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Sample records for regulation programmed death-1

  1. CD4(+) type II NKT cells mediate ICOS and programmed death-1-dependent regulation of type 1 diabetes.

    Science.gov (United States)

    Kadri, Nadir; Korpos, Eva; Gupta, Shashank; Briet, Claire; Löfbom, Linda; Yagita, Hideo; Lehuen, Agnes; Boitard, Christian; Holmberg, Dan; Sorokin, Lydia; Cardell, Susanna L

    2012-04-01

    Type 1 diabetes (T1D) is a chronic autoimmune disease that results from T cell-mediated destruction of pancreatic β cells. CD1d-restricted NKT lymphocytes have the ability to regulate immunity, including autoimmunity. We previously demonstrated that CD1d-restricted type II NKT cells, which carry diverse TCRs, prevented T1D in the NOD mouse model for the human disease. In this study, we show that CD4(+) 24αβ type II NKT cells, but not CD4/CD8 double-negative NKT cells, were sufficient to downregulate diabetogenic CD4(+) BDC2.5 NOD T cells in adoptive transfer experiments. CD4(+) 24αβ NKT cells exhibited a memory phenotype including high ICOS expression, increased cytokine production, and limited display of NK cell markers, compared with double-negative 24αβ NKT cells. Blocking of ICOS or the programmed death-1/programmed death ligand 1 pathway was shown to abolish the regulation that occurred in the pancreas draining lymph nodes. To our knowledge, these results provide for the first time cellular and molecular information on how type II CD1d-restricted NKT cells regulate T1D.

  2. Checkpoint Inhibition: Programmed Cell Death 1 and Programmed Cell Death 1 Ligand Inhibitors in Hodgkin Lymphoma.

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    Villasboas, Jose Caetano; Ansell, Stephen

    2016-01-01

    Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by a reactive immune infiltrate surrounding relatively few malignant cells. In this scenario, active immune evasion seems to play a central role in allowing tumor progression. Immune checkpoint inhibitor pathways are normal mechanisms of T-cell regulation that suppress immune effector function following an antigenic challenge. Hodgkin lymphoma cells are able to escape immune surveillance by co-opting these mechanisms. The programmed cell death 1 (PD-1) pathway in particular is exploited in HL as the malignant Hodgkin and Reed-Sternberg cells express on their surface cognate ligands (PD-L1/L2) for the PD-1 receptor and thereby dampen the T-cell-mediated antitumoral response. Monoclonal antibodies that interact with and disrupt the PD-1:PD-L1/L2 axis have now been developed and tested in early-phase clinical trials in patients with advanced HL with encouraging results. The remarkable clinical activity of PD-1 inhibitors in HL highlights the importance of immune checkpoint pathways as therapeutic targets in HL. In this review, we discuss the rationale for targeting PD-1 and PD-L1 in the treatment of HL. We will evaluate the published clinical data on the different agents and highlight the safety profile of this class of agents. We discuss the available evidence on the use of biomarkers as predictors of response to checkpoint blockade and summarize the areas under active investigation in the use of PD-1/PD-L1 inhibitors for the treatment of HL.

  3. Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

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    Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

    2015-01-01

    Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

  4. CD4+ type II NKT cells mediate ICOS and programmed death-1-dependent regulation of type 1 diabetes

    DEFF Research Database (Denmark)

    Kadri, Nadir; Korpos, Eva; Gupta, Shashank

    2012-01-01

    Type 1 diabetes (T1D) is a chronic autoimmune disease that results from T cell-mediated destruction of pancreatic ß cells. CD1d-restricted NKT lymphocytes have the ability to regulate immunity, including autoimmunity. We previously demonstrated that CD1d-restricted type II NKT cells, which carry ...

  5. Drug of the year: programmed death-1 receptor/programmed death-1 ligand-1 receptor monoclonal antibodies.

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    Robert, Caroline; Soria, Jean-Charles; Eggermont, Alexander M M

    2013-09-01

    Programmed death-1 receptor (PD-1)/its ligand (PD-L1) antibodies have changed the landscape in oncology in 2013. The most mature results have been obtained in advanced melanoma patients. They indicate important response rates and high quality responses or prolonged duration. Also in renal cancer and in lung cancer remarkable activity has been demonstrated. Thus it is clear that these antibodies have a very broad potential and trials in many tumour types are being initiated. Breaking tolerance at the tumour site is a potent phenomenon and the potential for synergy with other checkpoint inhibitors such as ipilimumab have also been demonstrated in 2013. Long term tumour control now seems achievable and thus the concept of a clinical cure is emerging by modulation of the immune system. These antibodies bring immunotherapy to the forefront and indicate that immune-modulation will be a key component of therapeutic strategies from now on. Because of all these reasons PD-1/PD-L1 antibodies are considered 'drug of the year'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection.

    Science.gov (United States)

    Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

    2015-11-03

    Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules including chemokine receptor type 5 (CXCR5), inducible T cell co-stimulator (ICOS), programmed death-1 (PD-1), ICOSL, PDL-1 and interleukin-21 (IL-21), of peripheral blood were comparatively measured in 42 primary renal allograft recipients within 1-3 years after transplantation. Among them, 24 patients had definite chronic rejection, while other 18 patients had normal renal function. Tfh-cell ratio was significantly increased with PD-1 down-regulation in the patients with chronic renal allograft rejection, while B cells and the alloimmune-regulating molecules studied did not show any appreciable change in parallel. The patients with chronic renal allograft rejection have a characteristic increase in circulating Tfh cells with a decrease in PD-1 expression. These pathological changes may be a therapeutic target for the treatment of chronic renal allograft rejection and can be useful as a clinical index for monitoring conditions of renal transplant.

  7. Dendritic Cells and Programmed Death-1 Blockade: A Joint Venture to Combat Cancer.

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    Versteven, Maarten; Van den Bergh, Johan M J; Marcq, Elly; Smits, Evelien L J; Van Tendeloo, Viggo F I; Hobo, Willemijn; Lion, Eva

    2018-01-01

    Two decades of clinical cancer research with dendritic cell (DC)-based vaccination have proved that this type of personalized medicine is safe and has the capacity to improve survival, but monotherapy is unlikely to cure the cancer. Designed to empower the patient's antitumor immunity, huge research efforts are set to improve the efficacy of next-generation DC vaccines and to find synergistic combinations with existing cancer therapies. Immune checkpoint approaches, aiming to breach immune suppression and evasion to reinforce antitumor immunity, have been a revelation in the immunotherapy field. Early success of therapeutic antibodies blocking the programmed death-1 (PD-1) pathway has sparked the development of novel inhibitors and combination therapies. Hence, merging immunoregulatory tumor-specific DC strategies with PD-1-targeted approaches is a promising path to explore. In this review, we focus on the role of PD-1-signaling in DC-mediated antitumor immunity. In the quest of exploiting the full potential of DC therapy, different strategies to leverage DC immunopotency by impeding PD-1-mediated immune regulation are discussed, including the most advanced research on targeted therapeutic antibodies, lessons learned from chemotherapy-induced immune activation, and more recent developments with soluble molecules and gene-silencing techniques. An overview of DC/PD-1 immunotherapy combinations that are currently under preclinical and clinical investigation substantiates the clinical potential of such combination strategies.

  8. Development and Fit-for-Purpose Validation of a Soluble Human Programmed Death-1 Protein Assay.

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    Ni, Yan G; Yuan, Xiling; Newitt, John A; Peterson, Jon E; Gleason, Carol R; Haulenbeek, Jonathan; Santockyte, Rasa; Lafont, Virginie; Marsilio, Frank; Neely, Robert J; DeSilva, Binodh; Piccoli, Steven P

    2015-07-01

    Programmed death-1 (PD-1) protein is a co-inhibitory receptor which negatively regulates immune cell activation and permits tumors to evade normal immune defense. Anti-PD-1 antibodies have been shown to restore immune cell activation and effector function-an exciting breakthrough in cancer immunotherapy. Recent reports have documented a soluble form of PD-1 (sPD-1) in the circulation of normal and disease state individuals. A clinical assay to quantify sPD-1 would contribute to the understanding of sPD-1-function and facilitate the development of anti-PD-1 drugs. Here, we report the development and validation of a sPD-1 protein assay. The assay validation followed the framework for full validation of a biotherapeutic pharmacokinetic assay. A purified recombinant human PD-1 protein was characterized extensively and was identified as the assay reference material which mimics the endogenous analyte in structure and function. The lower limit of quantitation (LLOQ) was determined to be 100 pg/mL, with a dynamic range spanning three logs to 10,000 pg/mL. The intra- and inter-assay imprecision were ≤15%, and the assay bias (percent deviation) was ≤10%. Potential matrix effects were investigated in sera from both normal healthy volunteers and selected cancer patients. Bulk-prepared frozen standards and pre-coated Streptavidin plates were used in the assay to ensure consistency in assay performance over time. This assay appears to specifically measure total sPD-1 protein since the human anti-PD-1 antibody, nivolumab, and the endogenous ligands of PD-1 protein, PDL-1 and PDL-2, do not interfere with the assay.

  9. Programmed cell death-1 and programmed cell death ligand-1 antibodies-induced dysthyroidism.

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    Jaafar, Jaafar; Fernandez, Eugenio; Alwan, Heba; Philippe, Jacques

    2018-05-01

    Monoclonal antibodies blocking the programmed cell death-1 (PD-1) or its ligand (PD-L1) are a group of immune checkpoints inhibitors (ICIs) with proven antitumor efficacy. However, their use is complicated by immune-related adverse events (irAEs), including endocrine adverse events (eAEs). We review the incidence, time to onset and resolution rate of dysthyroidism induced by PD-1/PD-L1 Ab, and the clinical, biological and radiological findings. We aim to discuss the potential mechanisms of PD-1/PD-L1 Ab-induced dysthyroidism, and to propose a management algorithm. We performed a literature search of available clinical trials regarding PD-1/PD-L1 Ab in the PubMed database. We selected all English language clinical trials that included at least 100 patients. We also present selected case series or reports, retrospective studies and reviews related to this issue. In patients treated with PD-1 Ab, hypothyroidism occurred in 2-10.1% and hyperthyroidism occurred in 0.9-7.8%. When thyroiditis was reported separately, it occurred in 0.34-2.6%. Higher rates were reported when PD-1 Ab were associated with other ICI or chemotherapy. The median time to onset of hyperthyroidism and hypothyroidism after PD-1 Ab initiation was 23-45 days and 2-3.5 months, respectively. Regarding PD-L1 Ab, hypothyroidism occurred in 0-10% and hyperthyroidism in 0.5-2% of treated patients. The average time to onset of dysthyroidism after PD-L1 Ab was variable and ranged from 1 day after treatment initiation to 31 months. Dysthyroidism occurs in up to 10% of patients treated with PD-1/PD-L1 Ab. Hypothyroidism and reversible destructive thyroiditis are the most frequent endocrine adverse events (eAE) in PD-1/PD-L1 treated patients. Immune and non-immune mechanisms are potentially involved, independently of the presence of thyroid antibodies. © 2018 The authors.

  10. Combined blockade of vascular endothelial growth factor and programmed death 1 pathways in advanced kidney cancer.

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    Einstein, David J; McDermott, David F

    2017-06-01

    Targeted and immune-based therapies have improved outcomes in advanced kidney cancer, yet novel strategies are needed to extend the duration of these benefits and expand them to more patients. Combined inhibition of vascular endothelial growth factor (VEGF) and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathways with therapeutic agents already in clinical use may offer such a strategy. Here, we describe the development and clinical evaluation of VEGF inhibitors and, separately, PD-1/PD-L1 inhibitors. We present preclinical evidence of interaction between these pathways and the rationale for combined blockade. Beyond well-known effects on pathologic angiogenesis, VEGF blockade also may decrease immune tolerance and enhance PD-1/PD-L1 blockade. We conclude with the results of several early trials of combined VEGF and PD-1/PD-L1 blockade, which demonstrate encouraging antitumor activity, and we pose questions for future study.

  11. Harnessing the immune system through programmed death-1 blockade in the management of Hodgkin lymphoma

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    Oncale MB

    2017-02-01

    Full Text Available Melody B Oncale, Hossein Maymani, Loretta J Nastoupil Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Immunotherapy is a rapidly evolving therapeutic option in the treatment of lymphoma. Neoplastic cells evade immune recognition through the programmed death (PD-1/PD-ligand immune checkpoint pathway. Several novel agents have been developed to restore the immune system’s ability to recognize and destroy cancer cells. Nivolumab and pembrolizumab are two anti-PD-1 antibodies that have demonstrated success in the treatment of refractory Hodgkin lymphoma. Harnessing the immune system’s ability to target neoplastic cells, ideally without the use of cytotoxic chemotherapeutic agents, is one way in which these novel agents are changing the therapeutic landscape in the treatment of lymphomas. Here, we review the emerging data regarding checkpoint inhibitors in the management of Hodgkin lymphoma, the unique adverse effects encountered with the use of these agents, and a practical approach to the management of these adverse effects. Additionally, we discuss upcoming trials that will further assess the promising future developments of checkpoint inhibition in the treatment of not only Hodgkin lymphoma but also other B cell lymphomas and myeloma. These agents offer immense promise of a future where many lymphomas can be treated without the toxic effects of chemotherapeutic agents. Keywords: Hodgkin lymphoma, programmed death-1, nivolumab, pembrolizumab, lymphoma

  12. Induction of painless thyroiditis in patients receiving programmed death 1 receptor immunotherapy for metastatic malignancies.

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    Orlov, Steven; Salari, Farnaz; Kashat, Lawrence; Walfish, Paul G

    2015-05-01

    Immunotherapies against immune checkpoints that inhibit T cell activation [cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1)] are emerging and promising treatments for several metastatic malignancies. However, the precise adverse effects of these therapies on thyroid gland function have not been well described. We report on 10 cases of painless thyroiditis syndrome (PTS) from a novel etiology, following immunotherapy with anti-PD-1 monoclonal antibodies (mAb) during treatment for metastatic malignancies. Six patients presented with transient thyrotoxicosis in which thyrotropin binding inhibitory immunoglobulins (TBII) were absent for all, whereas four patients had evidence of positive antithyroid antibodies. All thyrotoxic patients required temporary beta-blocker therapy and had spontaneous resolution of thyrotoxicosis with subsequent hypothyroidism. Four patients presented with hypothyroidism without a detected preceding thyrotoxic phase, occurring 6-8 weeks after initial drug exposure. All of these patients had positive antithyroid antibodies and required thyroid hormone replacement therapy for a minimum of 6 months. Patients receiving anti-PD-1 mAb therapy should be monitored for signs and symptoms of PTS which may require supportive treatment with beta-blockers or thyroid hormone replacement. The anti-PD-1 mAb is a novel exogenous cause of PTS and provides new insight into the possible perturbations of the immune network that may modulate the development of endogenous PTS, including cases of sporadic and postpartum thyroiditis.

  13. Increased soluble programmed death-1 (sPD-1) is associated with disease activity and radiographic progression in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Greisen, S R; Rasmussen, T K; Stengaard-Pedersen, K

    2014-01-01

    OBJECTIVES: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought to be implica......OBJECTIVES: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought...... Questionnaire (HAQ) score, immunoglobulin M rheumatoid factor (IgM-RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, C-reactive protein (CRP), interleukin-21 (IL-21), and total Sharp score (TSS). We also measured sPD-1 in plasma from healthy volunteers (HV) (n = 20) and in plasma and synovial fluid...

  14. Effect of Gamma Knife Radiosurgery and Programmed Cell Death 1 Receptor Antagonists on Metastatic Melanoma

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    Hubbard, Molly; Nordmann, Tyler; Sperduto, Paul W; Clark, H. Brent; Hunt, Matthew A

    2017-01-01

    Learning objectives To evaluate radiation-induced changes in patients with brain metastasis secondary to malignant melanoma who received treatment with Gamma Knife radiosurgery (GKRS) and programmed cell death 1 (PD-1) receptor antagonists. Introduction  Stereotactic radiosurgery and chemotherapeutics are used together for treatment of metastatic melanoma and have been linked to delayed radiation-induced vasculitic leukoencephalopathy (DRIVL). There have been reports of more intense interactions with new immunotherapeutics targeting PD-1 receptors, but their interactions have not been well described and may result in an accelerated response to GKRS. Here we present data on subjects treated with this combination from a single institution. Methods Records from patients who underwent treatment for metastatic melanoma to the brain with GKRS from 2011 to 2016 were reviewed. Demographics, date of brain metastasis diagnosis, cause of death when applicable, immunotherapeutics, and imaging findings were recorded. The timing of radiation therapy and medications were also documented.  Results A total of 79 subjects were treated with GKRS, and 66 underwent treatment with both GKRS and immunotherapy. Regarding the 30 patients treated with anti-PD-1 immunotherapy, 21 patients received pembrolizumab, seven patients received nivolumab, and two patients received pembrolizumab and nivolumab. Serial imaging was available for interpretation in 25 patients, with 13 subjects who received GKRS and anti-PD-1 immunotherapy less than six weeks of each other. While four subjects had indeterminate/mixed findings on subsequent magnetic resonance imaging (MRI), nine subjects were noted to have progression. Two of these patients showed progression but subsequent imaging revealed a decrease in progression or improvement on MRI to previously targeted lesions by GKRS. None of the 13 subjects had surgery following their combined therapies. Conclusions This data suggests that there is need for

  15. Neurological Complications Associated With Anti-Programmed Death 1 (PD-1) Antibodies.

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    Kao, Justin C; Liao, Bing; Markovic, Svetomir N; Klein, Christopher J; Naddaf, Elie; Staff, Nathan P; Liewluck, Teerin; Hammack, Julie E; Sandroni, Paola; Finnes, Heidi; Mauermann, Michelle L

    2017-10-01

    Neurological complications are an increasingly recognized consequence of the use of anti-programmed death 1 (PD-1) antibodies in the treatment of solid-organ tumors, with an estimated frequency of 4.2%. To date, the clinical spectrum and optimum treatment approach are not established. To investigate the frequency, clinical spectrum, and optimum treatment approach to neurological complications associated with anti-PD-1 therapy. This single-center, retrospective cohort study was conducted from either September or December 2014 (the approval dates of the study drugs by the US Food and Drug Administration) to May 19, 2016. All patients receiving anti-PD-1 monoclonal antibodies were identified using the Mayo Cancer Pharmacy Database. Patients with development of neurological symptoms within 12 months of anti-PD-1 therapy were included. Patients with neurological complications directly attributable to metastatic disease or other concurrent cancer-related treatments were excluded. Clinical and pathological characteristics, time to development of neurological symptoms, and modified Rankin Scale (mRS) score. Among 347 patients treated with anti-PD1 monoclonal antibodies (pembrolizumab or nivolumab), 10 (2.9%) developed subacute onset of neurological complications. Seven patients were receiving pembrolizumab, and 3 patients were receiving nivolumab. The patients included 8 men and 2 women. Their median age was 71 years (age range, 31-78 years). Neurological complications occurred after a median of 5.5 (range, 1-20) cycles of anti-PD-1 inhibitors. Complications included myopathy (n = 2), varied neuropathies (n = 4), cerebellar ataxia (n = 1), autoimmune retinopathy (n = 1), bilateral internuclear ophthalmoplegia (n = 1), and headache (n = 1). Peripheral neuropathies included axonal and demyelinating polyradiculoneuropathies (n = 2), length-dependent neuropathies (n = 1), and asymmetric vasculitic neuropathy (n = 1). The time to maximum

  16. Anti-Bovine Programmed Death-1 Rat–Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle

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    Tomohiro Okagawa

    2017-06-01

    Full Text Available Blockade of immunoinhibitory molecules, such as programmed death-1 (PD-1/PD-ligand 1 (PD-L1, is a promising strategy for reinvigorating exhausted T cells and preventing disease progression in a variety of chronic infections. Application of this therapeutic strategy to cattle requires bovinized chimeric antibody targeting immunoinhibitory molecules. In this study, anti-bovine PD-1 rat–bovine chimeric monoclonal antibody 5D2 (Boch5D2 was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus (BLV. Purified Boch5D2 was capable of detecting bovine PD-1 molecules expressed on cell membranes in flow cytometric analysis. In particular, Biacore analysis determined that the binding affinity of Boch5D2 to bovine PD-1 protein was similar to that of the original anti-bovine PD-1 rat monoclonal antibody 5D2. Boch5D2 was also capable of blocking PD-1/PD-L1 binding at the same level as 5D2. The immunomodulatory and therapeutic effects of Boch5D2 were evaluated by in vivo administration of the antibody to a BLV-infected calf. Inoculated Boch5D2 was sustained in the serum for a longer period. Boch5D2 inoculation resulted in activation of the proliferation of BLV-specific CD4+ T cells and decrease in the proviral load of BLV in the peripheral blood. This study demonstrates that Boch5D2 retains an equivalent biochemical function to that of the original antibody 5D2 and is a candidate therapeutic agent for regulating antiviral immune response in vivo. Clinical efficacy of PD-1/PD-L1 blockade awaits further experimentation with a large number of animals.

  17. Increased circulating follicular helper T cells with decreased programmed death-1 in chronic renal allograft rejection

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    Shi, Jian; Luo, Fengbao; Shi, Qianqian; Xu, Xianlin; He, Xiaozhou; Xia, Ying

    2015-01-01

    Background Chronic antibody-mediated rejection is a major issue that affects long-term renal allograft survival. Since follicular helper T (Tfh) cells promote the development of antigen-specific B cells in alloimmune responses, we investigated the potential roles of Tfh cells, B cells and their alloimmune-regulating molecules in the pathogenesis of chronic renal allograft rejection in this study. Methods The frequency of Tfh, B cells and the levels of their alloimmune-regulating molecules inc...

