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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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

  4. 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.

  5. 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

  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. 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

  8. 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

  9. 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

  10. 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.

  11. 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)

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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).

  18. 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...

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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...

  4. 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.

  5. 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.

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

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    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.

  7. 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

  8. 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....

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  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. 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....

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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)

  9. 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)

  10. 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

  11. 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.

  12. 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.

  13. 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)

  14. 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.

  15. 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

  16. 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.

  17. 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...

  18. 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.)

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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)

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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...

  17. 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

  18. 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.

  19. 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.

  20. Examining parents' ratings of middle-school students' academic self-regulation using principal axis factoring analysis.

    Science.gov (United States)

    Chen, Peggy P; Cleary, Timothy J; Lui, Angela M

    2015-09-01

    This study examined the reliability and validity of a parent rating scale, the Self-Regulation Strategy Inventory: Parent Rating Scale (SRSI-PRS), using a sample of 451 parents of sixth- and seventh-grade middle-school students. Principal axis factoring (PAF) analysis revealed a 3-factor structure for the 23-item SRSI-PRS: (a) Managing Behavior and Learning (α = .92), (b) Maladaptive Regulatory Behaviors (α = .76), and (c) Managing Environment (α = .84). The majority of the observed relations between these 3 subscales, and the SRSI-SR, student motivation beliefs, and student mathematics grades were statistically significant and in the small to medium range. After controlling for various student variables and motivation indices of parental involvement, 2 SRSI-PRS factors (Managing Behavior and Learning, Maladaptive Regulatory Behaviors) reliably predicted students' achievement in their mathematics course. This study provides initial support for the validity and reliability of the SRSI-PRS and underscores the advantages of obtaining parental ratings of students' SRL behaviors. (c) 2015 APA, all rights reserved).

  1. 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.

  2. 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.

  3. 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

  4. 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...

  5. MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma

    Science.gov (United States)

    Beckers, Anneleen; Van Peer, Gert; Carter, Daniel R.; Gartlgruber, Moritz; Herrmann, Carl; Agarwal, Saurabh; Helsmoortel, Hetty H.; Althoff, Kristina; Molenaar, Jan J.; Cheung, Belamy B.; Schulte, Johannes H.; Benoit, Yves; Shohet, Jason M.; Westermann, Frank; Marshall, Glenn M.; Vandesompele, Jo; De Preter, Katleen; Speleman, Frank

    2016-01-01

    LIN28B has been identified as an oncogene in various tumor entities, including neuroblastoma, a childhood cancer that originates from neural crest-derived cells, and is characterized by amplification of the MYCN oncogene. Recently, elevated LIN28B expression levels were shown to contribute to neuroblastoma tumorigenesis via let-7 dependent de-repression of MYCN. However, additional insight in the regulation of LIN28B in neuroblastoma is lacking. Therefore, we have performed a comprehensive analysis of the regulation of LIN28B in neuroblastoma, with a specific focus on the contribution of miRNAs. We show that MYCN regulates LIN28B expression in neuroblastoma tumors via two distinct parallel mechanisms. First, through an unbiased LIN28B-3′UTR reporter screen, we found that miR-26a-5p and miR-26b-5p regulate LIN28B expression. Next, we demonstrated that MYCN indirectly affects the expression of miR-26a-5p, and hence regulates LIN28B, therefor establishing a MYCN-miR-26a-5p-LIN28B regulatory axis. Second, we provide evidence that MYCN regulates LIN28B expression via interaction with the LIN28B promotor, establishing a direct MYCN-LIN28B regulatory axis. We believe that these findings mark LIN28B as an important effector of the MYCN oncogenic phenotype and underlines the importance of MYCN-regulated miRNAs in establishing the MYCN-driven oncogenic process. PMID:26123663

  6. 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.

  7. 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…

  8. 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.

  9. 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...

  10. 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.

  11. 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.

  12. Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

    Science.gov (United States)

    Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

    2017-07-01

    Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic

  13. 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.

  14. [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.

  15. 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.

  16. 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.

  17. 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.

  18. Modularity of gene-regulatory networks revealed in sea-star development

    Directory of Open Access Journals (Sweden)

    Degnan Bernard M

    2011-01-01

    Full Text Available Abstract Evidence that conserved developmental gene-regulatory networks can change as a unit during deutersostome evolution emerges from a study published in BMC Biology. This shows that genes consistently expressed in anterior brain patterning in hemichordates and chordates are expressed in a similar spatial pattern in another deuterostome, an asteroid echinoderm (sea star, but in a completely different developmental context (the animal-vegetal axis. This observation has implications for hypotheses on the type of development present in the deuterostome common ancestor. See research article: http://www.biomedcentral.com/1741-7007/8/143/abstract

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Effect of Relative Marker Movement on the Calculation of the Foot Torsion Axis Using a Combined Cardan Angle and Helical Axis Approach

    Science.gov (United States)

    Graf, Eveline S.; Wright, Ian C.; Stefanyshyn, Darren J.

    2012-01-01

    The two main movements occurring between the forefoot and rearfoot segment of a human foot are flexion at the metatarsophalangeal joints and torsion in the midfoot. The location of the torsion axis within the foot is currently unknown. The purpose of this study was to develop a method based on Cardan angles and the finite helical axis approach to calculate the torsion axis without the effect of flexion. As the finite helical axis method is susceptible to error due to noise with small helical rotations, a minimal amount of rotation was defined in order to accurately determine the torsion axis location. Using simulation, the location of the axis based on data containing noise was compared to the axis location of data without noise with a one-sample t-test and Fisher's combined probability score. When using only data with helical rotation of seven degrees or more, the location of the torsion axis based on the data with noise was within 0.2 mm of the reference location. Therefore, the proposed method allowed an accurate calculation of the foot torsion axis location. PMID:22666303

  4. Effect of Relative Marker Movement on the Calculation of the Foot Torsion Axis Using a Combined Cardan Angle and Helical Axis Approach

    Directory of Open Access Journals (Sweden)

    Eveline S. Graf

    2012-01-01

    Full Text Available The two main movements occurring between the forefoot and rearfoot segment of a human foot are flexion at the metatarsophalangeal joints and torsion in the midfoot. The location of the torsion axis within the foot is currently unknown. The purpose of this study was to develop a method based on Cardan angles and the finite helical axis approach to calculate the torsion axis without the effect of flexion. As the finite helical axis method is susceptible to error due to noise with small helical rotations, a minimal amount of rotation was defined in order to accurately determine the torsion axis location. Using simulation, the location of the axis based on data containing noise was compared to the axis location of data without noise with a one-sample t-test and Fisher's combined probability score. When using only data with helical rotation of seven degrees or more, the location of the torsion axis based on the data with noise was within 0.2 mm of the reference location. Therefore, the proposed method allowed an accurate calculation of the foot torsion axis location.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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....

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Broadening the cancer and cognition landscape: the role of self-regulatory challenges.

    Science.gov (United States)

    Arndt, Jamie; Das, Enny; Schagen, Sanne B; Reid-Arndt, Stephanie A; Cameron, Linda D; Ahles, Tim A

    2014-01-01

    The potentially detrimental effects of cancer and related treatments on cognitive functioning have emerged as one of the key foci of cancer survivorship research, but little is known about how psychological variables other than depression influence these relationships. To illustrate the potential of social psychological perspectives, we examine how a self-regulatory analysis and specific self-regulatory challenges of contending with cancer-related expectancies and stereotypes provide conceptual frameworks for understanding some of the potential causes and consequences of cancer-related cognitive deficits. Literatures on cancer-related cognitive deficits, self-regulatory ego depletion, expectancy stereotypes, and their points of convergence are briefly reviewed. A review and conceptual integration of relevant literatures suggest that coping with cancer can impair self-regulatory capacity. There is an overlap between cognitive deficits associated with self-regulatory challenge and with cancer and its treatment, and restoring self-regulatory resources can attenuate cancer-related cognitive deficits. Examination of specific regulatory challenges of contending with expectancies and stereotypes related to treatment suggests insights that can inform when and among whom cognitive deficits may most likely emerge. Integrating social psychological ideas with a substantial knowledge base can illustrate novel research trajectories that can deepen our understanding of cancer-related cognitive deficits and their impact on psychosocial well-being. Copyright © 2013 John Wiley & Sons, Ltd.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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)

  2. 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

  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. 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.

  5. 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...

  6. An intersectional gene regulatory strategy defines subclass diversity of C. elegans motor neurons.

    Science.gov (United States)

    Kratsios, Paschalis; Kerk, Sze Yen; Catela, Catarina; Liang, Joseph; Vidal, Berta; Bayer, Emily A; Feng, Weidong; De La Cruz, Estanisla Daniel; Croci, Laura; Consalez, G Giacomo; Mizumoto, Kota; Hobert, Oliver

    2017-07-05

    A core principle of nervous system organization is the diversification of neuron classes into subclasses that share large sets of features but differ in select traits. We describe here a molecular mechanism necessary for motor neurons to acquire subclass-specific traits in the nematode Caenorhabditis elegans . Cholinergic motor neuron classes of the ventral nerve cord can be subdivided into subclasses along the anterior-posterior (A-P) axis based on synaptic connectivity patterns and molecular features. The conserved COE-type terminal selector UNC-3 not only controls the expression of traits shared by all members of a neuron class, but is also required for subclass-specific traits expressed along the A-P axis. UNC-3, which is not regionally restricted, requires region-specific cofactors in the form of Hox proteins to co-activate subclass-specific effector genes in post-mitotic motor neurons. This intersectional gene regulatory principle for neuronal subclass diversification may be conserved from nematodes to mice.

  7. 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.

  8. 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.

  9. 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)

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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...

  2. 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...

  3. 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

  4. 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.

  5. Improvement of off-axis SABR plan verification results by using adapted dose reconstruction algorithms for the Octavius 4D system.

    Science.gov (United States)

    Jeevanandam, Prakash; Agnew, Christina E; Irvine, Denise M; McGarry, Conor K

    2018-04-01

    Stereotactic ablative body radiotherapy (SABR) for lung patients can be performed with volumetric-modulated arc therapy (VMAT) plans using off-axis target geometry to allow treatment in their CBCT verified position. For patient-specific quality assurance measurements using the PTW Octavius 4D phantom (PTW, Freiburg, Germany) (OCT4D) in conjunction with an Octavius 1000SRS array (OCT1000) (PTW, Freiburg, Germany), repositioning the phantom off-axis is required to ensure the measurement area coincides with the tumor. The aim of this work is to quantify delivery errors using an array repositioned off-axis and evaluate new software which incorporates corrections for off-axis phantom measurements. Dynamic conformal arcs and 25 lung SABR plans were created with the isocenter at the patient midline and the target volume off-axis. Measurements were acquired with an OCT4D phantom in conjunction with a 729 array (PTW, Freiburg, Germany) (OCT729) placed at isocenter. These plans were recalculated and delivered to both the OCT729 and OCT1000 arrays repositioned so that the high-dose region was at the center of the phantom. Comparisons were made using VeriSoft v7.0 (PTW, Freiburg, Germany) and the newly implemented version 7.1 with 2%/2 mm gamma criterion (10% threshold) and results correlated with off-axis distance to the tumor. Average pass rates for VeriSoft v7.0 significantly reduced from 92.7 ± 2.4% to 84.9 ± 4.1% when the phantom was repositioned compared to the isocenter setup for the OCT729. The gamma pass rates significantly decreased the further the phantom was moved off-axis. Significantly higher pass rates were observed for the OCT1000 of 95.7 ± 3.6% and a significant decrease in gamma pass rate with off-axis phantom distance was again observed. In contrast, even with phantom repositioning, the pass rates for analysis with VeriSoft v7.1 were 93.7 ± 2.1% and 99.4 ± 1.1% for OCT729 and OCT1000, respectively. No significant difference in gamma pass rate

  6. 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.

  7. 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)

  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. 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)

  10. Regulatory T cells in chronic lymphocytic leukemia: implication for immunotherapeutic interventions.

    Science.gov (United States)

    Jadidi-Niaragh, Farhad; Ghalamfarsa, Ghasem; Yousefi, Mehdi; Tabrizi, Mina Hajifaraj; Shokri, Fazel

    2013-08-01

    Identification of regulatory T cells (Tregs) has led to breaking the dichotomy of the Th1/Th2 axis in the immunopathology of several diseases such as autoimmune diseases and cancer. Despite the presence of extensive information about immunobiology of Tregs in pathogenesis of autoimmune diseases, little is known about the frequency and function of these cells in hematologic malignancies, particularly chronic lymphocytic leukemia (CLL). Recent data have demonstrated increased frequency and intact functional capacity of CD4(+) Tregs in CLL patients. However, the precise role of these cells in the immunopathology of CLL is not well known. While targeting Tregs in cancer diseases seems to be an interesting immunotherapeutic approach, such therapeutic interventions in CLL might be deleterious due to suppression of the tumor-specific adaptive and innate immune responses. Thus, the precise biological and regulatory functions of all Tregs subsets should be carefully investigated before planning any immunotherapeutic interventions based on targeting of Tregs. In this communication, we review the recent data published on immunobiology of Tregs in CLL and discuss about the possibility of targeting Tregs in CLL.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  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. 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....

  18. 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

  19. 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.

  20. 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

  1. 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...

  2. Optical performance of inclined south-north single-axis tracked solar panels

    International Nuclear Information System (INIS)

    Li, Zhimin; Liu, Xinyue; Tang, Runsheng

    2010-01-01

    To investigate optical performance of the inclined south-north single-axis (ISN-axis, in short) tracked solar panels, a mathematical procedure to estimate the annual collectible radiation on fixed and tracked panels was suggested based on solar geometry and monthly horizontal radiation. For solar panels tracking about ISN-axis, the yearly optimal tilt-angle of ISN-axis for maximizing annual solar gain was about 3 o deviating from the site latitude in most of China except in areas with poor solar resources, and the maximum annual collectible radiation on ISN-axis tracked panels was about 97-98% of that on dual-axis tracked panels; whereas for ISN-axis tracked panels with the tilt-angle of ISN-axis being adjusted four times in a year at three fixed tilt-angles, the annual collectible radiation was almost close to that on dual-axis tracked panels, the optimum date of tilt-angle adjustment of ISN-axis was 23 days from the equinoxes, and the optimum tilt-angle adjustment value for each adjustment was about 22 o . Compared to fixed south-facing solar panels inclined at an optimal tilt-angle, the increase in the annual solar gain due to using ISN-axis sun tracking was above 30% in the areas with abundant solar resources and less than 20% in the areas with poor solar resources.

  3. Long Noncoding RNA-1604 Orchestrates Neural Differentiation through the miR-200c/ZEB Axis.

    Science.gov (United States)

    Weng, Rong; Lu, Chenqi; Liu, Xiaoqin; Li, Guoping; Lan, Yuanyuan; Qiao, Jing; Bai, Mingliang; Wang, Zhaojie; Guo, Xudong; Ye, Dan; Jiapaer, Zeyidan; Yang, Yiwei; Xia, Chenliang; Wang, Guiying; Kang, Jiuhong

    2018-03-01

    Clarifying the regulatory mechanisms of embryonic stem cell (ESC) neural differentiation is helpful not only for understanding neural development but also for obtaining high-quality neural progenitor cells required by stem cell therapy of neurodegenerative diseases. Here, we found that long noncoding RNA 1604 (lncRNA-1604) was highly expressed in cytoplasm during neural differentiation, and knockdown of lncRNA-1604 significantly repressed neural differentiation of mouse ESCs both in vitro and in vivo. Bioinformatics prediction and mechanistic analysis revealed that lncRNA-1604 functioned as a novel competing endogenous RNA of miR-200c and regulated the core transcription factors ZEB1 and ZEB2 during neural differentiation. Furthermore, we also demonstrated the critical role of miR-200c and ZEB1/2 in mouse neural differentiation. Either introduction of miR-200c sponge or overexpression of ZEB1/2 significantly reversed the lncRNA-1604 knockdown-induced repression of mouse ESC neural differentiation. Collectively, these findings not only identified a previously unknown role of lncRNA-1604 and ZEB1/2 but also elucidated a new regulatory lncRNA-1604/miR-200c/ZEB axis in neural differentiation. Stem Cells 2018;36:325-336. © 2017 AlphaMed Press.

  4. 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....

  5. 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

  6. 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.

  7. 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.

  8. 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...

  9. The vertebrate Hox gene regulatory network for hindbrain segmentation: Evolution and diversification: Coupling of a Hox gene regulatory network to hindbrain segmentation is an ancient trait originating at the base of vertebrates.

    Science.gov (United States)

    Parker, Hugo J; Bronner, Marianne E; Krumlauf, Robb

    2016-06-01

    Hindbrain development is orchestrated by a vertebrate gene regulatory network that generates segmental patterning along the anterior-posterior axis via Hox genes. Here, we review analyses of vertebrate and invertebrate chordate models that inform upon the evolutionary origin and diversification of this network. Evidence from the sea lamprey reveals that the hindbrain regulatory network generates rhombomeric compartments with segmental Hox expression and an underlying Hox code. We infer that this basal feature was present in ancestral vertebrates and, as an evolutionarily constrained developmental state, is fundamentally important for patterning of the vertebrate hindbrain across diverse lineages. Despite the common ground plan, vertebrates exhibit neuroanatomical diversity in lineage-specific patterns, with different vertebrates revealing variations of Hox expression in the hindbrain that could underlie this diversification. Invertebrate chordates lack hindbrain segmentation but exhibit some conserved aspects of this network, with retinoic acid signaling playing a role in establishing nested domains of Hox expression. © 2016 WILEY Periodicals, Inc.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  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. 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.

  20. 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.

  1. 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.

  2. 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.

  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. 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

  5. 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.

  6. 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.

  7. 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

  8. [Kennedy V Axis assessment in an Italian outpatient and inpatient population].

    Science.gov (United States)

    Mundo, Emanuela; Bonalume, Laura; Del Corno, Franco; Madeddu, Fabio; Lang, Margherita

    2010-01-01

    Kennedy Axis V or K Axis acts is an alternative tool to the DSM-IVTR Global Assessment of Functioning (GAF) Scale, that many researchers describe as a scale with poor inter-rater reliability and clinical utility. Unlike the GAF scale, K Axis provides a multidimensional and multiaxial approach to measure personal, social and interpersonal functioning in psychiatric outpatients and inpatients. In this study, we examined K Axis's inter-raters reliability by using it with an Italian clinical population. Clinicians used Kennedy Axis V to assess global functioning among 180 inpatients, in 9 psychiatric services in Lombardia and Piemonte. Patients were divided into 4 different diagnostic groups, according to the DSM-IV-TR criteria. Intraclass correlations between two independent raters's scores reveal high level of interrater reliability for all K Axis scales (0,633 < ICC < 0,813). Highly significant results in the Kruskal-Wallis test demonstrate that the patient diagnosis influence all the scales scores. Significant differences in patients functioning profiles in all K Axis scales, apart from Violence one, were noted between different diagnosis groups. In this study high level of raters agreement was noted, even if K Axis scales were used in different mental health services from different clinicians. K Axis scales provide a useful profile of patient global functioning, in line with the specific pathology.

  9. Family history study of the familial coaggregation of borderline personality disorder with axis I and nonborderline dramatic cluster axis II disorders.

    Science.gov (United States)

    Zanarini, Mary C; Barison, Leah K; Frankenburg, Frances R; Reich, D Bradford; Hudson, James I

    2009-08-01

    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 Revised Family History Questionnaire-a semistructured interview of demonstrated reliability. Of these 445 subjects, 341 met both DIB-R and DSM-III-R criteria for BPD and 104 met DSM-III-R criteria for another type of personality disorder (and neither criteria set for BPD). The psychopathology of 1,580 first-degree relatives of borderline probands and 472 relatives of axis II comparison subjects was assessed. Using structural models for familial coaggregation, it was found that BPD coaggregates with major depression, dysthymic disorder, bipolar I disorder, alcohol abuse/dependence, drug abuse/dependence, panic disorder, social phobia, obsessive-compulsive disorder, generalized anxiety disorder, posttraumatic stress disorder, somatoform pain disorder, and all four axis II disorders studied. Taken together, the results of this study suggest that common familial factors, particularly in the areas of affective disturbance and impulsivity, contribute to borderline personality disorder.

  10. Plasma levels of gastrointestinal regulatory peptides in patients receiving maintenance hemodialysis

    International Nuclear Information System (INIS)

    Hegbrant, J.; Thysell, H.; Ekmann, R.

    1991-01-01

    The fasting plasma levels of nine gastrointestinal regulatory peptides were measured by radioimmunoassay in 13 stable patients with chronic renal failure, receiving hemodialysis treatment regularly and compared with those of ten healthy controls. The plasma concentrations of gastrin-releasing peptide, motilin, neurotensin, pancreatic polypeptide, peptide YY, somatostatin, substance P, and vasoactive intestinal peptide were increased. The plasma level of gastrin was not statistically different from that of the control (p=0.077). It is concluded that patients with chronic renal failure, receiving hemodialysis treatment regularly, have increased concentrations of eight of nine measured gastrointestinal regulatory peptides. The elevated levels of gastrointestinal peptides in patients with chronic renal failure may contribute to uremic gastrointestinal symptoms and dysfunctions. It is necessary to make a renal function evaluation before interpreting measured plasma levels of gastrointestinal regulatory peptides. 62 refs., 2 tabs

  11. 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.

  12. 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...

  13. 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...

  14. European regulatory tools for advanced therapy medicinal products.

    Science.gov (United States)

    Flory, Egbert; Reinhardt, Jens

    2013-12-01

    Increasing scientific knowledge and technical innovations in the areas of cell biology, biotechnology and medicine resulted in the development of promising therapeutic approaches for the prevention and treatment of human diseases. Advanced therapy medicinal products (ATMPs) reflect a complex and innovative class of biopharmaceuticals as these products are highly research-driven, characterised by innovative manufacturing processes and heterogeneous with regard to their origin, type and complexity. This class of ATMP integrates gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineering products and are often individualized and patient-specific products. Multiple challenges arise from the nature of ATMPs, which are often developed by micro, small and medium sized enterprises, university and academia, for whom regulatory experiences are limited and regulatory requirements are challenging. Regulatory guidance such as the reflection paper on classification of ATMPs and guidelines highlighting product-specific issues support academic research groups and pharmaceutical companies to foster the development of safe and effective ATMPs. This review provides an overview on the European regulatory aspects of ATMPs and highlights specific regulatory tools such as the ATMP classification procedure, a discussion on the hospital exemption for selected ATMPs as well as borderline issues towards transplants/transfusion products.

  15. 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.

  16. Inflammation Is an Important Covariate for the Crosstalk of Sleep and the HPA Axis in Rheumatoid Arthritis.

    Science.gov (United States)

    Straub, Rainer H; Detert, Jaqueline; Dziurla, René; Fietze, Ingo; Loeschmann, Peter-Andreas; Burmester, Gerd R; Buttgereit, Frank

    2017-01-01

    Rheumatoid arthritis (RA) patients have sleep problems, and inflammation influences sleep. We demonstrated that sleep quality improves during intensified treatment with methotrexate (MTX) or etanercept (ETA). Since the hypothalamic-pituitary-adrenal (HPA) axis is involved in sleep regulation, this study investigated the interrelation between sleep parameters, inflammation as objectified by C-reactive protein (CRP), and serum cortisol and adrenocorticotropic hormone (ACTH) levels. Thirty-one eligible patients (disease activity score, DAS28CRP ≥3.2) participated in a 16-week, open, prospective study of HPA axis outcomes. MTX was initiated in 15 patients (female-to-male ratio 9/6) and ETA in 16 patients (14/2). Clinical, laboratory (after polysomnography [PSG] between 8 and 9 a.m.), sleep (PSG), and HPA axis outcome parameters (after PSG between 8 and 9 a.m.) were recorded at baseline and week 16. Clinical characteristics of patients markedly improved throughout the study (e.g., DAS28CRP: p Sleep efficiency and wake time after sleep onset markedly improved in the ETA group. Serum cortisol and ACTH did not change during observation. At baseline, serum cortisol levels were negatively correlated to sleep efficiency; this may depend on inflammation, because controlling for CRP eliminated this negative correlation. After ETA treatment, serum cortisol had a high positive correlation with total sleep time, sleep efficiency, and a negative correlation with wake time before and after sleep onset, which was not eliminated by controlling for CRP. In RA patients, the data indicate that inflammation is an important covariate for the crosstalk of sleep and the HPA axis. © 2017 S. Karger AG, Basel.

  17. Effects of the APC materials on c-axis correlated pinning effects in a-axis oriented Y123/2D APC multilayer films

    International Nuclear Information System (INIS)

    Takamura, M.; Mukaida, M.; Horii, S.; Ichinose, A.; Kita, R.; Namba, M.; Awaji, S.; Watanabe, K.; Matsumoto, K.; Yoshida, Y.; Teranishi, R.; Yamada, K.; Mori, N.

