shape and amplitude with those calculated using the full phase space data. The central axis depth dose curves and dose profiles at various depths have been compared using an automated electron beam commissioning procedure. The comparison has demonstrated that our method is capable of deriving the energy spectra for the Varian accelerator electron beams investigated. We have implemented this method in the electron beam commissioning procedure for Monte Carlo electron beam dose calculations. (author)

  16. Prospective investigation of the hypothalamo-pituitary-adrenal axis in patients with tularemia.

    Science.gov (United States)

    Demiraslan, Hayati; Şimşek, Yasin; Tanriverdi, Fatih; Doğanay, Mehmet; Keleştemur, Hasan Fahrettin

    2015-01-01

    To investigate prospectively the hypothalamo-pituitary-adrenal (HPA) axis by adrenocorticotropic hormone (ACTH) stimulation test. Tularemia was diagnosed according to guidelines. An ACTH stimulation test (1 µg) and a dexamethasone suppression test (DST; 1 mg) were performed in patients in the acute phase of tularemia before antibiotic treatment and in the chronic phase. Nineteen patients (mean age: 41.0 ± 13.2 years; 57.9% female) with tularemia were enrolled in the study in 2011 and 2012. Cortisol response to ACTH stimulation test was sufficient in all patients during the acute phase. After the DST, the cortisol was not suppressed during the acute phase in only one patient. The median control time of 11 patients after acute tularemia was 13 months. During the chronic phase, cortisol response to ACTH stimulation was normal in all patients, and after DST cortisol was suppressed in all patients. The peak cortisol level after the ACTH stimulation test in the acute phase was higher than that in the chronic phase, but the difference was not statistically significant. The HPA axis of patients with tularemia was not significantly affected in the acute and chronic phases.

  17. Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry.

    Science.gov (United States)

    Sandhu, Kiran V; Sherwin, Eoin; Schellekens, Harriët; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2017-01-01

    The microbial population residing within the human gut represents one of the most densely populated microbial niche in the human body with growing evidence showing it playing a key role in the regulation of behavior and brain function. The bidirectional communication between the gut microbiota and the brain, the microbiota-gut-brain axis, occurs through various pathways including the vagus nerve, the immune system, neuroendocrine pathways, and bacteria-derived metabolites. This axis has been shown to influence neurotransmission and the behavior that are often associated with neuropsychiatric conditions. Therefore, research targeting the modulation of this gut microbiota as a novel therapy for the treatment of various neuropsychiatric conditions is gaining interest. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth, and environment. However, it is diet composition and nutritional status that has repeatedly been shown to be one of the most critical modifiable factors regulating the gut microbiota at different time points across the lifespan and under various health conditions. Thus the microbiota is poised to play a key role in nutritional interventions for maintaining brain health. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Emerging targets in cancer management: role of the CXCL12/CXCR4 axis

    Directory of Open Access Journals (Sweden)

    Cojoc M

    2013-09-01

    Full Text Available Monica Cojoc,1 Claudia Peitzsch,1 Franziska Trautmann,1 Leo Polishchuk,2 Gennady D Telegeev,2 Anna Dubrovska11OncoRay National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden, Germany; 2Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, UkraineAbstract: The chemokine CXCL12 (SDF-1 and its cell surface receptor CXCR4 were first identified as regulators of lymphocyte trafficking to the bone marrow. Soon after, the CXCL12/CXCR4 axis was proposed to regulate the trafficking of breast cancer cells to sites of metastasis. More recently, it was established that CXCR4 plays a central role in cancer cell proliferation, invasion, and dissemination in the majority of malignant diseases. The stem cell concept of cancer has revolutionized the understanding of tumorigenesis and cancer treatment. A growing body of evidence indicates that a subset of cancer cells, referred to as cancer stem cells (CSCs, plays a critical role in tumor initiation, metastatic colonization, and resistance to therapy. Although the signals generated by the metastatic niche that regulate CSCs are not yet fully understood, accumulating evidence suggests a key role of the CXCL12/CXCR4 axis. In this review we focus on physiological functions of the CXCL12/CXCR4 signaling pathway and its role in cancer and CSCs, and we discuss the potential for targeting this pathway in cancer management.Keywords: epithelial-to-mesenchymal transition, cancer stem cells, metastasis

  19. Radiation practices and regulatory control

    International Nuclear Information System (INIS)

    1997-01-01

    The general principles to be observed in the regulatory control of ionizing radiation use and practices are specified in the guide. It also takes into account of additions and alterations needed for for compliance with the European Union (EU) directives that have not been mentioned in other STUK/ST-guides. (6 refs.)

  20. Management systems for regulatory authorities

    International Nuclear Information System (INIS)

    Mpandanyama, Rujeko Lynette

    2015-02-01

    For a regulatory body to fulfil its statutory obligations, there is need to develop and implement a regulatory management system that has the necessary arrangements for achieving and maintaining high quality performance in regulating the safety of nuclear and radiation facilities under its authority. Hence, the regulatory management system needs to fully integrate the human resources, processes and physical resources of the organization. This study sought to provide an understanding of the concept, principles, policies and fundamentals of management systems as they relate to regulatory systems in the field of radiation protection and to make appropriate recommendations to ensure that an effective management system exists for the control of ionizing radiation and radiation sources and addresses all relevant stakeholders in Zimbabwe. A comparative analysis was done on the current management status and the ideal management system, which led to the identification of the gaps existing. The main key that was found to be of significance was lack of linkages between processes and management tools within the institution. (au)