  18. IL-1β but not programmed death-1 and programmed death-ligand pathway is critical for the human Th17 response to M. tuberculosis

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    Emmanuel Stephen-Victor

    2016-11-01

    Full Text Available The programmed death-1 (PD-1- programmed death ligand-1 (PD-L1 and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies of Mycobacterium tuberculosis. Specifically, M. tuberculosis-induced PD-L1 orchestrates expansion of regulatory T cells (Tregs and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response to M. tuberculosis has not been investigated. In the present report, we demonstrate that M. tuberculosis and M. tuberculosis-derived antigen fractions have differential abilities to mediate human monocyte and dendritic cell (DC-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells. Importantly, we observed that blockade of PD-L1 or PD-1 did not significantly modify either the frequencies of Th17 cells or the production of IL-17 from CD4+ T cells though IFN-γ response was significantly enhanced. On the contrary, IL-1β from monocytes and DCs were critical for the Th17 response to M. tuberculosis. Together, our results indicate that IL-1β but not members of the programmed death pathway is critical for human Th17 response to M. tuberculosis

  19. IL-1β, But Not Programed Death-1 and Programed Death Ligand Pathway, Is Critical for the Human Th17 Response to Mycobacterium tuberculosis

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    Stephen-Victor, Emmanuel; Sharma, Varun Kumar; Das, Mrinmoy; Karnam, Anupama; Saha, Chaitrali; Lecerf, Maxime; Galeotti, Caroline; Kaveri, Srinivas V.; Bayry, Jagadeesh

    2016-01-01

    The programed death-1 (PD-1)–programed death ligand-1 (PD-L1) and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies of Mycobacterium tuberculosis. Specifically, M. tuberculosis-induced PD-L1 orchestrates expansion of regulatory T cells and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response to M. tuberculosis has not been investigated. In the present report, we demonstrate that M. tuberculosis and M. tuberculosis-derived antigen fractions have differential abilities to mediate human monocyte- and dendritic cell (DC)-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells. Importantly, we observed that blockade of PD-L1 or PD-1 did not significantly modify either the frequencies of Th17 cells or the production of IL-17 from CD4+ T cells though IFN-γ response was significantly enhanced. On the contrary, IL-1β from monocytes and DCs were critical for the Th17 response to M. tuberculosis. Together, our results indicate that IL-1β, but not members of the programed death pathway, is critical for human Th17 response to M. tuberculosis. PMID:27867382

  20. Structure and interactions of the human programmed cell death 1 receptor.

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    Cheng, Xiaoxiao; Veverka, Vaclav; Radhakrishnan, Anand; Waters, Lorna C; Muskett, Frederick W; Morgan, Sara H; Huo, Jiandong; Yu, Chao; Evans, Edward J; Leslie, Alasdair J; Griffiths, Meryn; Stubberfield, Colin; Griffin, Robert; Henry, Alistair J; Jansson, Andreas; Ladbury, John E; Ikemizu, Shinji; Carr, Mark D; Davis, Simon J

    2013-04-26

    PD-1, a receptor expressed by T cells, B cells, and monocytes, is a potent regulator of immune responses and a promising therapeutic target. The structure and interactions of human PD-1 are, however, incompletely characterized. We present the solution nuclear magnetic resonance (NMR)-based structure of the human PD-1 extracellular region and detailed analyses of its interactions with its ligands, PD-L1 and PD-L2. PD-1 has typical immunoglobulin superfamily topology but differs at the edge of the GFCC' sheet, which is flexible and completely lacks a C" strand. Changes in PD-1 backbone NMR signals induced by ligand binding suggest that, whereas binding is centered on the GFCC' sheet, PD-1 is engaged by its two ligands differently and in ways incompletely explained by crystal structures of mouse PD-1 · ligand complexes. The affinities of these interactions and that of PD-L1 with the costimulatory protein B7-1, measured using surface plasmon resonance, are significantly weaker than expected. The 3-4-fold greater affinity of PD-L2 versus PD-L1 for human PD-1 is principally due to the 3-fold smaller dissociation rate for PD-L2 binding. Isothermal titration calorimetry revealed that the PD-1/PD-L1 interaction is entropically driven, whereas PD-1/PD-L2 binding has a large enthalpic component. Mathematical simulations based on the biophysical data and quantitative expression data suggest an unexpectedly limited contribution of PD-L2 to PD-1 ligation during interactions of activated T cells with antigen-presenting cells. These findings provide a rigorous structural and biophysical framework for interpreting the important functions of PD-1 and reveal that potent inhibitory signaling can be initiated by weakly interacting receptors.

  1. Structure-guided development of a high-affinity human Programmed Cell Death-1: Implications for tumor immunotherapy

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    Lázár-Molnár, Eszter; Scandiuzzi, Lisa; Basu, Indranil; Quinn, Thomas; Sylvestre, Eliezer; Palmieri, Edith; Ramagopal, Udupi A.; Nathenson, Stanley G.; Guha, Chandan; Almo, Steven C.

    2017-03-01

    Programmed Cell Death-1 (PD-1) is an inhibitory immune receptor, which plays critical roles in T cell co-inhibition and exhaustion upon binding to its ligands PD-L1 and PD-L2. We report the crystal structure of the human PD-1 ectodomain and the mapping of the PD-1 binding interface. Mutagenesis studies confirmed the crystallographic interface, and resulted in mutant PD-1 receptors with altered affinity and ligand-specificity. In particular, a high-affinity mutant PD-1 (HA PD-1) exhibited 45 and 30-fold increase in binding to PD-L1 and PD-L2, respectively, due to slower dissociation rates. This mutant (A132L) was used to engineer a soluble chimeric Ig fusion protein for cell-based and in vivo studies. HA PD-1 Ig showed enhanced binding to human dendritic cells, and increased T cell proliferation and cytokine production in a mixed lymphocyte reaction (MLR) assay. Moreover, in an experimental model of murine Lewis lung carcinoma, HA PD-1 Ig treatment synergized with radiation therapy to decrease local and metastatic tumor burden, as well as in the establishment of immunological memory responses. Our studies highlight the value of structural considerations in guiding the design of a high-affinity chimeric PD-1 Ig fusion protein with robust immune modulatory properties, and underscore the power of combination therapies to selectively manipulate the PD-1 pathway for tumor immunotherapy.

  2. Structure-guided development of a high-affinity human Programmed Cell Death-1: Implications for tumor immunotherapy

    Directory of Open Access Journals (Sweden)

    Eszter Lázár-Molnár

    2017-03-01

    Full Text Available Programmed Cell Death-1 (PD-1 is an inhibitory immune receptor, which plays critical roles in T cell co-inhibition and exhaustion upon binding to its ligands PD-L1 and PD-L2. We report the crystal structure of the human PD-1 ectodomain and the mapping of the PD-1 binding interface. Mutagenesis studies confirmed the crystallographic interface, and resulted in mutant PD-1 receptors with altered affinity and ligand-specificity. In particular, a high-affinity mutant PD-1 (HA PD-1 exhibited 45 and 30-fold increase in binding to PD-L1 and PD-L2, respectively, due to slower dissociation rates. This mutant (A132L was used to engineer a soluble chimeric Ig fusion protein for cell-based and in vivo studies. HA PD-1 Ig showed enhanced binding to human dendritic cells, and increased T cell proliferation and cytokine production in a mixed lymphocyte reaction (MLR assay. Moreover, in an experimental model of murine Lewis lung carcinoma, HA PD-1 Ig treatment synergized with radiation therapy to decrease local and metastatic tumor burden, as well as in the establishment of immunological memory responses. Our studies highlight the value of structural considerations in guiding the design of a high-affinity chimeric PD-1 Ig fusion protein with robust immune modulatory properties, and underscore the power of combination therapies to selectively manipulate the PD-1 pathway for tumor immunotherapy.

  3. Modulation of expression of Programmed Death-1 by administration of probiotic Dahi in DMH-induced colorectal carcinogenesis in rats.

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    Mohania, Dheeraj; Kansal, Vinod K; Kumar, Manoj; Nagpal, Ravinder; Yamashiro, Yuichiro; Marotta, Francesco

    2013-09-01

    Interaction of probiotic bacteria with the host immune system elicits beneficial immune modulating effects. Although, there are many published studies on interaction of probiotics with immune system focusing on activation of immune system by bacterial cell wall through the engagement of Toll-like receptor family; very few studies have focused on molecules involved in the T-cell activation, and not much work has been executed to study the correlation of probiotics and programmed death-1 in colorectal carcinogenesis in animal models. Hence, the present study was carried out to assess the effect of probiotic Dahi on expression of programmed death (PD-1) in colorectum of 1, 2-dimethylhydrazine treated Wistar rats. DMH was injected subcutaneously at the rate of 40 mg/kg body weight per animal twice a week for 2 weeks. A total of 168 male Wistar rats were randomly allocated to seven groups, each group having twenty-four animals. The rats were euthanized at the 8th, 16th and 32nd week of the experiment and examined for the expression of PD-1 in colorectal tissues by immunohistochemical staining. Expression of PD-1 was observed in colorectal tissues of normal and DMH-treated rats. Feeding rats with probiotic Dahi or the treatment with piroxicam decreased the expression of PD-1 in DMH-induced colorectal mucosa, and the combined treatment with probiotic Dahi and piroxicam was significantly more effective in reducing the expression of PD-1. PD-1 expressed independent of carcinogen administration in normal colonic mucosa and may play a role in modulation of immune response in DMH-induced colorectal carcinogenesis. The present study suggests that probiotic Dahi can be used as an effective chemopreventive agent in the management of colorectal cancer.

  4. Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer.

    Science.gov (United States)

    Chatterjee, Jayanta; Dai, Wei; Aziz, Nor Haslinda Abd; Teo, Pei Yun; Wahba, John; Phelps, David L; Maine, Christian J; Whilding, Lynsey M; Dina, Roberto; Trevisan, Giorgia; Flower, Kirsty J; George, Andrew J T; Ghaem-Maghami, Sadaf

    2017-07-01

    Purpose: We aimed to establish whether programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression, in ovarian cancer tumor tissue and blood, could be used as biomarkers for discrimination of tumor histology and prognosis of ovarian cancer. Experimental Design: Immune cells were separated from blood, ascites, and tumor tissue obtained from women with suspected ovarian cancer and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumor-associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses. Results: Biomarkers from the discovery cohort that associated with PD-L1 + cells were found. PD-L1 + CD14 + cells and PD-L1 + CD11c + cells in the monocyte gate showed a distinct expression pattern when comparing benign tumors and epithelial ovarian cancers (EOCs)-confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1 + and PD-L1 + CD14 + cells in the monocyte gate performed better than the well-established tumor marker CA-125 alone. Plasma soluble PD-L1 was elevated in patients with EOC compared with healthy women and patients with benign ovarian tumors. Low total PD-1 + expression on lymphocytes was associated with improved survival. Conclusions: Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti-PD-1/PD-L1 therapy in ovarian cancer. Clin Cancer Res; 23(13); 3453-60. ©2016 AACR . ©2016 American Association for Cancer Research.

  5. Programmed death-1 (PD-1)-dependent functional impairment of CD4(+) T cells in recurrent genital papilloma.

    Science.gov (United States)

    Chang, Dong-Yeop; Song, Sang Hoon; You, Sooseong; Lee, Jino; Kim, Jihye; Racanelli, Vito; Son, Hwancheol; Shin, Eui-Cheol

    2014-08-01

    Genital papilloma is caused by human papilloma virus (HPV) infection and recurs frequently. Although T cells are known to play a critical role in the control of HPV infection and papilloma development, the function and phenotype of these cells in the lesion remain to be elucidated. In the present study, we examined the function and phenotype of CD4(+) T cells isolated from the lesions of primary (n = 9) and recurrent (n = 11) genital papillomas. In recurrent papillomas, the frequency of proliferating (Ki-67(+)) CD4(+) T cells was significantly reduced compared with primary papillomas. Cytokine production was evaluated by intracellular cytokine staining in anti-CD3/anti-CD28-stimulated CD4(+) T cells. CD4(+) T cells from recurrent lesions showed impaired production of IL-2, IFN-γ, and TNF-α. Of interest, the frequency of cytokine-producing CD4(+) T cells significantly correlated with the frequency of Ki-67(+)CD4(+) T cells. We also studied expression of programmed death-1 (PD-1), a T-cell exhaustion marker. The frequency of PD-1(+)CD4(+) T cells was significantly increased in recurrent lesions and inversely correlated with the frequency of cytokine-producing CD4(+) T cells. The functional significance of PD-1 expression was determined in blocking assays with anti-PD-L1, which restored cytokine production of CD4(+) T cells from recurrent lesions. Taken together, in recurrent genital papilloma lesions, proliferation, and cytokine production by CD4(+) T cells are impaired and the PD-1/PD-L1 interaction is responsible for the functional impairment of CD4(+) T cells.

  6. The risk stratification and prognostic evaluation of soluble programmed death-1 on patients with sepsis in emergency department.

    Science.gov (United States)

    Zhao, Yongzhen; Jia, Yumei; Li, Chunsheng; Fang, Yingying; Shao, Rui

    2018-01-01

    To evaluate the efficacy of soluble programmed death-1 (sPD-1) for risk stratification and prediction of 28-day mortality in patients with sepsis, we compared serum sPD-1 with procalcitonin (PCT), C-reactive protein (CRP), and the Mortality in Emergency Department Sepsis (MEDS) score. A total of 60 healthy volunteers and 595 emergency department (ED) patients were recruited for this prospective cohort study. According to the severity of their condition on ED arrival, the patients were allocated to the systemic inflammatory response syndrome group (130 cases), sepsis group (276 cases), severe sepsis group (121 cases), and septic shock group (68 cases). In addition, all patients with sepsis were also divided into the survivor group (349 cases) and nonsurvivor group (116 cases) according to the 28-day outcomes. When the severity of sepsis increased, the levels of sPD-1 gradually increased. The levels of sPD-1, PCT, CRP and the MEDS score were also higher in the nonsurvivor group compared to the survivor group. Logistic regression suggested that sPD-1, PCT, and the MEDS score were independent risk factors for 28-day mortality of patients with sepsis. Area under the curve (AUC) of sPD-1, PCT and the MEDS score for 28-day mortality was 0.725, 0.693, and 0.767, respectively, and the AUC was improved when all 3 factors were combined (0.843). Serum sPD-1 is positively correlated with the severity of sepsis, and it is valuable for risk stratification of patients and prediction of 28-day mortality. Combining sPD-1 with PCT and the MEDS score improves the prognostic evaluation. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Soluble Programmed Death 1 (PD-1) Is Decreased in Patients With Immune Thrombocytopenia (ITP): Potential Involvement of PD-1 Pathway in ITP Immunopathogenesis.

    Science.gov (United States)

    Birtas Atesoglu, Elif; Tarkun, Pinar; Demirsoy, Esra Terzi; Geduk, Ayfer; Mehtap, Ozgur; Batman, Adnan; Kaya, Fatih; Cekmen, Mustafa Baki; Gulbas, Zafer; Hacıhanefioglu, Abdullah

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune disease characterized by dysregulation of T cells. Programmed death (PD) 1 and programmed death 1 ligand 1 (PD-L1) are cosignaling molecules, and the major role of the PD-1 pathway is the inhibition of self-reactive T cells and to protect against autoimmune diseases. We measured levels of serum soluble PD 1 (sPD-1) and serum soluble PD-L1 (sPD-L1) in 67 patients with ITP (24 newly diagnosed ITP [ndITP], 43 chronic ITP [cITP]) and 21 healthy controls (HCs). We determined decreased serum sPD-1 levels both in patients with ndITP and in patients with cITP when compared to HC. Moreover, there was a positive correlation between sPD-1 levels and platelet counts. The sPD-L1 levels were decreased in patients with ndITP when compared to patients with cITP. This is the first study investigating PD-1 signaling pathway in ITP. Decreased sPD-1 levels may have a role in ITP pathogenesis as without the inhibitory regulation of PD-1, sustained activation of T cells may cause inflammatory responses which is the case in ITP. © The Author(s) 2014.

  8. Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia.

    Science.gov (United States)

    Zhou, Qing; Munger, Meghan E; Highfill, Steven L; Tolar, Jakub; Weigel, Brenda J; Riddle, Megan; Sharpe, Arlene H; Vallera, Daniel A; Azuma, Miyuki; Levine, Bruce L; June, Carl H; Murphy, William J; Munn, David H; Blazar, Bruce R

    2010-10-07

    Tumor-induced immune defects can weaken host immune response and permit tumor cell growth. In a systemic model of murine acute myeloid leukemia (AML), tumor progression resulted in increased regulatory T cells (Treg) and elevation of program death-1 (PD-1) expression on CD8(+) cytotoxic T cells (CTLs) at the tumor site. PD-1 knockout mice were more resistant to AML despite the presence of similar percentage of Tregs compared with wild type. In vitro, intact Treg suppression of CD8(+) T-cell responses was dependent on PD-1 expression by T cells and Tregs and PD-L1 expression by antigen-presenting cells. In vivo, the function of adoptively transferred AML-reactive CTLs was reduced by AML-associated Tregs. Anti-PD-L1 monoclonal antibody treatment increased the proliferation and function of CTLs at tumor sites, reduced AML tumor burden, and resulted in long-term survivors. Treg depletion followed by PD-1/PD-L1 blockade showed superior efficacy for eradication of established AML. These data demonstrated that interaction between PD-1 and PD-L1 can facilitate Treg-induced suppression of T-effector cells and dampen the antitumor immune response. PD-1/PD-L1 blockade coupled with Treg depletion represents an important new approach that can be readily translated into the clinic to improve the therapeutic efficacy of adoptive AML-reactive CTLs in advanced AML disease.

  9. Programmed Death-1 Inhibition in Cancer With a Focus on Non-Small Cell Lung Cancer: Rationale, Nursing Implications, and Patient Management Strategies.

    Science.gov (United States)

    2016-06-01

    Programmed death-1 (PD-1) immune checkpoint inhibitors are novel immuno-oncology agents. Unlike chemotherapy or targeted agents, which inhibit tumor cell proliferation or induce tumor cell death, immune checkpoint inhibitors are designed to stimulate a patient's own immune system to eliminate tumors. As a result of their mechanism of action, PD-1 pathway inhibitors are associated with adverse events (AEs) with immunologic etiologies, termed immune-mediated AEs (imAEs). These include skin and gastrointestinal AEs, and endocrine, hepatic, renal, and respiratory AEs, including pneumonitis. Most imAEs can be effectively managed with treatment interruption/discontinuation and/or steroids or other immunosuppressive agents. A specialist consult may be required in some cases, and endocrine imAEs may require permanent hormone replacement therapy. This article provides an overview of PD-1 inhibitors, including the potential mechanism of action, key clinical trial data, and strategies for managing patients who may receive PD-1 inhibitors for the treatment of non-small cell lung cancer. Information in the article comes from PubMed literature searches and the author's experience with these agents in clinical trials. Oncology clinicians must thoroughly assess baseline functioning and symptoms and be vigilant for imAEs, which require prompt diagnosis and management. A good understanding of the clinical profile of PD-1 pathway inhibitors is instrumental in helping clinicians manage patients receiving these new therapies.

  10. Programmed Death-1 expression on Epstein Barr virus specific CD8+ T cells varies by stage of infection, epitope specificity, and T-cell receptor usage.

    Directory of Open Access Journals (Sweden)

    Thomas C Greenough

    Full Text Available BACKGROUND: Programmed Death-1 (PD-1 is an inhibitory member of the CD28 family of molecules expressed on CD8+ T cells in response to antigenic stimulation. To better understand the role of PD-1 in antiviral immunity we examined the expression of PD-1 on Epstein-Barr virus (EBV epitope-specific CD8+ T cells during acute infectious mononucleosis (AIM and convalescence. METHODOLOGY/PRINCIPAL FINDINGS: Using flow cytometry, we observed higher frequencies of EBV-specific CD8+ T cells and higher intensity of PD-1 expression on EBV-specific CD8+ T cells during AIM than during convalescence. PD-1 expression during AIM directly correlated with viral load and with the subsequent degree of CD8+ T cell contraction in convalescence. Consistent differences in PD-1 expression were observed between CD8+ T cells with specificity for two different EBV lytic antigen epitopes. Similar differences were observed in the degree to which PD-1 was upregulated on these epitope-specific CD8+ T cells following peptide stimulation in vitro. EBV epitope-specific CD8+ T cell proliferative responses to peptide stimulation were diminished during AIM regardless of PD-1 expression and were unaffected by blocking PD-1 interactions with PD-L1. Significant variability in PD-1 expression was observed on EBV epitope-specific CD8+ T cell subsets defined by V-beta usage. CONCLUSIONS/SIGNIFICANCE: These observations suggest that PD-1 expression is not only dependent on the degree of antigen presentation, but also on undefined characteristics of the responding cell that segregate with epitope specificity and V-beta usage.

  11. Fibrinogen cleavage products and Toll-like receptor 4 promote the generation of programmed cell death 1 ligand 2-positive dendritic cells in allergic asthma.