    2009-01-01

    For a-axis oriented and c-axis in-plane aligned YBa 2 Cu 3 O 7-δ /artificial pinning center (Y123/APC) alternately-layered thin films, effects of the APC materials on the multilayer structures are discussed. Pr123, (Y 1-x Pr x )123 and Gd 2 CuO 4 (Gd214) were used as APCs. The multilayer structure was observed for Y123/Pr123 films and Y123/Gd214 films. However, some grains are also grown in the Y123/Gd214 film. For the Y123/Pr123 multilayer film, each Pr123 layer act as two-dimensional APCs (2D APCs) in the magnetic field angular dependences of the critical current density. The growth mechanism of the multilayer structure in the Y123/2D APC films is discussed by a transmission electron microscopy and an atomic force microscope. It is found that two conditions are needed to obtain the c-axis correlated pinning effects by 2D APC in the a-axis oriented and c-axis in-plane aligned Y123/APC multilayer films: the same structure as Y123; Y-free APC materials.

  18. 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.

  19. 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.

  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. 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...

  2. 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.

  3. 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,

  4. 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)

  5. 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...

  6. 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...

  7. 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.

  8. Modal Parameter Identification of New Design of Vertical Axis Wind Turbine

    DEFF Research Database (Denmark)

    Chougule, Prasad; Nielsen, Søren R.K.

    2013-01-01

    Vertical axis wind turbines have lower power efficiency than the horizontal axis wind turbines. However vertical axis wind turbines are proven to be economical and noise free on smaller scale. A new design of three bladed vertical axis wind turbine by using two airfoils in construction of each...... blade has been proposed to improve power efficiency. The purpose of two airfoils in blade design of vertical axis wind turbine is to create high lift which in turns gives higher power output. In such case the structural parameter identification is important to understand the system behavior due to its...... first kind of design before experimental analysis. Therefore a study is carried out to determine the natural frequency to avoid unstable state of the system due to rotational frequency of rotor. The present paper outlines a conceptual design of vertical axis wind turbine and a modal analysis by using...

  9. 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.

  10. 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

  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. Adversity-driven changes in hypothalamic-pituitary-adrenal axis functioning during adolescence

    NARCIS (Netherlands)

    Laceulle, O.M.; Nederhof, Esther; van Aken, M.A.G.; Ormel, Johan

    2017-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during

  13. 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)

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Requirement of Osteopontin in the migration and protection against Taxol-induced apoptosis via the ATX-LPA axis in SGC7901 cells

    Directory of Open Access Journals (Sweden)

    Huang Zuhu

    2011-03-01

    Full Text Available Abstract Background Autotaxin (ATX possesses lysophospholipase D (lyso PLD activity, which converts lysophosphatidylcholine (LPC into lysophosphatidic acid (LPA. The ATX-LPA signaling axis has been implicated in angiogenesis, chronic inflammation and tumor progression. Osteopontin (OPN is an important chemokine involved in the survival, proliferation, migration, invasion and metastasis of gastric cancer cells. The focus of the present study was to investigate the relationship between the ATX-LPA axis and OPN. Results In comparison with non-treated cells, we found that the ATX-LPA axis up-regulated OPN expression by 1.92-fold in protein levels and 1.3-fold in mRNA levels. The ATX-LPA axis activates LPA2, Akt, ERK and ELK-1 and also protects SGC7901 cells from apoptosis induced by Taxol treatment. Conclusions This study provides the first evidence that expression of OPN induced by ATX-LPA axis is mediated by the activation of Akt and MAPK/ERK pathways through the LPA2 receptor. In addition, OPN is required for the protective effects of ATX-LPA against Taxol-induced apoptosis and ATX-LPA-induced migration of SGC7901 cells.

  19. Differences among doses for neuro-axis radiotherapy planning in the gonadal region

    International Nuclear Information System (INIS)

    Lima, F.F de; Vilela, E.C.; Oliveira, F.L.; Filho, J.A.

    2015-01-01

    Radiotherapy can disrupt the functioning of the hypothalamic-pituitary axis, directly causing ovarian deficiencies, such as the decrease in fertility or damage that renders the uterus incapable of accommodating the growth of a fetus. However, these issues have become increasingly important to a growing number of pediatric and adolescent cancer survivors. The whole-body, cranial-spinal axis, as well as abdomen and pelvic region irradiations may expose the ovaries to radiation and may cause premature ovarian failure, whereas doses above 35 Gy cranial can affect the hypothalamic-pituitary functions. This study performed a comparison of four doses of radiotherapy planning techniques for the neural axis. For this analysis, technical simulations were performed for the treatment of medulloblastoma in four different planning, applied in a RANDO anthropomorphic phantom and dosimeters (TLD-100). The radiation fields in the 1”st and 2”nd planning were 40 x 5 cm”2 and 17 x 5 cm”2 with 4.0 cm depth, in which doses were 0.03 and 0.05 Gy / day and 0.11 and 0.09 Gy / days, on the right and left sides, respectively. The 3”rd and 4”th measured planning 32 x 7 cm”2 and 18 x 7 cm”2, with a 2 cm gap and a 4.0 and 5.0 cm depth, in which doses were 1.08 and 0.2 Gy/day and 1.14 and 0.14 Gy/day, on the left and right sides, respectively. It could be observed that the doses in the ovaries in the 3”rd and 4”th schedules proved to be larger than the doses in the 1 s t and 2 n d planning. This is caused by the spinal field width and the depth of the second spinal field, which is 1.0 cm more than the field of the 1”st and 2”nd planning. These differences should be observed in image planning, as incorrect measures can cause damage in the treatment finish. (authors)

  20. 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.

  1. THE LIMITED EFFECT OF COINCIDENT ORIENTATION ON THE CHOICE OF INTRINSIC AXIS (.).

    Science.gov (United States)

    Li, Jing; Su, Wei

    2015-06-01

    The allocentric system computes and represents general object-to-object spatial relationships to provide a spatial frame of reference other than the egocentric system. The intrinsic frame-of-reference system theory, which suggests people learn the locations of objects based upon an intrinsic axis, is important in research about the allocentric system. The purpose of the current study was to determine whether the effect of coincident orientation on the choice of intrinsic axis was limited. Two groups of participants (24 men, 24 women; M age = 24 yr., SD = 2) encoded different spatial layouts in which the objects shared the coincident orientation of 315° and 225° separately at learning perspective (0°). The response pattern of partial-scene-recognition task following learning reflected different strategies for choosing the intrinsic axis under different conditions. Under the 315° object-orientation condition, the objects' coincident orientation was as important as the symmetric axis in the choice of the intrinsic axis. However, participants were more likely to choose the symmetric axis as the intrinsic axis under the 225° object-orientation condition. The results suggest the effect of coincident orientation on the choice of intrinsic axis is limited.

  2. 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.

  3. Nuclear reactor decommissioning: an analysis of the regulatory environments

    International Nuclear Information System (INIS)

    Cantor, R.

    1986-08-01

    In the next several decades, the electric utility industry will be faced withthe retirement of 50,000 megawatts (mW) of nuclear capacity. Responsibility for the financial and technical burdens this activity entails has been delegated to the utilities operating the reactors. However, the operators will have to perform the tasks of reactor decommissioning within the regulatory environment dictated by federal, state and local regulations. The purpose of this study was to highlight some of the current and likely trends in regulations and regulatory practices that will significantly affect the costs, technical alternatives and financing schemes encountered by the electric utilities and their customers. To identify significant trends and practices among regulatory bodies and utilities, a reviw of these factors was undertaken at various levels in the regulatory hierarchy. The technical policies were examined in reference to their treatment of allowed technical modes, restoration of the plant site including any specific recognition of the residual radioactivity levels, and planning requirements. The financial policies were examined for specification of acceptable financing arrangements, mechanisms which adjust for changes in the important parameters used to establish the fund, tax and rate-base treatments of the payments to and earnings on the fund, and whether or not escalation and/or discounting were considered in the estimates of decommissioning costs. The attitudes of regulators toward financial risk, the tax treatment of the decommissioning fund, and the time distribution of the technical mode were found to have the greatest effect on the discounted revenue requirements. Under plausible assumptions, the cost of a highly restricted environment is about seven times that of the minimum revenue requirement environment for the plants that must be decommissioned in the next three decades

  4. 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.

  5. On the generation of short-axis and radial long-axis slices in thallium-201 myocardial perfusion single-photon emission tomography

    International Nuclear Information System (INIS)

    Hastenberg, R.P.J.M. van; Eindhoven Univ. of Technology; Kemernik, G.J.; Hasman, A.

    1996-01-01

    We tried to develop fully automatic reorientation algorithms in thallium-201 myocardial perfusion single-photon emission tomography, and tested a method to evaluate the quality of reorientation. The left ventricle was automatically segmented using count density information, contours generated with Laplacian operators in both transaxial and sagittal slices, and morphological and positional characteristics of the contours. Reorientation was automatically performed based on knowledge of the long axis of a second degree surface fitted to the myocardial wall. We tried to achieve improvement in reorientation without relying on any functional description of left ventricular shape. Quality of reorientation was evaluated and improved using interactive tools in combination with radial long-axis slices. Two groups of 50 patients, after stress and rest, were analysed using the traditional manual and the fully automatic procedures. Automatic segmentation was successful in 98 out of 100 cases, and automatic reorientation was of reasonable quality. Reorientation obtained with the radial long-axis slices tool was better than after traditional manual or automatic reorientation. Automatic reorientation based on second degree surface fitting was in our hands less successful than reported in the literature. The tool using radial long-axis slices provides a better standard for testing reorientation algorithms than the traditional manual method. (orig.)

  6. 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.

  7. 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)

  8. 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.

  9. Design and implementation of five-axis transformation function in CNC system

    Directory of Open Access Journals (Sweden)

    Wang Feng

    2014-04-01

    Full Text Available To implement five-axis functions in CNC system, based on domestic system Lan Tian series, an improved design method for the system software structure is proposed in this paper. The numerical control kernel of CNC system is divided into the task layer and the motion layer. A five-axis transformation unit is integrated into the motion layer. After classifying five-axis machines into different types and analyzing their geometry information, the five-axis kinematic library is designed according to the abstract factory pattern. Furthermore, by taking CA spindle-tilting machine as an example, the forward and the inverse kinematic transformations are deduced. Based on the new software architecture and the five-axis kinematic library, algorithms of RTCP (rotation tool center point control and 3D radius compensation for end-milling are designed and realized. The milling results show that, with five-axis functions based on such software structure, the instructions with respect to the cutter’s position and orientation can be directly carried out in the CNC system.

  10. 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.

  11. Theory of coherent c-axis Josephson tunneling between layered superconductors

    International Nuclear Information System (INIS)

    Arnold, G. B.; Klemm, R. A.

    2000-01-01

    We calculate exactly the Josephson current for c-axis coherent tunneling between two layered superconductors, each with internal coherent tight-binding intra- and interlayer quasiparticle dispersions. Our results also apply when one or both of the superconductors is a bulk material, and include the usually neglected effects of surface states. For weak tunneling, our results reduce to our previous results derived using the tunneling Hamiltonian. Our results are also correct for strong tunneling. However, the c-axis tunneling expressions of Tanaka and Kashiwaya are shown to be incorrect in any limit. In addition, we consider the c-axis coherent critical current between two identical layered superconductors twisted an angle φ 0 about the c axis with respect to each other. Regardless of the order-parameter symmetry, our coherent tunneling results using a tight-binding intralayer quasiparticle dispersion are inconsistent with the recent c-axis twist bicrystal Bi 2 Sr 2 CaCu 2 O 8+δ twist junction experiments of Li et al. [Li et al., Phys. Rev. Lett. 83, 4160 (1999)]. (c) 2000 The American Physical Society

  12. Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine fetal lungs in late gestation

    Directory of Open Access Journals (Sweden)

    Côté Mélissa

    2010-11-01

    Full Text Available Abstract Background Lung maturation is modulated by several factors, including glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA axis-related components, with proposed or described local regulatory systems analogous to the HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were studied in the mouse developing lung during a period overlapping the surge of surfactant production. Methods Expression of genes encoding for corticotropin-releasing hormone (CRH, CRH receptors (CRHR 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC, melanocortin receptor 2 (MC2R, and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD 15.5, 16.5, and 17.5, and was also quantified in primary mesenchymal- and epithelial cell-enriched cultures. In addition, the capability of CRH and adrenocorticotropic hormone (ACTH to stimulate pulmonary expression of enzymes involved in the adrenal pathway of glucocorticoid synthesis was addressed, as well as the glucocorticoid production by fetal lung explants. Results We report that all the studied genes are expressed in fetal lungs according to different patterns. On GD 15.5, Mc2r showed peaks in expression in samples that have previously presented high mRNA levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase (Cyp11b1. Crhr1 mRNA co-localized with Pomc mRNA in cells surrounding the proximal epithelium on GD 15.5 and 16.5. A transition in expression sites toward distal epithelial cells was observed between GD 15.5 and 17.5 for all the studied genes. CRH or ACTH stimulation of genes involved in the adrenal pathway of glucocorticoid synthesis was not observed in lung explants on GD 15.5, whereas CRH significantly increased expression of 21-hydroxylase (Cyp21a1 on GD 17.5. A deoxycorticosterone production by fetal lung explants was observed. Conclusions Temporal and spatial

  13. 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.

  14. Intensity-modulated radiotherapy for nasopharyngeal carcinoma: Clinical correlation of dose to the pharyngo-esophageal axis and dysphagia

    International Nuclear Information System (INIS)

    Fua, Tsien F.; Corry, June; Milner, Alvin D.; Cramb, Jim; Walsham, Sue F.; Peters, Lester J.

    2007-01-01

    Purpose: The aim of this study was to quantify the dose delivered to the pharyngo-esophageal axis using different intensity-modulated radiation therapy (IMRT) techniques for treatment of nasopharyngeal carcinoma and to correlate this with acute swallowing toxicity. Methods and Materials: The study population consisted of 28 patients treated with IMRT between February 2002 and August 2005: 20 with whole field IMRT (WF-IMRT) and 8 with IMRT fields junctioned with an anterior neck field with central shielding (j-IMRT). Dose to the pharyngo-esophageal axis was measured using dose-volume histograms. Acute swallowing toxicity was assessed by review of dysphagia grade during treatment and enteral feeding requirements. Results: The mean pharyngo-esophageal dose was 55.2 Gy in the WF-IMRT group and 27.2 Gy in the j-IMRT group, p < 0.001. Ninety-five percent (19/20) of the WF-IMRT group developed Grade 3 dysphagia compared with 62.5% (5/8) of the j-IMRT group, p = 0.06. Feeding tube duration was a median of 38 days for the WF-IMRT group compared with 6 days for the j-IMRT group, p = 0.04. Conclusions: Clinical vigilance must be maintained when introducing new technology to ensure that unanticipated adverse effects do not result. Although newer planning systems can reduce the dose to the pharyngo-esophageal axis with WF-IMRT, the j-IMRT technique is preferred at least in patients with no gross disease in the lower neck

  15. 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

  16. 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.

  17. 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...

  18. Polycyclic aromatic hydrocarbons and dibutyl phthalate disrupt dorsal-ventral axis determination via the Wnt/{beta}-catenin signaling pathway in zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Fairbairn, Elise A., E-mail: efairbairn@ucdavis.edu [University of California Davis, Bodega Marine Laboratory, P.O. Box 247, Bodega Bay, CA 94923 (United States); Bonthius, Jessica, E-mail: jessica.bonthius@gmail.com [University of California Davis, Bodega Marine Laboratory, P.O. Box 247, Bodega Bay, CA 94923 (United States); Cherr, Gary N., E-mail: gncherr@ucdavis.edu [University of California Davis, Bodega Marine Laboratory, P.O. Box 247, Bodega Bay, CA 94923 (United States); Department of Environmental Toxicology, University of California Davis, Davis, CA 95616 (United States); Department of Nutrition, University of California Davis, Davis, CA 95616 (United States)

    2012-11-15

    The canonical Wnt/{beta}-catenin signaling pathway is critical during early teleost development for establishing the dorsal-ventral axis. Within this pathway, GSK-3{beta}, a key regulatory kinase in the Wnt pathway, regulates {beta}-catenin degradation and thus the ability of {beta}-catenin to enter nuclei, where it can activate expression of genes that have been linked to the specification of the dorsal-ventral axis. In this study, we describe the morphological abnormalities that resulted in zebrafish embryos when axis determination was disrupted by environmental contaminants. These abnormalities were linked to abnormal nuclear accumulation of {beta}-catenin. Furthermore, we demonstrated that the developmental abnormalities and altered nuclear {beta}-catenin accumulation occurred when embryos were exposed to commercial GSK-3{beta} inhibitors. Zebrafish embryos were exposed to commercially available GSK-3 inhibitors (GSK-3 Inhibitor IX and 1-azakenpaullone), or common environmental contaminants (dibutyl phthalate or the polycyclic aromatic hydrocarbons phenanthrene and fluorene) from the 2 to 8-cell stage through the mid-blastula transition (MBT). These embryos displayed morphological abnormalities at 12.5 h post-fertilization (hpf) that were comparable to embryos exposed to lithium chloride (LiCl) (300 mM LiCl for 10 min, prior to the MBT), a classic disruptor of embryonic axis determination. Whole-mount immunolabeling and laser scanning confocal microscopy were used to localize {beta}-catenin. The commercial GSK-3 Inhibitors as well as LiCl, dibutyl phthalate, fluorene and phenanthrene all induced an increase in the levels of nuclear {beta}-catenin throughout the embryo, indicating that the morphological abnormalities were a result of disruption of Wnt/{beta}-catenin signaling during dorsal-ventral axis specification. The ability of environmental chemicals to directly or indirectly target GSK-3{beta} was assessed. Using Western blot analysis, the ability of these

  19. A tale of three labels: translating the JUPITER trial data into regulatory claims.

    Science.gov (United States)

    Ridker, Paul M

    2011-08-01

    Whether a pivotal randomized trial will be interpreted in a similar and consistent manner by different regulatory agencies is uncertain as policy perspectives may play a role in data interpretation and the translation of trial results into clinical practice. Using a contemporary example, to compare and contrast regulatory claims in the United States, Europe, and Canada that derive from a pivotal clinical trial. The recently completed JUPITER trial of rosuvastatin as compared to placebo conducted among 17,802 men and women with LDL-C JUPITER trial provides an opportunity to compare and contrast how regulatory agencies in the United States, Canada, and Europe chose to interpret an identical database. Labeling indications based on earlier statin trials of primary and secondary prevention were also reviewed. JUPITER demonstrated a 44% reduction (p JUPITER trial population by stipulating that those eligible for treatment should be older men and women with hsCRP >2 mg/L, plus one additional risk factor for heart disease. The Canadian label is silent on age and hsCRP (the major trial inclusion criterion), stipulating instead that treatment can be considered for those with 'at least two conventional risk factors for cardiovascular disease,' a group more inclusive than that studied. In contrast, the European Medicines Agency label limits treatment only to 'high risk individuals' ignoring hsCRP and using instead a post hoc definition of 'high risk' that comprised a subgroup of less than 10% of the study population who contributed but 67 events to the study total and did not show statistical significance when compared to placebo. None of the regulatory labels included the trial primary endpoint; instead, each focused on separate and different components of the primary endpoint. Similar discrepancies were found between European and North American regulatory agencies with regard to earlier pivotal trials of statins for primary prevention, but not for secondary prevention. The

  20. Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis

    Science.gov (United States)

    Čupić, Željko; Marković, Vladimir M.; Maćešić, Stevan; Stanojević, Ana; Damjanović, Svetozar; Vukojević, Vladana; Kolar-Anić, Ljiljana

    2016-03-01

    Dynamic properties of a nonlinear five-dimensional stoichiometric model of the hypothalamic-pituitary-adrenal (HPA) axis were systematically investigated. Conditions under which qualitative transitions between dynamic states occur are determined by independently varying the rate constants of all reactions that constitute the model. Bifurcation types were further characterized using continuation algorithms and scale factor methods. Regions of bistability and transitions through supercritical Andronov-Hopf and saddle loop bifurcations were identified. Dynamic state analysis predicts that the HPA axis operates under basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation. Dynamic properties of the stress-control axis have not been characterized experimentally, but modelling suggests that the proximity to a supercritical Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to external stimuli and adjust to new conditions and stability, i.e., the capacity to return to the original dynamic state afterwards, which is essential for maintaining homeostasis. The analysis presented here reflects the properties of a low-dimensional model that succinctly describes neurochemical transformations underlying the HPA axis. However, the model accounts correctly for a number of experimentally observed properties of the stress-response axis. We therefore regard that the presented analysis is meaningful, showing how in silico investigations can be used to guide the experimentalists in understanding how the HPA axis activity changes under chronic disease and/or specific pharmacological manipulations.

  1. 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)

  2. 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.

  3. 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.

  4. Safety culture as a matter of regulatory control and regulatory effectiveness

    International Nuclear Information System (INIS)

    Camargo, C.T.M.; Furieri, E.B.; Arrieta, L.A.I.; Almeida, C.U.C.

    2002-01-01

    More than 15 years have passed since the term 'safety culture' was introduced by the International Nuclear Safety Advisory Group (INSAG), and although the concept now is widely accepted, practical applications and characteristics have been disseminated mainly for nuclear power plant operating organizations. There is still a lack of international guidance on the use of safety culture as a regulatory matter and on the application of the concept within regulatory organizations. This work explores the meaning of safety culture in two different fields: as an element of safety management systems it shall be a matter of regulatory control; as a complementary tool for quality management it should be used to enhance regulatory effectiveness. Brazilian recent experience on regulating nuclear power reactors provide some examples on how the concept of safety culture may influence regulatory strategies and regulatory management. (author)

  5. 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.

  6. [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.

  7. FORECAST: Regulatory effects cost analysis software manual -- Version 4.1. Revision 1

    International Nuclear Information System (INIS)

    Lopez, B.; Sciacca, F.W.

    1996-07-01

    The FORECAST program was developed to facilitate the preparation of the value-impact portion of NRC regulatory analyses. This PC program integrates the major cost and benefit considerations that may result from a proposed regulatory change. FORECAST automates much of the calculations typically needed in a regulatory analysis and thus reduces the time and labor required to perform these analyses. More importantly, its integrated and consistent treatment of the different value-impact considerations should help assure comprehensiveness, uniformity, and accuracy in the preparation of NRC regulatory analyses. The Current FORECAST Version 4.1 has been upgraded from the previous version and now includes an uncertainty package, an automatic cost escalation package, and other improvements. In addition, it now explicitly addresses public health impacts, occupational health impacts, onsite property damage, and government costs. Thus, FORECAST Version 4.1 can treat all attributes normally quantified in a regulatory analysis

  8. Functional Implications of the IL-23/IL-17 Immune Axis in Schizophrenia.

    Science.gov (United States)

    Debnath, Monojit; Berk, Michael

    2017-12-01

    The aetiology of schizophrenia seems to stem from complex interactions amongst environmental, genetic, metabolic, immunologic and oxidative components. Chronic low-grade inflammation has been persistently linked to schizophrenia, and this has primarily been based on the findings derived from Th1/Th2 cytokine balance. While the IL-23/IL-17 axis plays crucial role in the pathogenesis of several immune-mediated disorders, it has remained relatively unexplored in neuropsychiatric disorders. Altered levels of cytokines related to IL-23/IL-17 axis have been observed in schizophrenia patients in a few studies. In addition, other indirect factors known to confer schizophrenia risk like complement activation and altered gut microbiota are shown to modulate the IL-23/IL-17 axis. These preliminary observations provide crucial clues about the functional implications of IL-23/IL-17 axis in schizophrenia. In this review, an attempt has been made to highlight the biology of IL-23/IL-17 axis and its relevance to schizophrenia risk and pathogenesis. Given the pathogenic potential of the IL-23/IL-17 axis, therapeutic targeting of this axis may be a promising approach to benefit patients suffering from this devastating disorder.

  9. Sequence-dependent rotation axis changes and interaction torque use in overarm throwing.

    Science.gov (United States)

    Hansen, Clint; Rezzoug, Nasser; Gorce, Philippe; Venture, Gentiane; Isableu, Brice

    2016-01-01

    We examined the role of rotation axes during an overarm throwing task. Participants performed such task and were asked to throw a ball at maximal velocity at a target. The purpose of this study was to examine whether the minimum inertia axis would be exploited during the throwing phases, a time when internal-external rotations of the shoulder are particularly important. A motion capture system was used to evaluate the performance and to compute the potential axes of rotation (minimum inertia axis, shoulder-centre of mass axis and the shoulder-elbow axis). More specifically, we investigated whether a velocity-dependent change in rotational axes can be observed in the different throwing phases and whether the control obeys the principle of minimum inertia resistance. Our results showed that the limbs' rotational axis mainly coincides with the minimum inertia axis during the cocking phase and with the shoulder-elbow axis during the acceleration phase. Besides these rotation axes changes, the use of interaction torque is also sequence-dependent. The sequence-dependent rotation axes changes associated with the use of interaction torque during the acceleration phase could be a key factor in the production of hand velocity at ball release.