    Science.gov (United States)

    Cho, Minkyoung; Lee, Jeong-Eun; Lim, Hoyong; Shin, Hyun-Woo; Khalmuratova, Roza; Choi, Garam; Kim, Hyuk Soon; Choi, Wahn Soo; Park, Young-Jun; Shim, Inbo; Kim, Byung-Seok; Kang, Chang-Yuil; Kim, Jae-Ouk; Tanaka, Shinya; Kubo, Masato; Chung, Yeonseok

    2017-10-14

    Inhaled protease allergens preferentially trigger T H 2-mediated inflammation in allergic asthma. The role of dendritic cells (DCs) on induction of T H 2 cell responses in allergic asthma has been well documented; however, the mechanism by which protease allergens induce T H 2-favorable DCs in the airway remains unclear. We sought to determine a subset of DCs responsible for T H 2 cell responses in allergic asthma and the mechanism by which protease allergens induce the DC subset in the airway. Mice were challenged intranasally with protease allergens or fibrinogen cleavage products (FCPs) to induce allergic airway inflammation. DCs isolated from mediastinal lymph nodes were analyzed for surface phenotype and T-cell stimulatory function. Anti-Thy1.2 and Mas-TRECK mice were used to deplete innate lymphoid cells and mast cells, respectively. Adoptive cell transfer, bone marrow DC culture, anti-IL-13, and Toll-like receptor (TLR) 4-deficient mice were used for further mechanistic studies. Protease allergens induced a remarkable accumulation of T H 2-favorable programmed cell death 1 ligand 2 (PD-L2) + DCs in mediastinal lymph nodes, which was significantly abolished in mice depleted of mast cells and, to a lesser extent, innate lymphoid cells. Mechanistically, FCPs generated by protease allergens triggered IL-13 production from wild-type mast cells but not from TLR4-deficient mast cells, which resulted in an increase in the number of PD-L2 + DCs. Intranasal administration of FCPs induced an increase in numbers of PD-L2 + DCs in the airway, which was significantly abolished in TLR4- and mast cell-deficient mice. Injection of IL-13 restored the PD-L2 + DC population in mice lacking mast cells. Our findings unveil the "protease-FCP-TLR4-mast cell-IL-13" axis as a molecular mechanism for generation of T H 2-favorable PD-L2 + DCs in allergic asthma and suggest that targeting the PD-L2 + DC pathway might be effective in suppressing allergic T-cell responses in the airway

  12. Pneumonitis and pneumonitis-related death in cancer patients treated with programmed cell death-1 inhibitors: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Cui P

    2017-09-01

    Full Text Available Peng-Fei Cui,1–3,* Jun-Xun Ma,1,* Fei-Xue Wang,1,* Jing Zhang,1 Hai-Tao Tao,1 Yi Hu1 1First Department of Medical Oncology, 2Department of Graduate Administration, Chinese PLA General Hospital, Beijing, 3Health Bureau of the 75709 Army, Central Theater of the Chinese PLA, Wuhan, China *These authors contributed equally to this work Purpose: We conducted a meta-analysis of published clinical trials to determine the relationship between the risks of pneumonitis and pneumonitis-related death and programmed cell death-1 (PD-1 inhibitor treatment in patients with cancer.Materials and methods: We examined clinical trials from the Medline and Google Scholar databases. Data from original studies and review articles were also cross-referenced and evaluated. Randomized Phase II and Phase III trials of pembrolizumab and nivolumab treatment in patients with cancer were eligible for the analysis. Information about the participants, all-grade and high-grade pneumonitis, and pneumonitis-related death was extracted from each study and analyzed.Results: After the exclusion of ineligible studies, 12 clinical trials were included in the analysis. The odds ratio (OR for all-grade pneumonitis after PD-1 inhibitor treatment was 4.59 (95% confidence interval [CI]: 2.51–8.37; P<0.00001, and the OR for high-grade pneumonitis after PD-1 inhibitor treatment was 3.83 (95% CI: 1.54–9.48; P=0.004. The OR for pneumonitis-related death after PD-1 inhibitor treatment was 2.47 (95% CI: 0.41–14.81; P=0.32. Moreover, the OR for all-grade pneumonitis after nivolumab/ipilimumab combination therapy versus nivolumab monotherapy was 3.54 (95% CI: 1.52–8.23; P=0.003, and that for high-grade pneumonitis after nivolumab/ipilimumab combination therapy versus nivolumab monotherapy was 2.35 (95% CI: 0.45–12.13; P=0.31. Treated cancer appeared to have no effect on the risk of pneumonitis.Conclusion: Our data showed that PD-1 inhibitors were associated with increased risks of all

  13. The Chloroplastic Protein THF1 Interacts with the Coiled-Coil Domain of the Disease Resistance Protein N′ and Regulates Light-Dependent Cell Death1[OPEN

    Science.gov (United States)

    Sekine, Ken-Taro; Wallon, Thérèse; Sugiwaka, Yuji; Kobayashi, Kappei

    2016-01-01

    One branch of plant immunity is mediated through nucleotide-binding/Leu-rich repeat (NB-LRR) family proteins that recognize specific effectors encoded by pathogens. Members of the I2-like family constitute a well-conserved subgroup of NB-LRRs from Solanaceae possessing a coiled-coil (CC) domain at their N termini. We show here that the CC domains of several I2-like proteins are able to induce a hypersensitive response (HR), a form of programmed cell death associated with disease resistance. Using yeast two-hybrid screens, we identified the chloroplastic protein Thylakoid Formation1 (THF1) as an interacting partner for several I2-like CC domains. Co-immunoprecipitations and bimolecular fluorescence complementation assays confirmed that THF1 and I2-like CC domains interact in planta and that these interactions take place in the cytosol. Several HR-inducing I2-like CC domains have a negative effect on the accumulation of THF1, suggesting that the latter is destabilized by active CC domains. To confirm this model, we investigated N′, which recognizes the coat protein of most Tobamoviruses, as a prototypical member of the I2-like family. Transient expression and gene silencing data indicated that THF1 functions as a negative regulator of cell death and that activation of full-length N′ results in the destabilization of THF1. Consistent with the known function of THF1 in maintaining chloroplast homeostasis, we show that the HR induced by N′ is light-dependent. Together, our results define, to our knowledge, novel molecular mechanisms linking light and chloroplasts to the induction of cell death by a subgroup of NB-LRR proteins. PMID:26951433

  14. Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti-programed death-ligand 1 (Avelumab).

    Science.gov (United States)

    Gill, Amanda L; Green, Samantha A; Abdullah, Shahed; Le Saout, Cecile; Pittaluga, Stefania; Chen, Hui; Turnier, Refika; Lifson, Jeffrey; Godin, Steven; Qin, Jing; Sneller, Michael C; Cuillerot, Jean-Marie; Sabzevari, Helen; Lane, H Clifford; Catalfamo, Marta

    2016-10-23

    The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target. Lymph node biopsies from HIV-infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV-infected rhesus macaques. PD-L1 expression was observed in cells with myloid/macrophage morphology in HIV-infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment. Administration of anti-PD-L1 in chronic SIV-infected rhesus macaques was well tolerated. Overall, these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans.

  15. Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV infected patients: results of a pilot safety study in rhesus macaques using anti–programed death-ligand 1 (Avelumab)

    Science.gov (United States)

    Gill, Amanda L.; Green, Samantha A.; Abdullah, Shahed; Le Saout, Cecile; Pittaluga, Stefania; Chen, Hui; Turnier, Refika; Lifson, Jeffrey; Godin, Steven; Qin, Jing; Sneller, Michael C.; Cuillerot, Jean-Marie; Sabzevari, Helen; Lane, H. Clifford; Catalfamo, Marta

    2016-01-01

    Objective: The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target. Methods: Lymph node biopsies from HIV-infected patients (n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in chronically SIV-infected rhesus macaques. Results: PD-L1 expression was observed in cells with myloid/macrophage morphology in HIV-infected lymph nodes. Administration of anti-PD-L1 was well tolerated, and no changes in body weights, hematologic, or chemistry parameters were observed during the study. Blockade of PD-L1 led to a trend of transient viral control after discontinuation of treatment. Conclusion: Administration of anti-PD-L1 in chronic SIV-infected rhesus macaques was well tolerated. Overall, these data warrant further investigation to assess the efficacy of anti-PD-L1 treatment on viral control in chronic SIV infection as a prelude to such therapy in humans. PMID:27490642

  16. Vitiligo-like lesions occurring in patients receiving anti-programmed cell death-1 therapies are clinically and biologically distinct from vitiligo.

    Science.gov (United States)

    Larsabal, Maiana; Marti, Aurélie; Jacquemin, Clément; Rambert, Jérôme; Thiolat, Denis; Dousset, Léa; Taieb, Alain; Dutriaux, Caroline; Prey, Sorilla; Boniface, Katia; Seneschal, Julien

    2017-05-01

    The use of anti-programmed cell death (PD)-1 therapies in metastatic tumors is associated with cutaneous side effects including vitiligo-like lesions. We sought to characterize clinically and biologically vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies by studying a case series of 8 patients with metastatic tumors and 30 control subjects with vitiligo. Eight patients receiving anti-PD-1 therapies with features of vitiligo-like lesions seen in our department were recruited. Clinical features and photographs were analyzed. For some patients, skin and blood samples were obtained. Results were compared with the vitiligo group. All patients developed lesions localized on photoexposed areas with a specific depigmentation pattern consisting of multiple flecked lesions without Koebner phenomenon. In contrast to vitiligo, patients receiving anti-PD-1 therapies who developed vitiligo-like lesions did not report any personal or family histories of vitiligo, thyroiditis, or other autoimmune disorders. Analysis of blood and skin samples revealed increased C-X-C motif ligand 10 levels in serum of patients developing vitiligo-like lesions, associated with skin infiltration of CD8 T-cells expressing C-X-C motif receptor 3 and producing elevated levels of interferon-γ and tumor necrosis factor-alfa. This cross-sectional study concerned a single center. Clinical and biological patterns of vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies differ from vitiligo, suggesting a different mechanism. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  17. Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials.

    Science.gov (United States)

    Khunger, Monica; Rakshit, Sagar; Pasupuleti, Vinay; Hernandez, Adrian V; Mazzone, Peter; Stevenson, James; Pennell, Nathan A; Velcheti, Vamsidhar

    2017-08-01

    Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use. MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian-Laird random effects models. We compared incidences between PD-1 and PD-L1 inhibitors and between treatment naive and previously treated patients. Nineteen trials (12 with PD-1 inhibitors [n = 3,232] and 7 with PD-L1 inhibitors [n = 1,806]) were identified. PD-1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD-L1 inhibitors (3.6%; 95% CI, 2.4%-4.9% vs 1.3%; 95% CI, 0.8%-1.9%, respectively; P = .001). PD-1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%-1.7% vs 0.4%; 95% CI, 0%-0.8%; P = .02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%-6.3% vs 2.8%; 95% CI, 1.7%- 4%; P = .03). There was a higher incidence of pneumonitis with use of PD-1 inhibitors compared with PD-L1 inhibitors. Higher rate of pneumonitis was more common in treatment naive patients. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  18. Vectorization in an oncolytic vaccinia virus of an antibody, a Fab and a scFv against programmed cell death -1 (PD-1) allows their intratumoral delivery and an improved tumor-growth inhibition.

    Science.gov (United States)

    Kleinpeter, Patricia; Fend, Laetitia; Thioudellet, Christine; Geist, Michel; Sfrontato, Nathalie; Koerper, Véronique; Fahrner, Catherine; Schmitt, Doris; Gantzer, Murielle; Remy-Ziller, Christelle; Brandely, Renée; Villeval, Dominique; Rittner, Karola; Silvestre, Nathalie; Erbs, Philippe; Zitvogel, Laurence; Quéméneur, Eric; Préville, Xavier; Marchand, Jean-Baptiste

    2016-01-01

    We report here the successful vectorization of a hamster monoclonal IgG (namely J43) recognizing the murine Programmed cell death-1 (mPD-1) in Western Reserve (WR) oncolytic vaccinia virus. Three forms of mPD-1 binders have been inserted into the virus: whole antibody (mAb), Fragment antigen-binding (Fab) or single-chain variable fragment (scFv). MAb, Fab and scFv were produced and assembled with the expected patterns in supernatants of cells infected by the recombinant viruses. The three purified mPD-1 binders were able to block the binding of mPD-1 ligand to mPD-1 in vitro . Moreover, mAb was detected in tumor and in serum of C57BL/6 mice when the recombinant WR-mAb was injected intratumorally (IT) in B16F10 and MCA 205 tumors. The concentration of circulating mAb detected after IT injection was up to 1,900-fold higher than the level obtained after a subcutaneous (SC) injection (i.e., without tumor) confirming the virus tropism for tumoral cells and/or microenvironment. Moreover, the overall tumoral accumulation of the mAb was higher and lasted longer after IT injection of WR-mAb1, than after IT administration of 10 µg of J43. The IT injection of viruses induced a massive infiltration of immune cells including activated lymphocytes (CD8 + and CD4 + ). Interestingly, in the MCA 205 tumor model, WR-mAb1 and WR-scFv induced a therapeutic control of tumor growth similar to unarmed WR combined to systemically administered J43 and superior to that obtained with an unarmed WR. These results pave the way for next generation of oncolytic vaccinia armed with immunomodulatory therapeutic proteins such as mAbs.

  19. Epigenetic regulation and fetal programming.

    Science.gov (United States)

    Gicquel, Christine; El-Osta, Assam; Le Bouc, Yves

    2008-02-01

    Fetal programming encompasses the role of developmental plasticity in response to environmental and nutritional signals during early life and its potential adverse consequences (risk of cardiovascular, metabolic and behavioural diseases) in later life. The first studies in this field highlighted an association between poor fetal growth and chronic adult diseases. However, environmental signals during early life may lead to adverse long-term effects independently of obvious effects on fetal growth. Adverse long-term effects reflect a mismatch between early (fetal and neonatal) environmental conditions and the conditions that the individual will confront later in life. The mechanisms underlying this risk remain unclear. However, experimental data in rodents and recent observations in humans suggest that epigenetic changes in regulatory genes and growth-related genes play a significant role in fetal programming. Improvements in our understanding of the biochemical and molecular mechanisms at play in fetal programming would make it possible to identify biomarkers for detecting infants at high risk of adult-onset diseases. Such improvements should also lead to the development of preventive and therapeutic strategies.

  20. 77 FR 12930 - Federal Acquisition Regulation: Socioeconomic Program Parity

    Science.gov (United States)

    2012-03-02

    ... (SDVOSB) Program, or the Women-Owned Small Business (WOSB) Program. DATES: Effective Date: April 2, 2012...) Program (see subpart 19.14); or (iv) Women-Owned Small Business (WOSB) Program (see subpart 19.15). (3... amending the Federal Acquisition Regulation (FAR) to implement a section of the Small Business Jobs Act of...

  1. Development of a safety and regulation systems simulation program II

    International Nuclear Information System (INIS)

    1985-05-01

    This report describes the development of a safety and regulation systems simulation program under contract to the Atomic Energy Control Board of Canada. A systems logic interaction simulation (SLISIM) program was developed for the AECB's HP-1000 computer which operates in the interactive simulation (INSIM) program environment. The SLISIM program simulates the spatial neutron dynamics, the regulation of the reactor power and in this version the CANDU-PHW 600 MW(e) computerized shutdown systems' trip parameters. The modular concept and interactive capability of the INSIM environment provides the user with considerable flexibility of the setup and control of the simulation

  2. 75 FR 33752 - Acquisition Regulation: Socioeconomic Programs

    Science.gov (United States)

    2010-06-15

    ... Under the Regulatory Flexibility Act D. Review Under the Paperwork Reduction Act E. Review Under the... 23.5, contracting activities shall use 923.570, Workplace Substance Abuse Programs at DOE Sites. 9... amended by correcting the clause reference in paragraph (a) to 970.5223-4, Workplace Substance Abuse...

  3. Prenatal Maternal Stress Programs Infant Stress Regulation

    Science.gov (United States)

    Davis, Elysia Poggi; Glynn, Laura M.; Waffarn, Feizal; Sandman, Curt A.

    2011-01-01

    Objective: Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress.…

  4. Regulation of Tumor Progression by Programmed Necrosis

    Directory of Open Access Journals (Sweden)

    Su Yeon Lee

    2018-01-01

    Full Text Available Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1, which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness.

  5. Redox regulation in metabolic programming and inflammation.

    Science.gov (United States)

    Griffiths, Helen R; Gao, Dan; Pararasa, Chathyan

    2017-08-01

    Energy metabolism and redox state are intrinsically linked. In order to mount an adequate immune response, cells must have an adequate and rapidly available energy resource to migrate to the inflammatory site, to generate reactive oxygen species using NADPH as a cofactor and to engulf bacteria or damaged tissue. The first responder cells of the innate immune response, neutrophils, are largely dependent on glycolysis. Neutrophils are relatively short-lived, dying via apoptosis in the process of bacterial killing through production of hypochlorous acid and release of extracellular NETs. Later on, the most prevalent recruited innate immune cells are monocytes. Their role is to complete a damage limitation exercise initiated by neutrophils and then, as re-programmed M2 macrophages, to resolve the inflammatory event. Almost twenty five years ago, it was noted that macrophages lose their glycolytic capacity and become anti-inflammatory after treatment with corticosteroids. In support of this we now understand that, in contrast to early responders, M2 macrophages are predominantly dependent on oxidative phosphorylation for energy. During early inflammation, polarisation towards M1 macrophages is dependent on NOX2 activation which, via protein tyrosine phosphatase oxidation and AKT activation, increases trafficking of glucose transporters to the membrane and consequently increases glucose uptake for glycolysis. In parallel, mitochondrial efficiency is likely to be compromised via nitrosylation of the electron transport chain. Resolution of inflammation is triggered by encounter with apoptotic membranes exposing oxidised phosphatidylserine that interact with the scavenger receptor, CD36. Downstream of CD36, activation of AMPK and PPARγ elicits mitochondrial biogenesis, arginase expression and a switch towards oxidative phosphorylation in the M2 macrophage. Proinflammatory cytokine production by M2 cells decreases, but anti-inflammatory and wound healing growth factor

  6. Mitochondrial apoptotic pathways induced by Drosophila programmed cell death regulators

    International Nuclear Information System (INIS)

    Claveria, Cristina; Torres, Miguel

    2003-01-01

    Multicellular organisms eliminate unwanted or damaged cells by cell death, a process essential to the maintenance of tissue homeostasis. Cell death is a tightly regulated event, whose alteration by excess or defect is involved in the pathogenesis of many diseases such as cancer, autoimmune syndromes, and neurodegenerative processes. Studies in model organisms, especially in the nematode Caenorhabditis elegans, have been crucial in identifying the key molecules implicated in the regulation and execution of programmed cell death. In contrast, the study of cell death in Drosophila melanogaster, often an excellent model organism, has identified regulators and mechanisms not obviously conserved in other metazoans. Recent molecular and cellular analyses suggest, however, that the mechanisms of action of the main programmed cell death regulators in Drosophila include a canonical mitochondrial pathway

  7. ISO New England: Results of Ancillary Service Pilot Programs, Alternative Technology Regulation Pilot Program and Demand Response Reserves Pilot Program

    Energy Technology Data Exchange (ETDEWEB)

    Lowell, Jon [ISO New England, Holyoke, MA (United States); Yoshimura, Henry [ISO New England, Holyoke, MA (United States)

    2011-10-26

    This PowerPoint presentation compares performance of pilot program assets and generation resources in alternative technology regulation and demand response reserves for flywheels and residential electric thermal storage.

  8. Deriving a site characterization program from applicable regulations

    International Nuclear Information System (INIS)

    Voegele, M.D.; Younker, J.L.; Alexander, D.H.

    1988-01-01

    The process of deriving a site characterization program from the applicable regulations was approached by the DOE through the use of two basic organizing principles. One organizing principle is a hierarchical structure of questions about regulatory criteria related to the acquisition of site data. This set of questions is called an issues hierarchy, and it provides a topical organizing framework for developing a site characterization program. The second basic organizing principle used by the DOE and its contractors to develop a site characterization program is called performance allocation. For each issue in the issues hierarchy, a resolution strategy is developed. These strategies involve the identification of elements of the disposal system that are relevant to isolation and containment of waste or to radiological safety. It is then possible to identify performance measures and information needed from the site characterization program. This information, coupled with information about confidence in existing data and the confidence required in the data to be obtained, allows the development of testing strategies for field programs

  9. Mitochondrial fission proteins regulate programmed cell death in yeast.

    Science.gov (United States)

    Fannjiang, Yihru; Cheng, Wen-Chih; Lee, Sarah J; Qi, Bing; Pevsner, Jonathan; McCaffery, J Michael; Hill, R Blake; Basañez, Gorka; Hardwick, J Marie

    2004-11-15

    The possibility that single-cell organisms undergo programmed cell death has been questioned in part because they lack several key components of the mammalian cell death machinery. However, yeast encode a homolog of human Drp1, a mitochondrial fission protein that was shown previously to promote mammalian cell death and the excessive mitochondrial fragmentation characteristic of apoptotic mammalian cells. In support of a primordial origin of programmed cell death involving mitochondria, we found that the Saccharomyces cerevisiae homolog of human Drp1, Dnm1, promotes mitochondrial fragmentation/degradation and cell death following treatment with several death stimuli. Two Dnm1-interacting factors also regulate yeast cell death. The WD40 repeat protein Mdv1/Net2 promotes cell death, consistent with its role in mitochondrial fission. In contrast to its fission function in healthy cells, Fis1 unexpectedly inhibits Dnm1-mediated mitochondrial fission and cysteine protease-dependent cell death in yeast. Furthermore, the ability of yeast Fis1 to inhibit mitochondrial fission and cell death can be functionally replaced by human Bcl-2 and Bcl-xL. Together, these findings indicate that yeast and mammalian cells have a conserved programmed death pathway regulated by a common molecular component, Drp1/Dnm1, that is inhibited by a Bcl-2-like function.

  10. THE PROGRAMED CELL DEATH REGULATORS OF ISOLATED MODEL SYSTEMS

    Directory of Open Access Journals (Sweden)

    D. V. Vatlitsov

    2016-06-01

    Full Text Available The technology evolution creates the prerequisites for the emergence of new informational concept and approaches to the formation of a fundamentally new principles of biological objects understanding. The aim was to study the activators of the programmed cell death in an isolated system model. Cell culture aging parameters were performed on flow cytometer. It had formed the theory that the changes in the concentrations of metal ions and increase their extracellular concentration had formed a negative gradient into the cells.regulation of cell death. It was shown that the metals ions concentrations.

  11. 34 CFR 280.3 - What regulations apply to this program?

    Science.gov (United States)

    2010-07-01

    ... SECONDARY EDUCATION, DEPARTMENT OF EDUCATION MAGNET SCHOOLS ASSISTANCE PROGRAM General § 280.3 What regulations apply to this program? The following regulations apply to the Magnet Schools Assistance Program: (a) The Education Department General Administrative Regulations (EDGAR), 34 CFR parts 75 (Direct...

  12. Nuclear regulation. NRC's security clearance program can be strengthened

    International Nuclear Information System (INIS)

    Fultz, Keith O.; Kruslicky, Mary Ann; Bagnulo, John E.

    1988-12-01

    that this policy is waived for about 99 percent of new employees. Waivers have become routine because waiting for background investigation results would adversely affect hiring and recruiting, according to NRC staff. NRC policies do not require reinvestigation of the backgrounds of nearly 50 percent of its clearance holders. Therefore, NRC does not know whether circumstances in some employees' lifestyles have changed, making them security risks. NRC security staff cited financial reasons for not requiring reinvestigations for all other employees. Further, NRC does not have accurate clearance information, for example, data to determine when reinvestigations are needed to effectively manage its program. In addition, for over a decade, NRC has debated the need for regulations to ensure that nuclear power plant employees requiring unescorted access to power plants do not pose a threat of radiological sabotage. NRC still has not decided whether it will issue a regulation or endorse industry-developed guidelines

  13. 75 FR 66686 - Defense Federal Acquisition Regulation Supplement; Balance of Payments Program Exemption for...

    Science.gov (United States)

    2010-10-29

    ... Federal Acquisition Regulation Supplement; Balance of Payments Program Exemption for Commercial... Balance of Payments Program for construction material that is commercial information technology. DATES... the Balance of Payments Program for commercial information technology to be used in overseas...

  14. Avoiding dual regulation of the Civilian Radioactive Waste Management Program

    International Nuclear Information System (INIS)

    Vlahakis, J.G.; Palabrica, R.J.

    1994-01-01

    The Office of Civilian Radioactive Waste Management (RW) has successfully negotiated the issuance of a Department of Energy (DOE) Headquarters Order that provides for exemption of RW from certain DOE directives. This exemption assures precedence of Nuclear Regulatory Commission (NRC) requirements in radiation protection, nuclear safety (including quality assurance), and safeguards and security of nuclear materials. This Order is necessary to avoid the unwarranted cost and potential confusion resulting from dual regulation of RW facilities and activities by DOE and NRC. Development of this Order involved a systematic review of applicable DOE directives and NRC requirements to identify potential overlaps and duplication when applied to the RW program. Following this review and extensive negotiations with appropriate DOE organizations responsible for directives development, this Order was issued as HQ 1321.1 on December 22, 1993

  15. Myeloid translocation genes differentially regulate colorectal cancer programs

    Science.gov (United States)

    Parang, Bobak; Bradley, Amber M.; Mittal, Mukul K.; Short, Sarah P.; Thompson, Joshua J.; Barrett, Caitlyn W.; Naik, Rishi D.; Bilotta, Anthony J.; Washington, Mary K.; Revetta, Frank L.; Smith, Jesse J.; Chen, Xi; Wilson, Keith T.; Hiebert, Scott W.; Williams, Christopher S.

    2016-01-01

    Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1−/− mice have progressive depletion of all intestinal secretory cells, and Mtg16−/− mice have a decrease in goblet cells. Furthermore, both Mtgr1−/− and Mtg16−/− mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc1638/+-dependent intestinal tumorigenesis. Mtgr1−/− mice, but not Mtg16−/− mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of ChIP-seq datasets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1−/− tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context dependent effect on intestinal tumorigenesis. PMID:27270437

  16. 78 FR 11745 - Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small...

    Science.gov (United States)

    2013-02-20

    .... As published, the final regulations contain two points where the word ``small'' was inadvertently... and procedure, Government procurement, Government property, Loan programs-business, Small businesses...

  17. 77 FR 11367 - Defense Federal Acquisition Regulation Supplement; Extension of the Test Program for Negotiation...

    Science.gov (United States)

    2012-02-24

    ...DoD is issuing a final rule amending the Defense Federal Acquisition Regulation Supplement to extend the program period for the DoD Test Program for Negotiation of Comprehensive Small Business Subcontracting Plans.

  18. 76 FR 31416 - Federal Acquisition Regulation; Oversight of Contractor Ethics Programs

    Science.gov (United States)

    2011-05-31

    ...-AL92 Federal Acquisition Regulation; Oversight of Contractor Ethics Programs AGENCY: Department of... that contractors have implemented the mandatory contractor business ethics program requirements. DATES... to Improve DoD's Oversight of Contractor Ethics Programs. The ethics program requirement flows from...

  19. 77 FR 12913 - Federal Acquisition Regulation; Women-Owned Small Business (WOSB) Program

    Science.gov (United States)

    2012-03-02

    ... 2010-015; Item I; Docket 2010-0015, Sequence 1] RIN 9000-AL97 Federal Acquisition Regulation; Women... Regulation (FAR) to implement the Small Business Administration's regulations establishing the Women-Owned Small Business (WOSB) Program. This rule authorizes the restriction of competition for Federal contracts...

  20. 76 FR 14566 - Federal Acquisition Regulation; Socioeconomic Program Parity

    Science.gov (United States)

    2011-03-16

    ... businesses and their relationship to the other small business programs. FAR Case 2010- 015, Women-Owned Small... Women- owned Small Business (WOSB) Federal Contract Program final rule, (75 FR 62258, October 7, 2010...-disabled veteran-owned small business concerns participation. * * * * * PART 19--SMALL BUSINESS PROGRAMS 19...

  1. Programmed death-1 receptor suppresses γ-IFN producing NKT cells in human tuberculosis.

    Science.gov (United States)

    Singh, Amar; Dey, Aparajit Ballav; Mohan, Anant; Mitra, Dipendra Kumar

    2014-05-01

    IFN-γ biased Th1 effector immune response is crucial for containment of Mycobacterium tuberculosis infection. Various T cell subsets with regulatory function dictate the generation of Th1 like cells. NKT cells are a specialized T cell subset known to be activated early in immune response and control T cell response via release of immunoregulatory cytokines like IFN-γ, IL-4 and IL-10. M. tuberculosis, with abundance of its cell wall lipids may potently activate NKT cells resulting in cytokine production and PD-1 expression. In this study, among 49 treatment naive active pulmonary tuberculosis patients, we found a higher percentage of PD1(+) NKT cells correlating with sputum bacillary load. Furthermore, blocking PD-1 increased the number of IFN-γ producing NKT cells by inhibiting their apoptosis. Moreover, peripheral frequency of NKT cells declined with therapy suggesting their role in host T cell response. In this study, we concluded that PD-1 preferentially induces apoptosis of IFN-γ producing NKT cells while sparing NKT cells that produce IL-4. Such a polarized NKT cell function may impose a Th2 bias on the ensuing effector T cell response leading to inefficient clearance of M. tuberculosis. Inhibiting PD-1 may therefore alter the T cell response in favor of the host by rescuing type 1 NKT cells from apoptosis and boosting Th1 effector T cell functions against M. tuberculosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Structure and Interactions of the Human Programmed Cell Death 1 Receptor

    Czech Academy of Sciences Publication Activity Database

    Cheng, X. X.; Veverka, Václav; Radhakrishnan, A.; Waters, L. C.; Muskett, F. W.; Morgan, S. H.; Huo, J. D.; Yu, C.; Evans, E. J.; Leslie, A. J.; Griffiths, M.; Stubberfield, C.; Griffin, R.; Henry, A. J.; Jansson, A.; Ladbury, J. E.; Ikemizu, S.; Carr, M. D.; Davis, S. J.

    2013-01-01

    Roč. 288, č. 17 (2013), s. 11771-11785 ISSN 0021-9258 Institutional support: RVO:61388963 Keywords : cell surface protein * N-terminal domain * T-cells * nucear magnetic resonance * PD-1 expression Subject RIV: CE - Biochemistry Impact factor: 4.600, year: 2013

  3. Insurance Regulation: The NAIC Accreditation Program Can be Improved

    National Research Council Canada - National Science Library

    DIngell, John

    2001-01-01

    ... environment of the insurance industry and insurance regulation. In addition, it has revised the way accreditation reviews are performed and scored and has improved training for members of review teams.

  4. 78 FR 60169 - Federal Acquisition Regulation; Pilot Program for Enhancement of Contractor Employee...

    Science.gov (United States)

    2013-09-30

    ... 9000-AM56 Federal Acquisition Regulation; Pilot Program for Enhancement of Contractor Employee... program enhancing whistleblower protections for contractor employees. DATES: Effective: September 30, 2013... contractor employees at FAR subpart 3.9. The pilot program is mandated by section 828, entitled ``Pilot...

  5. 75 FR 37733 - Regulation of Fuels and Fuel Additives: Modifications to Renewable Fuel Standard Program

    Science.gov (United States)

    2010-06-30

    ... Regulation of Fuels and Fuel Additives: Modifications to Renewable Fuel Standard Program AGENCY... direct final rule to amend the Renewable Fuel Standard program requirements on May 10, 2010. Because EPA... Fuel Standard program requirements, published on May 10, 2010. We stated in that direct final rule that...

  6. Mitochondrial fission proteins regulate programmed cell death in yeast

    OpenAIRE

    Fannjiang, Yihru; Cheng, Wen-Chih; Lee, Sarah J.; Qi, Bing; Pevsner, Jonathan; McCaffery, J. Michael; Hill, R. Blake; Basañez, Gorka; Hardwick, J. Marie

    2004-01-01

    The possibility that single-cell organisms undergo programmed cell death has been questioned in part because they lack several key components of the mammalian cell death machinery. However, yeast encode a homolog of human Drp1, a mitochondrial fission protein that was shown previously to promote mammalian cell death and the excessive mitochondrial fragmentation characteristic of apoptotic mammalian cells. In support of a primordial origin of programmed cell death involving mitochondria, we fo...

  7. Modification of reference temperature program in reactor regulating system

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Sung Sik; Lee, Byung Jin; Kim, Se Chang; Cheong, Jong Sik [Korea Power Engineering Company, Inc., Seoul (Korea, Republic of); Kim, Ji In; Doo, Jin Yong [Korea Electric Power Cooperation, Yonggwang (Korea, Republic of)

    1999-12-31

    In Yonggwang nuclear units 3 and 4 currently under commercial operation, the cold temperature was very close to the technical specification limit of 298 deg C during initial startup testing, which was caused by the higher-than-expected reactor coolant system flow. Accordingly, the reference temperature (Tref) program needed to be revised to allow more flexibility for plant operations. In this study, the method of a specific test performed at Yonggwang nuclear unit 4 to revise the Tref program was described and the test results were discussed. In addition, the modified Tref program was evaluated on its potential impacts on system performance and safety. The methods of changing the Tref program and the associated pressurizer level setpoint program were also explained. Finally, for Ulchin nuclear unit 3 and 4 currently under initial startup testing, the effects of reactor coolant system flow rate on the coolant temperature were evaluated from the thermal hydraulic standpoint and an optimum Tref program was recommended. 6 refs., 4 figs., 2 tabs. (Author)

  8. Modification of reference temperature program in reactor regulating system

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Sung Sik; Lee, Byung Jin; Kim, Se Chang; Cheong, Jong Sik [Korea Power Engineering Company, Inc., Seoul (Korea, Republic of); Kim, Ji In; Doo, Jin Yong [Korea Electric Power Cooperation, Yonggwang (Korea, Republic of)

    1998-12-31

    In Yonggwang nuclear units 3 and 4 currently under commercial operation, the cold temperature was very close to the technical specification limit of 298 deg C during initial startup testing, which was caused by the higher-than-expected reactor coolant system flow. Accordingly, the reference temperature (Tref) program needed to be revised to allow more flexibility for plant operations. In this study, the method of a specific test performed at Yonggwang nuclear unit 4 to revise the Tref program was described and the test results were discussed. In addition, the modified Tref program was evaluated on its potential impacts on system performance and safety. The methods of changing the Tref program and the associated pressurizer level setpoint program were also explained. Finally, for Ulchin nuclear unit 3 and 4 currently under initial startup testing, the effects of reactor coolant system flow rate on the coolant temperature were evaluated from the thermal hydraulic standpoint and an optimum Tref program was recommended. 6 refs., 4 figs., 2 tabs. (Author)

  9. Understanding Federal regulations as guidelines for classical biological control programs

    Science.gov (United States)

    Michael E. Montgomery

    2011-01-01

    This chapter reviews the legislation and rules that provide the foundation for federal regulation of the introduction of natural enemies of insects as biological control agents. It also outlines the steps for complying with regulatory requirements, using biological control of Adelges tsugae Annand, the hemlock woolly adelgid (HWA), as an example. The...

  10. 34 CFR 400.3 - What other regulations apply to the Vocational and Applied Technology Education Programs?

    Science.gov (United States)

    2010-07-01

    ... Applied Technology Education Programs? 400.3 Section 400.3 Education Regulations of the Offices of the... VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION PROGRAMS-GENERAL PROVISIONS § 400.3 What other regulations apply to the Vocational and Applied Technology Education Programs? The following regulations apply to the...

  11. The omniscient placenta: Metabolic and epigenetic regulation of fetal programming.

    Science.gov (United States)

    Nugent, Bridget M; Bale, Tracy L

    2015-10-01

    Fetal development could be considered a sensitive period wherein exogenous insults and changes to the maternal milieu can have long-term impacts on developmental programming. The placenta provides the fetus with protection and necessary nutrients for growth, and responds to maternal cues and changes in nutrient signaling through multiple epigenetic mechanisms. The X-linked enzyme O-linked-N-acetylglucosamine transferase (OGT) acts as a nutrient sensor that modifies numerous proteins to alter various cellular signals, including major epigenetic processes. This review describes epigenetic alterations in the placenta in response to insults during pregnancy, the potential links of OGT as a nutrient sensor to placental epigenetics, and the implications of placental epigenetics in long-term neurodevelopmental programming. We describe the role of placental OGT in the sex-specific programming of hypothalamic-pituitary-adrenal (HPA) axis programming deficits by early prenatal stress as an example of how placental signaling can have long-term effects on neurodevelopment. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. 34 CFR 614.3 - What regulations apply to this program?

    Science.gov (United States)

    2010-07-01

    ... POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION PREPARING TOMORROW'S TEACHERS TO USE TECHNOLOGY § 614.3 What... Technology: (a) The Education Department General Administrative Regulations (EDGAR) as follows: (1) 34 CFR... 34 Education 3 2010-07-01 2010-07-01 false What regulations apply to this program? 614.3 Section...

  13. 76 FR 67370 - Federal Property Management Regulation (FPMR); Procurement Sources and Programs

    Science.gov (United States)

    2011-11-01

    ... to agency management and personnel. List of Subjects in 41 CFR Part 101-26 Procurement sources and... MANAGEMENT REGULATIONS PART 101-26--PROCUREMENT SOURCES AND PROGRAMS 0 1. The authority for 41 CFR part 101...; Docket Number 2011-017; Sequence 1] RIN 3090-AJ19 Federal Property Management Regulation (FPMR...

  14. 78 FR 73702 - Federal Travel Regulation (FTR); Telework Travel Expenses Test Programs

    Science.gov (United States)

    2013-12-09

    ...; Docket Number 2013-0012, Sequence 1] RIN 3090-AJ23 Federal Travel Regulation (FTR); Telework Travel...). ACTION: Final rule. SUMMARY: GSA is amending the Federal Travel Regulation (FTR) to incorporate the Telework Enhancement Act of 2010, which establishes and authorizes telework travel expenses test programs...

  15. 77 FR 30227 - Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small...

    Science.gov (United States)

    2012-05-22

    ... Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small Business Technology... public Webinar and Roundtable Meetings regarding its proposal to amend its regulations governing size and eligibility for the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR...

  16. 34 CFR 637.3 - What regulations apply to the Minority Science and Engineering Improvement Program?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What regulations apply to the Minority Science and... Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION MINORITY SCIENCE AND ENGINEERING IMPROVEMENT PROGRAM General § 637.3 What regulations apply to the Minority Science and Engineering...

  17. 76 FR 18066 - Regulation of Fuels and Fuel Additives: Changes to Renewable Fuel Standard Program

    Science.gov (United States)

    2011-04-01

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 80 Regulation of Fuels and Fuel Additives: Changes to Renewable Fuel Standard Program CFR Correction In Title 40 of the Code of Federal Regulations, Parts 72 to...-generating foreign producers and importers of renewable fuels for which RINs have been generated by the...

  18. 75 FR 58329 - Federal Travel Regulation (FTR); Relocation Expenses Test Programs

    Science.gov (United States)

    2010-09-24

    ... of test programs and possible extensions from 24 months to four years; Redesignates current section... conducting test programs. C. Executive Order 12866 This regulation is excepted from the definition of... adding ``12'' in its place. Sec. 300-80.6 [Amended] 0 3. Amend Sec. 300.80-6 by-- 0 a. Removing the word...

  19. 77 FR 28520 - Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small...

    Science.gov (United States)

    2012-05-15

    ... SMALL BUSINESS ADMINISTRATION 13 CFR Part 121 RIN 3245-AG46 Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small Business Technology Transfer (STTR) Program AGENCY: Small Business Administration. ACTION: Proposed rule. SUMMARY: The U.S. Small Business Administration...

  20. 42 CFR 50.402 - To what program do these regulations apply?

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false To what program do these regulations apply? 50.402 Section 50.402 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS POLICIES OF GENERAL APPLICABILITY Public Health Service Grant Appeals Procedure § 50.402 To what program do...

  1. 42 CFR 59.1 - To what programs do these regulations apply?

    Science.gov (United States)

    2010-10-01

    ... FOR FAMILY PLANNING SERVICES Project Grants for Family Planning Services § 59.1 To what programs do... 42 Public Health 1 2010-10-01 2010-10-01 false To what programs do these regulations apply? 59.1... of voluntary family planning projects. These projects shall consist of the educational, comprehensive...

  2. Gene program-specific regulation of PGC-1{alpha} activity

    DEFF Research Database (Denmark)

    Schmidt, Søren F; Mandrup, Susanne

    2011-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1 α (PGC-1α) activation coordinates induction of the hepatic fasting response through coactivation of numerous transcription factors and gene programs. In the June 15, 2011, issue of Genes & Development, Lustig and colleagues (pp....... 1232-1244) demonstrated that phosphorylation of PGC-1α by the p70 ribosomal protein S6 kinase 1 (S6K1) specifically interfered with the interaction between PGC-1α and HNF4α in liver and blocked the coactivation of the gluconeogenic target genes. This demonstrates how independent fine-tuning of gene...

  3. 75 FR 18377 - Supplemental Nutrition Assistance Program, Regulation Restructuring: Issuance Regulation Update...

    Science.gov (United States)

    2010-04-12

    ... Program participants and households, the number and type of authorized food retailers and authorized... Gold, Chief, Retailer Management and Issuance Branch, Benefit Redemption Division at Food and Nutrition....'' Furthermore, retailers were required to provide change above 99 cents in the form of coupons as well to ensure...

  4. Promoting Self-regulated Learning of Brazilian Preservice Student Teachers: Results of an Intervention Program

    Directory of Open Access Journals (Sweden)

    Danielle Ribeiro Ganda

    2018-02-01

    Full Text Available Self-regulation is the process by which individuals monitor, control, and reflect on their learning. Self-regulated students have motivational, metacognitive, affective, and behavioral characteristics that enhance their learning. As the importance of self-regulated learning is well acknowledged by research nowadays, the aim of this study is to examine the effectiveness of an innovative course designed to promote self-regulated learning among Brazilian preservice student teachers. The innovative approach was developed in the format of a program of intervention based heavily on self-reflection. The content involved student exposure to self-reflexive activities, lectures on the self-regulated learning framework, and theoretical tasks aimed at fostering self-regulation of students in a double perspective: as a student and as a future teacher. The efficacy of the approach was tested by comparison with both the results of students who had taken a course with theoretical content only and those who had not taken any course at all. The sample consisted of 109 students in 4 different freshman classes in a Teacher Education Program in a Brazilian public university in an inner city in the state of São Paulo. The research was conducted using a quasi-experimental design with three stages: pretest, intervention, and posttest. The classes were randomly assigned to experimental and control conditions as follows: an experimental group involving intervention, an experimental group exposed to theory, and two control groups not taking the course. Before and after the intervention program, all the participants responded to the Learning and Study Strategies Inventory and the Self-efficacy for Self-regulated Learning scales. Overall, the results showed that the intervention program format had a positive impact in enhancing student self-regulation. Moreover, students in both the experimental groups reported both higher gains in self-efficacy for self-regulated learning

  5. Tuned In emotion regulation program using music listening: Effectiveness for adolescents in educational settings

    Directory of Open Access Journals (Sweden)

    Genevieve Anita Dingle

    2016-06-01

    Full Text Available This paper presents an effectiveness study of Tuned In, a novel emotion regulation intervention that uses participant selected music to evoke emotions in session and teaches participants emotional awareness and regulation skills. The group program content is informed by a two dimensional model of emotion (arousal, valence, along with music psychology theories about how music evokes emotional responses. The program has been evaluated in two samples of adolescents: 41 at risk adolescents (76% males; Mage = 14.8 years attending an educational re-engagement program and 216 students (100% females; Mage = 13.6 years attending a mainstream secondary school. Results showed significant pre- to post-program improvements in measures of emotion awareness, identification, and regulation (p < .01 to p = .06 in the smaller at risk sample and all p < .001 in the mainstream school sample. Participant ratings of engagement and likelihood of using the strategies learned in the program were high. Tuned In shows promise as a brief emotion regulation intervention for adolescents, and these findings extend an earlier study with young adults. Tuned In is a-theoretical in regard to psychotherapeutic approach and could be integrated with other program components as required.

  6. Tuned In Emotion Regulation Program Using Music Listening: Effectiveness for Adolescents in Educational Settings.

    Science.gov (United States)

    Dingle, Genevieve A; Hodges, Joseph; Kunde, Ashleigh

    2016-01-01

    This paper presents an effectiveness study of Tuned In, a novel emotion regulation intervention that uses participant selected music to evoke emotions in session and teaches participants emotional awareness and regulation skills. The group program content is informed by a two dimensional model of emotion (arousal, valence), along with music psychology theories about how music evokes emotional responses. The program has been evaluated in two samples of adolescents: 41 "at risk" adolescents (76% males; M age = 14.8 years) attending an educational re-engagement program and 216 students (100% females; M age = 13.6 years) attending a mainstream secondary school. Results showed significant pre- to post-program improvements in measures of emotion awareness, identification, and regulation (p < 0.01 to p = 0.06 in the smaller "at risk" sample and all p < 0.001 in the mainstream school sample). Participant ratings of engagement and likelihood of using the strategies learned in the program were high. Tuned In shows promise as a brief emotion regulation intervention for adolescents, and these findings extend an earlier study with young adults. Tuned In is a-theoretical in regard to psychotherapeutic approach and could be integrated with other program components as required.