  10. Optimal pitching axis location of flapping wings for efficient hovering flight.

    Science.gov (United States)

    Wang, Q; Goosen, J F L; van Keulen, F

    2017-09-01

    Flapping wings can pitch passively about their pitching axes due to their flexibility, inertia, and aerodynamic loads. A shift in the pitching axis location can dynamically alter the aerodynamic loads, which in turn changes the passive pitching motion and the flight efficiency. Therefore, it is of great interest to investigate the optimal pitching axis for flapping wings to maximize the power efficiency during hovering flight. In this study, flapping wings are modeled as rigid plates with non-uniform mass distribution. The wing flexibility is represented by a linearly torsional spring at the wing root. A predictive quasi-steady aerodynamic model is used to evaluate the lift generated by such wings. Two extreme power consumption scenarios are modeled for hovering flight, i.e. the power consumed by a drive system with and without the capacity of kinetic energy recovery. For wings with different shapes, the optimal pitching axis location is found such that the cycle-averaged power consumption during hovering flight is minimized. Optimization results show that the optimal pitching axis is located between the leading edge and the mid-chord line, which shows close resemblance to insect wings. An optimal pitching axis can save up to 33% of power during hovering flight when compared to traditional wings used by most of flapping wing micro air vehicles (FWMAVs). Traditional wings typically use the straight leading edge as the pitching axis. With the optimized pitching axis, flapping wings show higher pitching amplitudes and start the pitching reversals in advance of the sweeping reversals. These phenomena lead to higher lift-to-drag ratios and, thus, explain the lower power consumption. In addition, the optimized pitching axis provides the drive system higher potential to recycle energy during the deceleration phases as compared to their counterparts. This observation underlines the particular importance of the wing pitching axis location for energy-efficient FWMAVs when

  11. 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.

  12. 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...

  13. 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...

  14. 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.

  15. A local-circulation model for Darrieus vertical-axis wind turbines

    Science.gov (United States)

    Masse, B.

    1986-04-01

    A new computational model for the aerodynamics of the vertical-axis wind turbine is presented. Based on the local-circulation method generalized for curved blades, combined with a wake model for the vertical-axis wind turbine, it differs markedly from current models based on variations in the streamtube momentum and vortex models using the lifting-line theory. A computer code has been developed to calculate the loads and performance of the Darrieus vertical-axis wind turbine. The results show good agreement with experimental data and compare well with other methods.

  16. 76 FR 21932 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2011-04-19

    ... statement therein, as follows: I. Introduction On February 4, 2011, the Financial Industry Regulatory...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting Approval of a... Financial Industry Regulatory Authority, Inc. (``FINRA'') to amend Rule 13806 of the Code of Arbitration...

  17. 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 ...

  18. 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.

  19. Alteration of the hypothalamic-pituitary-gonadal axis in estrogen- and androgen-treated adult male leopard frog, Rana pipiens

    Directory of Open Access Journals (Sweden)

    Jones Jeremy T

    2005-01-01

    Full Text Available Abstract Background Gonadal steroids, in particular 5 alpha-dihydrotestosterone (DHT and 17 beta-estradiol (E2, have been shown to feed back on the hypothalamic-pituitary-gonadal (HPG axis of the ranid frog. However, questions still remain on how DHT and E2 impact two of the less-studied components of the ranid HPG axis, the hypothalamus and the gonad, and if the feedback effects are consistently negative. Thus, the goal of the study was to examine the effects of DHT and E2 upon the HPG axis of the gonadally-intact, sexually mature male leopard frogs, Rana pipiens. Methods R. pipiens were implanted with silastic capsules containing either cholesterol (Ch, a control, DHT, or E2 for 10 or 30 days. At each time point, steroid-induced changes in hypothalamic GnRH and pituitary LH concentrations, circulating luteinizing hormone (LH, and testicular histology were examined. Results Frogs implanted with DHT or E2 for 10 days did not show significant alterations in the HPG axis. In contrast, frogs implanted with hormones for 30 days had significantly lower circulating LH (for both DHT and E2, decreased pituitary LH concentration (for E2 only, and disrupted spermatogenesis (for both DHT and E2. The disruption of spermatogenesis was qualitatively similar between DHT and E2, although the effects of E2 were consistently more potent. In both DHT and E2-treated animals, a marked loss of all pre-meiotic germ cells was observed, although the loss of secondary spermatogonia appeared to be the primary cause of disrupted spermatogenesis. Unexpectedly, the presence of post-meiotic germ cells was either unaffected or enhanced by DHT or E2 treatment. Conclusions Overall, these results showed that both DHT and E2 inhibited circulating LH and disrupted spermatogenesis progressively in a time-dependent manner, with the longer duration of treatment producing the more pronounced effects. Further, the feedback effects exerted by both steroid hormones upon the HPG axis were

  20. 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

  1. Alleviating action of OK-432 (Picibanil) on the myelosuppression in medulloblastoma patients induced by whole axis irradiation

    International Nuclear Information System (INIS)

    Aoki, Yoshiro

    1982-01-01

    The test subjects termed as OK-432 group which consist of 4 patients of Medulloblastoma and 2 of Pinealoma, underwent the whole axis irradiation in combination with OK-432. The control group consisting of 9 Medulloblastoma patients was subjected to the same radiation treatment without OK-432. Six of the nine patients (66.7%) irradiated showed the decrease of peripheral white blood cell counts down to 2,500, whereas, only two of six patients showed a similar decrement in OK-432 group. Three of the nine patients (33.3%) in the control group showed the decrease of white blood cell down to 2,000, but only one of the six patients in OK-432 group. The neutrophil counts decreased below the level of 1,000 in three of the nine patients (33.3%) in the control group, but none in the OK-432 group. The platelet counts decreased below the level of 100,000 in five of the nine patients (55.6%) in the control group during the irradiation period, but only one patient in the OK-432 group showed a decrease down to 100,000 counts. Three of the nine patients (33.3%) in the control group had to be stopped irradiation due to the severe leukopenia and thrombocytopenia, in contrast to the OK-432 group, which completed whole axis irradiation without interruption. These results seem to indicate that OK-432 alleviated the myelosuppression induced in patients by whole axis irradiation. This alleviating action of OK-432 is considered to be applicable to the treatment of Medulloblastoma patients. (J.P.N.)

  2. Alleviating action of OK-432 (Picibanil) on the myelosuppression in Medulloblastoma patients induced by whole axis irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Aoki, Yoshiro (National Inst. of Radiological Sciences, Chiba (Japan))

    1982-11-01

    The test subjects termed as OK-432 group which consist of 4 patients of Medulloblastoma and 2 of Pinealoma, underwent the whole axis irradiation in combination with OK-432. The control group consisting of 9 Medulloblastoma patients was subjected to the same radiation treatment without OK-432. Six of the nine patients (66.7%) irradiated showed the decrease of peripheral white blood cell counts down to 2,500, whereas, only two of six patients showed a similar decrement in OK-432 group. Three of the nine patients (33.3%) in the control group showed the decrease of white blood cell down to 2,000, but only one of the six patients in OK-432 group. The neutrophil counts decreased below the level of 1,000 in three of the nine patients (33.3%) in the control group, but none in the OK-432 group. The platelet counts decreased below the level of 100,000 in five of the nine patients (55.6%) in the control group during the irradiation period, but only one patient in the OK-432 group showed a decrease down to 100,000 counts. Three of the nine patients (33.3%) in the control group had to be stopped irradiation due to the severe leukopenia and thrombocytopenia, in contrast to the OK-432 group, which completed whole axis irradiation without interruption. These results seem to indicate that OK-432 alleviated the myelosuppression induced in patients by whole axis irradiation. This alleviating action of OK-432 is considered to be applicable to the treatment of Medulloblastoma patients.

  3. Space cutter compensation method for five-axis nonuniform rational basis spline machining

    Directory of Open Access Journals (Sweden)

    Yanyu Ding

    2015-07-01

    Full Text Available In view of the good machining performance of traditional three-axis nonuniform rational basis spline interpolation and the space cutter compensation issue in multi-axis machining, this article presents a triple nonuniform rational basis spline five-axis interpolation method, which uses three nonuniform rational basis spline curves to describe cutter center location, cutter axis vector, and cutter contact point trajectory, respectively. The relative position of the cutter and workpiece is calculated under the workpiece coordinate system, and the cutter machining trajectory can be described precisely and smoothly using this method. The three nonuniform rational basis spline curves are transformed into a 12-dimentional Bézier curve to carry out discretization during the discrete process. With the cutter contact point trajectory as the precision control condition, the discretization is fast. As for different cutters and corners, the complete description method of space cutter compensation vector is presented in this article. Finally, the five-axis nonuniform rational basis spline machining method is further verified in a two-turntable five-axis machine.

  4. 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.

  5. 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

  6. The development and testing of a novel cross axis wind turbine

    Science.gov (United States)

    Chong, W. T.; Muzammil, W. K.; Gwani, M.; Wong, K. H.; Fazlizan, A.; Wang, C. T.; Poh, S. C.

    2016-06-01

    A novel cross axis wind turbine (CAWT) which comprises of a cross axis blades arrangement was presented and investigated experimentally. The CAWT is a new type of wind turbine that extracts wind energy from airflow coming from the horizontal and vertical directions. The wind turbine consists of three vertical blades and six horizontal blades arranged in a cross axis orientation. Hubs in the middle of the CAWT link the horizontal and vertical blades through connectors to form the CAWT. The study used a 45° deflector to guide the oncoming airflow upward (vertical wind direction). The results from the study showed that the CAWT produced significant improvements in power output and rotational speed performance compared to a conventional straight-bladed vertical axis wind turbine (VAWT).

  7. Precision grip responses to unexpected rotational perturbations scale with axis of rotation.

    Science.gov (United States)

    De Gregorio, Michael; Santos, Veronica J

    2013-04-05

    It has been established that rapid, pulse-like increases in precision grip forces ("catch-up responses") are elicited by unexpected translational perturbations and that response latency and strength scale according to the direction of linear slip relative to the hand as well as gravity. To determine if catch-up responses are elicited by unexpected rotational perturbations and are strength-, axis-, and/or direction-dependent, we imposed step torque loads about each of two axes which were defined relative to the subject's hand: the distal-proximal axis away from and towards the subject's palm, and the grip axis which connects the two fingertips. Precision grip responses were dominated initially by passive mechanics and then by active, unimodal catch-up responses. First dorsal interosseous activity, marking the start of the catch-up response, began 71-89 ms after the onset of perturbation. The onset latency, shape, and duration (217-231 ms) of the catch-up response were not affected by the axis, direction, or magnitude of the rotational perturbation, while strength was scaled by axis of rotation and slip conditions. Rotations about the grip axis that tilted the object away from the palm and induced rotational slip elicited stronger catch-up responses than rotations about the distal-proximal axis that twisted the object between the digits. To our knowledge, this study is the first to investigate grip responses to unexpected torque loads and to show characteristic, yet axis-dependent, catch-up responses for conditions other than pure linear slip. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. New capacitive low-g triaxial accelerometer with low cross-axis sensitivity

    International Nuclear Information System (INIS)

    Hsu, Yu-Wen; Chen, Jen-Yi; Chien, Hsin-Tang; Chen, Sheah; Lin, Shih-Ting; Liao, Lu-Po

    2010-01-01

    This work describes a compact accelerometer, which integrates three spring-proof mass systems into a single structure to sense triaxial motion. It has a size of 1.3 × 1.28 mm 2 and an operating range of ±1 g. Silicon-on-glass (SOG) micromachining and deep reactive-ion etching (DRIE)-based process are adopted to fabricate this accelerometer with a high-aspect-ratio sensing structure. The accelerometer has an excellent z-axis output sensitivity of 1.434 V g −1 and a high resolution of 49 µg Hz −1/2 . The sensitivity and minimum cross-axis sensitivity of the x-axis in-plane accelerometer are 1.442 V g −1 and 0.03% and those of the y-axis accelerometer are 1.241 V g −1 and 0.21%, respectively. The new in-plane and out-of-plane accelerometer design exhibits high cross-axis sensitivity immunity, high sensitivity and high linearity suggesting that the triaxial accelerometer has the potential for use in future applications in consumer goods and the cellular phone marketþ

  13. 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.

  14. Dual axis translation apparatus and system for translating an optical beam and related method

    Science.gov (United States)

    Cassidy, Kelly

    1991-01-01

    A dual axis translation device and system in accordance with this invention, for translating an optical beam along both an x-axis and a y-axis which are perpendicular to one another, has a beam directing means acting on said optical beam for directing the beam along a particular path transverse to said x and y axes. An arrangement supporting said beam directing means for movement in the x and y direction within a given plane is provided. The arrangement includes a first means for translating said beam directing means along the x-axis in said given plane in order to translate the beam along said x-axis. The arrangement comprises a second means for translating said beam directing means along the y-axis in said given plane in order to translate the beam along said y-axis.

  15. Dysregulation of the HPA axis as a core pathophysiology mediating co-morbid depression in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Xin eDu

    2015-03-01

    Full Text Available There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression, and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic-pituitary-adrenal (HPA axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioural deficits and/or mood disorders. Dysregulation of the HPA axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, anti-depressant drugs such as the selective serotonin reuptake inhibitors (SSRI have been shown to alter HPA axis activity. In this review, we will summarize the current state of knowledge regarding HPA axis pathology in Alzheimer’s, Parkinson’s and Huntington’s diseases, differentiating between prodromal and later stages of disease progression where possible. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the pre-clinical evidence to better inform prospective, intervention studies.

  16. 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.

  17. Food and the circadian activity of the hypothalamic-pituitary-adrenal axis

    Directory of Open Access Journals (Sweden)

    A.M.O. Leal

    1997-12-01

    Full Text Available Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or" zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states

  18. 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...

  19. Design and analysis of a semi-submersible vertical axis wind turbine

    OpenAIRE

    Siddique, Muhammad Abu Zafar

    2017-01-01

    Wind energy are deployed by two types of wind turbines. They are Horizontal Axis Wind Turbine (HAWT) and Vertical Axis Wind Turbine (VAWT), classified according to their axis of rotation. In recent years, offshore wind energy playing a vital role in the wind turbine industry due to high intensity of air, less turbulent and comparatively clean and easily employed in large area which is difficult to manage for onshore or near-shore. The advantages of HAWTs are now facing different challenge in ...

  20. 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...

  1. 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.

  2. 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…

  3. 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

  4. Combined Structural Optimization and Aeroelastic Analysis of a Vertical Axis Wind Turbine

    DEFF Research Database (Denmark)

    Roscher, Björn; Ferreira, Carlos Simao; Bernhammer, Lars O.

    2015-01-01

    Floating offshore wind energy poses challenges on the turbine design. A possible solution is vertical axis wind turbines, which are possibly easier to scale-up and require less components (lower maintenance) and a smaller floating structure than horizontal axis wind turbines. This paper presents...... a structural optimization and aeroelastic analysis of an optimized Troposkein vertical axis wind turbine to minimize the relation between the rotor mass and the swept area. The aeroelastic behavior of the different designs has been analyzed using a modified version of the HAWC2 code with the Actuator Cylinder...... model to compute the aerodynamics of the vertical axis wind turbine. The combined shape and topology optimization of a vertical axis wind turbine show a minimum mass to area ratio of 1.82 kg/m2 for blades with varying blade sections from a NACA 0040 at the attachment points to a NACA 0015...

  5. 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.

  6. 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

  7. [Effect of Electroacupuncture on Hypothalamus-Pituitary-Ovary (HPO) Axis in Rats with Peri-menopausal Depression].

    Science.gov (United States)

    Jiang, Xi-Rong; Ren, Lu; Li, Chun-Ri

    2017-02-25

    To observe the effect of electroacupuncture (EA) on the hormones derived from the hypothalamus-pituitary-ovary (HPO) axis, so as to explore the neuroendocrine mechanism induced by EA on rats with perimenopausal depression disorder. Sixty female sprague-dawley rats were randomly divided into blank control group, model group, sham-operation (sham) group, clomipramine group, and electroacupuncture (EA) group, with 12 rats in each group. Perimenopausal depression model was established by bilateral ovariectomy combined with chronic unpredictable stimulation.The EA group received continuous treatment at "Baihui" (GV 20), "Shenshu" (BL 23) and "Sanyinjiao" (SP 6) once a day for 28 days. Estrous cycle and sucrose preference test were monitored, and serum estradiol (E 2 ), luteinizing hormone (LH), gonadotropin releasing hormone (GnRH), and β-endorphin (β-EP) were detected by ELISA. Compared to the blank control group, sugar water consumpution rates decreased in the model group and sham group ( P Electroacupuncture can relieve the symptoms of rat with perimenopausal depression by regulating the hormone secretion in HPO axis.

  8. 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.

  9. 75 FR 63878 - Self-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate...

    Science.gov (United States)

    2010-10-18

    ...-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of...(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory...

  10. Oblique Axis Body Fracture: An Unstable Subtype of Anderson Type III Odontoid Fractures—Apropos of Two Cases

    Directory of Open Access Journals (Sweden)

    Hirokazu Takai

    2016-01-01

    Full Text Available Purpose. Anderson type III odontoid fractures have traditionally been considered stable and treated conservatively. However, unstable cases with unfavorable results following conservative treatment have been reported. Methods. We present the cases of two patients who sustained minimally displaced Anderson type III fractures with a characteristic fracture pattern that we refer to as “oblique type axis body fracture.” Results. The female patients aged 90 and 72 years, respectively, were both diagnosed with minimally displaced Anderson type III fractures. Both fractures had a characteristic “oblique type” fracture pattern. The first patient was treated conservatively with cervical spine immobilization in a semirigid collar. However, gross displacement was noted at the 6-week follow-up visit. The second patient was therefore treated operatively by C1–C3/4 posterior fusion and the course was uneventful. Conclusions. Oblique type axis body fractures resemble a highly unstable subtype of Anderson type III fractures with the potential of severe secondary deformity following conservative treatment, irrespective of initial grade of displacement. The authors therefore warrant a high index of suspicion for this injury and suggest early operative stabilization.

  11. Maximum Feedrate Interpolator for Multi-axis CNC Machining with Jerk Constraints

    OpenAIRE

    Beudaert , Xavier; Lavernhe , Sylvain; Tournier , Christophe

    2012-01-01

    A key role of the CNC is to perform the feedrate interpolation which means to generate the setpoints for each machine tool axis. The aim of the VPOp algorithm is to make maximum use of the machine tool respecting both tangential and axis jerk on rotary and linear axes. The developed algorithm uses an iterative constraints intersection approach. At each sampling period, all the constraints given by each axis are expressed and by intersecting all of them the allowable interval for the next poin...

  12. Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

    Science.gov (United States)

    Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

    2017-04-01

    Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Soil treatment technologies: Comparison of field experiences

    International Nuclear Information System (INIS)

    Hodges, H.I.; Jackson, D.W.; Kline, K.

    1992-01-01

    A number of on-site soil treatment technologies are available for closure of oil-field waste pits, leaking underground storage tank (LUST) sites, and general hydrocarbon contamination. This paper will contrast Separation Systems Consultants, Inc.'s (SSCI's) field experiences with the following soil restoration techniques: (1) Land Treatment using indigenous microbes; (2) Land Farming using commercial microbes; (3) Low Temperature Thermal Treatment; (4) Solidification. The technologies will be contrasted in terms of regulatory constraints and requirements, key set-up and maintenance consideration, selection factors. Included in the regulatory contrast is the authors' perception of regulatory attitudes toward the techniques. Because this paper is based on actual field experience and projects, the practical aspects of making the technologies work is emphasized

  14. 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

  15. 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.

  16. Evolution of Cis-Regulatory Elements and Regulatory Networks in Duplicated Genes of Arabidopsis.

    Science.gov (United States)

    Arsovski, Andrej A; Pradinuk, Julian; Guo, Xu Qiu; Wang, Sishuo; Adams, Keith L

    2015-12-01

    Plant genomes contain large numbers of duplicated genes that contribute to the evolution of new functions. Following duplication, genes can exhibit divergence in their coding sequence and their expression patterns. Changes in the cis-regulatory element landscape can result in changes in gene expression patterns. High-throughput methods developed recently can identify potential cis-regulatory elements on a genome-wide scale. Here, we use a recent comprehensive data set of DNase I sequencing-identified cis-regulatory binding sites (footprints) at single-base-pair resolution to compare binding sites and network connectivity in duplicated gene pairs in Arabidopsis (Arabidopsis thaliana). We found that duplicated gene pairs vary greatly in their cis-regulatory element architecture, resulting in changes in regulatory network connectivity. Whole-genome duplicates (WGDs) have approximately twice as many footprints in their promoters left by potential regulatory proteins than do tandem duplicates (TDs). The WGDs have a greater average number of footprint differences between paralogs than TDs. The footprints, in turn, result in more regulatory network connections between WGDs and other genes, forming denser, more complex regulatory networks than shown by TDs. When comparing regulatory connections between duplicates, WGDs had more pairs in which the two genes are either partially or fully diverged in their network connections, but fewer genes with no network connections than the TDs. There is evidence of younger TDs and WGDs having fewer unique connections compared with older duplicates. This study provides insights into cis-regulatory element evolution and network divergence in duplicated genes. © 2015 American Society of Plant Biologists. All Rights Reserved.

  17. Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

    Science.gov (United States)

    Li, Hong-Yan; Zhao, Ying-Hua; Zeng, Min-Jie; Fang, Fang; Li, Min; Qin, Ting-Ting; Ye, Lu-Yu; Li, Hong-Wei; Qu, Rong; Ma, Shi-Ping

    2017-11-01

    Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties. The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD. Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD. In addition, we examined corticosterone and glucocorticoid receptor (GR) levels to evaluate hypothalamic-pituitary-adrenal (HPA) axis function. Furthermore, hippocampal neurogenesis was assessed by testing doublecortin (DCX) levels, and neurotrophic molecule levels were also investigated in the hippocampus of rats. We found that unpredictable chronic mild stress (UCMS) rats displayed lost body weight, decreased sucrose consumption in SPT, reduced locomotive activity in OFT, and increased immobility time in FST. Chronic treatment with SSD (0.75, 1.50 mg/kg) remarkably ameliorated the behavioral deficiency induced by UCMS procedure. SSD administration downregulated elevated serum corticosterone levels, as well as alleviated the suppression of GR expression and nuclear translocation caused by UCMS, suggesting that SSD is able to remit the dysfunction of HPA axis. In addition, Western blot and immunohistochemistry analysis showed that SSD treatment significantly increased the generation of neurons in the hippocampus of UCMS rats indicated by elevated DCX levels. Moreover, hippocampal neurotrophic molecule levels of UCMS rats such as phosphorylated cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were raised after SSD treatment. Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.

  18. Measurement of off-axis and peripheral skin dose using radiochromic film

    International Nuclear Information System (INIS)

    Butson, Martin J.; Yu, P.K.N.; Metcalfe, P.E.

    1998-01-01

    A radiotherapy skin dose profile can be obtained with radiochromic film. The central axis skin dose relative to D max for a 10x10cm 2 field size was found to be 22%, 17% and 15.5% for 6 MV, 10 MV and 18 MV photon beams. Peripheral dose increased with increasing field size. At 10 MV the skin dose 2 cm outside the geometric field edge was measured as 6%, 10% and 17% for 10x10cm 2 , 20x20cm 2 and 30x30cm 2 field sizes respectively. Off-axis skin dose decreased as distance increased from central axis for fields with Perspex block trays. For a 20x20cm 2 field, an approximately 5-8% drop in percentage skin dose was observed from central axis to the beam edge. (author)

  19. 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.

  20. Preparation of safety regulatory requirements for new technology like digital system

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-08-15

    The current regulatory requirements on digital instrumentation and control system have been reviewed by JNES, considering international trend discussed in DICWG of MDEP. MDEP DICWG held in OECD/NEA gives the opportunity to identify the convergence of applicable standards. The working group's activities include: identifying and prioritising the member countries' challenges, practices, and needs regarding standards and regulatory guidance on digital instrumentation and control; identifying areas of importance and needs for convergence of existing standards and guidance or development of new standards; sharing of information; and identifying common positions among the member countries for areas of particular importance and need. The DICWG drafted common positions on specific issues which are based on the existing standards, national regulatory guidance, best practices, and group inputs using an agreed process and framework. The following four general common positions have been discussed in this fiscal year. The Treatment of Common Cause Failure Resulting from Software within Digital Safety Systems, The Treatment of Hardware Description Language(HDL) Programmed Devices for Use in Nuclear Safety System, Factory Acceptance Test and Site Acceptance Test, The Use of Automatic Tests to Perform Surveilance for Digital Systems. (author)

  1. SU-F-T-473: Evaluation of Off-Axis And Peripheral Dose Using Different Detectors

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, B; Prakasarao, A; Singaravelu, G [Anna University, Chennai, TamilNadu (India); Palraj, T; Rai, R [Dr. Rai Memorial Cancer Institute, Chennai, TamilNadu (India)

    2016-06-15

    Purpose: In radiation therapy, measurement of off-axis and peripheral dose is a tedious task. The dose distribution along the beam central axis give only part of the information required for an accurate dose description inside the patient. Dose distributions in 2-D and 3-D are determined with central axis data in conjunction with off-axis dose profiles. Combining a central axis dose distribution with off-axis data results in volume dose matrix that provides 2-D and 3-D information on dose distribution. By considering the importance of these two parameters this study investigates and compares the off axis and peripheral dose measurement using Ionization chamber, MOSFET, Radiochromic film and EDR2 film. Methods: In the measurement of off-axis and peripheral doses 0.6cc farmer type chamber, EDR-2 film, MD-55 radiochromic film and MOSFET detectors were used for both 6MV and 15MV beams. The off-axis and peripheral dose was measured at every 1 cm interval by changing the position of the couch without disturbing the other experimental setup in particular, the phantom with detector position. Results: Readings were obtained for both 6MV and 15MV photon beams at SSD technique for various field size using MOSFET, Ionization chamber and Radiochromic film. The results shows the percentage difference between various detectors for various field sizes. For Peripheral dose measurement were taken from the edge of the field size and for off axis it is measured form central axis dose. Conclusion: In conclusion, our study shows that no detector is ideal and only a comparison between different detectors highlights the weaknesses of each detector. MOSFET provides adequate dose assessment in off-axis and peripheral regions in 6MV and 15MV photon beams. Film dosimetry in general a convenient method to generate one- and two-dimensional dose distributions. The result of this indicates that MOSFET is flexible tool for relative dosimetry as films.