  7. William D. Ford Federal Direct Loan Program. Final Regulations. Federal Register, Department of Education, 34 CFR Part 685

    Science.gov (United States)

    National Archives and Records Administration, 2014

    2014-01-01

    The purpose of this regulatory action is to amend the regulations governing the William D. Ford Federal Direct Loan (Direct Loan) Program (§ 685.200 of title 34 of the Code of Federal Regulations (CFR)). These regulations strengthen and improve administration of the Federal Direct PLUS Loan Program authorized under title IV of the Higher Education…

  8. MANAGING NEWLY ESTABLISHED PESTS: Growers, scientists and regulators collaborate on European grapevine moth program

    Directory of Open Access Journals (Sweden)

    Monica Cooper

    2014-10-01

    Full Text Available The first detection of the European grapevine moth in North America triggered the establishment of federal and state regulatory programs that (1 identified the insect's geographic range in California, (2 developed and implemented detection and management programs, (3 regulated the movement of plant material and equipment to minimize the threat of dispersal, (4 incorporated research-based information developed by subject-matter experts into policy decisions and (5 promoted a wide-reaching educational program for grape growers, the public and local officials. The action plan, developed and carried out through a coordinated program that included multiple government agencies, university scientists and the agricultural community, drastically reduced insect populations and limited the distribution in California vineyards such that some previously infested areas were removed from quarantine regulation.

  9. Developmental programming of energy balance regulation: is physical activity more 'programmable' than food intake?

    Science.gov (United States)

    Zhu, Shaoyu; Eclarinal, Jesse; Baker, Maria S; Li, Ge; Waterland, Robert A

    2016-02-01

    Extensive human and animal model data show that environmental influences during critical periods of prenatal and early postnatal development can cause persistent alterations in energy balance regulation. Although a potentially important factor in the worldwide obesity epidemic, the fundamental mechanisms underlying such developmental programming of energy balance are poorly understood, limiting our ability to intervene. Most studies of developmental programming of energy balance have focused on persistent alterations in the regulation of energy intake; energy expenditure has been relatively underemphasised. In particular, very few studies have evaluated developmental programming of physical activity. The aim of this review is to summarise recent evidence that early environment may have a profound impact on establishment of individual propensity for physical activity. Recently, we characterised two different mouse models of developmental programming of obesity; one models fetal growth restriction followed by catch-up growth, and the other models early postnatal overnutrition. In both studies, we observed alterations in body-weight regulation that persisted to adulthood, but no group differences in food intake. Rather, in both cases, programming of energy balance appeared to be due to persistent alterations in energy expenditure and spontaneous physical activity (SPA). These effects were stronger in female offspring. We are currently exploring the hypothesis that developmental programming of SPA occurs via induced sex-specific alterations in epigenetic regulation in the hypothalamus and other regions of the central nervous system. We will summarise the current progress towards testing this hypothesis. Early environmental influences on establishment of physical activity are likely an important factor in developmental programming of energy balance. Understanding the fundamental underlying mechanisms in appropriate animal models will help determine whether early life

  10. Results from two workshops: Developing and amending regulations and funding state radiation control programs

    International Nuclear Information System (INIS)

    Parker, G.

    1993-09-01

    The first section of this document presents the results of a technical workshop on the process of regulations development and amendment sponsored by the Nuclear Regulatory Commission (NRC). This workshop focused on methods for reducing the time it takes to promulgate regulations to help those States that are having difficulty meeting the three-year deadline for adopting new NRC regulations. Workshop participants responded to six questions, reviewed the procedures used by various States for revising and adopting changes to their regulations, and reviewed the time-flow charts used by various States. This workshop was designed to provide guidance to States that are promulgating and revising regulations. The second section of this document summarizes the proceedings of a technical workshop, also sponsored by the NRC, on funding radiation control programs that emphasized fee schedules and effective strategies for the 1990s. This workshop focused on determining the true costs of running a program, on setting realistic fees for the various categories of licenses, and on the most efficient methods for sending invoices, recording receipts, depositing money received, and issuing licenses. Workshop participants responded to seven questions; reviewed the methods various States use to determine true costs; reviewed the procedure that the various States use to produce invoices and licenses; reviewed the procedures that the States are required to abide by when they receive money; and reviewed the method used by the NRC to determine the cost of its various programs

  11. 14 CFR 1204.1503 - Programs and activities subject to these regulations.

    Science.gov (United States)

    2010-01-01

    ... regulations. 1204.1503 Section 1204.1503 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION ADMINISTRATIVE AUTHORITY AND POLICY Intergovernmental Review of National Aeronautics and Space Administration... publishes in the Federal Register a description of the Agency's programs and activities that are subject to...

  12. Self-Regulated Learning Using Multimedia Programs in Dentistry Postgraduate Students: A Multimethod Approach

    Science.gov (United States)

    Lloret, Miguel; Aguila, Estela; Lloret, Alejandro

    2009-01-01

    The purpose of this study was to study the effect of a multimedia computing program on the production of activities and self-regulated learning processes in 18 students of the Dentistry postdegree (Celaya, Mexico). A multi-method design (quasi-experimental, pretest-post-test and qualitative: Think aloud protocol) was used. Self-regulated…

  13. 78 FR 58202 - Federal Tort Claims Act (FTCA) Medical Malpractice Program Regulations: Clarification of FTCA...

    Science.gov (United States)

    2013-09-23

    ...) Medical Malpractice Program Regulations: Clarification of FTCA Coverage for Services Provided to Non... not limit coverage to childhood vaccinations; and (3) To add the following new example as subsection 6... that have substantial direct effects on the states, the relationship between the national government...

  14. 77 FR 17352 - Federal Acquisition Regulation; Women-Owned Small Business (WOSB) Program

    Science.gov (United States)

    2012-03-26

    ...-AL97 Federal Acquisition Regulation; Women-Owned Small Business (WOSB) Program Correction In rule...) * * * -- (24) 52.219-29, Notice of Set-Aside for Economically Disadvantaged Women-Owned Small Business (EDWOSB... Disadvantaged Women- Owned Small Business Concerns. * * * * * Notice of Set-Aside for Economically Disadvantaged...

  15. 15 CFR 20.2 - Programs or activities to which these regulations apply.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Programs or activities to which these regulations apply. 20.2 Section 20.2 Commerce and Foreign Trade Office of the Secretary of Commerce... adopted by an elected, general purpose legislative body which: (i) Provides benefits or assistance to...

  16. Improving Emotion Regulation and Sibling Relationship Quality: The More Fun with Sisters and Brothers Program

    Science.gov (United States)

    Kennedy, Denise E.; Kramer, Laurie

    2008-01-01

    We examined the role of emotion regulation (ER) in improving sibling relationship quality (SRQ) by evaluating the More Fun With Sisters and Brothers Program where 4- to 8-year-old siblings from 95 families were taught emotional and social competencies. Parents reported on SRQ and ER, and sibling interactions were observed in homes. SRQ and ER…

  17. 34 CFR 356.3 - What regulations apply to this program?

    Science.gov (United States)

    2010-07-01

    ... SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION DISABILITY AND REHABILITATION... purposefully requires inclusion of children with disabilities or individuals with mental disabilities as... 34 Education 2 2010-07-01 2010-07-01 false What regulations apply to this program? 356.3 Section...

  18. The Abbott School Construction Program: NJ Department of Education Proposed Facilities Regulations. Analysis of Preschool Issues

    Science.gov (United States)

    Ponessa, Joan; Boylan, Ellen

    2004-01-01

    This report on preschool facilities analyzes regulations proposed by the New Jersey Department of Education (NJDOE) to implement the Educational Facilities Construction and Financing Act. (EFCFA). EFCFA, which authorizes and governs New Jersey's public school construction program, was enacted in July 2000 to implement the State Supreme Court's…

  19. Self-Regulation Programs for At-Risk Youth: Are Teachers Affected Too?

    Science.gov (United States)

    Lichtinger, Einat; Leichtentritt, Judith

    2016-01-01

    This study examines changes experienced by teachers of youth at socioeconomic risk during and after conducting self-regulation programs with their students. Participants' self-reports were classified into 3 change models. Teachers in the 1st model reported changes in their interaction with the school, their role with the students, and their own…

  20. Updating of the program for simulation of Darlington shutdown and regulation systems

    International Nuclear Information System (INIS)

    1988-07-01

    This report describes the current status of the developments of a simulation of the Darlington Nuclear Generating Station shutdown and regulating systems, DARSIM done under contract to the Atomic Energy Control Board (AECB). The DARSIM program simulates the spatial neutron dynamics, the regulation of the reactor power, and shutdown system 1 and shutdown system 2 software. The DARSIM program operates in the interactive simulation program environment. DARSIM was installed on the APOLLO computer at the AECB and a version for an IBM-PC was also provided for the exclusive use of the AECB. Shutdown system software was updated to incorporate the latest revisions in the functional specifications. Additional developments have been provided to assist in the use and interpretation of the DARSIM results

  1. Effectiveness of a self-regulated remedial program for handwriting difficulties.

    Science.gov (United States)

    Van Waelvelde, Hilde; De Roubaix, Amy; Steppe, Lien; Troubleyn, Evy; De Mey, Barbara; Dewitte, Griet; Debrabant, Julie; Van de Velde, Dominique

    2017-09-01

    Handwriting difficulties may have pervasive effects on a child's school performance. I Can! is a remedial handwriting program with a focus on self-regulated learning and applying motor learning principles combined with a behavioural approach. It is developed for typically developing children with handwriting problems. The study aim was to evaluate the program's effectiveness. Thirty-one children aged 7-8 year participated in a cross-over study. Handwriting quality and speed were repeatedly assessed by means of the Systematic Screening of Handwriting Difficulties test. Difficulties addressed were fluency in letter formation, fluency in letter connections, letter height, regularity of letter height, space between words, and line path. Mixed model analysis revealed improved quality of writing and speed for all children but significantly more improvement in handwriting quality for the children participating in the program. Although writing speed improved over time, no additional effects of the program occurred. 'I Can!' is found to be an effective instructive program to ameliorate handwriting quality in typically developing children with handwriting difficulties. The program's success was by a therapy burst of only 7 weeks focusing on the child's self-regulated learning capacities, within an individualized education plan according to their needs and goals.

  2. 41 CFR 101-6.2103 - What programs and activities of GSA are subject to these regulations?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true What programs and... Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS...? The Administrator publishes in the Federal Register a list of GSA's programs and activities that are...

  3. The Power of Politic and Lobbying Parties in the Australian Accounting Regulation Reform Program

    OpenAIRE

    Suwaldiman, Suwaldiman

    2004-01-01

    This paper argues that Australian accounting regulations seem to be close to the government or political approach in its setting process. CLERP (Corporate Law Economic Reform Program) proposed by government can be viewed as changes made by Federal Government in the structure of setting accounting standards that show a substantial shift in power from the two professional accounting bodies; ICAA (The Institute of Certified Accountants in Australia) and ASCPA (Australian Society of Certified Pra...

  4. The Power Of Politic and Lobbying Parties in the Australian Accounting Regulation Reform Program

    OpenAIRE

    Suwaldiman, Suwaldiman

    2009-01-01

    This paper argues that Australian accounting regulations seem to be close to the government or political approach in its setting process. CLERP (Corporate Law Economic Reform Program) proposed by government can be viewed as changes made by Federal Government in the structure of setting accounting standards that show a substantial shift in power from the two professional accounting bodies; ICAA (The Institute of Certified Accountants in Australia) and ASCPA (Australian Society of Certified Pra...

  5. Self-regulated learning using multimedia programs in Dentistry posgraduate students. A multimethod approach

    Directory of Open Access Journals (Sweden)

    Miguel Rivas LLORET

    2009-10-01

    Full Text Available The purpose of this study was to study the effect of a multimedia computing program on the production of activities and self-regulated learning processes in 18 students of the Dentistry postdegree (Celaya, Mexico. A multi-method design (quasi-experimental, pretest-post-test and qualitative: Think aloud protocol was used. Self-regulated activities were identified with the MSLQ questionnaire. Results of the MSLQ pretest/post-test questionnaire didn't show an intervention effect. In contrast, the qualitative methodology allowed the registration of a high frequency of self-regulated dimensions on the metacognitive area, on the making of inferences (cognitive area, and on the planning time and effort (behavioural area. Our data revealed the usefulness of a qualitative methodology for the understanding of the complex nature of the self-regulatory processes on learning environments based on computers.

  6. Smiling is fun: a Coping with Stress and Emotion Regulation Program.

    Science.gov (United States)

    Botella, Cristina; Mira, Adriana; Garcia-Palacios, Azucena; Quero, Soledad; Navarro, Ma Vicenta; Riera López Del Amo, Antonio; Molinari, Guadalupe; Castilla, Diana; Moragrega, Inés; Soler, Carla; Alcañiz, Mariano; Baños, Rosa Maria

    2012-01-01

    Emotional disorders (Anxiety disorders and Mood disorders) are one of the most common health problems worldwide, and their economic costs are very high. People suffering from emotional disorders often use maladaptive emotion regulation strategies and have low coping behaviour that contributes to the presence of clinical symptoms. For this reason, it is important to develop strategies to monitor coping and promote emotion regulation in people exposed to high levels of stress. Information and Communication Technologies (ICT) can help us in this task. Recent systematic reviews of literature on evidence-based CBT treatments delivered via the Internet show that these approaches are effective. We have developed an intervention program ICT based: Coping with Stress and Emotion Regulation Program (Smiling is Fun), a self-applied program via the Internet. Smiling is Fun follows a transdiagnostic perspective, and it is based on CBT techniques. However, it also includes other psychological strategies to improve positive mood. The aim of the present work is to describe Smiling is Fun and the study designed to test its efficacy.

  7. Mixed Integer Linear Programming based machine learning approach identifies regulators of telomerase in yeast.

    Science.gov (United States)

    Poos, Alexandra M; Maicher, André; Dieckmann, Anna K; Oswald, Marcus; Eils, Roland; Kupiec, Martin; Luke, Brian; König, Rainer

    2016-06-02

    Understanding telomere length maintenance mechanisms is central in cancer biology as their dysregulation is one of the hallmarks for immortalization of cancer cells. Important for this well-balanced control is the transcriptional regulation of the telomerase genes. We integrated Mixed Integer Linear Programming models into a comparative machine learning based approach to identify regulatory interactions that best explain the discrepancy of telomerase transcript levels in yeast mutants with deleted regulators showing aberrant telomere length, when compared to mutants with normal telomere length. We uncover novel regulators of telomerase expression, several of which affect histone levels or modifications. In particular, our results point to the transcription factors Sum1, Hst1 and Srb2 as being important for the regulation of EST1 transcription, and we validated the effect of Sum1 experimentally. We compiled our machine learning method leading to a user friendly package for R which can straightforwardly be applied to similar problems integrating gene regulator binding information and expression profiles of samples of e.g. different phenotypes, diseases or treatments. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. 45 CFR 660.3 - What programs and activities of the Foundation are subject to these regulations?

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false What programs and activities of the Foundation are... (Continued) NATIONAL SCIENCE FOUNDATION INTERGOVERNMENTAL REVIEW OF THE NATIONAL SCIENCE FOUNDATION PROGRAMS AND ACTIVITIES § 660.3 What programs and activities of the Foundation are subject to these regulations...

  9. 49 CFR 17.3 - What programs and activities of the Department are subject to these regulations?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What programs and activities of the Department are subject to these regulations? 17.3 Section 17.3 Transportation Office of the Secretary of Transportation INTERGOVERNMENTAL REVIEW OF DEPARTMENT OF TRANSPORTATION PROGRAMS AND ACTIVITIES § 17.3 What programs and activities...

  10. Programming of the appetite-regulating neural network: a link between maternal overnutrition and the programming of obesity?

    Science.gov (United States)

    Mühlhäusler, B S

    2007-01-01

    The concept of a functional foetal "appetite regulatory neural network" is a new and potentially critical one. There is a growing body of evidence showing that the nutritional environment to which the foetus is exposed during prenatal and perinatal development has long-term consequences for the function of the appetite-regulating neural network and therefore the way in which an individual regulates energy balance throughout later life. This is of particular importance in the context of evidence obtained from a wide range of epidemiological studies, which have shown that individuals exposed to an elevated nutrient supply before birth have an increased risk of becoming obese as children and adults. This review summarises the key pieces of experimental evidence, by our group and others, that have contributed to our current understanding of the programming of appetite, and highlights the important questions that are yet to be answered. It is clear that this area of research has the potential to generate, within the next few years, interventions that could begin to alleviate the adverse long-term consequences of being exposed to an elevated nutrient supply before birth.

  11. Nuclear adaptor Ldb1 regulates a transcriptional program essential for the maintenance of hematopoietic stem cells.

    Science.gov (United States)

    Li, LiQi; Jothi, Raja; Cui, Kairong; Lee, Jan Y; Cohen, Tsadok; Gorivodsky, Marat; Tzchori, Itai; Zhao, Yangu; Hayes, Sandra M; Bresnick, Emery H; Zhao, Keji; Westphal, Heiner; Love, Paul E

    2011-02-01

    The nuclear adaptor Ldb1 functions as a core component of multiprotein transcription complexes that regulate differentiation in diverse cell types. In the hematopoietic lineage, Ldb1 forms a complex with the non-DNA-binding adaptor Lmo2 and the transcription factors E2A, Scl and GATA-1 (or GATA-2). Here we demonstrate a critical and continuous requirement for Ldb1 in the maintenance of both fetal and adult mouse hematopoietic stem cells (HSCs). Deletion of Ldb1 in hematopoietic progenitors resulted in the downregulation of many transcripts required for HSC maintenance. Genome-wide profiling by chromatin immunoprecipitation followed by sequencing (ChIP-Seq) identified Ldb1 complex-binding sites at highly conserved regions in the promoters of genes involved in HSC maintenance. Our results identify a central role for Ldb1 in regulating the transcriptional program responsible for the maintenance of HSCs.

  12. BVES Regulates Intestinal Stem Cell Programs and Intestinal Crypt Viability after Radiation

    Science.gov (United States)

    Reddy, Vishruth K.; Short, Sarah P.; Barrett, Caitlyn W.; Mittal, Mukul K.; Keating, Cody E.; Thompson, Joshua J.; Harris, Elizabeth I.; Revetta, Frank; Bader, David M.; Brand, Thomas; Washington, M. Kay; Williams, Christopher S.

    2016-01-01

    Blood Vessel Epicardial Substance (BVES/Popdc1) is a junctional-associated transmembrane protein that is underexpressed in a number of malignancies and regulates epithelial-to-mesenchymal transition. We previously identified a role for BVES in regulation of the Wnt pathway, a modulator of intestinal stem cell programs, but its role in small intestinal (SI) biology remains unexplored. We hypothesized that BVES influences intestinal stem cell programs and is critical to SI homeostasis after radiation injury. At baseline, Bves−/− mice demonstrated increased crypt height, as well as elevated proliferation and expression of the stem cell marker Lgr5 compared to wildtype (WT) mice. Intercross with Lgr5-EGFP reporter mice confirmed expansion of the stem cell compartment in Bves−/− mice. To examine stem cell function after BVES deletion, we employed ex vivo 3D-enteroid cultures. Bves−/− enteroids demonstrated increased stemness compared to WT, when examining parameters such as plating efficiency, stem spheroid formation, and retention of peripheral cystic structures. Furthermore, we observed increased proliferation, expression of crypt-base columnar “CBC” and “+4” stem cell markers, amplified Wnt signaling, and responsiveness to Wnt activation in the Bves−/− enteroids. Bves expression was downregulated after radiation in WT mice. Moreover, after radiation, Bves−/− mice demonstrated significantly greater small intestinal crypt viability, proliferation, and amplified Wnt signaling in comparison to WT mice. Bves−/− mice also demonstrated elevations in Lgr5 and Ascl2 expression, and putative damage-responsive stem cell populations marked by Bmi1 and TERT. Therefore, BVES is a key regulator of intestinal stem cell programs and mucosal homeostasis. PMID:26891025

  13. An application of nonlinear programming to the design of regulators of a linear-quadratic formulation

    Science.gov (United States)

    Fleming, P.

    1983-01-01

    A design technique is proposed for linear regulators in which a feedback controller of fixed structure is chosen to minimize an integral quadratic objective function subject to the satisfaction of integral quadratic constraint functions. Application of a nonlinear programming algorithm to this mathematically tractable formulation results in an efficient and useful computer aided design tool. Particular attention is paid to computational efficiency and various recommendations are made. Two design examples illustrate the flexibility of the approach and highlight the special insight afforded to the designer. One concerns helicopter longitudinal dynamics and the other the flight dynamics of an aerodynamically unstable aircraft.

  14. 28 CFR 30.3 - What programs and activities of the Department are subject to these regulations?

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false What programs and activities of the Department are subject to these regulations? 30.3 Section 30.3 Judicial Administration DEPARTMENT OF JUSTICE... Department are subject to these regulations? The Attorney General publishes in the Federal Register a list of...

  15. 25 CFR 900.5 - Effect of these regulations on Federal program guidelines, manual, or policy directives.

    Science.gov (United States)

    2010-04-01

    ... SELF-DETERMINATION AND EDUCATION ASSISTANCE ACT General Provisions § 900.5 Effect of these regulations... 25 Indians 2 2010-04-01 2010-04-01 false Effect of these regulations on Federal program guidelines, manual, or policy directives. 900.5 Section 900.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE...