  2. An additional reference axis improves femoral rotation alignment in image-free computer navigation assisted total knee arthroplasty.

    Science.gov (United States)

    Inui, Hiroshi; Taketomi, Shuji; Nakamura, Kensuke; Sanada, Takaki; Tanaka, Sakae; Nakagawa, Takumi

    2013-05-01

    Few studies have demonstrated improvement in accuracy of rotational alignment using image-free navigation systems mainly due to the inconsistent registration of anatomical landmarks. We have used an image-free navigation for total knee arthroplasty, which adopts the average algorithm between two reference axes (transepicondylar axis and axis perpendicular to the Whiteside axis) for femoral component rotation control. We hypothesized that addition of another axis (condylar twisting axis measured on a preoperative radiograph) would improve the accuracy. One group using the average algorithm (double-axis group) was compared with the other group using another axis to confirm the accuracy of the average algorithm (triple-axis group). Femoral components were more accurately implanted for rotational alignment in the triple-axis group (ideal: triple-axis group 100%, double-axis group 82%, P<0.05). Copyright © 2013 Elsevier Inc. All rights reserved.

  3. 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.

  4. 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

  5. Small polarons and c-axis transport in highly anisotropic metals

    International Nuclear Information System (INIS)

    Ho, A.F.; Schofield, A.J.

    2002-09-01

    Motivated by the anomalous c-axis transport properties of the quasi two-dimensional metal, Sr 2 RuO 4 , and some of its relatives, we have studied the interlayer hopping of single electrons that are coupled strongly to c-axis bosons. We find a c-axis resistivity that reflects the in-plane electronic scattering in the low and very high temperature limits (relative to the characteristic temperature of the boson T boson ). For temperatures near the T boson , a broad maximum in the resistivity can appear for sufficiently strong electron-boson coupling. This feature may account for the observed 'metallic to non-metallic crossover' seen in these layered oxides, where the boson may be a phonon. (author)

  6. Analisis Semiotika Makna Pesan pada Iklan Axis Versi “Iritologi – Menatap Masa Depan”

    Directory of Open Access Journals (Sweden)

    Puri Sulistiyawati

    2016-02-01

    Full Text Available Abstrak Tujuan dari penelitian ini adalah untuk mengetahui dan menganalisis makna pesan dalam iklan Axis versi “Iritologi – Menatap masa depan” di televisi dengan menggunakan pendekatan semiotika Roland Barthes. Dari analisis yang telah dilakukan berdasarkan makna denotasi, konotasi dan mitos dalam iklan Axis versi “iritologi – Menatap masa depan”, dapat diketahui bahwa iklan Axis memiliki konsep yang sangat sederhana, dengan mengusung tema tentang kebiasaan remaja dalam memanfaatkan media sosial. Dari visual iklan yang ditampilkan menguatkan pesan bahwa produk Axis ini menyasar remaja sebagai target audience, remaja atau pelajar adalah konsumen yang mendambakan produk dengan kalitas baik namun dengan harga yang terjangkau. Meski menyasar remaja, namun dalam target marketnya Axis tetap menyasar semua kalangan. Setting tempat atau latar pada iklan yang ditampilkan pun sebagai representasi bahwa Axis dapat dijangkau oleh semua kalangan ekonomi khususnya masyarakat menengah kebawah. Makna Mitos dalam iklan Axis ini tersirat pada scene tertentu. Secara umum iklan ini menyampaikan bahwa selfie dan media sosial sebagai bagian dari kehidupan masyaraka khususnya generasi muda, sebagai sarana untuk berinteraksi dan menunjukan eksistensinya kepada komunitas. Melalui foto yang diunggah pada media sosial, khalayak merepresentasikan perasaan maupun kegiatan yang sedang di lakukannya. Sehingga hal tersebut memicu kebutuhan akan jaringan komunikasi yang lancar dan ekonomis. Kata Kunci: iklan, axis, semiotika, mitos  Abstract The purpose of this research was to determine and analyze the meaning of message in Axis advertisement version “Iritologi – Menatap masa depan” on television using Roland Barthes semiotic approach. Analysis has been done based on the meaning of denotation, connotation and myth in Axis advertisement version “Iritologi – Menatap masa depan”, it can be seen that Axis advertisement has a simple concept, with a theme of

  7. Off-axis dose equivalent due to secondary neutrons from uniform scanning proton beams during proton radiotherapy

    Science.gov (United States)

    Islam, M. R.; Collums, T. L.; Zheng, Y.; Monson, J.; Benton, E. R.

    2013-11-01

    The production of secondary neutrons is an undesirable byproduct of proton therapy and it is important to quantify the contribution from secondary neutrons to patient dose received outside the treatment volume. The purpose of this study is to investigate the off-axis dose equivalent from secondary neutrons experimentally using CR-39 plastic nuclear track detectors (PNTD) at ProCure Proton Therapy Center, Oklahoma City, OK. In this experiment, we placed several layers of CR-39 PNTD laterally outside the treatment volume inside a phantom and in air at various depths and angles with respect to the primary beam axis. Three different proton beams with max energies of 78, 162 and 226 MeV and 4 cm modulation width, a 5 cm diameter brass aperture, and a small snout located 38 cm from isocenter were used for the entire experiment. Monte Carlo simulations were also performed based on the experimental setup using a simplified snout configuration and the FLUKA Monte Carlo radiation transport code. The measured ratio of secondary neutron dose equivalent to therapeutic primary proton dose (H/D) ranged from 0.3 ± 0.08 mSv Gy-1 for 78 MeV proton beam to 37.4 ± 2.42 mSv Gy-1 for 226 MeV proton beam. Both experiment and simulation showed a similar decreasing trend in dose equivalent with distance to the central axis and the magnitude varied by a factor of about 2 in most locations. H/D was found to increase as the energy of the primary proton beam increased and higher H/D was observed at 135° compared to 45° and 90°. The overall higher H/D in air indicates the predominance of external neutrons produced in the nozzle rather than inside the body.

  8. Off-axis dose equivalent due to secondary neutrons from uniform scanning proton beams during proton radiotherapy

    International Nuclear Information System (INIS)

    Islam, M R; Collums, T L; Monson, J; Benton, E R; Zheng, Y

    2013-01-01

    The production of secondary neutrons is an undesirable byproduct of proton therapy and it is important to quantify the contribution from secondary neutrons to patient dose received outside the treatment volume. The purpose of this study is to investigate the off-axis dose equivalent from secondary neutrons experimentally using CR-39 plastic nuclear track detectors (PNTD) at ProCure Proton Therapy Center, Oklahoma City, OK. In this experiment, we placed several layers of CR-39 PNTD laterally outside the treatment volume inside a phantom and in air at various depths and angles with respect to the primary beam axis. Three different proton beams with max energies of 78, 162 and 226 MeV and 4 cm modulation width, a 5 cm diameter brass aperture, and a small snout located 38 cm from isocenter were used for the entire experiment. Monte Carlo simulations were also performed based on the experimental setup using a simplified snout configuration and the FLUKA Monte Carlo radiation transport code. The measured ratio of secondary neutron dose equivalent to therapeutic primary proton dose (H/D) ranged from 0.3 ± 0.08 mSv Gy −1  for 78 MeV proton beam to 37.4 ± 2.42 mSv Gy −1  for 226 MeV proton beam. Both experiment and simulation showed a similar decreasing trend in dose equivalent with distance to the central axis and the magnitude varied by a factor of about 2 in most locations. H/D was found to increase as the energy of the primary proton beam increased and higher H/D was observed at 135° compared to 45° and 90°. The overall higher H/D in air indicates the predominance of external neutrons produced in the nozzle rather than inside the body. (paper)

  9. Gut microbiota’s effect on mental health: The gut-brain axis

    Directory of Open Access Journals (Sweden)

    Megan Clapp

    2017-09-01

    Full Text Available The bidirectional communication between the central nervous system and gut microbiota, referred to as the gut-brain-axis, has been of significant interest in recent years. Increasing evidence has associated gut microbiota to both gastrointestinal and extragastrointestinal diseases. Dysbiosis and inflammation of the gut have been linked to causing several mental illnesses including anxiety and depression, which are prevalent in society today. Probiotics have the ability to restore normal microbial balance, and therefore have a potential role in the treatment and prevention of anxiety and depression. This review aims to discuss the development of the gut microbiota, the linkage of dysbiosis to anxiety and depression, and possible applications of probiotics to reduce symptoms.

  10. 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

  11. An Update on Modifications to Water Treatment Plant Model

    Science.gov (United States)

    Water treatment plant (WTP) model is an EPA tool for informing regulatory options. WTP has a few versions: 1). WTP2.2 can help in regulatory analysis. An updated version (WTP3.0) will allow plant-specific analysis (WTP-ccam) and thus help meet plant-specific treatment objectives...

  12. 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...

  13. 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...

  14. Active Design Method for the Static Characteristics of a Piezoelectric Six-Axis Force/Torque Sensor

    OpenAIRE

    Liu, Jun; Li, Min; Qin, Lan; Liu, Jingcheng

    2014-01-01

    To address the bottleneck issues of an elastic-style six-axis force/torque sensor (six-axis force sensor), this work proposes a no-elastic piezoelectric six-axis force sensor. The operating principle of the piezoelectric six-axis force sensor is analyzed, and a structural model is constructed. The static-active design theory of the piezoelectric six-axis force sensor is established, including a static analytical/mathematical model and numerical simulation model (finite element model). A piezo...

  15. Evolution of hypothalamus-pituitary growth axis among fish, amphibian, birds and mammals

    Directory of Open Access Journals (Sweden)

    Moaeen-Ud-Din M.

    2015-01-01

    Full Text Available Hypothalamus-pituitary growth axis (HP growth axis regulates animal growth and development in pre-natal and post natal life governed by many factors. However, until recently, the evolutionary history of this axis among lineages is not understood. Aim of the present study was to understand the major events in evolution and evolutionary history and trend of HP growth axis. The diversity among Homo sapience, Mus musculus, Rattus norvegicus, Gallus gallus, Danio rerio and Xenopus laevis was determined for genes involved in HP growth axis in current study. Sequences of HP growth axis genes were retrieved from NCBI (http://www.ncbi.nlm.nih.gov/. Nucleotide diversity using Kimura’s two-parameter method; codon-based test of positive selection using the Nei-Gojobori; equality of evolutionary rate with Tajima's relative rate test and phylogenetic history using the RelTime method were estimated in MEGA6. Estimates of the coefficients of evolutionary differentiation based on nucleotides and amino acids substitution patterns of HP growth axis genes showed contrasting evolutionary patterns among the lineages. The results demonstrated that although these genes might have crucial functional roles in each of the species, however, their sequence divergence did not necessarily reflect similar molecular evolution among the species. Codon-based test of positive selection revealed that Human vs Mouse, Chicken vs Rat, Human vs Rat and Mouse vs Rat had similar and higher non synonymous substitutions (P > 0.05. Higher rate of non-synonymous substitutions at similar orthologs level among species indicated a similar positive selection pressure in these species. Results for relative rate test assessed with the chi-squared test showed difference on unique mutations among lineages at synonymous and non synonymous sites except Chicken vs Mouse, Human vs Mouse, Chicken vs Rat, Human vs Rat and Mouse vs Rat. This indicated that the mutagenic process that generates

  16. Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

    Science.gov (United States)

    van Bodegom, Miranda; Homberg, Judith R.; Henckens, Marloes J. A. G.

    2017-01-01

    Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA-axis

  17. 78 FR 62784 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2013-10-22

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer... 5210 (Publication of Transactions and Quotations) October 4, 2013. I. Introduction On August 15, 2013, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

  18. Research on the aerodynamic characteristics of a lift drag hybrid vertical axis wind turbine

    Directory of Open Access Journals (Sweden)

    Xiaojing Sun

    2016-01-01

    Full Text Available Compared with a drag-type vertical axis wind turbines, one of the greatest advantages for a lift-type vertical axis wind turbines is its higher power coefficient (Cp. However, the lift-type vertical axis wind turbines is not a self-starting turbine as its starting torque is very low. In order to combine the advantage of both the drag-type and the lift-type vertical axis wind turbines, a lift drag hybrid vertical axis wind turbines was designed in this article and its aerodynamics and starting performance was studied in detail with the aid of computational fluid dynamics simulations. Numerical results indicate that the power coefficient of this lift drag hybrid vertical axis wind turbines declines when the distance between its drag-type blades and the center of rotation of the turbine rotor increases, whereas its starting torque can be significantly improved. Studies also show that unlike the lift-type vertical axis wind turbines, this lift drag hybrid-type vertical axis wind turbines could be able to solve the problem of low start-up torque. However, the installation position of the drag blade is very important. If the drag blade is mounted very close to the spindle, the starting torque of the lift drag hybrid-type vertical axis wind turbines may not be improved at all. In addition, it has been found that the power coefficient of the studied vertical axis wind turbines is not as good as expected and possible reasons have been provided in this article after the pressure distribution along the surfaces of the airfoil-shaped blades of the hybrid turbine was analyzed.

  19. Modal Analysis on Fluid-Structure Interaction of MW-Level Vertical Axis Wind Turbine Tower

    Directory of Open Access Journals (Sweden)

    Tan Jiqiu

    2014-05-01

    Full Text Available In order to avoid resonance problem of MW-level vertical axis wind turbine induced by wind, a flow field model of the MW-level vertical axis wind turbine is established by using the fluid flow control equations, calculate flow’s velocity and pressure of the MW-level vertical axis wind turbine and load onto tower’s before and after surface, study the Modal analysis of fluid-structure interaction of MW-level vertical axis wind turbine tower. The results show that fluid-structure interaction field of MW- level vertical axis wind turbine tower has little effect on the modal vibration mode, but has a great effect on its natural frequency and the maximum deformation, and the influence will decrease with increasing of modal order; MW-level vertical axis wind turbine tower needs to be raised the stiffness and strength, its structure also needs to be optimized; In the case of satisfy the intensity, the larger the ratio of the tower height and wind turbines diameter, the more soft the MW-level vertical axis wind turbine tower, the lower its frequency.

  20. Patient-Focused Benefit-Risk Analysis to Inform Regulatory Decisions: The European Union Perspective.

    Science.gov (United States)

    Mühlbacher, Axel C; Juhnke, Christin; Beyer, Andrea R; Garner, Sarah

    Regulatory decisions are often based on multiple clinical end points, but the perspectives used to judge the relative importance of those end points are predominantly those of expert decision makers rather than of the patient. However, there is a growing awareness that active patient and public participation can improve decision making, increase acceptance of decisions, and improve adherence to treatments. The assessment of risk versus benefit requires not only information on clinical outcomes but also value judgments about which outcomes are important and whether the potential benefits outweigh the harms. There are a number of mechanisms for capturing the input of patients, and regulatory bodies within the European Union are participating in several initiatives. These can include patients directly participating in the regulatory decision-making process or using information derived from patients in empirical studies as part of the evidence considered. One promising method that is being explored is the elicitation of "patient preferences." Preferences, in this context, refer to the individual's evaluation of health outcomes and can be understood as statements regarding the relative desirability of a range of treatment options, treatment characteristics, and health states. Several methods for preference measurement have been proposed, and pilot studies have been undertaken to use patient preference information in regulatory decision making. This article describes how preferences are currently being considered in the benefit-risk assessment context, and shows how different methods of preference elicitation are used to support decision making within the European context. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  1. Cloning and bioinformatic analysis of lovastatin biosynthesis regulatory gene lovE.

    Science.gov (United States)

    Huang, Xin; Li, Hao-ming

    2009-08-05

    Lovastatin is an effective drug for treatment of hyperlipidemia. This study aimed to clone lovastatin biosynthesis regulatory gene lovE and analyze the structure and function of its encoding protein. According to the lovastatin synthase gene sequence from genebank, primers were designed to amplify and clone the lovastatin biosynthesis regulatory gene lovE from Aspergillus terrus genomic DNA. Bioinformatic analysis of lovE and its encoding animo acid sequence was performed through internet resources and software like DNAMAN. Target fragment lovE, almost 1500 bp in length, was amplified from Aspergillus terrus genomic DNA and the secondary and three-dimensional structures of LovE protein were predicted. In the lovastatin biosynthesis process lovE is a regulatory gene and LovE protein is a GAL4-like transcriptional factor.

  2. 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 ...

  3. 75 FR 21686 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-04-26

    ... to pay arbitration awards to remain in the securities industry presents regulatory risks and is...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule... Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC'' or...

  4. 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.

  5. Brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis adaptation processes in a depressive-like state induced by chronic restraint stress.

    Science.gov (United States)

    Naert, Gaelle; Ixart, Guy; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

    2011-01-01

    Depression is potentially life-threatening. The most important neuroendocrine abnormality in this disorder is hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. Recent findings suggest that all depression treatments may boost the neurotrophin production especially brain-derived neurotrophic factor (BDNF). Moreover, BDNF is highly involved in the regulation of HPA axis activity. The aim of this study was to determine the impact of chronic stress (restraint 3h/day for 3 weeks) on animal behavior and HPA axis activity in parallel with hippocampus, hypothalamus and pituitary BDNF levels. Chronic stress induced changes in anxiety (light/dark box test) and anhedonic states (sucrose preference test) and in depressive-like behavior (forced swimming test); general locomotor activity and body temperature were modified and animal body weight gain was reduced by 17%. HPA axis activity was highly modified by chronic stress, since basal levels of mRNA and peptide hypothalamic contents in CRH and AVP and plasma concentrations in ACTH and corticosterone were significantly increased. The HPA axis response to novel acute stress was also modified in chronically stressed rats, suggesting adaptive mechanisms. Basal BDNF contents were increased in the hippocampus, hypothalamus and pituitary in chronically stressed rats and the BDNF response to novel acute stress was also modified. This multiparametric study showed that chronic restraint stress induced a depressive-like state that was sustained by mechanisms associated with BDNF regulation. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Team structure and regulatory focus: the impact of regulatory fit on team dynamic.

    Science.gov (United States)

    Dimotakis, Nikolaos; Davison, Robert B; Hollenbeck, John R

    2012-03-01

    We report a within-teams experiment testing the effects of fit between team structure and regulatory task demands on task performance and satisfaction through average team member positive affect and helping behaviors. We used a completely crossed repeated-observations design in which 21 teams enacted 2 tasks with different regulatory focus characteristics (prevention and promotion) in 2 organizational structures (functional and divisional), resulting in 84 observations. Results suggested that salient regulatory demands inherent in the task interacted with structure to determine objective and subjective team-level outcomes, such that functional structures were best suited to (i.e., had best fit with) tasks with a prevention regulatory focus and divisional structures were best suited to tasks with a promotion regulatory focus. This contingency finding integrates regulatory focus and structural contingency theories, and extends them to the team level with implications for models of performance, satisfaction, and team dynamics.

  7. The Mechanical Axis of the First Ray: A Radiographic Assessment in Hallux Abducto Valgus Evaluation.

    Science.gov (United States)

    LaPorta, Guido A; Nasser, Ellianne M; Mulhern, Jennifer L; Malay, D Scot

    2016-01-01

    The present report describes a new method of hallux abducto valgus deformity correction planning using the mechanical axis of the medial column (mechanical axis planning). This method of radiographic evaluation identifies an ideal position for the first metatarsal after correction and is useful regardless of the surgical procedure chosen. We retrospectively reviewed 200 radiographs to identify a "normal" value for the mechanical axis angle. We reviewed 100 radiographs of patients with hallux abducto valgus deformity (deformity group) and 100 radiographs of patients without hallux abducto valgus deformity (control group). The deformity group revealed an M1-M2 anatomic axis angle of 13.5° ± 2.83° and an M1-M2 mechanical axis angle of 11.58° ± 1°. The control group revealed an M1-M2 anatomic axis angle of 7.5° ± 1.76° and an M1-M2 mechanical axis angle of 11.19° ± 0.9°. The differences in the M1-M2 anatomic axis angle and M1-M2 mechanical axis angle were statistically significant between the control and deformity groups. We sought to provide a reliable method for planning hallux abducto valgus deformity correction by aligning the mechanical axis of the medial column and the mechanical axis of the first ray to the "normal" value of 11° to reduce the deformity. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  8. HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients.

    Science.gov (United States)

    Jokinen, Jussi; Nordström, Peter

    2008-11-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behaviour and age-associated alterations in HPA axis functioning may render elderly individuals more susceptible to HPA dysregulation related to mood disorders. Research on HPA axis function in suicide prediction in elderly mood disorder patients is sparse. The study sample consisted of 99 depressed elderly inpatients 65 years of age or older admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. The hypothesis was that elderly mood disorder inpatients who fail to suppress cortisol in the dexamethasone suppression test (DST) are at higher risk of suicide. The DST non-suppression distinguished between suicides and survivors in elderly depressed inpatients and the suicide attempt at the index episode was a strong predictor for suicide. Additionally, the DST non-suppression showed higher specificity and predictive value in the suicide attempter group. Due to age-associated alterations in HPA axis functioning, the optimal cut-off for DST non-suppression in suicide prediction may be higher in elderly mood disorder inpatients. These data demonstrate the importance of attempted suicide and DST non-suppression as predictors of suicide risk in late-life depression and suggest the use for neuroendocrine testing of HPA axis functioning as a complementary tool in suicide prevention.

  9. 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.

  10. 75 FR 5157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-02-01

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... Consolidated FINRA Rulebook January 25, 2010. On December 2, 2009, the Financial Industry Regulatory Authority... later in the rulebook consolidation process. It is therefore ordered, pursuant to Section 19(b)(2) of...

  11. 77 FR 47470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2012-08-08

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Withdrawal of Proposed Rule Change To Adopt FINRA Rule 2231 (Customer Account Statements) in the Consolidated FINRA Rulebook August 2, 2012. On April 22, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a...

  12. 76 FR 21084 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2011-04-14

    ... Securities April 8, 2011. I. Introduction On March 3, 2011, the Financial Industry Regulatory Authority, Inc... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64283; File No. SR-FINRA-2011-012] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer...

  13. Electromechanical three-axis development for remote handling in the Hot Experimental Facility

    International Nuclear Information System (INIS)

    Garin, J.; Bolfing, B.J.; Satterlee, P.E.; Babcock, S.M.

    1981-01-01

    A three-axis closed-loop position control system has been designed and installed on an overhead bridge, carriage, tube hoist for automotive positioning of manipulation at a remotely maintained work site. The system provides accurate (within 3 min) and repeatable three-axis positioning of the manipulator. The position control system has been interfaced to a supervisory minicomputer system that provides teach-playback capability of manipulator positioning and color graphic display of the three-axis system position

  14. Unusual aneurysm of the pancreas arcade by occlusion of the celiac axis

    International Nuclear Information System (INIS)

    Wrazidlo, W.; Jonas, J.; Wittek, M.

    1987-01-01

    This is a report about a rare aneurysm of the pancreas arcade - the angiography showing an occlusion of the celiac axis. Using a diagram of the arterial phase of the angiography, the morphology of the collateral circulation between the celiac axis and the superior mesenteric artery is described. The reason of the occlusion of the celiac axis formed collateral circulation and the origin of the aneurysm and the therapeutic steps to be taken are discussed. (orig.) [de

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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)

  20. 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

  1. Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review.

    Science.gov (United States)

    Azuma, Kagaku; Zhou, Qian; Niwa, Masami; Kubo, Kin-Ya

    2017-08-03

    Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid (GC). Epidemiologic studies suggest that masticatory dysfunction in aged individuals, such as that resulting from tooth loss and periodontitis, acting as a source of chronic stress, activates the HPA axis, leading to increases in circulating GCs and eventually inducing various physical and psychological diseases, such as cognitive impairment, cardiovascular disorders, and osteoporosis. Recent studies demonstrated that masticatory stimulation or chewing during stressful conditions suppresses the hyperactivity of the HPA axis via GCs and GC receptors within the hippocampus, and ameliorates chronic stress-induced hippocampus-dependent cognitive deficits. Here, we provide a comprehensive overview of current research regarding the association between mastication, the hippocampus, and HPA axis activity. We also discuss several potential molecular mechanisms involved in the interactions between mastication, hippocampal function, and HPA axis activity.

  2. Congenital axis dysmorphism in a medieval skeleton : …secunda a vertendo epistropheus….

    Science.gov (United States)

    Travan, Luciana; Saccheri, Paola; Toso, Francesco; Crivellato, Enrico

    2013-05-01

    We describe here the axis dysmorphism that we observed in the skeletal remains of a human child dug up from a fifteenth century cemetery located in north-eastern Italy. This bone defect is discussed in the light of pertinent literature. We performed macroscopical examination and CT scan analysis of the axis. Axis structure was remarkably asymmetric. Whilst the left half exhibited normal morphology, the right one was smaller than normal, and its lateral articular surface showed horizontal orientation. In addition, the odontoid process appeared leftward deviated and displayed a supplementary articular-like facet situated on the right side of its surface. These findings suggest a diagnosis of unilateral irregular segmentation of atlas and axis, a rare dysmorphism dependent upon disturbances of notochordal development in early embryonic life. Likewise other malformations of the craniovertebral junction, this axis defect may alter the delicate mechanisms of upper neck movements and cause a complex series of clinical symptoms. This is an emblematic case whereby human skeletal remains may provide valuable information on the anatomical defects of craniovertebral junction.

  3. 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 ...

  4. Resveratrol ameliorates the anxiety- and depression-like behavior of subclinical hypothyroidism rat: possible involvement of the HPT axis, HPA axis, and Wnt/β-catenin pathway

    Directory of Open Access Journals (Sweden)

    Jinfang eGe

    2016-05-01

    Full Text Available Metabolic disease subclinical hypothyroidism (SCH is closely associated with depression-like behavior both in human and animal studies, and our previous studies have identified the antidepressant effect of resveratrol (RES in stressed rat model. The aim of this study was to investigate whether RES would manifest an antidepressant effect in SCH rat model and explore the possible mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization, after which the model rats in the RES and LT4 groups received a daily intragastric injection of RES at the dose of 15 mg/kg or LT4 at the dose of 60 μg/kg for 16 days, respectively. The rats’ plasma concentrations of thyroid hormones were measured. Behavioral performance and hypothalamic-pituitary-adrenal (HPA activity were evaluated. The protein expression levels of the Wnt/β-catenin in the hippocampus were detected by western blot. The results showed that RES treatment down-regulated the elevated plasma thyroid stimulating hormone (TSH concentration and the hypothalamic mRNA expression of thyrotropin releasing hormone (TRH in the SCH rats. RES-treated rats showed increased rearing frequency and distance in the OFT, increased sucrose preference in the SPT, and decreased immobility in the FST compared with SCH rats. The ratio of the adrenal gland weight to body weight, the plasma corticosterone levels and the hypothalamic CRH mRNA expression were reduced in the RES-treated rats. Moreover, RES treatment up-regulated the relative ratio of phosphorylated-GSK3β (p-GSK3β/GSK3β and protein levels of p-GSK3β, cyclinD1 and c-myc, while down-regulating the relative ratio of phosphorylated-β-catenin (p-β-catenin/β-catenin and expression of GSK3β in the hippocampus. These findings suggest that RES exerts anxiolytic- and antidepressant-like effect in SCH rats by down-regulating hyperactivity of the HPA axis and regulating both the HPT axis and the Wnt/β-catenin pathway.

  5. 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

  6. HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients.

    Science.gov (United States)

    Jokinen, Jussi; Nordström, Peter

    2009-07-01

    Hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis is a consistent finding in Major Depressive Disorder (MDD) and most prospective studies of HPA-axis function have found that non-suppressors in the dexamethasone suppression test (DST) are more likely to commit suicide during follow-up. The results of studies on HPA-axis function and attempted suicide are less consistent. Suicide attempts are more common among young people than the elderly, whereas suicide is more common among the elderly. The impact of age related changes in HPA-axis system activity in relation to suicidal behaviour across the lifecycle may be of importance. The aim of the present study was to investigate the DST results in 36 young adult (30 years or younger) inpatients with mood disorder, with (n=18) and without suicide attempt at the index episode. The DST non-suppressor rate was 25% among young mood disorder inpatients. DST non-suppression was associated with suicide attempt and post-dexamethasone serum cortisol at 11:00 p.m. was significantly higher in suicide attempters compared to non-attempters. The DST non-suppressor rate was 39% in young adult suicide attempters compared with 11% in non-attempters. The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behaviour. The present findings motivate to include HPA axis measures in the assessment of depression in young adults.

  7. The ROS/SUMO Axis Contributes to the Response of Acute Myeloid Leukemia Cells to Chemotherapeutic Drugs

    Directory of Open Access Journals (Sweden)

    Guillaume Bossis

    2014-06-01

    Full Text Available Chemotherapeutic drugs used in the treatment of acute myeloid leukemias (AMLs are thought to induce cancer cell death through the generation of DNA double-strand breaks. Here, we report that one of their early effects is the loss of conjugation of the ubiquitin-like protein SUMO from its targets via reactive oxygen species (ROS-dependent inhibition of the SUMO-conjugating enzymes. Desumoylation regulates the expression of specific genes, such as the proapoptotic gene DDIT3, and helps induce apoptosis in chemosensitive AMLs. In contrast, chemotherapeutics do not activate the ROS/SUMO axis in chemoresistant cells. However, pro-oxidants or inhibition of the SUMO pathway by anacardic acid restores DDIT3 expression and apoptosis in chemoresistant cell lines and patient samples, including leukemic stem cells. Finally, inhibition of the SUMO pathway decreases tumor growth in mice xenografted with AML cells. Thus, targeting the ROS/SUMO axis might constitute a therapeutic strategy for AML patients resistant to conventional chemotherapies.

  8. Analysis of deuterium relaxation-derived methyl axis order parameters and correlation with local structure

    International Nuclear Information System (INIS)

    Mittermaier, Anthony; Kay, Lewis E.; Forman-Kay, Julie D.

    1999-01-01

    Methyl axis (S2axis) and backbone NH (S2NH) order parameters derived from eight proteins have been analyzed. Similar distribution profiles for Ala S2axis and S2NH order parameters were observed. A good correlation between the two S2axis values of Val and Leu methyl groups is noted, although differences between order parameters can arise. The relation of S2axis or S2NH to solvent accessibility and packing density has also been investigated. Correlations are weak, likely reflecting the importance of collective, non-local motions in proteins. The lack of correlation between these simple structural parameters and dynamics emphasizes the importance of motional studies to fully characterize proteins

  9. 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

  10. Risk-informing special treatment requirements for reactors

    International Nuclear Information System (INIS)

    McKenna, E.M.; Reed, T.A.

    2001-01-01

    The U.S. Nuclear Regulatory Commission (NRC) is proposing to make regulatory changes to the scope of structures, systems, and components (SSCs) requiring special treatment. ''Special treatment requirements'' refers to those specific examples of regulations that are applied in order to provide a high degree of assurance that SSC will be capable of performing their intended functions when needed. The current scope of SSCs covered by the special treatment requirements governing commercial nuclear reactors is deterministically based and stems primarily from the evaluation of selected design basis events, as described in updated final safety analysis reports (UFSARs). This regulatory framework provides reasonable assurance of no undue risk to the health and safety of the public. However, recent advances in technology, coupled with operating reactor experience, have suggested that an alternative approach that would use a risk-informed process for evaluating SSC safety significance, would, in turn, result in a more focused determination of which SSCs should receive special treatment requirements. (author)

  11. 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.

  12. 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)

  13. Optimal shape of a cold-neutron triple-axis spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Lefmann, K., E-mail: lefmann@fys.ku.d [Nanoscience and eScience Centers, Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen O (Denmark); European Spallation Source, University of Lund, St. Algatan 4, Lund (Sweden); Filges, U. [Laboratory for Development and Methods, Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Treue, F. [Nanoscience and eScience Centers, Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen O (Denmark); Kirkensgard, J.J.K. [Institute of Nature and Models, Roskilde University (Denmark); Department of Basic Sciences and Environment, Faculty of Life Sciences, University of Copenhagen (Denmark); Plesner, B. [Institute of Nature and Models, Roskilde University (Denmark); Hansen, K.S. [Institute of Nature and Models, Roskilde University (Denmark); Mid-Greenland High School, Nuuk, Greenland (Denmark); Kleno, K.H. [Nanoscience and eScience Centers, Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen O (Denmark); European Spallation Source, University of Lund, St. Algatan 4, Lund (Sweden)

    2011-04-01

    We have performed a McStas optimization of the primary spectrometer for a generic 40 m long, cold-neutron triple-axis spectrometer with a doubly focusing monochromator. The optimal design contains an elliptically focusing guide, a virtual source point before a low-grade PG monochromator, and non-equidistant focusing at the monochromator. The flux at 5 meV shows a gain factor 12 over the 'classical' design with a straight 12x3cm{sup 2}, m=2 guide and a vertically focusing PG monochromator. In addition, the energy resolution was found to be improved. This unexpectedly large design improvement agrees with the Liouville theorem and can be understood as the product of many smaller gain factors, combined with a more optimal utilization of the beam divergence within the guide. Our results may be relevant for a possible upgrade of a number of cold-neutron triple-axis spectrometers-and for a possible triple-axis spectrometer at the European Spallation Source.

  14. THERMAL DISPLACEMENT OF CRANKSHAFT AXIS OF SLOW-SPEED MARINE ENGINE

    Directory of Open Access Journals (Sweden)

    Lech Murawski

    2016-08-01

    Full Text Available The paper presents analysis of displacement of a crankshaft axis caused by temperature of marine, slow-speed main engine. Information of thermal displacement of a power transmission system axis is significant during a shaft line alignment and a crankshaft springing analysis. Warmed-up main engine is a source of deformations of an engine body as well as a ship hull in the area of an engine room and hence axis of a crankshaft and a shaftline. Engines' producers recommend the model of parallel displacement of the crankshaft axis under the influence of an engine heat. The model gives us the value (one number! of the crankshaft axis displacement in the hot propulsion system's condition. This model may be too simple in some cases. Presented numerical analyses are based on temperature measurements of the main engine body and the ship hull during a sea voyage. The paper presents computations of MAN B&W K98MC type engine (power: 40000 kW, revolutions: 94 rpm mounted on 4500 TEU container ship (length: 290 m. Propulsion system is working in nominal, steady-state conditions; it is the basic assumption during the analyses. Numerical analyses were preformed with usage of Nastran software based on Finite Element Method. The FEM model of the engine body comprised over 800 thousand degree of freedom. Stiffness of the ship hull (mainly double bottom with the foundation was modelled by a simple cuboid. Material properties of that cuboid were determined on the base of separately performed calculations.

  15. Determinants of the epithelial-muscular axis on embryonic stem cell-derived gut-like structures.

    Science.gov (United States)

    Luo, Yi; Takaki, Miyako; Misawa, Hiromi; Matsuyoshi, Hiroko; Sasahira, Tomonori; Chihara, Yoshitomo; Fujii, Kiyomu; Ohmori, Hitoshi; Kuniyasu, Hiroki

    2010-01-01

    Dome-like structures with epithelial-muscular layers resembling the gut have been derived from mouse embryonic stem (ES) cells. These domes have been reported to show spontaneous contractions and are called ES gut. In the present study, we examined the epithelial-muscular axis of these domes by detecting differentiation markers. A normal epithelial-muscular axis was exhibited in the domes with spontaneous motility, whereas the domes without spontaneous motility showed either an inverted or obscure axis. To investigate the factors affecting the epithelial-muscular axis, we examined the expression of hedgehog signaling factors in the domes. Expression of hedgehog family factors was detected in the epithelial components of the domes with motility, whereas this expression was inverted or obscure in the domes without motility. Out of the 25 domes, 10 of the 10 motility (+) domes showed a normal epithelial-muscular axis, whereas 14 of the 15 motility (-) domes lacked a normal epithelial-muscular axis. This implies that activin A upregulated the expression of sonic hedgehog and intestinal alkaline phosphatase in the embryoid bodies. These findings suggest that the motility of the ES gut depends on the domes' epithelial-muscular axis. Copyright © 2010 S. Karger AG, Basel.

  16. 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.

  17. The emergence of treatment wetlands

    International Nuclear Information System (INIS)

    Cole, S.

    1998-01-01

    Judging by the growing number of wetlands built for wastewater treatment around the world, this natural technology seems to have firmly established roots. After almost 30 years of use in wastewater treatment, constructed treatment wetlands now number over 500 in Europe and 600 in North America. Marsh-type surface flow systems are most common in North America, but subsurface flow wetlands, where wastewater flows beneath the surface of a gravel-rock bed, predominate in Europe. The inexpensive, low maintenance technology is in high demand in Central America, Eastern Europe, and Asia. New applications, from nitrate-contaminated ground water to effluent from high-intensity livestock operations, are also increasing. But in the United States, treatment-wetland technology has not yet gained national regulatory acceptance. Some states and EPA regions are eager to endorse them, but others are wary of this nontraditional method of treating wastewater. In part, this reluctance exists because the technology is not yet completely understood. Treatment wetlands also pose a potential threat to wildlife attracted to this new habitat -an ecosystem exposed to toxic compounds. New efforts are under way, however, to place the technology onto firmer scientific and regulatory ground. Long-term demonstration and monitoring field studies are currently probing the inner workings of wetlands and their water quality capabilities to provide better data on how to design more effective systems. A recent study of US policy and regulatory issues surrounding treatment wetlands has recommended that the federal government actively promote the technology and clear the regulatory roadblocks to enable wider use. Proponents argue that the net environmental benefits of constructed wetlands, such as restoring habitat and increasing wetlands inventory, should be considered. 8 refs., 6 photos

  18. 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...

  19. The anteroposterior axis of the tibia in Korean patients undergoing total knee replacement.

    Science.gov (United States)

    Kim, C W; Seo, S S; Kim, J H; Roh, S M; Lee, C R

    2014-11-01

    The aim of this study was to find anatomical landmarks for rotational alignment of the tibial component in total knee replacement (TKR) in a CT-based study. Pre-operative CT scanning was performed on 94 South Korean patients (nine men, 85 women, 188 knees) with osteoarthritis of the knee joint prior to TKR. The tibial anteroposterior (AP) axis was defined as a line perpendicular to the femoral surgical transepicondylar axis and passing through the centre of the posterior cruciate ligament (PCL). The angles between the defined tibial AP axis and anatomical landmarks at various levels of the tibia were measured. The mean values of the angles between the defined tibial AP axis and the line connecting the anterior border of the proximal third of the tibia to the centre of the PCL was -0.2° (-17 to 14.1, sd 4.1). This was very close to the defined tibial axis, and remained so regardless of lower limb alignment and the degree of tibial bowing. Therefore, AP axis defined as described, is a reliable anatomical landmark for rotational alignment of tibial components. ©2014 The British Editorial Society of Bone & Joint Surgery.

  20. Adolescent Survivors of Hurricane Katrina: A Pilot Study of Hypothalamic-Pituitary-Adrenal Axis Functioning

    Science.gov (United States)

    Pfefferbaum, Betty; Tucker, Phebe; Nitiéma, Pascal

    2015-01-01

    Background: The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important biological component of the stress response commonly studied through the measurement of cortisol. Limited research has examined HPA axis dysregulation in youth exposed to disasters. Objective: This study examined HPA axis activation in adolescent Hurricane Katrina…

  1. 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.

  2. 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...

  3. 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

  4. PRMT8 Controls the Pluripotency and Mesodermal Fate of Human Embryonic Stem Cells By Enhancing the PI3K/AKT/SOX2 Axis.

    Science.gov (United States)

    Jeong, Ho-Chang; Park, Soon-Jung; Choi, Jong-Jin; Go, Young-Hyun; Hong, Soon-Ki; Kwon, Ok-Seon; Shin, Joong-Gon; Kim, Rae-Kwon; Lee, Mi-Ok; Lee, Su-Jae; Shin, Hyoung Doo; Moon, Sung-Hwan; Cha, Hyuk-Jin

    2017-09-01

    Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferase 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions. Direct interaction of membrane-localized PRMT8 with p85, a regulatory subunit of PI3K, was associated with accumulation of phosphoinositol 3-phosphate and consequently high AKT activity. Furthermore, the SOX2 induction, which was controlled by the PRMT8/PI3K/AKT axis, was linked to mesodermal lineage differentiation. Thus, we propose that PRMT8 in hESCs plays an important role not only in maintaining pluripotency but also in controlling mesodermal differentiation through bFGF signaling toward the PI3K/AKT/SOX2 axis. Stem Cells 2017;35:2037-2049. © 2017 AlphaMed Press.

  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. Tooth axis and skeletal structures in mandibular molar vertical sections in jaw deformity with facial asymmetry using MPR images

    International Nuclear Information System (INIS)

    Nojima, Kunihiko; Yokose, Taishi; Ishii, Takenobu; Kobayashi, Makoto; Nishii, Yasushi

    2007-01-01

    asymmetry in the buccolingual inclination of the tooth axis of the molar region during presurgical orthodontic treatment is important in achieving favorable post-treatment occlusal stability and facial symmetry. (author)

  7. 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.

  8. Active design method for the static characteristics of a piezoelectric six-axis force/torque sensor.

    Science.gov (United States)

    Liu, Jun; Li, Min; Qin, Lan; Liu, Jingcheng

    2014-01-02

    To address the bottleneck issues of an elastic-style six-axis force/torque sensor (six-axis force sensor), this work proposes a no-elastic piezoelectric six-axis force sensor. The operating principle of the piezoelectric six-axis force sensor is analyzed, and a structural model is constructed. The static-active design theory of the piezoelectric six-axis force sensor is established, including a static analytical/mathematical model and numerical simulation model (finite element model). A piezoelectric six-axis force sensor experimental prototype is developed according to the analytical mathematical model and numerical simulation model, and selected static characteristic parameters (including sensitivity, isotropic degree and cross-coupling) are tested using this model with three approaches. The measured results are in agreement with the analytical results from the static-active design method. Therefore, this study has successfully established a foundation for further research into the piezoelectric multi-axis force sensor and an overall design approach based on static characteristics.

  9. Method for the mechanical axis alignment of the linear induction accelerator

    International Nuclear Information System (INIS)

    Li Hong; China Academy of Engineering Physics, Mianyang; Yao Jin; Liu Yunlong; Zhang Linwen; Deng Jianjun

    2004-01-01

    Accurate mechanical axis alignment is a basic requirement for assembling a linear induction accelerator (LIA). The total length of an LIA is usually over thirty or fifty meters, and it consists of many induction cells. By using a laser tracker a new method of mechanical axis alignment for LIA is established to achieve the high accuracy. This paper introduces the method and gives implementation step and point position measure errors of the mechanical axis alignment. During the alignment process a 55 m-long alignment control survey net is built, and the theoretic revision of the coordinate of the control survey net is presented. (authors)

  10. 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...

  11. Modal Analysis on Fluid-Structure Interaction of MW-Level Vertical Axis Wind Turbine Tower

    OpenAIRE

    Tan Jiqiu; Zhong Dingqing; Wang Qiong

    2014-01-01

    In order to avoid resonance problem of MW-level vertical axis wind turbine induced by wind, a flow field model of the MW-level vertical axis wind turbine is established by using the fluid flow control equations, calculate flow’s velocity and pressure of the MW-level vertical axis wind turbine and load onto tower’s before and after surface, study the Modal analysis of fluid-structure interaction of MW-level vertical axis wind turbine tower. The results show that fluid-structure interaction fie...

  12. 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...

  13. 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...

  14. 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...

  15. 77 FR 34379 - Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory...

    Science.gov (United States)

    2012-06-11

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD06-6-000] Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold a joint meeting...

  16. Regulatory T-Cell Augmentation or Interleukin-17 Inhibition Prevents Calcineurin Inhibitor-Induced Hypertension in Mice.

    Science.gov (United States)

    Chiasson, Valorie L; Pakanati, Abhinandan R; Hernandez, Marcos; Young, Kristina J; Bounds, Kelsey R; Mitchell, Brett M

    2017-07-01

    The immunosuppressive calcineurin inhibitors cyclosporine A and tacrolimus alter T-cell subsets and can cause hypertension, vascular dysfunction, and renal toxicity. We and others have reported that cyclosporine A and tacrolimus decrease anti-inflammatory regulatory T cells and increase proinflammatory interleukin-17-producing T cells; therefore, we hypothesized that inhibition of these effects using noncellular therapies would prevent the hypertension, endothelial dysfunction, and renal glomerular injury induced by calcineurin inhibitor therapy. Daily treatment of mice with cyclosporine A or tacrolimus for 1 week significantly decreased CD4 + /FoxP3 + regulatory T cells in the spleen and lymph nodes, as well as induced hypertension, vascular injury and dysfunction, and glomerular mesangial expansion in mice. Daily cotreatment with all-trans retinoic acid reported to increase regulatory T cells and decrease interleukin-17-producing T cells, prevented all of the detrimental effects of cyclosporine A and tacrolimus. All-trans retinoic acid also increased regulatory T cells and prevented the hypertension, endothelial dysfunction, and glomerular injury in genetically modified mice that phenocopy calcineurin inhibitor-treated mice (FKBP12-Tie2 knockout). Treatment with an interleukin-17-neutralizing antibody also increased regulatory T-cell levels and prevented the hypertension, endothelial dysfunction, and glomerular injury in cyclosporine A-treated and tacrolimus-treated mice and FKBP12-Tie2 knockout mice, whereas an isotype control had no effect. Augmenting regulatory T cells and inhibiting interleukin-17 signaling using noncellular therapies prevents the cardiovascular and renal toxicity of calcineurin inhibitors in mice. © 2017 American Heart Association, Inc.

  17. 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

  18. 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.

  19. 76 FR 60106 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-09-28

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... 14, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

  20. 75 FR 41254 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-07-15

    ... registered capacity, may work in other investment-related industries, such as financial planning, or may seek...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule..., 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and...

  1. Early experience and sex interact to influence limbic-hypothalamic-pituitary-adrenal-axis function after acute alcohol administration in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Barr, C S; Newman, T K; Lindell, S; Becker, M L; Shannon, C; Champoux, M; Suomi, S J; Higley, J D

    2004-07-01

    Studies in rodents demonstrate sex differences in neuroendocrine stress axis activity after treatment with alcohol. In abstinent alcoholics, atypical depressives, and individuals with posttraumatic stress disorder, limbic-hypothalamic-pituitary-adrenal (LHPA)-axis activity is often blunted; among females in these patient populations, however, resistance to glucocorticoid feedback and increased pituitary reactivity is observed. Early parental loss is a major life stressor and is a risk factor for both affective disturbances and LHPA-axis abnormalities later in life. We wanted to determine whether sex and early life parental absence would interact to influence alcohol-induced alterations in LHPA-axis activity after exposure to ethanol in macaques. Animals were reared with their mothers in social groups (MR, n = 94) or without adults in peer-only groups (PR, n = 79). At 5 years of age, they received an intravenous infusion of alcohol (2-2.2 g/kg), and the effects of alcohol, sex, and rearing condition on ACTH and cortisol levels were analyzed by ANOVA. Peer-reared females had higher ACTH levels than did PR males, MR females, and MR males after alcohol infusion. Alcohol-induced cortisol levels were not affected by sex and rearing condition. These findings suggest that there are sex differences in glucocorticoid negative feedback, pituitary responsivity, or release of ACTH secretagogues among individuals exposed to early life stress and emphasize the importance of considering sex effects when studying LHPA-axis dysregulation in alcoholism and other stress-related neuropsychiatric disorders.

  2. Equilibrium and stability of off-axis periodically focused particle beams

    International Nuclear Information System (INIS)

    Moraes, J.S.; Pakter, R.; Rizzato, F.B.

    2004-01-01

    A general equation for the centroid motion of free, continuous, intense beams propagating off axis in solenoidal periodic focusing fields is derived. The centroid equation is found to be independent of the specific beam distribution and may exhibit unstable solutions. A new Vlasov equilibrium for off-axis beam propagation is also obtained. The properties of the equilibrium and the relevance of centroid motion to beam confinement are discussed

  3. Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function.

    Science.gov (United States)

    Di Iorio, Christina R; Carey, Caitlin E; Michalski, Lindsay J; Corral-Frias, Nadia S; Conley, Emily Drabant; Hariri, Ahmad R; Bogdan, Ryan

    2017-06-01

    Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Quality management of the nuclear regulatory body. Peer discussions on regulatory practices

    International Nuclear Information System (INIS)

    2001-09-01

    This report is the outcome of the ninth series of peer discussions on regulatory practices entitled Nuclear Regulatory Body Quality Management, held in March and May 2001, and which involved the participation of senior nuclear regulators from 23 IAEA Member States. This report conveys the essence of two peer group discussions and highlights some good practices identified by the participating senior regulators. The objective of the discussions was to share experiences of regulatory bodies in implementing QM systems in their own work so as to ensure that the regulatory control over the licensees is effective and efficient and is commensurate with the mandate assigned by their governments. The shared experiences and good practices presented in the report, however, do not necessarily reflect the views of and good practices endorsed by the governments of the nominating Member States, the organizations to which the regulators belong, or the IAEA. The report sets down the peer group's experience in developing, implementing and evaluating QM within their regulatory bodies and identifies points to bear in mind when introducing such a system. This report is structured so that it covers the subject matter under the main headings of: application of quality management to regulatory work; development and implementation of quality management; assessment and improvement of performance; and good practices

  5. High-accuracy self-calibration method for dual-axis rotation-modulating RLG-INS

    Science.gov (United States)

    Wei, Guo; Gao, Chunfeng; Wang, Qi; Wang, Qun; Long, Xingwu

    2017-05-01

    Inertial navigation system has been the core component of both military and civil navigation systems. Dual-axis rotation modulation can completely eliminate the inertial elements constant errors of the three axes to improve the system accuracy. But the error caused by the misalignment angles and the scale factor error cannot be eliminated through dual-axis rotation modulation. And discrete calibration method cannot fulfill requirements of high-accurate calibration of the mechanically dithered ring laser gyroscope navigation system with shock absorbers. This paper has analyzed the effect of calibration error during one modulated period and presented a new systematic self-calibration method for dual-axis rotation-modulating RLG-INS. Procedure for self-calibration of dual-axis rotation-modulating RLG-INS has been designed. The results of self-calibration simulation experiment proved that: this scheme can estimate all the errors in the calibration error model, the calibration precision of the inertial sensors scale factor error is less than 1ppm and the misalignment is less than 5″. These results have validated the systematic self-calibration method and proved its importance for accuracy improvement of dual -axis rotation inertial navigation system with mechanically dithered ring laser gyroscope.