  16. School menus in Santa Catarina: Evaluation with respect to the National School Food Program regulations

    Directory of Open Access Journals (Sweden)

    Glenda Marreira Vidal

    2015-06-01

    Full Text Available OBJECTIVE: To assess compliance of school menu planning with the National School Food Program's regulations. METHODS: This cross-sectional study analyzed 133 menus for 542 schools in 49 municipalities of the state of Santa Catarina. The menus were assessed according to the National School Food Program's regulations, the "Dietary Guidelines for the Brazilian Population" and the "Qualitative Evaluation of Menu Components for Schools". The data were analyzed by descriptive statistics. RESULTS: Nearly all (98.5% municipalities met the requirement of technical responsibility for menu development and 81.0% acquired foods from family farms. The menus contained fruits (87.2% and non-starchy vegetables (94.0%, but the frequencies of fruits and non-starchy vegetables were smaller than two to three times a week. The most common high-sodium and high-fat foods were commercially processed meats (53.0%, but their frequency was smaller than once a week. Likewise, the frequencies of beverages (natural fruit juice, coffee, and tea were smaller than once a week. Most menus (85.1% repeated foods during the week, and only 3.0% of the menus listed organic foods. CONCLUSION: Some school menus from Santa Catarina need to be revised with respect to the frequency of fruits and non-starchy vegetables, high-sugar foods, high-sodium foods, and high-fat foods, and need to increase food diversity and variety.

  17. Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program.

    Science.gov (United States)

    Lee, Eun Ju; Jan, Arif Tasleem; Baig, Mohammad Hassan; Ashraf, Jalaluddin Mohammad; Nahm, Sang-Soep; Kim, Yong-Woon; Park, So-Young; Choi, Inho

    2016-08-01

    Differentiation of muscle satellite cells (MSCs) involves interaction of the proteins present in the extracellular matrix (ECM) with MSCs to regulate their activity, and therefore phenotype. Herein, we report fibromodulin (FMOD), a member of the proteoglycan family participating in the assembly of ECM, as a novel regulator of myostatin (MSTN) during myoblast differentiation. In addition to having a pronounced effect on the expression of myogenic marker genes [myogenin (MYOG) and myosin light chain 2 (MYL2)], FMOD was found to maintain the transcriptional activity of MSTN Moreover, coimmunoprecipitation and in silico studies performed to investigate the interaction of FMOD helped confirm that it antagonizes MSTN function by distorting its folding and preventing its binding to activin receptor type IIB. Furthermore, in vivo studies revealed that FMOD plays an active role in healing by increasing satellite cell recruitment to sites of injury. Together, these findings disclose a hitherto unrecognized regulatory role for FMOD in MSCs and highlight new mechanisms whereby FMOD circumvents the inhibitory effects of MSTN and triggers myoblast differentiation. These findings offer a basis for the design of novel MSTN inhibitors that promote muscle regeneration after injury or for the development of pharmaceutical agents for the treatment of different muscle atrophies.-Lee, E. J., Jan, A. T., Baig, M. H., Ashraf, J. M., Nahm, S.-S., Kim, Y.-W., Park, S.-Y., Choi, I. Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program. © FASEB.

  18. Transcultural Analysis of the Effectiveness of a Program to Promote Self-Regulated Learning in Mozambique, Chile, Portugal, and Spain

    Science.gov (United States)

    Rosário, Pedro; Núñez, José Carlos; Trigo, Luisa; Guimarães, Carina; Fernández, Estrella; Cerezo, Rebeca; Fuentes, Sonia; Orellana, Marcela; Santibáñez, América; Fulano, Celso; Ferreira, Ângelo; Figueiredo, Mirela

    2015-01-01

    The current investigation aims at assessing the effectiveness of an intervention program designed to enhance self-regulated learning (SRL) strategies at the university level, with students from different cultural, linguistic, and educational backgrounds. The central tool of the program is a set of letters in which a fictional first-year student…

  19. 49 CFR 17.6 - What procedures apply to the selection of programs and activities under these regulations?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What procedures apply to the selection of programs and activities under these regulations? 17.6 Section 17.6 Transportation Office of the Secretary of Transportation INTERGOVERNMENTAL REVIEW OF DEPARTMENT OF TRANSPORTATION PROGRAMS AND ACTIVITIES § 17.6 What...

  20. Evaluation of the Preschool Situational Self-Regulation Toolkit (PRSIST) Program for Supporting children's early self-regulation development: study protocol for a cluster randomized controlled trial.

    Science.gov (United States)

    Howard, Steven J; Vasseleu, Elena; Neilsen-Hewett, Cathrine; Cliff, Ken

    2018-01-24

    For children with low self-regulation in the preschool years, the likelihood of poorer intellectual, health, wealth and anti-social outcomes in adulthood is overwhelming. Yet this knowledge has not yielded a framework for understanding self-regulatory change, nor generated particularly successful methods for enacting this change. Reconciling insights from cross-disciplinary theory, research and practice, this study seeks to implement a newly developed program of low-cost and routine practices and activities for supporting early self-regulatory development within preschool contexts and to evaluate its effect on children's self-regulation, executive function and school readiness; and educator perceived knowledge, attitudes and self-efficacy related to self-regulation. The Early Start to Self-Regulation study is a cluster randomized, controlled trial for evaluating benefits of the Preschool Situational Self-Regulation Toolkit (PRSIST) program, when implemented by early childhood educators, compared with routine practice. The PRSIST program combines professional learning, adult practices, child activities and connections to the home to support children's self-regulation development. Fifty preschool centers in New South Wales, Australia, will be selected to ensure a range of characteristics, namely: National Quality Standards (NQS) ratings, geographic location and socioeconomic status. After collection of baseline child and educator data, participating centers will then be randomly allocated to one of two groups, stratified by NQS rating: (1) an intervention group (25 centers) that will implement the PRSIST program; or (2) a control group (25 centers) that will continue to engage in practice as usual. Primary outcomes at the child level will be two measures of self-regulation: Head-Toes-Knees-Shoulders task and the PRSIST observational assessment. Secondary outcomes at the child level will be adult-reported measures of child self-regulation, executive function and

  1. The Role of Programmed Cell Death Regulator LSD1 in Nematode-Induced Syncytium Formation

    Science.gov (United States)

    Matuszkiewicz, Mateusz; Sobczak, Miroslaw; Cabrera, Javier; Escobar, Carolina; Karpiński, Stanislaw; Filipecki, Marcin

    2018-01-01

    Cyst-forming plant-parasitic nematodes are common pests of many crops. They inject secretions into host cells to induce the developmental and metabolic reprogramming that leads to the formation of a syncytium, which is the sole food source for growing nematodes. As in other host-parasite models, avirulence leads to rapid and local programmed cell death (PCD) known as the hypersensitive response (HR), whereas in the case of virulence, PCD is still observed but is limited to only some cells. Several regulators of PCD were analyzed to understand the role of PCD in compatible plant–nematode interactions. Thus, Arabidopsis plants carrying recessive mutations in LESION SIMULATING DISEASE1 (LSD1) family genes were subjected to nematode infection assays with juveniles of Heterodera schachtii. LSD1 is a negative and conditional regulator of PCD, and fewer and smaller syncytia were induced in the roots of lsd1 mutants than in wild-type Col-0 plants. Mutation in LSD ONE LIKE2 (LOL2) revealed a pattern of susceptibility to H. schachtii antagonistic to lsd1. Syncytia induced on lsd1 roots compared to Col0 showed significantly retarded growth, modified cell wall structure, increased vesiculation, and some myelin-like bodies present at 7 and 12 days post-infection. To place these data in a wider context, RNA-sequencing analysis of infected and uninfected roots was conducted. During nematode infection, the number of transcripts with changed expression in lsd1 was approximately three times smaller than in wild-type plants (1440 vs. 4206 differentially expressed genes, respectively). LSD1-dependent PCD in roots is thus a highly regulated process in compatible plant–nematode interactions. Two genes identified in this analysis, coding for AUTOPHAGY-RELATED PROTEIN 8F and 8H were down-regulated in syncytia in the presence of LSD1 and showed an increased susceptibility to nematode infection contrasting with lsd1 phenotype. Our data indicate that molecular regulators belonging to the

  2. The Role of Programmed Cell Death Regulator LSD1 in Nematode-Induced Syncytium Formation

    Directory of Open Access Journals (Sweden)

    Mateusz Matuszkiewicz

    2018-03-01

    Full Text Available Cyst-forming plant-parasitic nematodes are common pests of many crops. They inject secretions into host cells to induce the developmental and metabolic reprogramming that leads to the formation of a syncytium, which is the sole food source for growing nematodes. As in other host-parasite models, avirulence leads to rapid and local programmed cell death (PCD known as the hypersensitive response (HR, whereas in the case of virulence, PCD is still observed but is limited to only some cells. Several regulators of PCD were analyzed to understand the role of PCD in compatible plant–nematode interactions. Thus, Arabidopsis plants carrying recessive mutations in LESION SIMULATING DISEASE1 (LSD1 family genes were subjected to nematode infection assays with juveniles of Heterodera schachtii. LSD1 is a negative and conditional regulator of PCD, and fewer and smaller syncytia were induced in the roots of lsd1 mutants than in wild-type Col-0 plants. Mutation in LSD ONE LIKE2 (LOL2 revealed a pattern of susceptibility to H. schachtii antagonistic to lsd1. Syncytia induced on lsd1 roots compared to Col0 showed significantly retarded growth, modified cell wall structure, increased vesiculation, and some myelin-like bodies present at 7 and 12 days post-infection. To place these data in a wider context, RNA-sequencing analysis of infected and uninfected roots was conducted. During nematode infection, the number of transcripts with changed expression in lsd1 was approximately three times smaller than in wild-type plants (1440 vs. 4206 differentially expressed genes, respectively. LSD1-dependent PCD in roots is thus a highly regulated process in compatible plant–nematode interactions. Two genes identified in this analysis, coding for AUTOPHAGY-RELATED PROTEIN 8F and 8H were down-regulated in syncytia in the presence of LSD1 and showed an increased susceptibility to nematode infection contrasting with lsd1 phenotype. Our data indicate that molecular regulators

  3. Emergency Response Program Designing Based On Case Study ERP Regulations In Ilam Gas Refinery

    Directory of Open Access Journals (Sweden)

    Mehdi Tahmasbi

    2015-08-01

    Full Text Available The study of Emergency response plan designing is one of the most important prevention approaches in crisis management. This study aims to design emergency response plan based on case study ERP regulations in Ilam gas refinery. On the basis of risk assessment and identification techniques such as HAZOP and FMEA in Ilam gas refinery the risks have been prioritized and then according to this prioritization the design of possible scenarios which have the highest rate of occurrence and the highest level of damage has been separated. Possible scenarios were simulated with PHAST software. Then emergency response program has been designed for the special mode or similar cases. According to the internal emergency response plan for Ilam gas refinery and predictable conditions of the process special instructions should be considered at the time of the incident to suffer the least damage on people and environment in the shortest time possible.

  4. Are Management-Based Regulations Effective? Evidence from State Pollution Prevention Programs

    Science.gov (United States)

    Bennear, Lori Snyder

    2007-01-01

    This paper evaluates a recent innovation in regulating risk called management-based regulation. Traditionally, risk regulation has either specified a particular means of achieving a risk-reduction goal or specified the goal and left the means of achieving that goal up to the regulated entity. In contrast, management-based regulation neither…

  5. 34 CFR 655.1 - Which programs do these regulations govern?

    Science.gov (United States)

    2010-07-01

    ... International Research and Studies Program (section 605); and (e) The Business and International Education... POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION INTERNATIONAL EDUCATION PROGRAMS-GENERAL PROVISIONS General... administration of the following programs in international education: (a) The National Resource Centers Program...

  6. Ratepayer-funded energy-efficiency programs in a restructuredelectri city industry: Issues and options for regulators andlegislators

    Energy Technology Data Exchange (ETDEWEB)

    Eto, Joseph; Goldman, Charles; Nadel, Stephen

    1998-05-01

    Electric industry restructuring requires state regulators and legislators to re-examine the purposes served by and the continuing need for ratepayer-funded energy-efficiency programs, as well as the mechanisms to collect funds for these programs and the institutions appropriate to administer them. This paper offers background to these issues and a series of recommendations based on analysis of recent state experiences. Our recommendations are summarized.

  7. POSSIBILITIES OF CREATIVE URBAN DEVELOPMENT AND CREATIVE FUTURE OF BUDAPEST ACCORDING TO THE NEW PROGRAMMING REGULATIONS AND DOCUMENTS

    OpenAIRE

    Szilágyi, Anna

    2013-01-01

    In the next programming period, starting in 2014, European cities face the challenge to become SMART cities focusing on sustainability, competitiveness and liveability. Does culture play a key role in this process, and if so, is the European Union aware of its importance? Do programming documents for the next period for Budapest express a recognizable will of the decision makers to transform the city to a Central-European creative capital? In my study, I examine the concepts and regulations o...

  8. Senescence-associated barley NAC (NAM, ATAF1,2, CUC) transcription factor interacts with radical-induced cell death 1 through a disordered regulatory domain

    DEFF Research Database (Denmark)

    Kjaersgaard, Trine; Jensen, Michael K; Christiansen, Michael W

    2011-01-01

    as a transcriptional activator suggesting that an involvement of HvNAC013 and HvNAC005 in senescence will be different. HvNAC013 interacted with barley radical-induced cell death 1 (RCD1) via the very C-terminal part of its TRD, outside of the region containing the LP motif. No significant secondary structure...... (NAM, ATAF1,2, CUC) TF family are up-regulated during senescence in barley (Hordeum vulgare). Both HvNAC005 and HvNAC013 bound the conserved NAC DNA target sequence. Computational and biophysical analyses showed that both proteins are intrinsically disordered in their large C-terminal domains, which...... was induced in the HvNAC013 TRD upon interaction with RCD1. RCD1 also interacted with regions dominated by intrinsic disorder in TFs of the MYB and basic helix-loop-helix families. We propose that RCD1 is a regulatory protein capable of interacting with many different TFs by exploiting their intrinsic...

  9. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  10. 28 CFR 30.6 - What procedures apply to the selection of programs and activities under these regulations?

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false What procedures apply to the selection of programs and activities under these regulations? 30.6 Section 30.6 Judicial Administration DEPARTMENT OF... consult with local elected officials. (b) Each state that adopts a process shall notify the Attorney...

  11. Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus

    Science.gov (United States)

    The transcription factor steroidogenic factor 1 (SF-1) is exclusively expressed in the brain in the ventral medial hypothalamic nucleus (VMH) and is required for the development of this nucleus. However, the physiological importance of transcriptional programs regulated by SF-1 in the VMH is not wel...

  12. Generic concept to program the time domain of self-assemblies with a self-regulation mechanism.

    Science.gov (United States)

    Heuser, Thomas; Steppert, Ann-Kathrin; Lopez, Catalina Molano; Zhu, Baolei; Walther, Andreas

    2015-04-08

    Nature regulates complex structures in space and time via feedback loops, kinetically controlled transformations, and under energy dissipation to allow non-equilibrium processes. Although man-made static self-assemblies realize excellent control over hierarchical structures via molecular programming, managing their temporal destiny by self-regulation is a largely unsolved challenge. Herein, we introduce a generic concept to control the time domain by programming the lifetimes of switchable self-assemblies in closed systems. We conceive dormant deactivators that, in combination with fast promoters, enable a unique kinetic balance to establish an autonomously self-regulating, transient pH-state, whose duration can be programmed over orders of magnitude-from minutes to days. Coupling this non-equilibrium state to pH-switchable self-assemblies allows predicting their assembly/disassembly fate in time, similar to a precise self-destruction mechanism. We demonstrate a platform approach by programming self-assembly lifetimes of block copolymers, nanoparticles, and peptides, enabling dynamic materials with a self-regulation functionality.

  13. The Abbott School Construction Program: Report on the NJ Department of Education Proposed Regulations on Long-Range Facilities Plans

    Science.gov (United States)

    Ponessa, Joan

    2004-01-01

    This report on Long Range Facilities Plans (LRFPs) analyzes regulations proposed by the New Jersey Department of Education (NJDOE) to implement the Educational Facilities Construction and Financing Act. (EFCFA). EFCFA, which authorizes and governs New Jersey's public school construction program, was enacted in July 2000 to implement the State…

  14. Adaptive dynamic programming for discrete-time linear quadratic regulation based on multirate generalised policy iteration

    Science.gov (United States)

    Chun, Tae Yoon; Lee, Jae Young; Park, Jin Bae; Choi, Yoon Ho

    2018-06-01

    In this paper, we propose two multirate generalised policy iteration (GPI) algorithms applied to discrete-time linear quadratic regulation problems. The proposed algorithms are extensions of the existing GPI algorithm that consists of the approximate policy evaluation and policy improvement steps. The two proposed schemes, named heuristic dynamic programming (HDP) and dual HDP (DHP), based on multirate GPI, use multi-step estimation (M-step Bellman equation) at the approximate policy evaluation step for estimating the value function and its gradient called costate, respectively. Then, we show that these two methods with the same update horizon can be considered equivalent in the iteration domain. Furthermore, monotonically increasing and decreasing convergences, so called value iteration (VI)-mode and policy iteration (PI)-mode convergences, are proved to hold for the proposed multirate GPIs. Further, general convergence properties in terms of eigenvalues are also studied. The data-driven online implementation methods for the proposed HDP and DHP are demonstrated and finally, we present the results of numerical simulations performed to verify the effectiveness of the proposed methods.

  15. Adaptive temperature regulation in the little bird in winter: predictions from a stochastic dynamic programming model.

    Science.gov (United States)

    Brodin, Anders; Nilsson, Jan-Åke; Nord, Andreas

    2017-09-01

    Several species of small birds are resident in boreal forests where environmental temperatures can be -20 to -30 °C, or even lower, in winter. As winter days are short, and food is scarce, winter survival is a challenge for small endothermic animals. A bird of this size will have to gain almost 10% of its lean body mass in fat every day to sustain overnight metabolism. Birds such as parids (titmice and chickadees) can use facultative hypothermia, a process in which body temperature is actively down-regulated to a specific level, to reduce heat loss and thus save energy. During cold winter nights, these birds may decrease body temperature from the normal from 42 ° down to 35 °C, or even lower in some species. However, birds are unable to move in this deep hypothermic state, making it a risky strategy if predators are around. Why, then, do small northern birds enter a potentially dangerous physiological state for a relatively small reduction in energy expenditure? We used stochastic dynamic programming to investigate this. Our model suggests that the use of nocturnal hypothermia at night is paramount in these biomes, as it would increase winter survival for a small northern bird by 58% over a winter of 100 days. Our model also explains the phenomenon known as winter fattening, and its relationship to thermoregulation, in northern birds.

  16. Developmental programming: impact of prenatal testosterone excess on pre- and postnatal gonadotropin regulation in sheep.

    Science.gov (United States)

    Manikkam, Mohan; Thompson, Robert C; Herkimer, Carol; Welch, Kathleen B; Flak, Jonathan; Karsch, Fred J; Padmanabhan, Vasantha

    2008-04-01

    The goal of this study was to explore mechanisms that mediate hypersecretion of LH and progressive loss of cyclicity in female sheep exposed during fetal life to excess testosterone. Our working hypothesis was that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH (but not FSH) secretion and, thus, hypersecretion of LH in adulthood, and that this results from altered developmental gene expression of GnRH and estradiol (E2) receptors, gonadotropin subunits, and paracrine factors that differentially regulate LH and FSH synthesis. We observed that, relative to controls, females exposed during fetal life to excess testosterone, as well as the nor-aromatizable androgen dihydrotestosterone, exhibited enhanced LH but not FSH responses to intermittent delivery of GnRH boluses under conditions in which endogenous LH (GnRH) pulses were suppressed. Luteinizing hormone hypersecretion was more evident in adults than in prepubertal females, and it was associated with development of acyclicity. Measurement of pituitary mRNA concentrations revealed that prenatal testosterone excess induced developmental changes in gene expression of pituitary GnRH and E2 receptors and paracrine modulators of LH and FSH synthesis in a manner consistent with subsequent amplification of LH release. Together, this series of studies suggests that prenatal testosterone excess, by its androgenic action, amplifies GnRH-induced LH response, leading to LH hypersecretion and acyclicity in adulthood, and that this programming involves developmental changes in expression of pituitary genes involved in LH and FSH release.

  17. Role of a Transcriptional Regulator in Programmed Cell Death and Plant Development

    Energy Technology Data Exchange (ETDEWEB)

    Julie M. Stone

    2008-09-13

    The long-term goal of this research is to understand the role(s) and molecular mechanisms of programmed cell death (PCD) in the controlling plant growth, development and responses to biotic and abiotic stress. We developed a genetic selection scheme to identify A. thaliana FB1-resistant (fbr) mutants as a way to find genes involved in PCD (Stone et al., 2000; Stone et al., 2005; Khan and Stone, 2008). The disrupted gene in fbr6 (AtSPL14) responsible for the FB1-insensitivity and plant architecture phenotypes encodes a plant-specific SBP DNA-binding domain transcriptional regulator (Stone et al., 2005; Liang et al., 2008). This research plan is designed to fill gaps in the knowledge about the role of SPL14 in plant growth and development. The work is being guided by three objectives aimed at determining the pathways in which SPL14 functions to modulate PCD and/or plant development: (1) determine how SPL14 functions in plant development, (2) identify target genes that are directly regulated by SPL14, and (3) identify SPL14 modifications and interacting proteins. We made significant progress during the funding period. Briefly, some major accomplishments are highlighted below: (1) To identify potential AtSPL14 target genes, we identified a consensus DNA binding site for the AtSPL14 SBP DNA-binding domain using systematic evolution of ligands by exponential selection (SELEX) and site-directed mutagenesis (Liang et al., 2008). This consensus binding site was used to analyze Affymetrix microarray gene expression data obtained from wild-type and fbr6 mutant plants to find possible AtSPL14-regulated genes. These candidate AtSPL14-regulated genes are providing new information on the molecular mechanisms linking plant PCD and plant development through modulation of the 26S proteasome. (2) Transgenic plants expressing epitope-tagged versions of AtSPL14 are being used to confirm the AtSPL14 targets (by ChIP-PCR) and further dissect the molecular interactions (Nazarenus, Liang

  18. Flipped Classroom with Problem Based Activities: Exploring Self-Regulated Learning in a Programming Language Course

    Science.gov (United States)

    Çakiroglu, Ünal; Öztürk, Mücahit

    2017-01-01

    This study intended to explore the development of self-regulation in a flipped classroom setting. Problem based learning activities were carried out in flipped classrooms to promote self-regulation. A total of 30 undergraduate students from Mechatronic department participated in the study. Self-regulation skills were discussed through students'…

  19. How Does Self-Regulation Affect Computer-Programming Achievement in a Blended Context?

    Science.gov (United States)

    Cigdem, Harun

    2015-01-01

    This study focuses on learners' self-regulation which is one of the essential skills for student achievement in blended courses. Research on learners' self-regulation skills in blended learning environments has gained popularity in recent years however only a few studies investigating the correlation between self-regulation skills and student…

  20. Loose regulation of medical marijuana programs associated with higher rates of adult marijuana use but not cannabis use disorder.