  6. Tilted c-Axis Thin-Film Bulk Wave Resonant Pressure Sensors With Improved Sensitivity

    OpenAIRE

    Anderås, Emil; Katardjiev, Ilia; Yantchev, Ventsislav

    2012-01-01

    Aluminum nitride thin film bulk wave resonant pressure sensors employing c- and tilted c-axis texture, have been fabricated and tested for their pressure sensitivities. The c-axis tilted FBAR pressure sensors demonstrate substantially higher pressure sensitivity compared to its c-axis oriented counterpart. More specifically the thickness plate quasi-shear resonance has demonstrated the highest pressure sensitivity while further being able to preserve its performance in liquid environment.

  7. 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)

  8. 77 FR 7218 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2012-02-10

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... thereunder,\\2\\ notice is hereby given that on January 30, 2012, Financial Industry Regulatory Authority, Inc.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

  9. 75 FR 59771 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the...

    Science.gov (United States)

    2010-09-28

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the Proposed Rule.... I. Introduction On July 27, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k... pertinent distribution-related information from its members in a timely fashion to facilitate its Regulation...

  10. 76 FR 50796 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-08-16

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Increase the Position Limit for Options on the Standard and Poor's... Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

  11. Techniques of analyzing the impacts of certain electric-utility ratemaking and regulatory-policy concepts. Bibliography

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-08-01

    This bibliography provides documentation for use by state public utility commissions and major nonregulated utilities in evaluating the applicability of a wide range of electric utility rate design and regulatory concepts in light of certain regulatory objectives. Part I, Utility Regulatory Objectives, contains 2084 citations on conservation of energy and capital; efficient use of facilities and resources; and equitable rates to electricity consumers. Part II, Rate Design Concepts, contains 1238 citations on time-of-day rates; seasonally-varying rates; cost-of-service rates; interruptible rates (including the accompanying use of load management techniques); declining block rates; and lifeline rates. Part III, Regulatory Concepts, contains 1282 references on restrictions on master metering; procedures for review of automatic adjustment clauses; prohibitions of rate or regulatory discrimination against solar, wind, or other small energy systems; treatment of advertising expenses; and procedures to protect ratepayers from abrupt termination of service.

  12. Regulatory difficulties in a developing country

    International Nuclear Information System (INIS)

    Jacobs, W.R. Jr.

    1978-01-01

    The regulatory agency assigned the task of regulating the initial entry into the field of nuclear power generation by a developing country has a very difficult job. Based on the authors' experience during the start-up and initial operation of Ko-Ri Unit I, the first power reactor in the Republic of Korea, observations on regulatory difficulties and recommendations for improved regulatory effectiveness are offered. The problem areas can be loosely grouped into three general categories: (1) Lack of adequate technical knowledge which is the basis for all effective regulation; (2) Difficulties with understanding and utilization of the required regulatory documentation; (3) Failure to establish the proper regulatory environment. Examples are cited from actual experience during the Ko-Ri Unit I start-up to demonstrate the impact that regulatory activities can have on a plant construction and testing programme. The problems encountered are not unique to developing countries but also exist in the United States of America. Recommendations are offered which should be beneficial to either newly formed regulatory agencies or agencies wishing to improve their abilities and effectiveness. These include: (1) Additional training of regulatory inspectors in plant operations; (2) Additional experience gained by participation in regulatory activities in other countries; (3) Increased attention given to regulatory documents, especially plant technical specifications; (4) Establishment of formal lines of communication between the utility and the regulatory agency; (5) Clear definition of regulatory responsibilities to avoid areas of overlapping jurisdiction; (6) Active participation by the regulatory staff very early in the project. It is hoped that these and other recommendations offered will greatly improve regulatory effectiveness and at the same time demonstrate that when the decision is made to 'go nuclear', a strong commitment must be made to develop and support a technically

  13. Regulatory control of nuclear power plants

    International Nuclear Information System (INIS)

    2002-01-01

    The purpose of this book is to support IAEA training courses and workshops in the field of regulatory control of nuclear power plants as well as to support the regulatory bodies of Member States in their own training activities. The target group is the professional staff members of nuclear safety regulatory bodies supervising nuclear power plants and having duties and responsibilities in the following regulatory fields: regulatory framework; regulatory organization; regulatory guidance; licensing and licensing documents; assessment of safety; and regulatory inspection and enforcement. Important topics such as regulatory competence and quality of regulatory work as well as emergency preparedness and public communication are also covered. The book also presents the key issues of nuclear safety such as 'defence-in-depth' and safety culture and explains how these should be taken into account in regulatory work, e.g. during safety assessment and regulatory inspection. The book also reflects how nuclear safety has been developed during the years on the basis of operating experience feedback and results of safety research by giving topical examples. The examples cover development of operating procedures and accident management to cope with complicated incidents and severe accidents to stress the importance of regulatory role in nuclear safety research. The main target group is new staff members of regulatory bodies, but the book also offers good examples for more experienced inspectors to be used as comparison and discussion basis in internal workshops organized by the regulatory bodies for refreshing and continuing training. The book was originally compiled on the basis of presentations provided during the two regulatory control training courses in 1997 and 1998. The textbook was reviewed at the beginning of the years 2000 and 2002 by IAEA staff members and consistency with the latest revisions of safety standards have been ensured. The textbook was completed in the

  14. Off-Axis Gaussian Beams with Random Displacement in Atmospheric Turbulence

    Directory of Open Access Journals (Sweden)

    Yahya Baykal

    2006-10-01

    Full Text Available Our recent work in which we study the propagation of the general Hermite-sinusoidal-Gaussian laser beams in wireless broadband access telecommunication systems is elaborated in this paper to cover the special case of an off-axis Gaussian beam. We mainly investigate the propagation characteristics in atmospheric turbulence of an off-axis Gaussian beam possessing Gaussian distributed random displacement parameters. Our interest is to search for different types of laser beams that will improve the performance of a wireless broadband access system when atmospheric turbulence is considered. Our formulation is based on the basic solution of the second order mutual coherence function evaluated at the receiver plane. For fixed turbulence strength, the coherence length calculated at the receiver plane is found to decrease as the variance of the random displacement is increased. It is shown that as the turbulence becomes stronger, coherence lengths due to off-axis Gaussian beams tend to approach the same value, irrespective of the variance of the random displacement. As expected, the beam spreading is found to be pronounced for larger variance of displacement parameter. Average intensity profiles when atmospheric turbulence is present are plotted for different values of the variance of the random displacement parameter of the off-axis Gaussian beam.

  15. Engineering the on-axis intensity of Bessel beam by a feedback tuning loop

    Science.gov (United States)

    Li, Runze; Yu, Xianghua; Yang, Yanlong; Peng, Tong; Yao, Baoli; Zhang, Chunmin; Ye, Tong

    2018-02-01

    The Bessel beam belongs to a typical class of non-diffractive optical fields that are characterized by their invariant focal profiles along the propagation direction. However, ideal Bessel beams only rigorously exist in theory; Bessel beams generated in the lab are quasi-Bessel beams with finite focal extensions and varying intensity profiles along the propagation axis. The ability to engineer the on-axis intensity profile to the desired shape is essential for many applications. Here we demonstrate an iterative optimization-based approach to engineering the on-axis intensity of Bessel beams. The genetic algorithm is used to demonstrate this approach. Starting with a traditional axicon phase mask, in the design process, the computed on-axis beam profile is fed into a feedback tuning loop of an iterative optimization process, which searches for an optimal radial phase distribution that can generate a generalized Bessel beam with the desired onaxis intensity profile. The experimental implementation involves a fine-tuning process that adjusts the originally targeted profile so that the optimization process can optimize the phase mask to yield an improved on-axis profile. Our proposed method has been demonstrated in engineering several zeroth-order Bessel beams with customized on-axis profiles. High accuracy and high energy throughput merit its use in many applications.

  16. HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS

    NARCIS (Netherlands)

    Roberts, Susanna; Keers, Robert; Lester, Kathryn J.; Coleman, Jonathan R. I.; Breen, Gerome; Arendt, Kristian; Blatter-Meunier, Judith; Cooper, Peter; Creswell, Cathy; Fjermestad, Krister; Havik, Odd E.; Herren, Chantal; Hogendoorn, Sanne M.; Hudson, Jennifer L.; Krause, Karen; Lyneham, Heidi J.; Morris, Talia; Nauta, Maaike; Rapee, Ronald M.; Rey, Yasmin; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Eley, Thalia C.; Wong, Chloe C. Y.

    2015-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive

  17. Multi-Axis Thrust Measurements of the EO-1 Pulsed Plasma Thruster

    Science.gov (United States)

    Arrington, Lynn A.; Haag, Thomas W.

    1999-01-01

    Pulsed plasma thrusters are low thrust propulsive devices which have a high specific impulse at low power. A pulsed plasma thruster is currently scheduled to fly as an experiment on NASA's Earth Observing-1 satellite mission. The pulsed plasma thruster will be used to replace one of the reaction wheels. As part of the qualification testing of the thruster it is necessary to determine the nominal thrust as a function of charge energy. These data will be used to determine control algorithms. Testing was first completed on a breadboard pulsed plasma thruster to determine nominal or primary axis thrust and associated propellant mass consumption as a function of energy and then later to determine if any significant off-axis thrust component existed. On conclusion that there was a significant off-axis thrust component with the bread-board in the direction of the anode electrode, the test matrix was expanded on the flight hardware to include thrust measurements along all three orthogonal axes. Similar off-axis components were found with the flight unit.

  18. Microfabrication and Characterization of an Integrated 3-Axis CMOS-MEMS Accelerometer

    Directory of Open Access Journals (Sweden)

    Hongwei QU

    2007-10-01

    Full Text Available This paper reports the fabrication and characterization of a monolithically integrated 3-axis CMOS-MEMS accelerometer with a single proof mass. An improved microfabrication process has been developed to solve the structure overheating and particle contamination problems in the plasma etching processes of device fabrication. The whole device is made of bulk silicon except for some short thin films for electrical isolation, allowing large sensing capacitance and flat device structure. A low-noise, low-power amplifier is designed for each axis, which provides 40 dB on-chip amplification and consumes only 1 mW power. Quasi-static and dynamic characterization of the fabricated device has been performed. The measured sensitivities of the lateral- and z-axis accelerometers are 560 mV/g and 320 mV/g, respectively, which can be tuned by simply varying the amplitude of the modulation signal. The over-all noise floors of the lateral- and z-axis are 12 μg/ÖHz and 110 μg/ÖHz, respectively when tested at 200 Hz.

  19. Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System.

    Science.gov (United States)

    Burford, Natalie G; Webster, Natalia A; Cruz-Topete, Diana

    2017-10-16

    The collective of endocrine organs acting in homeostatic regulation-known as the hypothalamic-pituitary-adrenal (HPA) axis-comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the release of glucocorticoids into the systemic circulation by the adrenal glands. Although the secretion of glucocorticoids serves to protect and maintain homeostasis in the typical operation at baseline levels, inadequate regulation can lead to physiologic and psychologic pathologies. The cardiovascular system is especially susceptible to prolonged dysregulation of the HPA axis and glucocorticoid production. There is debate about whether cardiovascular health risks arise from the direct detrimental effects of stress axis activation or whether pathologies develop secondary to the accompanying metabolic strain of excess glucocorticoids. In this review, we will explore the emerging research that indicates stress does have direct effects on the cardiovascular system via the HPA axis activation, with emphasis on the latest research on the impact of glucocorticoids signaling in the vasculature and the heart.

  20. 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

  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. 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

  3. 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)

  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. 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.

  6. Cognition and HPA axis reactivity in mildly to moderately depressed outpatients

    DEFF Research Database (Denmark)

    Krogh, Jesper; Videbech, Poul; Renvillard, Signe Groth

    2012-01-01

    Background: Patients with depression display neurobiological changes of the hypothalamic-pituitary axis as well as cognitive disturbances. Aims: To assess any association between hypothalamus-pituitary-adrenal (HPA) axis reactivity and memory-related cognitive functions. Methods: Depressed...... the following day at the same times. Results: Patients and controls did not differ on any memory-related cognitive skills. After dexamethasone the cortisol level was 1.7 nmol/l higher (95% CI 0.0-2.8, P =¿0.05) in depressed patients compared with controls. In the control group, but not in the patients...... after dexamethasone and visuo-spatial memory primarily driven by the healthy controls. Otherwise, no association were found between HPA axis reactivity and memory-related cognitive function....

  7. The application of image processing in the measurement for three-light-axis parallelity of laser ranger

    Science.gov (United States)

    Wang, Yang; Wang, Qianqian

    2008-12-01

    When laser ranger is transported or used in field operations, the transmitting axis, receiving axis and aiming axis may be not parallel. The nonparallelism of the three-light-axis will affect the range-measuring ability or make laser ranger not be operated exactly. So testing and adjusting the three-light-axis parallelity in the production and maintenance of laser ranger is important to ensure using laser ranger reliably. The paper proposes a new measurement method using digital image processing based on the comparison of some common measurement methods for the three-light-axis parallelity. It uses large aperture off-axis paraboloid reflector to get the images of laser spot and white light cross line, and then process the images on LabVIEW platform. The center of white light cross line can be achieved by the matching arithmetic in LABVIEW DLL. And the center of laser spot can be achieved by gradation transformation, binarization and area filter in turn. The software system can set CCD, detect the off-axis paraboloid reflector, measure the parallelity of transmitting axis and aiming axis and control the attenuation device. The hardware system selects SAA7111A, a programmable vedio decoding chip, to perform A/D conversion. FIFO (first-in first-out) is selected as buffer.USB bus is used to transmit data to PC. The three-light-axis parallelity can be achieved according to the position bias between them. The device based on this method has been already used. The application proves this method has high precision, speediness and automatization.

  8. Bifunctional Rhodamine Probes of Myosin Regulatory Light Chain Orientation in Relaxed Skeletal Muscle Fibers

    Science.gov (United States)

    Brack, Andrew S.; Brandmeier, Birgit D.; Ferguson, Roisean E.; Criddle, Susan; Dale, Robert E.; Irving, Malcolm

    2004-01-01

    The orientation of the regulatory light chain (RLC) region of the myosin heads in relaxed skinned fibers from rabbit psoas muscle was investigated by polarized fluorescence from bifunctional rhodamine (BR) probes cross-linking pairs of cysteine residues introduced into the RLC. Pure 1:1 BR-RLC complexes were exchanged into single muscle fibers in EDTA rigor solution for 30 min at 30°C; ∼60% of the native RLC was removed and stoichiometrically replaced by BR-RLC, and >85% of the BR-RLC was located in the sarcomeric A-bands. The second- and fourth-rank order parameters of the orientation distributions of BR dipoles linking RLC cysteine pairs 100-108, 100-113, 108-113, and 104-115 were calculated from polarized fluorescence intensities, and used to determine the smoothest RLC orientation distribution—the maximum entropy distribution—consistent with the polarized fluorescence data. Maximum entropy distributions in relaxed muscle were relatively broad. At the peak of the distribution, the “lever” axis, linking Cys707 and Lys843 of the myosin heavy chain, was at 70–80° to the fiber axis, and the “hook” helix (Pro830–Lys843) was almost coplanar with the fiber and lever axes. The temperature and ionic strength of the relaxing solution had small but reproducible effects on the orientation of the RLC region. PMID:15041671

  9. Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Masashi Ohno

    Full Text Available Curcumin is a hydrophobic polyphenol derived from turmeric, a traditional Indian spice. Curcumin exhibits various biological functions, but its clinical application is limited due to its poor absorbability after oral administration. A newly developed nanoparticle curcumin shows improved absorbability in vivo. In this study, we examined the effects of nanoparticle curcumin (named Theracurmin on experimental colitis in mice.BALB/c mice were fed with 3% dextran sulfate sodium (DSS in water. Mucosal cytokine expression and lymphocyte subpopulation were analyzed by real-time PCR and flow cytometry, respectively. The profile of the gut microbiota was analyzed by real-time PCR.Treatment with nanoparticle curcumin significantly attenuated body weight loss, disease activity index, histological colitis score and significantly improved mucosal permeability. Immunoblot analysis showed that NF-κB activation in colonic epithelial cells was significantly suppressed by treatment with nanoparticle curcumin. Mucosal mRNA expression of inflammatory mediators was significantly suppressed by treatment with nanoparticle curcumin. Treatment with nanoparticle curcumin increased the abundance of butyrate-producing bacteria and fecal butyrate level. This was accompanied by increased expansion of CD4+ Foxp3+ regulatory T cells and CD103+ CD8α- regulatory dendritic cells in the colonic mucosa.Treatment with nanoparticle curcumin suppressed the development of DSS-induced colitis potentially via modulation of gut microbial structure. These responses were associated with induction of mucosal immune cells with regulatory properties. Nanoparticle curcumin is one of the promising candidates as a therapeutic option for the treatment of IBD.

  10. Industry petition for rulemaking on the disposal of below-regulatory-concern wastes

    International Nuclear Information System (INIS)

    Tipton, T.E.

    1989-01-01

    The Nuclear Management and Resources Council, Inc., in conjunction with the Edison Electric Institute, plans to submit a petition for rulemaking entitled Petition for Rulemaking Regarding Disposal of Below Regulatory Concern Wastes from commercial Nuclear Power Plants to the U.S. Nuclear Regulatory Commission (NRC). This petition for rulemaking, which is being filed pursuant to 10CFR2.802 and 10CFR2, Appendix B of the Code of Federal Regulations, requests the NRC to promulgate a rule authorizing the treatment and disposal of low-level radioactive wastes (LLW) determined to be below regulatory concern (BRC) in other than licensed LLW disposal facilities. The proposed rule will apply only to LLW generated at commercial nuclear power plants. The petition is based on detailed scientific and technical data derived through an extensive research program conducted by the Electric Power Research Institute, Inc. It addresses the 14 decision criteria that the NRC will employ in judging whether to grant the petition. The petition also provides an environmental assessment and finding of no significant impact and regulatory analysis. The purpose of the environmental assessment is to discuss alternatives, consequences, and impacts analyzed to support the recommendation of the proposed rule. The regulatory analysis addresses the need for and consequences of the proposed regulatory action as it relates to the protection of public health and safety

  11. Self-regulatory fatigue in hematologic malignancies: impact on quality of life, coping, and adherence to medical recommendations.

    Science.gov (United States)

    Solberg Nes, Lise; Ehlers, Shawna L; Patten, Christi A; Gastineau, Dennis A

    2013-03-01

    Hematopoietic stem cell transplantation (HSCT) is an intensive cancer therapy entailing numerous physical, emotional, cognitive, and practical challenges. Patients' ability to adjust and cope with such challenges may depend on their ability to exert control over cognitive, emotional, and behavioral processes, that is, ability to self-regulate. Self-regulatory capacity is a limited resource that can be depleted or fatigued (i.e., "self-regulatory fatigue"), particularly in the context of stressful life events such as cancer diagnosis and treatment. This is one of the first studies to examine self-regulatory fatigue in a cancer population. The current study aimed to (1) extract items for a specific scale of self-regulatory capacity and (2) examine the impact of such capacity on adaptation in patients with hematologic malignancies preparing for HSCT. Factor analysis of four existing scales gauging psychological adjustment and well-being in 314 patients preparing for HSCT (63% male and 89% Caucasian) identified 23 items (α = 0.85) related to self-regulatory control or fatigue. This measure was then examined using existing clinical data obtained from 178 patients (57% male and 91% Caucasian) undergoing treatment for hematologic malignancies in relationship to quality of life, coping, and self-reported adherence to physicians' recommendations. Controlling for pain severity, physical fatigue, and depression, self-regulatory fatigue scores were incrementally associated with decreased quality of life, use of avoidance coping strategies, and decreased adherence to physicians' recommendations. These results emphasize the potential role of self-regulatory capacity in coping with and adjusting to hematologic cancers and future research is warranted.

  12. Design, Fabrication, and Modeling of a Novel Dual-Axis Control Input PZT Gyroscope

    Directory of Open Access Journals (Sweden)

    Cheng-Yang Chang

    2017-10-01

    Full Text Available Conventional gyroscopes are equipped with a single-axis control input, limiting their performance. Although researchers have proposed control algorithms with dual-axis control inputs to improve gyroscope performance, most have verified the control algorithms through numerical simulations because they lacked practical devices with dual-axis control inputs. The aim of this study was to design a piezoelectric gyroscope equipped with a dual-axis control input so that researchers may experimentally verify those control algorithms in future. Designing a piezoelectric gyroscope with a dual-axis control input is more difficult than designing a conventional gyroscope because the control input must be effective over a broad frequency range to compensate for imperfections, and the multiple mode shapes in flexural deformations complicate the relation between flexural deformation and the proof mass position. This study solved these problems by using a lead zirconate titanate (PZT material, introducing additional electrodes for shielding, developing an optimal electrode pattern, and performing calibrations of undesired couplings. The results indicated that the fabricated device could be operated at 5.5±1 kHz to perform dual-axis actuations and position measurements. The calibration of the fabricated device was completed by system identifications of a new dynamic model including gyroscopic motions, electromechanical coupling, mechanical coupling, electrostatic coupling, and capacitive output impedance. Finally, without the assistance of control algorithms, the “open loop sensitivity” of the fabricated gyroscope was 1.82 μV/deg/s with a nonlinearity of 9.5% full-scale output. This sensitivity is comparable with those of other PZT gyroscopes with single-axis control inputs.

  13. Design, Fabrication, and Modeling of a Novel Dual-Axis Control Input PZT Gyroscope.

    Science.gov (United States)

    Chang, Cheng-Yang; Chen, Tsung-Lin

    2017-10-31

    Conventional gyroscopes are equipped with a single-axis control input, limiting their performance. Although researchers have proposed control algorithms with dual-axis control inputs to improve gyroscope performance, most have verified the control algorithms through numerical simulations because they lacked practical devices with dual-axis control inputs. The aim of this study was to design a piezoelectric gyroscope equipped with a dual-axis control input so that researchers may experimentally verify those control algorithms in future. Designing a piezoelectric gyroscope with a dual-axis control input is more difficult than designing a conventional gyroscope because the control input must be effective over a broad frequency range to compensate for imperfections, and the multiple mode shapes in flexural deformations complicate the relation between flexural deformation and the proof mass position. This study solved these problems by using a lead zirconate titanate (PZT) material, introducing additional electrodes for shielding, developing an optimal electrode pattern, and performing calibrations of undesired couplings. The results indicated that the fabricated device could be operated at 5.5±1 kHz to perform dual-axis actuations and position measurements. The calibration of the fabricated device was completed by system identifications of a new dynamic model including gyroscopic motions, electromechanical coupling, mechanical coupling, electrostatic coupling, and capacitive output impedance. Finally, without the assistance of control algorithms, the "open loop sensitivity" of the fabricated gyroscope was 1.82 μV/deg/s with a nonlinearity of 9.5% full-scale output. This sensitivity is comparable with those of other PZT gyroscopes with single-axis control inputs.

  14. 75 FR 27606 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-05-17

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 27, 2010, the Financial Industry... restated following the formation of FINRA through the consolidation of NASD and the member regulatory...

  15. A Miniature Magnetic-Force-Based Three-Axis AC Magnetic Sensor with Piezoelectric/Vibrational Energy-Harvesting Functions

    Directory of Open Access Journals (Sweden)

    Chiao-Fang Hung

    2017-02-01

    Full Text Available In this paper, we demonstrate a miniature magnetic-force-based, three-axis, AC magnetic sensor with piezoelectric/vibrational energy-harvesting functions. For magnetic sensing, the sensor employs a magnetic–mechanical–piezoelectric configuration (which uses magnetic force and torque, a compact, single, mechanical mechanism, and the piezoelectric effect to convert x-axis and y-axis in-plane and z-axis magnetic fields into piezoelectric voltage outputs. Under the x-axis magnetic field (sine-wave, 100 Hz, 0.2–3.2 gauss and the z-axis magnetic field (sine-wave, 142 Hz, 0.2–3.2 gauss, the voltage output with the sensitivity of the sensor are 1.13–26.15 mV with 8.79 mV/gauss and 1.31–8.92 mV with 2.63 mV/gauss, respectively. In addition, through this configuration, the sensor can harness ambient vibrational energy, i.e., possessing piezoelectric/vibrational energy-harvesting functions. Under x-axis vibration (sine-wave, 100 Hz, 3.5 g and z-axis vibration (sine-wave, 142 Hz, 3.8 g, the root-mean-square voltage output with power output of the sensor is 439 mV with 0.333 μW and 138 mV with 0.051 μW, respectively. These results show that the sensor, using this configuration, successfully achieves three-axis magnetic field sensing and three-axis vibration energy-harvesting. Due to these features, the three-axis AC magnetic sensor could be an important design reference in order to develop future three-axis AC magnetic sensors, which possess energy-harvesting functions, for practical industrial applications, such as intelligent vehicle/traffic monitoring, processes monitoring, security systems, and so on.