    Science.gov (United States)

    Williams, Arthur Robin; Santaella-Tenorio, Julian; Mauro, Christine M; Levin, Frances R; Martins, Silvia S

    2017-11-01

    Most US states have passed medical marijuana laws (MMLs), with great variation in program regulation impacting enrollment rates. We aimed to compare changes in rates of marijuana use, heavy use and cannabis use disorder across age groups while accounting for whether states enacted medicalized (highly regulated) or non-medical mml programs. Difference-in-differences estimates with time-varying state-level MML coded by program type (medicalized versus non-medical). Multi-level linear regression models adjusted for state-level random effects and covariates as well as historical trends in use. Nation-wide cross-sectional survey data from the US National Survey of Drug Use and Health (NSDUH) restricted use data portal aggregated at the state level. Participants comprised 2004-13 NSDUH respondents (n ~ 67 500/year); age groups 12-17, 18-25 and 26+ years. States had implemented eight medicalized and 15 non-medical MML programs. Primary outcome measures included (1) active (past-month) marijuana use; (2) heavy use (> 300 days/year); and (3) cannabis use disorder diagnosis, based on DSM-IV criteria. Covariates included program type, age group and state-level characteristics throughout the study period. Adults 26+ years of age living in states with non-medical MML programs increased past-month marijuana use 1.46% (from 4.13 to 6.59%, P = 0.01), skewing towards greater heavy marijuana by 2.36% (from 14.94 to 17.30, P = 0.09) after MMLs were enacted. However, no associated increase in the prevalence of cannabis use disorder was found during the study period. Our findings do not show increases in prevalence of marijuana use among adults in states with medicalized MML programs. Additionally, there were no increases in adolescent or young adult marijuana outcomes following MML passage, irrespective of program type. Non-medical marijuana laws enacted in US states are associated with increased marijuana use, but only among adults aged 26+ years. Researchers and

  1. Implementation of training programs in self-regulated learning strategies in Moodle format: results of a experience in higher education.

    Science.gov (United States)

    Núñez, José Carlos; Cerezo, Rebeca; Bernardo, Ana; Rosário, Pedro; Valle, Antonio; Fernández, Estrella; Suárez, Natalia

    2011-04-01

    This paper tests the efficacy of an intervention program in virtual format intended to train studying and self-regulation strategies in university students. The aim of this intervention is to promote a series of strategies which allow students to manage their learning processes in a more proficient and autonomous way. The program has been developed in Moodle format and hosted by the Virtual Campus of the University of Oviedo. The present study had a semi-experimental design, included an experimental group (n=167) and a control one (n=206), and used pretest and posttest measures (self-regulated learning strategies' declarative knowledge, self-regulated learning macro-strategy planning-execution-assessment, self-regulated learning strategies on text, surface and deep learning approaches, and academic achievement). Data suggest that the students enrolled in the training program, comparing with students in the control group, showed a significant improvement in their declarative knowledge, general and on text use of learning strategies, increased their deep approach to learning, decreased their use of a surface approach and, in what concerns to academic achievement, statistically significant differences have been found in favour of the experimental group.

  2. Pbx and Prdm1a transcription factors differentially regulate subsets of the fast skeletal muscle program in zebrafish

    Directory of Open Access Journals (Sweden)

    Zizhen Yao

    2013-04-01

    The basic helix–loop–helix factor Myod initiates skeletal muscle differentiation by directly and sequentially activating sets of muscle differentiation genes, including those encoding muscle contractile proteins. We hypothesize that Pbx homeodomain proteins direct Myod to a subset of its transcriptional targets, in particular fast-twitch muscle differentiation genes, thereby regulating the competence of muscle precursor cells to differentiate. We have previously shown that Pbx proteins bind with Myod on the promoter of the zebrafish fast muscle gene mylpfa and that Pbx proteins are required for Myod to activate mylpfa expression and the fast-twitch muscle-specific differentiation program in zebrafish embryos. Here we have investigated the interactions of Pbx with another muscle fiber-type regulator, Prdm1a, a SET-domain DNA-binding factor that directly represses mylpfa expression and fast muscle differentiation. The prdm1a mutant phenotype, early and increased fast muscle differentiation, is the opposite of the Pbx-null phenotype, delayed and reduced fast muscle differentiation. To determine whether Pbx and Prdm1a have opposing activities on a common set of genes, we used RNA-seq analysis to globally assess gene expression in zebrafish embryos with single- and double-losses-of-function for Pbx and Prdm1a. We find that the levels of expression of certain fast muscle genes are increased or approximately wild type in pbx2/4-MO;prdm1a−/− embryos, suggesting that Pbx activity normally counters the repressive action of Prdm1a for a subset of the fast muscle program. However, other fast muscle genes require Pbx but are not regulated by Prdm1a. Thus, our findings reveal that subsets of the fast muscle program are differentially regulated by Pbx and Prdm1a. Our findings provide an example of how Pbx homeodomain proteins act in a balance with other transcription factors to regulate subsets of a cellular differentiation program.

  3. 40 CFR 122.32 - As an operator of a small MS4, am I regulated under the NPDES storm water program?

    Science.gov (United States)

    2010-07-01

    ... regulated under the NPDES storm water program? 122.32 Section 122.32 Protection of Environment ENVIRONMENTAL... operator of a small MS4, am I regulated under the NPDES storm water program? (a) Unless you qualify for a... a petition to the NPDES permitting authority to require an NPDES permit for your discharge of storm...

  4. Regulations Pertaining to Section 8 of Chapter 636 of the Acts of 1974, Regarding Magnet School Facilities (Subsection 37I), and Magnet Educational Programs (Subsection 37J).

    Science.gov (United States)

    Massachusetts State Dept. of Education, Boston.

    Racial balance is the primary goal of the regulations presented in this document. For the purpose of expending funds under these regulations, the terms "magnet school facilities" and "magnet educational program" are defined and school eligibility requirements are listed. Program requirements are also listed along with proposals…

  5. 34 CFR 400.2 - What programs are governed by these regulations?

    Science.gov (United States)

    2010-07-01

    ... for Gifted and Talented Vocational Education Students Program (34 CFR part 419). (16) Business and... Institutions (34 CFR part 422). (18) Vocational Education Dropout Prevention Program (34 CFR part 423). (19...

  6. [Effects of an Integrated Internet Addiction Prevention Program on Elementary Students' Self-regulation and Internet Addiction].

    Science.gov (United States)

    Mun, So Youn; Lee, Byoung Sook

    2015-04-01

    The purpose of this study was to develop an integrated internet addiction prevention program and test its effects on the self-regulation and internet addiction of elementary students who are at risk for internet addiction. A quasi-experimental study with a nonequivalent control group pretest-posttest design was used. Participants were assigned to the experimental group (n=28) or control group (n=28). Contents of the program developed in this study included provision of information about internet addiction, interventions for empowerment and methods of behavioral modification. A pre-test and two post-tests were done to identify the effects of the program and their continuity. Effects were testified using Repeated measures ANOVA, simple effect analysis, and Time Contrast. The self-regulation of the experimental group after the program was significantly higher than the control group. The score for internet addiction self-diagnosis and the internet use time in the experimental group were significantly lower than the control group. The effects of the integrated internet addiction prevention program for preventing internet addiction in elementary students at risk for internet addiction were validated.

  7. 34 CFR 655.3 - What regulations apply to the International Education Programs?

    Science.gov (United States)

    2010-07-01

    ... Foreign Language and Area Studies or Foreign Language and International Studies); (2) 34 CFR part 657 (Foreign Language and Area Studies Fellowships Program); (3) 34 CFR part 658 (Undergraduate International Studies and Foreign Language Program); (4) 34 CFR part 660 (International Research and Studies Program...

  8. 75 FR 82567 - Federal Acquisition Regulation; Repeal of the Small Business Competitiveness Demonstration Program

    Science.gov (United States)

    2010-12-30

    ... Competitiveness Demonstration Program AGENCY: Department of Defense (DoD), General Services Administration (GSA... of the Small Business Competitiveness Demonstration Program, to meet the requirements of section 1335... (15 U.S.C. 644 note), the Small Business Competitiveness Demonstration Program. In accordance with the...

  9. Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment

    OpenAIRE

    Kong, Wei; Wanda, Soo-Young; Zhang, Xin; Bollen, Wendy; Tinge, Steven A.; Roland, Kenneth L.; Curtiss, Roy

    2008-01-01

    We have devised and constructed a biological containment system designed to cause programmed bacterial cell lysis with no survivors. We have validated this system, using Salmonella enterica serovar Typhimurium vaccines for antigen delivery after colonization of host lymphoid tissues. The system is composed of two parts. The first component is Salmonella typhimurium strain χ8937, with deletions of asdA and arabinose-regulated expression of murA, two genes required for peptidoglycan synthesis a...

  10. Developmental programming of energy balance regulation: Is physical activity more "programmable" than food intake

    Science.gov (United States)

    Extensive human and animal model data show that environmental influences during critical periods of prenatal and early postnatal development can cause persistent alterations in energy balance regulation. Although a potentially important factor in the worldwide obesity epidemic, the fundamental mecha...

  11. 76 FR 79485 - Interstate Land Sales Registration Program (Regulations J, K, and L)

    Science.gov (United States)

    2011-12-21

    ... Secretary's consumer protection functions relating to ILSA.\\2\\ Accordingly, effective July 21, 2011, the... Vol. 76 Wednesday, No. 245 December 21, 2011 Part VII Bureau of Consumer Financial Protection 12... Regulations#0;#0; [[Page 79486

  12. 77 FR 76215 - Small Business Size Regulations, Small Business Innovation Research (SBIR) Program and Small...

    Science.gov (United States)

    2012-12-27

    ... overall goal of simplification and maximization of benefits for small businesses, SBA proposed amendments... franchisee. F. Section 121.704--When SBA Determines Size and Eligibility SBA's proposed regulations for the...

  13. 77 FR 43080 - Federal Acquisition Regulation; Information Collection; Make-or-Buy Program

    Science.gov (United States)

    2012-07-23

    ... by make-or-buy decisions under certain Government prime contracts. Accordingly, FAR 15.407-2, Make-or...; Information Collection; Make-or- Buy Program AGENCIES: Department of Defense (DOD), General Services... requirement concerning Make- or-Buy Program. Public comments are particularly invited on: Whether this...

  14. 78 FR 31552 - Federal Acquisition Regulation; Submission for OMB Review; Make-or-Buy Program

    Science.gov (United States)

    2013-05-24

    ... socio-economic policies may be affected by make-or-buy decisions under certain Government prime...; Submission for OMB Review; Make- or-Buy Program AGENCIES: Department of Defense (DOD), General Services... collection requirement concerning the Make-or-Buy Program. A notice was published in the Federal Register at...

  15. Ecological effects of a long-term flood program in a flow-regulated river

    Directory of Open Access Journals (Sweden)

    Sabine Mannes

    2009-03-01

    Full Text Available Le régime hydrologique naturel de la grande majorité des rivières du globe a été modifié par une régulation artificielle, qui a profondément affecté la morphologie fluviale et la vie aquatique. L’intégration de critères hydrologiques comme le débit et la température dans les programmes de restauration constitue une étape importante pour la gestion de rivière. Cet article synthétise les observations, en terme de qualité physicochimique de l’eau et de biocénose aquatique, des effets d’une programmation de crues sur le long terme (15 crues artificielles en huit ans sur la rivière Spöl, dans le Parc National Suisse. Du fait des lâchers d’eau hypolimnétiques (issues des eaux profondes, ces crues ont peu d’impact sur les paramètres physiques et chimiques. La biomasse du périphyton a été réduite par les premières crues, puis s’est maintenue à des niveaux faibles pendant toute la période étudiée. La richesse spécifique, la biomasse et la densité de macro-invertébrés ont aussi été significativement réduites, et l’association de macroinvertébrés a évolué vers des taxons plus résistants aux perturbations. La qualité des habitats piscicoles, en particulier pour les zones de frai, a été sensiblement améliorée par les inondations. Une analyse plus approfondie a montré que la réponse de la biocénose à des crues d’ampleur similaire a changé pendant la période d’étude en parallèle avec la modification de la composition des associations biotiques.The natural flow regime of many rivers on the globe has been altered by regulation, strongly influencing river morphology and aquatic biota. The incorporation of regimebased criteria such as flow and temperature regimes in restoration plans is an important step in river management. This paper summarizes the effects of a long-term flood program (15 floods over 8 years on the river Spöl, Swiss National Park, on water physico-chemistry and river

  16. c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses

    Directory of Open Access Journals (Sweden)

    Dana Piovesan

    2017-04-01

    Full Text Available Summary: Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses. Enhanced expression of T-bet resulted in aberrant plasma cell differentiation within the germinal center, mediated by CXCR3 expression. These findings identify a dual role for c-Myb in limiting inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Identifying such intrinsic regulators of specialized antibody responses can assist in vaccine design and therapeutic intervention in B-cell-mediated immune disorders. : Piovesan et al. examine how B cells establish transcriptional programs that result in tailored responses to invading pathogens. The authors find that the transcription factor c-Myb represses the T-bet-mediated anti-viral program in B cells. c-Myb limits inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Keywords: B cells, c-Myb, T-bet, immunoglobulin, CXCR3, plasma cell, germinal center

  17. Quality Managment Program (QMP) report: A review of quality management programs developed in response to Title 10, Section 35.32 of the Code of Federal Regulations

    Energy Technology Data Exchange (ETDEWEB)

    Witte, M.C.

    1994-10-01

    In July of 1991, the Nuclear Regulatory Commission published a Final Rule in the Federal Register amending regulations governing medical therapeutic administrations of byproduct material and certain uses of radioactive sodium iodide. These amendments required implementation of a Quality Management Program (QMP) to provide high confidence that the byproduct material -- or radiation from byproduct material -- will be administered as directed by an authorized user physician. Herein, this rule is referred to as the QM rule. The Final Rule was published after two proposed rules had been published in the Federal Register.

  18. The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells

    Science.gov (United States)

    Labrecque, Mark P.; Takhar, Mandeep K.; Nason, Rebecca; Santacruz, Stephanie; Tam, Kevin J.; Massah, Shabnam; Haegert, Anne; Bell, Robert H.; Altamirano-Dimas, Manuel; Collins, Colin C.; Lee, Frank J.S.; Prefontaine, Gratien G.; Cox, Michael E.; Beischlag, Timothy V.

    2016-01-01

    Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1α and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1. In this report, we further characterized the role Rb plays in mediating hypoxia-regulated genetic programs by stably ablating Rb expression with retrovirally-introduced short hairpin RNA in LNCaP and 22Rv1 human prostate cancer cells. DNA microarray analysis revealed that loss of Rb in conjunction with hypoxia leads to aberrant expression of hypoxia-regulated genetic programs that increase cell invasion and promote neuroendocrine differentiation. For the first time, we have established a direct link between hypoxic tumor environments, Rb inactivation and progression to late stage metastatic neuroendocrine prostate cancer. Understanding the molecular pathways responsible for progression of benign prostate tumors to metastasized and lethal forms will aid in the development of more effective prostate cancer therapies. PMID:27015368

  19. Toxicity regulation of radioactive liquid waste effluent from CANDU stations - lessons from Ontario's MISA program

    International Nuclear Information System (INIS)

    Rodgers, D.W.

    2009-01-01

    Toxicity testing became an issue for Ontario's CANDU stations, when it was required under Ontario's MISA regulations for the Electricity Generation Sector. In initial tests, radioactive liquid waste (RLW) effluent was intermittently toxic to both rainbow trout and Daphnia. Significant differences in RLW toxicity were apparent among stations and contributing streams. Specific treatment systems were designed for three stations, with the fourth electing to use existing treatment systems. Stations now use a combination of chemical analysis and treatment to regulate RLW toxicity. Studies of Ontario CANDU stations provide a basis for minimizing costs and environmental effects of new nuclear stations. (author)

  20. Self-regulated learning in higher education: strategies adopted by computer programming students when supported by the SimProgramming approach

    Directory of Open Access Journals (Sweden)

    Daniela Pedrosa

    Full Text Available Abstract The goal of the SimProgramming approach is to help students overcome their learning difficulties in the transition from entry-level to advanced computer programming, developing an appropriate set of learning strategies. We implemented it at the University of Trás-os-Montes e Alto Douro (Portugal, in two courses (PM3 and PM4 of the bachelor programmes in Informatics Engineering and ICT. We conducted semi-structured interviews with students (n=38 at the end of the courses, to identify the students’ strategies for self-regulation of learning in the assignment. We found that students changed some of their strategies from one course edition to the following one and that changes are related to the SimProgramming approach. We believe that changes to the educational approach were appropriate to support the assignment goals. We recommend applying the SimProgramming approach in other educational contexts, to improve educational practices by including techniques to help students in their learning.

  1. Chloroplasts activity and PAP-signaling regulate programmed cell death in Arabidopsis

    KAUST Repository

    Bruggeman, Quentin; Mazubert, Christelle; Prunier, Florence; Lugan, Raphael; Chan, Kai Xun; Phua, Su Yin; Pogson, Barry J.; Krieger-Liszkay, Anja; Delarue, Marianne; Benhamed, Moussa; Bergounioux, Catherine; Raynaud, Cé cile

    2016-01-01

    Programmed cell death (PCD) is a crucial process both for plant development and responses to biotic and abiotic stress. There is accumulating evidence that chloroplasts may play a central role during plant PCD as for mitochondria in animal cells

  2. CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart

    NARCIS (Netherlands)

    M. Gomez-Velazquez (Melisa); C. Badia-Careaga (Claudio); Lechuga-Vieco, A.V. (Ana Victoria); Nieto-Arellano, R. (Rocio); Tena, J.J. (Juan J.); Rollan, I. (Isabel); Alvarez, A. (Alba); Torroja, C. (Carlos); Caceres, E.F. (Eva F.); Roy, A. (Anna); N.J. Galjart (Niels); Delgado-Olguin, P. (Paul); F. Sánchez-Cabo (Fátima); Enriquez, J.A. (Jose Antonio); Gomez-Skarmeta, J.L. (Jose Luis); M. Manzanares (Miguel)

    2017-01-01

    textabstractCardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such

  3. Regulation and perceived compliance: Nonpoint pollution reduction programs in four states

    International Nuclear Information System (INIS)

    Floyd, D.W.; MacLeod, M.A.

    1993-01-01

    Examining nonpoint-source water pollution programs in foresty is one way of looking at the complicated policy questions of striking a balance between voluntary and regulatory approaches to forest management on private lands. States have developed a variety of approaches in this area from completely voluntary to highly regulatory to archeive compliance. This article looks at several aspects: federal requirements, program types, predictive behavior theories, and specific state programs (Ohio, West Virginia, Maryland, Massachusetts). The study results indicate a significant difference in preceived compliance based on program type: as stringency increases, perceived compliance increases. The authors suggest that successful forestry nonpoint source water pollution reduction plans should combine regulatory and educational elements. 16 refs., 3 tabs

  4. Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs.

    Science.gov (United States)

    Spiegel, Ivo; Mardinly, Alan R; Gabel, Harrison W; Bazinet, Jeremy E; Couch, Cameron H; Tzeng, Christopher P; Harmin, David A; Greenberg, Michael E

    2014-05-22

    The nervous system adapts to experience by inducing a transcriptional program that controls important aspects of synaptic plasticity. Although the molecular mechanisms of experience-dependent plasticity are well characterized in excitatory neurons, the mechanisms that regulate this process in inhibitory neurons are only poorly understood. Here, we describe a transcriptional program that is induced by neuronal activity in inhibitory neurons. We find that, while neuronal activity induces expression of early-response transcription factors such as Npas4 in both excitatory and inhibitory neurons, Npas4 activates distinct programs of late-response genes in inhibitory and excitatory neurons. These late-response genes differentially regulate synaptic input to these two types of neurons, promoting inhibition onto excitatory neurons while inducing excitation onto inhibitory neurons. These findings suggest that the functional outcomes of activity-induced transcriptional responses are adapted in a cell-type-specific manner to achieve a circuit-wide homeostatic response. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Down-regulation of E protein activity augments an ILC2 differentiation program in the thymus

    Science.gov (United States)

    Innate lymphoid cells (ILCs) are important regulators in various immune responses. Current paradigm states that all newly-made ILCs originate from common lymphoid progenitors (CLP) in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation. Une...

  6. 75 FR 26025 - Regulation of Fuels and Fuel Additives: Modifications to Renewable Fuel Standard Program

    Science.gov (United States)

    2010-05-10

    ... technologies, we have created new definitions for membrane separation and raw starch hydrolysis. We also... technical errors and areas within the final RFS2 regulations that could benefit from clarification or... benefit from clarification or modification. As a result, we are making the following amendments to the...