  16. Anteroposterior axis patterning by early canonical Wnt signaling during hemichordate development

    Science.gov (United States)

    Darras, Sébastien; Fritzenwanker, Jens H.; Uhlinger, Kevin R.; Farrelly, Ellyn; Pani, Ariel M.; Hurley, Imogen A.; Norris, Rachael P.; Osovitz, Michelle; Terasaki, Mark; Wu, Mike; Aronowicz, Jochanan; Kirschner, Marc; Gerhart, John C.

    2018-01-01

    The Wnt family of secreted proteins has been proposed to play a conserved role in early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis is based predominantly on data from vertebrate embryogenesis as well as planarian regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling endows cells with positional information along the A/P axis. Outside of these phyla, there is strong support for a conserved role of cWnt signaling in the repression of anterior fates, but little comparative support for a conserved role in promotion of posterior fates. We further test the hypothesis by investigating the role of cWnt signaling during early patterning along the A/P axis of the hemichordate Saccoglossus kowalevskii. We have cloned and investigated the expression of the complete Wnt ligand and Frizzled receptor complement of S. kowalevskii during early development along with many secreted Wnt modifiers. Eleven of the 13 Wnt ligands are ectodermally expressed in overlapping domains, predominantly in the posterior, and Wnt antagonists are localized predominantly to the anterior ectoderm in a pattern reminiscent of their distribution in vertebrate embryos. Overexpression and knockdown experiments, in combination with embryological manipulations, establish the importance of cWnt signaling for repression of anterior fates and activation of mid-axial ectodermal fates during the early development of S. kowalevskii. However, surprisingly, terminal posterior fates, defined by posterior Hox genes, are unresponsive to manipulation of cWnt levels during the early establishment of the A/P axis at late blastula and early gastrula. We establish experimental support for a conserved role of Wnt signaling in the early specification of the A/P axis during deuterostome body plan diversification, and further build support for an ancestral role of this pathway in early evolution of the bilaterian A/P axis. We find strong support for a role of cWnt in

  17. 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

  18. Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder.

    Science.gov (United States)

    Keating, Charlotte; Dawood, Tye; Barton, David A; Lambert, Gavin W; Tilbrook, Alan J

    2013-04-29

    Oxytocin is known for its capacity to facilitate social bonding, reduce anxiety and for its actions on the stress hypothalamopituitary adrenal (HPA) axis. Since oxytocin can physiologically suppress activity of the HPA axis, clinical applications of this neuropeptide have been proposed in conditions where the function of the HPA axis is dysregulated. One such condition is major depressive disorder (MDD). Dysregulation of the HPA system is the most prominent endocrine change seen with MDD, and normalizing the HPA axis is one of the major targets of recent treatments. The potential clinical application of oxytocin in MDD requires improved understanding of its relationship to the symptoms and underlying pathophysiology of MDD. Previous research has investigated potential correlations between oxytocin and symptoms of MDD, including a link between oxytocin and treatment related symptom reduction. The outcomes of studies investigating whether antidepressive treatment (pharmacological and non-pharmacological) influences oxytocin concentrations in MDD, have produced conflicting outcomes. These outcomes suggest the need for an investigation of the influence of a single treatment class on oxytocin concentrations, to determine whether there is a relationship between oxytocin, the HPA axis (e.g., oxytocin and cortisol) and MDD. Our objective was to measure oxytocin and cortisol in patients with MDD before and following treatment with selective serotonin reuptake inhibitors, SSRI. We sampled blood from arterial plasma. Patients with MDD were studied at the same time twice; pre- and post- 12 weeks treatment, in an unblinded sequential design (clinicaltrials.govNCT00168493). Results did not reveal differences in oxytocin or cortisol concentrations before relative to following SSRI treatment, and there were no significant relationships between oxytocin and cortisol, or these two physiological variables and psychological symptom scores, before or after treatment. These outcomes

  19. Design Of Rotor Blade For Vertical Axis Wind Turbine Using Double Aerofoil

    DEFF Research Database (Denmark)

    Chougule, Prasad; Ratkovich, Nicolas Rios; Kirkegaard, Poul Henning

    Nowadays, small vertical axis wind turbines are receiving more attention compared to horizontal wind turbines due to their suitability in urban use because they generate less noise, have bird free turbines and lower cost. There is few vertical axis wind turbines design with good power curve....... However, the efficiency of power extraction has not been improved. Therefore, an attempt has been made to utilize high lift technology in practice for vertical axis wind turbines in order to improve power efficiency. High lift is obtained by double aerofoil elements mainly used in aeroplane wing design....... In this current work two aerofoils are used to design a rotor blade for a vertical axis wind turbine to improve the power efficiency on the rotor. Double aerofoil blade design consists of a main aerofoil and a slat aerofoil. The parameters related to position and orientation of the slat aerofoil with respect...

  20. 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.

  1. 75 FR 53998 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-09-02

    ... characteristics and risks of security futures. \\6\\ 15 U.S.C. 78o-3(b)(6). B. Self-Regulatory Organization's...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend the Security Futures Risk Disclosure Statement August 27, 2010...

  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. 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

  4. 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

  5. Application of the Self-Regulatory Model in Dealing with Encopresis.

    Science.gov (United States)

    Grimes, Lynn

    1983-01-01

    Behavioral techniques along with a self-regulation methodology were used successfully to decrease encopretic behaviors in a 9-year-old male. Kanfer's self-regulatory model appears to be generalizable to any child with the cognitive ability to understand that he or she has a problem and to make decisions about treatment. (Author/PN)

  6. A Wavelet Bicoherence-Based Quadratic Nonlinearity Feature for Translational Axis Condition Monitoring

    Directory of Open Access Journals (Sweden)

    Yong Li

    2014-01-01

    Full Text Available The translational axis is one of the most important subsystems in modern machine tools, as its degradation may result in the loss of the product qualification and lower the control precision. Condition-based maintenance (CBM has been considered as one of the advanced maintenance schemes to achieve effective, reliable and cost-effective operation of machine systems, however, current vibration-based maintenance schemes cannot be employed directly in the translational axis system, due to its complex structure and the inefficiency of commonly used condition monitoring features. In this paper, a wavelet bicoherence-based quadratic nonlinearity feature is proposed for translational axis condition monitoring by using the torque signature of the drive servomotor. Firstly, the quadratic nonlinearity of the servomotor torque signature is discussed, and then, a biphase randomization wavelet bicoherence is introduced for its quadratic nonlinear detection. On this basis, a quadratic nonlinearity feature is proposed for condition monitoring of the translational axis. The properties of the proposed quadratic nonlinearity feature are investigated by simulations. Subsequently, this feature is applied to the real-world servomotor torque data collected from the X-axis on a high precision vertical machining centre. All the results show that the performance of the proposed feature is much better than that of original condition monitoring features.

  7. 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.

  8. RGM regulates BMP-mediated secondary axis formation in the sea anemone Nematostella vectensis.

    Science.gov (United States)

    Leclère, Lucas; Rentzsch, Fabian

    2014-12-11

    Patterning of the metazoan dorsoventral axis is mediated by a complex interplay of BMP signaling regulators. Repulsive guidance molecule (RGM) is a conserved BMP coreceptor that has not been implicated in axis specification. We show that NvRGM is a key positive regulator of BMP signaling during secondary axis establishment in the cnidarian Nematostella vectensis. NvRGM regulates first the generation and later the shape of a BMP-dependent Smad1/5/8 gradient with peak activity on the side opposite the NvBMP/NvRGM/NvChordin expression domain. Full knockdown of Smad1/5/8 signaling blocks the formation of endodermal structures, the mesenteries, and the establishment of bilateral symmetry, while altering the gradient through partial NvRGM or NvBMP knockdown shifts the boundaries of asymmetric gene expression and the positioning of the mesenteries along the secondary axis. These findings provide insight into the diversification of axis specification mechanisms and identify a previously unrecognized role for RGM in BMP-mediated axial patterning. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Estimating the spin axis orientation of the Echostar-2 box-wing geosynchronous satellite

    Science.gov (United States)

    Earl, Michael A.; Somers, Philip W.; Kabin, Konstantin; Bédard, Donald; Wade, Gregg A.

    2018-04-01

    For the first time, the spin axis orientation of an inactive box-wing geosynchronous satellite has been estimated from ground-based optical photometric observations of Echostar-2's specular reflections. Recent photometric light curves obtained of Echostar-2 over four years suggest that unusually bright and brief specular reflections were occurring twice within an observed spin period. These bright and brief specular reflections suggested two satellite surfaces with surface normals separated by approximately 180°. The geometry between the satellite, the Sun, and the observing location at the time of each of the brightest observed reflections, was used to estimate Echostar-2's equatorial spin axis orientation coordinates. When considering prograde and retrograde rotation, Echostar-2's spin axis orientation was estimated to have been located within 30° of either equatorial coordinate pole. Echostar-2's spin axis was observed to have moved approximately 180° in right ascension, within a time span of six months, suggesting a roughly one year spin axis precession period about the satellite's angular momentum vector.

  10. Axis I and II disorders as long-term predictors of mental distress: a six-year prospective follow-up of substance-dependent patients

    Directory of Open Access Journals (Sweden)

    Landheim Anne

    2007-06-01

    Full Text Available Abstract Background A high prevalence of lifetime psychiatric disorders among help-seeking substance abusers has been clearly established. However, the long-term course of psychiatric disorders and mental distress among help-seeking substance abusers is still unclear. The aim of this research was to examine the course of mental distress using a six-year follow-up study of treatment-seeking substance-dependent patients, and to explore whether lifetime Axis I and II disorders measured at admission predict the level of mental distress at follow-up, when age, sex, and substance-use variables measured both at baseline and at follow-up are controlled for. Methods A consecutive sample of substance dependent in- and outpatients (n = 287 from two counties of Norway were assessed at baseline (T1 with the Composite International Diagnostic Interview (Axis I, Millon's Clinical Multiaxial Inventory (Axis II, and the Hopkins Symptom Checklist (HSCL-25 (mental distress. At follow-up (T2, 48% (137/287 subjects, 29% women were assessed with the HSCL-25, the Alcohol Use Disorders Identification Test, and the Drug Use Disorders Identification Test. Results The stability of mental distress is a main finding and the level of mental distress remained high after six years, but was significantly lower among abstainers at T2, especially among female abstainers. Both the number of and specific lifetime Axis I disorders (social anxiety disorder, generalized anxiety disorder, and somatization disorder, the number of and specific Axis II disorders (anxious and impulsive personality disorders, and the severity of substance-use disorder at the index admission were all independent predictors of a high level of mental distress at follow-up, even when we controlled for age, sex, and substance use at follow-up. Conclusion These results underscore the importance of diagnosing and treating both substance-use disorder and non-substance-use disorder Axis I and Axis II disorders in

  11. 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...

  12. Hypothalamic-pituitary-adrenal axis tonus is associated with hippocampal microstructural asymmetry

    DEFF Research Database (Denmark)

    Madsen, Kathrine Skak; Jernigan, Terry L; Iversen, Pernille

    2012-01-01

    It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is gr......It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since....... Observed associations raise a number of possibilities, among them an asymmetric role of the hippocampus on HPA-axis regulation, or conversely, that individual variations in secreted cortisol, perhaps associated with stress, may have lateralized effects on hippocampal microstructure. Our results point...

  13. Nanoscratch Characterization of GaN Epilayers on c- and a-Axis Sapphire Substrates

    Directory of Open Access Journals (Sweden)

    Wen Hua-Chiang

    2010-01-01

    Full Text Available Abstract In this study, we used metal organic chemical vapor deposition to form gallium nitride (GaN epilayers on c- and a-axis sapphire substrates and then used the nanoscratch technique and atomic force microscopy (AFM to determine the nanotribological behavior and deformation characteristics of the GaN epilayers, respectively. The AFM morphological studies revealed that pile-up phenomena occurred on both sides of the scratches formed on the GaN epilayers. It is suggested that cracking dominates in the case of GaN epilayers while ploughing during the process of scratching; the appearances of the scratched surfaces were significantly different for the GaN epilayers on the c- and a-axis sapphire substrates. In addition, compared to the c-axis substrate, we obtained higher values of the coefficient of friction (μ and deeper penetration of the scratches on the GaN a-axis sapphire sample when we set the ramped force at 4,000 μN. This discrepancy suggests that GaN epilayers grown on c-axis sapphire have higher shear resistances than those formed on a-axis sapphire. The occurrence of pile-up events indicates that the generation and motion of individual dislocation, which we measured under the sites of critical brittle transitions of the scratch track, resulted in ductile and/or brittle properties as a result of the deformed and strain-hardened lattice structure.

  14. 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.)

  15. 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

  16. 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.

  17. 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)

  18. Kalman Filter for Estimation of Sensor Acceleration Using Six - axis Inertial Sensor

    International Nuclear Information System (INIS)

    Lee, Jung Keun

    2015-01-01

    Although an accelerometer is a sensor that measures acceleration, it cannot be used by itself to measure the acceleration when the orientation of the sensor changes. This paper introduces a Kalman filter for the estimation of a sensor acceleration based on a six-axis inertial sensor (i.e., a three-axis accelerometer and three-axis gyroscope). The novelty of the proposed Kalman filter lies in the fact that its state vector includes not only the tilt angle variable but also the sensor acceleration. Thus, the filter can explicitly estimate the latter with a high accuracy. The accuracy of acceleration estimates were validated experimentally under three different dynamic conditions, using an optical motion capture system. It could be concluded that the performance of the proposed Kalman filter was comparable to that of the state-of-the-art estimation algorithm employed by the Xsens MTw. The proposed algorithm may be more suitable than inertial/magnetic sensor-based algorithms for various applications adopting six-axis inertial sensors

  19. 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...

  20. 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.

  1. 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

  2. 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

  3. Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions

    DEFF Research Database (Denmark)

    Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A

    2015-01-01

    OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched...... for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation...... of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. DESIGN: Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls...

  4. Elastic-plastic analysis of an axi-symmetric problem by a finite element method

    International Nuclear Information System (INIS)

    Isozaki, Toshikuni

    1984-06-01

    Generally speaking, many structures are designed and fabricated on the basis of an axi-symmetric structure. Finite Element Method is the capable method to solve these axi-symmetric problems beyond the elastic limit. As the first step to solve these problems, the computer program for the elastic-plastic analysis of the axi-symmetric problem is composed. The basic program is based upon that described in Zienkiewicz's text book to solve the elastic plane stress problem, taking the plastic stress matrix by Yamada's method into consideration and it is converted to solve the axi-symmetric problem. For the verification of the program, the plane strain problem of a cylindrical tube under internal pressure was solved. The computed results were compared with those shown in ADINA's user's manual. They showed close agreement. (author)

  5. Slicing algorithms for multi-axis 3-D metal printing of overhangs

    International Nuclear Information System (INIS)

    Lee, Kyu Bok; Jee, Hae Seong

    2015-01-01

    A group of 3D metal printing or Additive metal manufacturing (AMM) processes, officially categorized as 'directed energy deposition (DED)' according to American Society for Testing and Materials (ASTM) classification, has enabled the building of full dense metallic tools and parts using metal powders precisely delivered and controlled with no powder bed. Mold making and metalworking are being taken in an entirely new direction. The overhang/undercut problem in DED processes, as much as other Additive manufacturing (AM) processes, has long remained unsolved, and the ones equipped with more than 3-axis tool mechanism turn out to be capable of depositing overhang/undercut features onto the part to be made. Multi-axis machines introduced for resolving the problem, however, require advanced preprocess software support for the process management that controls multi-axis tool paths. This study proposes slicing algorithms, sophisticatedly designed for the control of the tool paths on a 5-axis base table, to build overhang/undercut features. A methodical approach, using an auto-partitioning algorithm for generating three-dimensional layer (3DL) information, is proposed in this study, and various overhang features, as case studies, have been investigated and implemented by using the proposed method.

  6. Slicing algorithms for multi-axis 3-D metal printing of overhangs

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyu Bok; Jee, Hae Seong [Hongik University, Seoul (Korea, Republic of)

    2015-11-15

    A group of 3D metal printing or Additive metal manufacturing (AMM) processes, officially categorized as 'directed energy deposition (DED)' according to American Society for Testing and Materials (ASTM) classification, has enabled the building of full dense metallic tools and parts using metal powders precisely delivered and controlled with no powder bed. Mold making and metalworking are being taken in an entirely new direction. The overhang/undercut problem in DED processes, as much as other Additive manufacturing (AM) processes, has long remained unsolved, and the ones equipped with more than 3-axis tool mechanism turn out to be capable of depositing overhang/undercut features onto the part to be made. Multi-axis machines introduced for resolving the problem, however, require advanced preprocess software support for the process management that controls multi-axis tool paths. This study proposes slicing algorithms, sophisticatedly designed for the control of the tool paths on a 5-axis base table, to build overhang/undercut features. A methodical approach, using an auto-partitioning algorithm for generating three-dimensional layer (3DL) information, is proposed in this study, and various overhang features, as case studies, have been investigated and implemented by using the proposed method.

  7. 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.

  8. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  9. 75 FR 2897 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-01-19

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule... hereby given that on December 23, 2009, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a... consolidation process, see Information Notice, March 12, 2008 (Rulebook Consolidation Process). NASD Rule 2450...

  10. The 20S proteasome as an assembly platform for the 19S regulatory complex

    DEFF Research Database (Denmark)

    Hendil, Klaus Aksel Bjørner; Kriegenburg, Franziska; Tanaka, Keiji

    2009-01-01

    26S proteasomes consist of cylindrical 20S proteasomes with 19S regulatory complexes attached to the ends. Treatment with high concentrations of salt causes the regulatory complexes to separate into two sub-complexes, the base, which is in contact with the 20S proteasome, and the lid, which...... is the distal part of the 19S complex. Here, we describe two assembly intermediates of the human regulatory complex. One is a dimer of the two ATPase subunits, Rpt3 and Rpt6. The other is a complex of nascent Rpn2, Rpn10, Rpn11, Rpn13, and Txnl1, attached to preexisting 20S proteasomes. This early assembly...... complex does not yet contain Rpn1 or any of the ATPase subunits of the base. Thus, assembly of 19S regulatory complexes takes place on preexisting 20S proteasomes, and part of the lid is assembled before the base....

  11. 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...

  12. 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...

  13. 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...

  14. The role of the hypothalamus-pituitary-adrenal/interrenal axis in mediating predator-avoidance trade-offs.

    Science.gov (United States)

    Harris, Breanna N; Carr, James A

    2016-05-01

    Maintaining energy balance and reproducing are important for fitness, yet animals have evolved mechanisms by which the hypothalamus-pituitary-adrenal/interrenal (HPA/HPI) axis can shut these activities off. While HPA/HPI axis inhibition of feeding and reproduction may have evolved as a predator defense, to date there has been no review across taxa of the causal evidence for such a relationship. Here we review the literature on this topic by addressing evidence for three predictions: that exposure to predators decreases reproduction and feeding, that exposure to predators activates the HPA/HPI axis, and that predator-induced activation of the HPA/HPI axis inhibits foraging and reproduction. Weight of evidence indicates that exposure to predator cues inhibits several aspects of foraging and reproduction. While the evidence from fish and mammals supports the hypothesis that predator cues activate the HPA/HPI axis, the existing data in other vertebrate taxa are equivocal. A causal role for the HPA axis in predator-induced suppression of feeding and reproduction has not been demonstrated to date, although many studies report correlative relationships between HPA activity and reproduction and/or feeding. Manipulation of HPA/HPI axis signaling will be required in future studies to demonstrate direct mediation of predator-induced inhibition of feeding and reproduction. Understanding the circuitry linking sensory pathways to their control of the HPA/HPI axis also is needed. Finally, the role that fear and anxiety pathways play in the response of the HPA axis to predator cues is needed to better understand the role that predators have played in shaping anxiety related behaviors in all species, including humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Evanescent wave scattering at off-axis incidence on multiple cylinders located near a surface

    International Nuclear Information System (INIS)

    Lee, Siu-Chun

    2015-01-01

    The scattering characteristics of an infinite cylinder are strongly influenced by the incidence angle relative to its axis. If the incident wave propagates in the plane normal to the axis of the cylinder, the polarization of the scattered wave remains unchanged and the scattered wave propagates in the same plan as the incident wave. At off-axis incidence such that the incident direction makes an oblique angle with the cylinder axis, the scattered wave is depolarized, and its spatial distribution becomes three-dimensional. This paper presents the scattering solution for oblique incidence on multiple parallel cylinders located near a planar interface by an evanescent wave that is generated by total internal reflection of the source wave propagating in the higher refractive index substrate. Hertz potentials are utilized to formulate the interaction of inhomogeneous waves with the cylinders, scattering at the substrate interface, and near field scattering between the cylinders. Analytic formulas are derived for the electromagnetic fields and Poynting vector of scattered radiation in the near-field and their asymptotic forms in the far-field. Numerical examples are shown to illustrate scattering of evanescent wave by multiple cylinders at off-axis incidence. - Highlights: • Developed an exact solution for off-axis incidence on multiple cylinders. • Included depolarization, near-field scattering, and Fresnel effect in theory. • Derived analytic formulas for scattered radiation in the far field. • Illustrated evanescent scattering at off-axis incidence by numerical data

  20. 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.

  1. Stressor-specific effects of sex on HPA axis hormones and activation of stress-related neurocircuitry.

    Science.gov (United States)

    Babb, Jessica A; Masini, Cher V; Day, Heidi E W; Campeau, Serge

    2013-11-01

    Experiencing stress can be physically and psychologically debilitating to an organism. Women have a higher prevalence of some stress-related mental illnesses, the reasons for which are unknown. These experiments explore differential HPA axis hormone release in male and female rats following acute stress. Female rats had a similar threshold of HPA axis hormone release following low intensity noise stress as male rats. Sex did not affect the acute release, or the return of HPA axis hormones to baseline following moderate intensity noise stress. Sensitive indices of auditory functioning obtained by modulation of the acoustic startle reflex by weak pre-pulses did not reveal any sexual dimorphism. Furthermore, male and female rats exhibited similar c-fos mRNA expression in the brain following noise stress, including several sex-influenced stress-related regions. The HPA axis response to noise stress was not affected by stage of estrous cycle, and ovariectomy significantly increased hormone release. Direct comparison of HPA axis hormone release to two different stressors in the same animals revealed that although female rats exhibit robustly higher HPA axis hormone release after restraint stress, the same effect was not observed following moderate and high intensity loud noise stress. Finally, the differential effect of sex on HPA axis responses to noise and restraint stress cannot readily be explained by differential social cues or general pain processing. These studies suggest the effect of sex on acute stress-induced HPA axis hormone activity is highly dependent on the type of stressor.

  2. 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)

  3. 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)

  4. Research of z-axis geometric dose efficiency in multi-detector computed tomography

    International Nuclear Information System (INIS)

    Kim, You Hyun; Kim, Moon Chan

    2006-01-01

    With the recent prevalence of helical CT and multi-slice CT, which deliver higher radiation dose than conventional CT due to overbeaming effect in X-ray exposure and interpolation technique in image reconstruction. Although multi-detector and helical CT scanner provide a variety of opportunities for patient dose reduction, the potential risk for high radiation levels in CT examination can't be overemphasized in spite of acquiring more diagnostic information. So much more concerns is necessary about dose characteristics of CT scanner, especially dose efficient design as well as dose modulation software, because dose efficiency built into the scanner's design is probably the most important aspect of successful low dose clinical performance. This study was conducted to evaluate z-axis geometric dose efficiency in single detector CT and each level multi-detector CT, as well as to compare z-axis dose efficiency with change of technical scan parameters such as focal spot size of tube, beam collimation, detector combination, scan mode, pitch size, slice width and interval. The results obtained were as follows; 1. SDCT was most highest and 4 MDCT was most lowest in z-axis geometric dose efficiency among SDCT, 4, 8, 16, 64 slice MDCT made by GE manufacture. 2. Small focal spot was 0.67-13.62% higher than large focal spot in z-axis geometric dose efficiency at MDCT. 3. Large beam collimation was 3.13-51.52% higher than small beam collimation in z-axis geometric dose efficiency at MDCT. Z-axis geometric dose efficiency was same at 4 slice MDCT in all condition and 8 slice MDCT of large beam collimation with change of detector combination, but was changed irregularly at 8 slice MDCT of small beam collimation and 16 slice MDCT in all condition with change of detector combination. 5. There was no significant difference for z-axis geometric dose efficiency between conventional scan and helical scan, and with change of pitch factor, as well as change of slice width or interval for

  5. 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

  6. 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...

  7. KWOC [Key-Word-Out-of-Context] Index of US Nuclear Regulatory Commission Regulatory Guide Series

    International Nuclear Information System (INIS)

    Jennings, S.D.

    1990-04-01

    To meet the objectives of the program funded by the Department of Energy (DOE)-Nuclear Energy (NE) Technology Support Programs, the Performance Assurance Project Office (PAPO) administers a Performance Assurance Information Program that collects, compiles, and distributes program-related information, reports, and publications for the benefit of the DOE-NE program participants. THE ''KWOC Index of US Nuclear Regulatory Commission Regulatory Guide Series'' is prepared as an aid in searching for specific topics in the US Nuclear Regulatory Commission, Regulatory Guide Series

  8. The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

    Science.gov (United States)

    Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian; Jin, Yi; Turner, Jacob; Moore, Amanda J; Saito, Rintaro; Yoshida, Kenichi; Ogawa, Seishi; Rodewald, Hans-Reimer; Lin, Yin C; Kawamoto, Hiroshi; Murre, Cornelis

    2017-05-16

    Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. 2002–2012: 10 Years of Research Progress in Horizontal-Axis Marine Current Turbines

    Directory of Open Access Journals (Sweden)

    Kai-Wern Ng

    2013-03-01

    Full Text Available Research in marine current energy, including tidal and ocean currents, has undergone significant growth in the past decade. The horizontal-axis marine current turbine is one of the machines used to harness marine current energy, which appears to be the most technologically and economically viable one at this stage. A number of large-scale marine current turbines rated at more than 1 MW have been deployed around the World. Parallel to the development of industry, academic research on horizontal-axis marine current turbines has also shown positive growth. This paper reviews previous research on horizontal-axis marine current turbines and provides a concise overview for future researchers who might be interested in horizontal-axis marine current turbines. The review covers several main aspects, such as: energy assessment, turbine design, wakes, generators, novel modifications and environmental impact. Future trends for research on horizontal-axis marine current turbines are also discussed.

  10. Disruption of the HPA-axis through corticosterone-release pellets induces robust depressive-like behavior and reduced BDNF levels in mice.

    Science.gov (United States)

    Demuyser, Thomas; Bentea, Eduard; Deneyer, Lauren; Albertini, Giulia; Massie, Ann; Smolders, Ilse

    2016-07-28

    The corticosterone mouse model is widely used in preclinical research towards a better understanding of mechanisms of major depression. One particular administration procedure is the subcutaneous implantation of corticosterone slow-release pellets. In this report we want to provide basic evidence, regarding behavioral changes, neurotransmitter and -modulator levels and some other relevant biomolecules after hypothalamic-pituitary-adrenal-axis distortion. We show that three weeks of corticosterone pellet exposure robustly induces depressive-like but not anxiety-like behavior in mice, accompanied by a significant decrease in hippocampal brain-derived neurotrophic factor levels, at five weeks after the start of treatment. Furthermore there is an overall decrease in plasma corticosterone levels after three weeks of treatment that lasts up until the five weeks' time point. On the other hand, no differences are observed in total monoamine, glutamate or d-serine levels, nor in glucocorticoid receptor expression, in various depression-related brain areas. Altogether this characterization delivers vital information, supplementary to existing literature, regarding the phenotyping of pellet-induced hypothalamic-pituitary-adrenal-axis disruption in mice following three weeks of continuous corticosterone exposure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Anatomy of an eradication effort: Removing Hawaii's illegally introduced axis deer

    Science.gov (United States)

    Hess, Steven C.; Muise, Jake; Schipper, Jan

    2015-01-01

    In February 2011, a rancher in the rural southern part of Hawaii Island reported a large mammal on her land. Her call mobilized several agencies led by the Big Island Invasive Species Committee (BIISC), a partnership to prevent, detect, and control the establishment and spread of invasive species, to sit up and take notice. Agency biologists installed camera traps to identify the animal, and a few months later verified the diagnostic field marks of a chervid with spots. The animal in questions was a chital, or axis deer (Axis axis)--a species native to tropical and subtropical India. Although the deer are abundant on the islands of Molokai, Lānai, and Maui, officials knew they weren't capable of swimming across the notoriously treacherous ʻAlenuihāhā channel, and subsequently suspected human intervention.

  12. Normal function of the hypothalamic-pituitary growth axis in three dwarf Friesian foals.

    Science.gov (United States)

    de Graaf-Roelfsema, E; Back, W; Keizer, H A; Stout, T A E; van der Kolk, J H

    2009-09-26

    Serial blood samples were collected from three dwarf Friesian foals to examine their endogenous growth hormone (GH) profiles, and the integrity of the GH-insulin-like growth factor-1 (IGF-1) axis was tested in one of them by examining its responses to the administration of GH-releasing hormone (GHRH) and to 10 days of treatment with recombinant equine GH. The basal serum concentrations of IGF-1 in the three dwarf foals were compared with those in nine age-matched normal foals. All the dwarf foals secreted endogenous GH. Stimulation with 7.0 microg/kg GHRH led to a 1400 per cent increase in plasma GH concentration in the dwarf foal tested, and 10 daily subcutaneous treatments with 20 microg/kg recombinant equine GH led to a 100 per cent increase in its serum IGF-1 concentration. The basal serum concentrations of IGF-1 in the dwarf foals were not significantly different from those of the normal foals.

  13. Radiation safety and regulatory aspects in Medical Facilities

    International Nuclear Information System (INIS)

    Banerjee, Sharmila

    2017-01-01

    Radiation safety and regulatory aspect of medical facilities are relevant in the context where radiation is used in providing healthcare to human patients. These include facilities, which carry out radiological procedures in diagnostic radiology, including dentistry, image-guided interventional procedures, nuclear medicine, and radiation therapy. The safety regulations provide recommendations and guidance on meeting the requirements for the safe use of radiation in medicine. The different safety aspects which come under its purview are the personnel involved in medical facilities where radiological procedures are performed which include the medical practitioners, radiation technologists, medical physicists, radiopharmacists, radiation protection and over and above all the patients. Regulatory aspects cover the guidelines provided by ethics committees, which regulate the administration of radioactive formulation in human patients. Nuclear medicine is a modality that utilizes radiopharmaceuticals either for diagnosis of physiological disorders related to anatomy, physiology and patho-physiology and for diagnosis and treatment of cancer

  14. 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.

  15. 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

  16. Determination of a sagittal plane axis of rotation for a dynamic office chair.

    Science.gov (United States)

    Bauer, C M; Rast, F M; Böck, C; Kuster, R P; Baumgartner, D

    2018-10-01

    This study investigated the location of the axis of rotation in sagittal plane movement of the spine in a free sitting condition to adjust the kinematics of a mobile seat for a dynamic chair. Dynamic office chairs are designed to avoid continuous isometric muscle activity, and to facilitate increased mobility of the back during sitting. However, these chairs incorporate increased upper body movement which could distract office workers from the performance of their tasks. A chair with an axis of rotation above the seat would facilitate a stable upper back during movements of the lower back. The selection of a natural kinematic pattern is of high importance in order to match the properties of the spine. Twenty-one participants performed four cycles of flexion and extension of the spine during an upper arm hang on parallel bars. The location of the axis of rotation relative to the seat was estimated using infrared cameras and reflective skin markers. The median axis of rotation across all participants was located 36 cm above the seat for the complete movement and 39 cm for both the flexion and extension phases, each with an interquartile range of 20 cm. There was no significant effect of the movement direction on the location of the axis of rotation and only a weak, non-significant correlation between body height and the location of the axis of rotation. Individual movement patterns explained the majority of the variance. The axis of rotation for a spinal flexion/extension movement is located above the seat. The recommended radius for a guide rail of a mobile seat is between 36 cm and 39 cm. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Cushing's Syndrome and Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy.

    Science.gov (United States)

    van Haalen, Femke M; van Dijk, Elon H C; Dekkers, Olaf M; Bizino, Maurice B; Dijkman, Greet; Biermasz, Nienke R; Boon, Camiel J F; Pereira, Alberto M

    2018-01-01

    Central serous chorioretinopathy (CSC), a specific form of macular degeneration, has been reported as presenting manifestation of Cushing's syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing's syndrome. It is important to know whether CSC patients should be screened for Cushing's syndrome. Although hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing's syndrome prevalence is increased among chronic CSC (cCSC) patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis. Cross-sectional study. 86 cCSC patients and 24 controls. Prevalence of Cushing's syndrome, HPA axis activity. None of the cCSC patients met the clinical or biochemical criteria of Cushing's syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires. No case of Cushing's syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing's syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

  18. Food irradiation—US regulatory considerations

    Science.gov (United States)

    Morehouse, Kim M.

    2002-03-01

    The use of ionizing radiation in food processing has received increased interest as a means of reducing the level of foodborne pathogens. This overview discusses the regulatory issues connected with the use of this technology in the United States. Several recent changes in the FDA's review process are discussed. These include the current policy that utilizes an expedited review process for petitions seeking approval of additives and technologies intended to reduce pathogen levels in food, and the recent USDA rule that eliminates the need for a separate rulemaking process by USDA for irradiation of meat and poultry. Recently promulgated rules and pending petitions before the FDA associated with the use of ionizing radiation for the treatment of foods are also discussed along with the current FDA labeling requirements for irradiated foods and the 1999 advanced notice of proposed rule on labeling. Another issue that is presented is the current status of the approval of packaging materials intended for food contact during irradiation treatment of foods.

  19. Food irradiation--US regulatory considerations

    International Nuclear Information System (INIS)

    Morehouse, Kim M.

    2002-01-01

    The use of ionizing radiation in food processing has received increased interest as a means of reducing the level of foodborne pathogens. This overview discusses the regulatory issues connected with the use of this technology in the United States. Several recent changes in the FDA's review process are discussed. These include the current policy that utilizes an expedited review process for petitions seeking approval of additives and technologies intended to reduce pathogen levels in food, and the recent USDA rule that eliminates the need for a separate rulemaking process by USDA for irradiation of meat and poultry. Recently promulgated rules and pending petitions before the FDA associated with the use of ionizing radiation for the treatment of foods are also discussed along with the current FDA labeling requirements for irradiated foods and the 1999 advanced notice of proposed rule on labeling. Another issue that is presented is the current status of the approval of packaging materials intended for food contact during irradiation treatment of foods

  20. 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.)

  1. miR-24-3p/FGFR3 Signaling as a Novel Axis Is Involved in Epithelial-Mesenchymal Transition and Regulates Lung Adenocarcinoma Progression

    Directory of Open Access Journals (Sweden)

    Pengyu Jing

    2018-01-01

    Full Text Available Our previous studies showed that Fibroblast growth factor receptor 3 (FGFR3 contributed to cell growth in lung cancer. However, the correlation between FGFR3 and tumor progression, coupled with the underlying mechanisms, are not fully understood. The clinical significance of FGFR3 was determined in two cohorts of clinical samples (n=22, n=78. A panel of biochemical assays and functional experiments was utilized to elucidate the underlying mechanisms and effects of FGFR3 and miR-24-3p on lung adenocarcinoma progression. Upregulated FGFR3 expression indicated an adverse prognosis for lung adenocarcinoma individuals and promoted metastatic potential of lung adenocarcinoma cells. Owing to the direct regulation towards FGFR3, miR-24-3p could interfere with the potential of proliferation, migration, and invasion in lung adenocarcinoma, following variations of EMT-related protein expression. As a significant marker of EMT, E-cadherin was negatively correlated with FGFR3, of which ectopic overexpression could neutralize the antitumour effects of miR-24-3p and reverse its regulatory effects on EMT markers. Taken together, these findings define a novel insight into the miR-24-3p/FGFR3 signaling axis in regulating lung adenocarcinoma progression and suggest that targeting the miR-24-3p/FGFR3 axis could be an effective and efficient way to prevent tumor progression.

  2. 77 FR 12098 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-02-28

    ... 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule... FINRA and at the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of the..., and C below, of the most significant aspects of such statements. A. Self-Regulatory Organization's...

  3. 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.

  4. Determination of the number of Vertical Axis Wind Turbine blades based on power spectrum

    Directory of Open Access Journals (Sweden)

    Fedak Waldemar

    2017-01-01

    Full Text Available Technology of wind exploitation has been applied widely all over the world and has already reached the level in which manufacturers want to maximize the yield with the minimum investment outlays. The main objective of this paper is the determination of the optimal number of blades in the Cup-Bladed Vertical Axis Wind Turbine. Optimizing the size of the Vertical Axis Wind Turbine allows the reduction of costs. The maximum power of the rotor is selected as the performance target. The optimum number of Vertical Axis Wind Turbine blades evaluation is based on analysis of a single blade simulation and its superposition for the whole rotor. The simulation of working blade was done in MatLab environment. Power spectrum graphs were prepared and compared throughout superposition of individual blades in the Vertical Axis Wind Turbine rotor. The major result of this research is the Vertical Axis Wind Turbine power characteristic. On the basis of the analysis of the power spectra, optimum number of the blades was specified for the analysed rotor. Power spectrum analysis of wind turbine enabled the specification of the optimal number of blades, and can be used regarding investment outlays and power output of the Vertical Axis Wind Turbine.

  5. Determination of the number of Vertical Axis Wind Turbine blades based on power spectrum

    Science.gov (United States)

    Fedak, Waldemar; Anweiler, Stanisław; Gancarski, Wojciech; Ulbrich, Roman

    2017-10-01

    Technology of wind exploitation has been applied widely all over the world and has already reached the level in which manufacturers want to maximize the yield with the minimum investment outlays. The main objective of this paper is the determination of the optimal number of blades in the Cup-Bladed Vertical Axis Wind Turbine. Optimizing the size of the Vertical Axis Wind Turbine allows the reduction of costs. The maximum power of the rotor is selected as the performance target. The optimum number of Vertical Axis Wind Turbine blades evaluation is based on analysis of a single blade simulation and its superposition for the whole rotor. The simulation of working blade was done in MatLab environment. Power spectrum graphs were prepared and compared throughout superposition of individual blades in the Vertical Axis Wind Turbine rotor. The major result of this research is the Vertical Axis Wind Turbine power characteristic. On the basis of the analysis of the power spectra, optimum number of the blades was specified for the analysed rotor. Power spectrum analysis of wind turbine enabled the specification of the optimal number of blades, and can be used regarding investment outlays and power output of the Vertical Axis Wind Turbine.

  6. The A/P axis in echinoderm ontogeny and evolution: evidence from fossils and molecules

    Science.gov (United States)

    Peterson, K. J.; Arenas-Mena, C.; Davidson, E. H.

    2000-01-01

    Even though echinoderms are members of the Bilateria, the location of their anterior/posterior axis has remained enigmatic. Here we propose a novel solution to the problem employing three lines of evidence: the expression of a posterior class Hox gene in the coeloms of the nascent adult body plan within the larva; the anatomy of certain early fossil echinoderms; and finally the relation between endoskeletal plate morphology and the associated coelomic tissues. All three lines of evidence converge on the same answer, namely that the location of the adult mouth is anterior, and the anterior/posterior axis runs from the mouth through the adult coelomic compartments. This axis then orients the animal such that there is but a single plane of symmetry dividing the animal into left and right halves. We tentatively hypothesize that this plane of symmetry is positioned along the dorsal/ventral axis. These axis identifications lead to the conclusion that the five ambulacra are not primary body axes, but instead are outgrowths from the central anterior/posterior axis. These identifications also shed insight into several other evolutionary mysteries of various echinoderm clades such as the independent evolution of bilateral symmetry in irregular echinoids, but do not elucidate the underlying mechanisms of the adult coelomic architecture.

  7. 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.

  8. 76 FR 9840 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-02-22

    .... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory..., and C below, of the most significant aspects of such statements. A. Self-Regulatory Organization's...

  9. Overview and Design of self-acting pitch control mechanism for vertical axis wind turbine using multi body simulation approach

    DEFF Research Database (Denmark)

    Chougule, Prasad; Nielsen, Søren R.K.

    2014-01-01

    Awareness about wind energy is constantly growing in the world. Especially a demand for small scale wind turbine is increasing and various products are available in market. There are mainly two types of wind turbines, horizontal axis wind turbine and vertical axis wind turbines. Horizontal axis...... wind turbines are suitable for high wind speed whereas vertical axis wind turbines operate relatively low wind speed area. Vertical axis wind turbines are cost effective and simple in construction as compared to the horizontal axis wind turbine. However, vertical axis wind turbines have inherent...

  10. Regulatory T cell effects in antitumor laser immunotherapy: a mathematical model and analysis

    Science.gov (United States)

    Dawkins, Bryan A.; Laverty, Sean M.

    2016-03-01

    Regulatory T cells (Tregs) have tremendous influence on treatment outcomes in patients receiving immunotherapy for cancerous tumors. We present a mathematical model incorporating the primary cellular and molecular components of antitumor laser immunotherapy. We explicitly model developmental classes of dendritic cells (DCs), cytotoxic T cells (CTLs), primary and metastatic tumor cells, and tumor antigen. Regulatory T cells have been shown to kill antigen presenting cells, to influence dendritic cell maturation and migration, to kill activated killer CTLs in the tumor microenvironment, and to influence CTL proliferation. Since Tregs affect explicitly modeled cells, but we do not explicitly model dynamics of Treg themselves, we use model parameters to analyze effects of Treg immunosuppressive activity. We will outline a systematic method for assigning clinical outcomes to model simulations and use this condition to associate simulated patient treatment outcome with Treg activity.

  11. Obesity and the hypothalamic-pituitary-adrenal axis in adolescent girls.

    Science.gov (United States)

    Hillman, Jennifer B; Dorn, Lorah D; Loucks, Tammy L; Berga, Sarah L

    2012-03-01

    Stress and stress-related concomitants, including hypothalamic-pituitary-adrenal (HPA) axis activation, are implicated in obesity and its attendant comorbidities. Little is known about this relationship in adolescents. To begin to address this important knowledge gap, we studied HPA axis activity in 262 healthy adolescent girls aged 11, 13, 15, and 17 years. We hypothesized that obesity would be correlated with increased HPA axis activity and reactivity. Measures of HPA axis activity included 3 blood samples obtained midday (between 1:00 and 2:00 pm) over the course of 40 minutes; overnight urine free cortisol; and cortisol levels 0, 20, and 40 minutes after venipuncture (cortisol reactivity). Measures of adiposity included body mass index (BMI), BMI z score (BMI-Z), percentage body fat, and fat distribution (central adiposity) assessed by dual-energy x-ray absorptiometry. Daytime levels of serum cortisol were inversely associated with BMI-Z and central adiposity (P cortisol excretion rate was positively correlated with BMI, BMI-Z, and central adiposity. There was blunting of cortisol response to venipuncture with increasing adiposity. Our results suggest that there may be reduced cortisol levels during the day and increased levels at night with increasing degree of adiposity. This study provides preliminary findings indicating an alteration of the circadian rhythm of cortisol with obesity. We conclude that obesity is associated with altered HPA activity in adolescent girls. The clinical implications of our findings require further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. The clinical correlation of regulatory T cells and cyclic adenosine monophosphate in enterovirus 71 infection.

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    Full Text Available Brainstem encephalitis (BE and pulmonary edema (PE are notable complications of enterovirus 71 (EV71 infection.This study investigated the immunoregulatory characterizations of EV71 neurological complications by disease severity and milrinone treatment.Patients <18 years with virologically confirmed EV71 infections were enrolled and divided into 2 groups: the hand, foot, and mouth disease (HFMD or BE group, and the autonomic nervous system (ANS dysregulation or PE group. Cytokine and cyclic adenosine monophosphate (cAMP levels, and the regulatory T cell (Tregs profiles of the patients were determined.Patients with ANS dysregulation or PE exhibited significantly low frequency of CD4(+CD25(+Foxp3+ and CD4(+Foxp3(+ T cells compared with patients with HFMD or BE. The expression frequency of CD4-CD8- was also significantly decreased in patients with ANS dysregulation or PE. Among patients with ANS dysregulation or PE, the expression frequency of CD4+Foxp3+ increased markedly after milrinone treatment, and was associated with reduction of plasma levels IL-6, IL-8 and IL-10. Plasma concentrations of cAMP were significantly decreased in patients with ANS dysregulation or PE compared with patients with HFMD or BE; however, cAMP levels increased after milrinone treatment.These findings suggested decreased different regulatory T populations and cAMP expression correlate with increased EV71 disease severity. Improved outcome after milrinone treatment may associate with increased regulatory T populations, cAMP expression and modulation of cytokines levels.

  13. 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...

  14. 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

  15. Risk-based Regulatory Evaluation Program methodology

    International Nuclear Information System (INIS)

    DuCharme, A.R.; Sanders, G.A.; Carlson, D.D.; Asselin, S.V.

    1987-01-01

    The objectives of this DOE-supported Regulatory Evaluation Progrwam are to analyze and evaluate the safety importance and economic significance of existing regulatory guidance in order to assist in the improvement of the regulatory process for current generation and future design reactors. A risk-based cost-benefit methodology was developed to evaluate the safety benefit and cost of specific regulations or Standard Review Plan sections. Risk-based methods can be used in lieu of or in combination with deterministic methods in developing regulatory requirements and reaching regulatory decisions

  16. Dynamics of the off axis intense beam propagation in a spiral inflector

    Energy Technology Data Exchange (ETDEWEB)

    Goswami, A., E-mail: animesh@vecc.gov.in; Sing Babu, P., E-mail: psb@vecc.gov.in; Pandit, V.S., E-mail: pandit@vecc.gov.in

    2017-01-01

    In this paper the dynamics of space charge dominated beam in a spiral inflector is discussed by developing equations of motion for centroid and beam envelope for the off axis beam propagation. Evolution of the beam centroid and beam envelope is studied as a function of the beam current for various input beam parameters. The transmission of beam through the inflector is also estimated as a function of the beam current for an on axis and off axis beam by tracking a large number of particles. Simulation studies show that shift of the centroid from the axis at the inflector entrance affects the centroid location at the exit of the inflector and causes reduction in the beam transmission. The centroid shift at the entrance in the horizontal plane (h plane) is more critical as it affects the centroid shift in the vertical plane (u plane) by a large amount near the inflector exit where the available aperture is small. The beam transmission is found to reduce with increase in the centroid shift as well as with the beam current.

  17. Methodology for the Systematic Assessment of the Regulatory Competence Needs (SARCoN) for Regulatory Bodies of Nuclear Installations

    International Nuclear Information System (INIS)

    2015-03-01

    A regulatory body’s competence is dependent, among other things, on the competence of its staff. A necessary, but not sufficient, condition for a regulatory body to be competent is that its staff can perform the tasks related to the functions of the regulatory body. In 2001, the IAEA published TECDOC 1254, Training the Staff of the Regulatory Body for Nuclear Facilities: A Competency Framework, which examines the manner in which the recognized regulatory functions of a nuclear regulatory body results in competence needs. Using the internationally recognized systematic approach to training, TECDOC 1254 provides a framework for regulatory bodies for managing training and developing, and maintaining the competence of its staff. It has been successfully used by many regulatory bodies all over the world, including States embarking on a nuclear power programme. 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 2013, the IAEA published Safety Reports Series No. 79, Managing Regulatory Body Competence, which provides generic guidance based on IAEA safety requirements in the development of a competence management system within a regulatory body’s integrated management system. An appendix in the Safety Report 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. This publication provides guidance for the analysis of required and existing competences to identify those required by the regulatory body to perform its functions and therefore associated needs for acquiring competences. Hence, it is equally applicable to the needs of States embarking on nuclear power

  18. 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

  19. Legal and Regulatory Frameworks for Decommissioning and Waste Management

    International Nuclear Information System (INIS)

    Leech, Jonathan

    2016-01-01

    Safe and efficient decommissioning and waste management requires clear structures for allocating responsibility and funding. Organisation of decommissioning and waste management activities and the regulatory environment within which those activities are undertaken should also allow the supply chain to prosper and, wherever possible, reduce barriers to international availability of resources and waste facilities. Radioactive waste treatment and disposal in particular raises both legal and political challenges to effective international co-operation, yet options for decommissioning and waste management are maximised where international barriers can be minimised. Added to this, international nuclear liabilities issues must be managed so as to avoid unnecessary deterrents to international mobility of capability within the decommissioning market. Contractual terms and insurance arrangements for international shipments of nuclear waste and materials will also need to take into account imminent changes to liabilities conventions, ensuring compliance and management of compliance costs (of both insurance and management time). This paper explores legal and commercial structures intended to support effective decommissioning and waste management and examines regulatory and commercial factors affecting the ability of facility operators to utilise internationally available capability. It focusses on: - strategic approaches developed in the UK to address decommissioning and waste management liabilities associated with the UK's first and second generation civil nuclear sites and comparison of those approaches with other jurisdictions with significant decommissioning liabilities; - liability and compliance risks associated with navigating international nuclear liabilities regimes in context of both mobility of decommissioning capability and international waste shipment; and - regulatory issues affecting international availability of waste treatment facilities, including

  20. 76 FR 9838 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-02-22

    .... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance..., and at the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of the... in sections A, B, and C below, of the most significant aspects of such statements. A. Self-Regulatory...