  7. Financial Sector Assessment Program : Malaysia - IOSCO Objectives and Principles of Securities Regulation

    OpenAIRE

    World Bank; International Monetary Fund

    2013-01-01

    The Securities Commission Malaysia (SC), as the supervisor of the capital markets, has developed a robust supervisory framework that exhibits high levels of implementation of the International Organization of Securities Commissions Objectives and Principles of Securities Regulation (IOSCO Principles) in most areas. The SC's independence will be buttressed by some changes to the legal provi...

  8. 77 FR 28786 - Disaster Assistance; Crisis Counseling Regular Program; Amendment to Regulation

    Science.gov (United States)

    2012-05-16

    ... (54 FR 11610) which reorganized its crisis counseling regulations for the reader's convenience, and... amounts because the incident date starts before the declaration date for almost all disasters. Under the... (RFA), 5 U.S.C. 601-612, as amended by the Small Business Regulatory Enforcement Fairness Act of 1996...

  9. E2F1-Mediated Induction of NFYB Attenuates Apoptosis via Joint Regulation of a Pro-Survival Transcriptional Program.

    Directory of Open Access Journals (Sweden)

    Xiaolei Jiang

    Full Text Available The E2F1 transcription factor regulates cell proliferation and apoptosis through the control of a considerable variety of target genes. Previous work has detailed the role of other transcription factors in mediating the specificity of E2F function. Here we identify the NF-YB transcription factor as a novel direct E2F1 target. Genome-wide expression analysis of the effects of NFYB knockdown on E2F1-mediated transcription identified a large group of genes that are co-regulated by E2F1 and NFYB. We also provide evidence that knockdown of NFYB enhances E2F1-induced apoptosis, suggesting a pro-survival function of the NFYB/E2F1 joint transcriptional program. Bioinformatic analysis suggests that deregulation of these NFY-dependent E2F1 target genes might play a role in sarcomagenesis as well as drug resistance.

  10. A non-linear programming approach to the computer-aided design of regulators using a linear-quadratic formulation

    Science.gov (United States)

    Fleming, P.

    1985-01-01

    A design technique is proposed for linear regulators in which a feedback controller of fixed structure is chosen to minimize an integral quadratic objective function subject to the satisfaction of integral quadratic constraint functions. Application of a non-linear programming algorithm to this mathematically tractable formulation results in an efficient and useful computer-aided design tool. Particular attention is paid to computational efficiency and various recommendations are made. Two design examples illustrate the flexibility of the approach and highlight the special insight afforded to the designer.

  11. 78 FR 21861 - Tribal Consultation on the Draft Regulations Governing the Tribal Transportation Program

    Science.gov (United States)

    2013-04-12

    ... Welcome and Introductions. 9:15 a.m.-9:30 a.m Brief history of 25 CFR part 170 and process for updating... following dates, at the following locations: Meeting date Location Time May 14, 2013 Anchorage, AK 9 a.m.-4... result of the enactment of SAFETEA-LU but the regulation was not revised at that time. MAP-21 effectively...

  12. miR-150-Mediated Foxo1 Regulation Programs CD8+ T Cell Differentiation.

    Science.gov (United States)

    Ban, Young Ho; Oh, Se-Chan; Seo, Sang-Hwan; Kim, Seok-Min; Choi, In-Pyo; Greenberg, Philip D; Chang, Jun; Kim, Tae-Don; Ha, Sang-Jun

    2017-09-12

    MicroRNA (miR)-150 is a developmental regulator of several immune-cell types, but its role in CD8 + T cells is largely unexplored. Here, we show that miR-150 regulates the generation of memory CD8 + T cells. After acute virus infection, miR-150 knockout (KO) mice exhibited an accelerated differentiation of CD8 + T cells into memory cells and improved production of effector cytokines. Additionally, miR-150 KO CD8 + T cells displayed an enhanced recall response and improved protection against infections with another virus and bacteria. We found that forkhead box O1 (Foxo1) and T cell-specific transcription factor 1 (TCF1) are upregulated during the early activation phase in miR-150 KO CD8 + T cells and that miR-150 directly targets and suppresses Foxo1. These results suggest that miR-150-mediated suppression of Foxo1 regulates the balance between effector and memory cell differentiation, which might aid in the development of improved vaccines and T cell therapeutics. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Regulation through revelation: the origin, politics, and impacts of the Toxics Release Inventory Program

    National Research Council Canada - National Science Library

    Hamilton, James

    2005-01-01

    ... of the TRI from its origin and implementation to its revision and retrenchment. The mix of case study and quantitative analysis shows how the TRI operates and how the information provided affects decisions in both the public and private sectors. The lessons drawn about the operation of information provision programs should be of interest to multiple audi...

  14. Grade Level Effects of the Incredible Years Teacher Training Program on Emotion Regulation and Attention

    Science.gov (United States)

    Murray, Desiree W.; Rabiner, David L.; Carrig, Madeline M.

    2014-01-01

    Professional development for teachers has historically been fairly didactic in nature (Garet et al., 2001; Rose & Church, 1998), which is believed to limit effectiveness and translation to teacher practice change (Fixsen, Naoom, Blase, Friedman, & Wallace, 2005). One well-established program with a more active, collaborative training…

  15. 7 CFR 4290.1940 - Integration of this part with other regulations applicable to USDA's programs.

    Science.gov (United States)

    2010-01-01

    ... Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Miscellaneous § 4290.1940 Integration of this... extent applicable to this part, the Secretary will comply with subpart D of 7 CFR part 1900 and RD...

  16. 77 FR 14303 - Federal Acquisition Regulation; Women-Owned Small Business (WOSB) Program

    Science.gov (United States)

    2012-03-09

    ... Economically Disadvantaged Women-Owned Small Business (EDWOSB) Concerns (APR 2012) (15 U.S.C. 637(m)).'' 4. On...: ``(25) 52.219-30, Notice of Set-Aside for Women-Owned Small Business (WOSB) Concerns Eligible Under the... Business Concerns Eligible Under the Women-Owned Small Business Program (APR 2012)'' [FR Doc. C1-2012-4475...

  17. 42 CFR 65a.1 - To what programs do these regulations apply?

    Science.gov (United States)

    2010-10-01

    ... (see parts 63 and 64a of this chapter), or (4) Research training support under the NIH AIDS Research..., INTERNSHIPS, TRAINING NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES HAZARDOUS SUBSTANCES BASIC RESEARCH... part apply to the award of grants to support programs for basic research and training directed towards...

  18. 75 FR 79964 - Regulation of Fuels and Fuel Additives: Modifications to Renewable Fuel Standard Program

    Science.gov (United States)

    2010-12-21

    ... renewable fuel facility to be considered biogas for purposes of Table 1 to Sec. 80.1426; --Sec. 80.1452(b... explained that many developers of ethanol facilities, including their own, sought to obtain construction permits without going through EPA's New Source Review (NSR) program, and were able to do so by obtaining...

  19. Actions and Achievements of Self-Regulated Learning in Personal Environments. Research on Students Participating in the Graduate Program in Preschool Education at the University of Granada

    Science.gov (United States)

    Chaves-Barboza, Eduardo; Trujillo-Torres, Juan Manuel; López-Núñez, Juan Antonio; Sola-Martínez, Tomás

    2017-01-01

    This paper is intended to study the self-regulated learning (SRL) process in personal learning environments (PLEs) among students participating in the Graduate Program for Preschool Education at the University of Granada (Spain). The study is focused on self-regulatory actions carried out by students, and on their self-regulated learning…

  20. Mating Disruption as a Suppression Tactic in Programs Targeting Regulated Lepidopteran Pests in US.

    Science.gov (United States)

    Lance, David R; Leonard, Donna S; Mastro, Victor C; Walters, Michelle L

    2016-07-01

    Mating disruption, the broadcast application of sex-attractant pheromone to reduce the ability of insects to locate mates, has proven to be an effective method for suppressing populations of numerous moth pests. Since the conception of mating disruption, the species-specificity and low toxicity of pheromone applications has led to their consideration for use in area-wide programs to manage invasive moths. Case histories are presented for four such programs where the tactic was used in the United States: Pectinophora gossypiella (pink bollworm), Lymantria dispar (gypsy moth), Epiphyas postvittana (light brown apple moth), and Lobesia botrana (European grapevine moth). Use of mating disruption against P. gossypiella and L. botrana was restricted primarily to agricultural areas and relied in part (P. gossypiella) or wholly (L. botrana) on hand-applied dispensers. In those programs, mating disruption was integrated with other suppression tactics and considered an important component of overall efforts that are leading toward eradication of the invasive pests from North America. By contrast, L. dispar and E. postvittana are polyphagous pests, where pheromone formulations have been applied aerially as stand-alone treatments across broad areas, including residential neighborhoods. For L. dispar, mating disruption has been a key component in the program to slow the spread of the infestation of this pest, and the applications generally have been well tolerated by the public. For E. postvittana, public outcry halted the use of aerially applied mating disruption after an initial series of treatments, effectively thwarting an attempt to eradicate this pest from California. Reasons for the discrepancies between these two programs are not entirely clear.

  1. Conference of Radiation Control Program Directors, Inc. (CRCPD). A model for networking, cooperation, resource sharing, information exchange and regulation harmonization

    International Nuclear Information System (INIS)

    2007-01-01

    The focus of the talk will be to introduce the participants to the Conference of Radiation Control Program Directors, Inc. (CRCPD) and their proven methods for networking, information exchange, regulation development and standardization, and radiation protection guidance on emerging technologies. The presentation will describe how radiation control programs and staff from all 50 states in the US work collaboratively to ensure adequate radiation protection standards are uniformly applied throughout the country by pooling of resources and networking between all the states and the federal government, as well as with international members and partners. The products of CRCPD, such as the Suggested State Regulations along with other relevant informational documents, will be discussed along with how participants can access these products for use in their respective countries. CRCPD and its members represent a comprehensive radiation regulatory structure, covering all radiation sources and activities, (radioactive materials, licensing, registration, radioactive waste, x-ray, accelerators, emergency response, environmental monitoring, radon, and security). Networks are in place for all radiation issues. At the completion of this presentation, the participants will better understand a proven method to develop and implement a cooperative partnership with other countries. They will also gain knowledge on how to access CRCPD products that can be tailored for their own use and how to request technical assistance from membership. (author)

  2. The Conference of Radiation Control Program Directors (CRCPD): a model for networking, cooperation, information exchange and regulation harmonization

    International Nuclear Information System (INIS)

    Gilley, Debbie Bray

    2008-01-01

    This presentation will be to introduce to the participants the Conference of Radiation Control Program Directors, Inc. (CRCPD) and the proven methods used by this organization for networking, information exchange, regulation development and standardization, and radiation protection guidance on emerging technologies. The presentation will describe how radiation control programs and staff from all 50 states in the US work collaboratively to ensure adequate radiation protection standards are uniformly applied throughout the country through the pooling of resources and networking between all the states and the federal government, as well as with international members and partners. The products of CRCPD, such as the Suggested State Regulations along with other relevant informational documents, will be discussed along with how participants can access these products for use in their respective countries. CRCPD and its members represent a comprehensive radiation regulatory structure, covering radioactive materials, radioactive waste, X-ray, accelerators, emergency response, environmental monitoring, radon, and security. Networks are in place for all radiation issues. After the presentation, participants will better understand how to develop and implement a cooperative partnership with other countries. They will also know how to access our products that can be tailored for their own use. They will also be informed of how to contact CRCPD and request technical assistance from one of our 1000 members through our international outreach initiative. (author)

  3. The Development of Danish OHS Regulation - Organizational Understanding and Program Theory

    DEFF Research Database (Denmark)

    Seim, Rikke; Jensen, Per Langaa; Møller, Niels

    2014-01-01

    in organizing OHS, 3) link between the companies’ overall strategic management and OHS and 4) continuously competence development for the health and safety representatives. In this paper we present and analyze the individual elements of the legislative amendment. Subsequent we investigate the organizational......This paper focuses on a major recent amendment of the Danish Working Environment regulation concerning the cooperation of health and safety between employees and employer. The amendment, which came into force in October 2010, consists of four elements: 1) change of terminology, 2) flexibility...

  4. CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart.

    Directory of Open Access Journals (Sweden)

    Melisa Gomez-Velazquez

    2017-08-01

    Full Text Available Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development.

  5. CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart

    Science.gov (United States)

    Gomez-Velazquez, Melisa; Badia-Careaga, Claudio; Lechuga-Vieco, Ana Victoria; Nieto-Arellano, Rocio; Rollan, Isabel; Alvarez, Alba; Torroja, Carlos; Caceres, Eva F.; Roy, Anna R.; Galjart, Niels; Sanchez-Cabo, Fatima; Enriquez, Jose Antonio; Gomez-Skarmeta, Jose Luis

    2017-01-01

    Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development. PMID:28846746

  6. CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart.

    Science.gov (United States)

    Gomez-Velazquez, Melisa; Badia-Careaga, Claudio; Lechuga-Vieco, Ana Victoria; Nieto-Arellano, Rocio; Tena, Juan J; Rollan, Isabel; Alvarez, Alba; Torroja, Carlos; Caceres, Eva F; Roy, Anna R; Galjart, Niels; Delgado-Olguin, Paul; Sanchez-Cabo, Fatima; Enriquez, Jose Antonio; Gomez-Skarmeta, Jose Luis; Manzanares, Miguel

    2017-08-01

    Cardiac progenitors are specified early in development and progressively differentiate and mature into fully functional cardiomyocytes. This process is controlled by an extensively studied transcriptional program. However, the regulatory events coordinating the progression of such program from development to maturation are largely unknown. Here, we show that the genome organizer CTCF is essential for cardiogenesis and that it mediates genomic interactions to coordinate cardiomyocyte differentiation and maturation in the developing heart. Inactivation of Ctcf in cardiac progenitor cells and their derivatives in vivo during development caused severe cardiac defects and death at embryonic day 12.5. Genome wide expression analysis in Ctcf mutant hearts revealed that genes controlling mitochondrial function and protein production, required for cardiomyocyte maturation, were upregulated. However, mitochondria from mutant cardiomyocytes do not mature properly. In contrast, multiple development regulatory genes near predicted heart enhancers, including genes in the IrxA cluster, were downregulated in Ctcf mutants, suggesting that CTCF promotes cardiomyocyte differentiation by facilitating enhancer-promoter interactions. Accordingly, loss of CTCF disrupts gene expression and chromatin interactions as shown by chromatin conformation capture followed by deep sequencing. Furthermore, CRISPR-mediated deletion of an intergenic CTCF site within the IrxA cluster alters gene expression in the developing heart. Thus, CTCF mediates local regulatory interactions to coordinate transcriptional programs controlling transitions in morphology and function during heart development.

  7. Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment.

    Science.gov (United States)

    Kong, Wei; Wanda, Soo-Young; Zhang, Xin; Bollen, Wendy; Tinge, Steven A; Roland, Kenneth L; Curtiss, Roy

    2008-07-08

    We have devised and constructed a biological containment system designed to cause programmed bacterial cell lysis with no survivors. We have validated this system, using Salmonella enterica serovar Typhimurium vaccines for antigen delivery after colonization of host lymphoid tissues. The system is composed of two parts. The first component is Salmonella typhimurium strain chi8937, with deletions of asdA and arabinose-regulated expression of murA, two genes required for peptidoglycan synthesis and additional mutations to enhance complete lysis and antigen delivery. The second component is plasmid pYA3681, which encodes arabinose-regulated murA and asdA expression and C2-regulated synthesis of antisense asdA and murA mRNA transcribed from the P22 P(R) promoter. An arabinose-regulated c2 gene is present in the chromosome. chi8937(pYA3681) exhibits arabinose-dependent growth. Upon invasion of host tissues, an arabinose-free environment, transcription of asdA, murA, and c2 ceases, and concentrations of their gene products decrease because of cell division. The drop in C2 concentration results in activation of P(R), driving synthesis of antisense mRNA to block translation of any residual asdA and murA mRNA. A highly antigenic alpha-helical domain of Streptococcus pneumoniae Rx1 PspA was cloned into pYA3681, resulting in pYA3685 to test antigen delivery. Mice orally immunized with chi8937(pYA3685) developed antibody responses to PspA and Salmonella outer membrane proteins. No viable vaccine strain cells were detected in host tissues after 21 days. This system has potential applications with other Gram-negative bacteria in which biological containment would be desirable.

  8. The C.L.E.A.N. program: Regulating legacy sites

    International Nuclear Information System (INIS)

    Stenson, R.E.; Clement, C.H.

    2002-01-01

    With the coming into force of the Canadian Nuclear Safety and Control Act (NSCA) on May 31, 2000 many sites, that were not subject to licensing under the previous Atomic Energy Control Act (AECA), now required regulatory review and possibly a licence to possess nuclear substances. To ensure consistency in approach, completeness in coverage, and compliance with internal procedures, the Contaminated Lands Evaluation and Assessment Network (CLEAN) program was developed. Over 200 contaminated lands sites required evaluation. Some of the issues and the interim recommendations to the Commission are discussed. (author)

  9. Medicare and Medicaid programs: Hospital Outpatient Prospective Payment and Ambulatory Surgical Center Payment Systems and Quality Reporting Programs; electronic reporting pilot; Inpatient Rehabilitation Facilities Quality Reporting Program; revision to Quality Improvement Organization regulations. Final rule with comment period.

    Science.gov (United States)

    2012-11-15

    This final rule with comment period revises the Medicare hospital outpatient prospective payment system (OPPS) and the Medicare ambulatory surgical center (ASC) payment system for CY 2013 to implement applicable statutory requirements and changes arising from our continuing experience with these systems. In this final rule with comment period, we describe the changes to the amounts and factors used to determine the payment rates for Medicare services paid under the OPPS and those paid under the ASC payment system. In addition, this final rule with comment period updates and refines the requirements for the Hospital Outpatient Quality Reporting (OQR) Program, the ASC Quality Reporting (ASCQR) Program, and the Inpatient Rehabilitation Facility (IRF) Quality Reporting Program. We are continuing the electronic reporting pilot for the Electronic Health Record (EHR) Incentive Program, and revising the various regulations governing Quality Improvement Organizations (QIOs), including the secure transmittal of electronic medical information, beneficiary complaint resolution and notification processes, and technical changes. The technical changes to the QIO regulations reflect CMS' commitment to the general principles of the President's Executive Order on Regulatory Reform, Executive Order 13563 (January 18, 2011).

  10. Epigenetic marks: regulators of livestock phenotypes and conceivable sources of missing variation in livestock improvement programs

    Directory of Open Access Journals (Sweden)

    Eveline M Ibeagha-Awemu

    2015-09-01

    Full Text Available Improvement in animal productivity has been achieved over the years through careful breeding and selection programs. Today, variations in the genome are gaining increasing importance in livestock improvement strategies. Genomic information alone however explains only a part of the phenotypic variance in traits. It is likely that a portion of the unaccounted variance is embedded in the epigenome. The epigenome encompasses epigenetic marks such as DNA methylation, histone tail modifications, chromatin remodeling and other molecules that can transmit epigenetic information such as non-coding RNA species. Epigenetic factors respond to external or internal environmental cues such as nutrition, pathogens and climate, and have the ability to change gene expression leading to emergence of specific phenotypes. Accumulating evidence shows that epigenetic marks influence gene expression and phenotypic outcome in livestock species. This review examines available evidence of the influence of epigenetic marks on livestock (cattle, sheep, goat and pig traits and discusses the potential for consideration of epigenetic markers in livestock improvement programs. However, epigenetic research activities on farm animal species are currently limited partly due to lack of recognition, funding and a global network of researchers. Therefore, considerable less attention has been given to epigenetic research in livestock species in comparison to extensive work in humans and model organisms. Elucidating therefore the epigenetic determinants of animal diseases and complex traits may represent one of the principal challenges to use epigenetic markers for further improvement of animal productivity.

  11. California's program: Indoor air problems aren't amenable to regulation

    International Nuclear Information System (INIS)

    Wesolowski, J.

    1993-01-01

    In 1982, California's legislature established an Indoor Air Quality Program (CIAQP) in the Department of Health Services to carry out research on the nature and extent of the indoor air problem (excluding industrial worksites), to find appropriate mitigation measures, and to promote and coordinate the efforts of other state agencies. Since indoor air problems usually are not amenable to regulatory solutions, regulatory authority was not included in the mandate. The program conducts research into a wide range of contaminants--radon, asbestos, formaldehyde, carbon monoxide, volatile organic compounds, environmental tobacco smoke (ETS), as well as into biological aerosols that cause such diseases as Legionnaires disease, tuberculosis, allergies, and asthma. Studies are also carried out to better understand the Sick Building Syndrome. The research includes field surveys to determine the exposure of the population to specific contaminants and experiments in the laboratory to develop protocols for reducing exposures. The research emphasizes measurement of exposure--concentration multiplied by the time a person is exposed--as opposed to measurement of concentration only

  12. Dietary regulation of developmental programming in ruminants: epigenetic modifications in the germline.

    Science.gov (United States)

    Sinclair, K D; Karamitri, A; Gardner, D S

    2010-01-01

    Ruminants have been utilised extensively to investigate the developmental origins of health and disease, with the sheep serving as the model species of choice to complement dietary studies in the rat and mouse. Surprisingly few studies, however, have investigated delayed effects of maternal undernutrition during pregnancy on adult offspring health and a consistent phenotype, together with underlying mechanistic pathways, has not emerged. Nevertheless, when broad consideration is given to all studies with ruminants it is apparent that interventions that are initiated very early in gestation, and/or prior to conception, lead to greater effects on adult physiology than those that are specifically targeted to late gestation. Effects induced following dietary interventions at the earliest stages of mammalian development have been shown to arise as a consequence of alterations to key epigenetic processes that occur in germ cells and pluripotent embryonic cells. Currently, our understanding of epigenetic programming in the germline is greatest for the mouse, and is considered in detail in this article together with what is known in ruminants. This species imbalance, however, looks set to change as fully annotated genomic maps are developed for domesticated large animal species, and with the advent of 'next-generation' DNA sequencing technologies that have the power to globally map the epigenome at single-base-pair resolution. These developments would help to address such issues as sexually dimorphic epigenetic alterations to DNA methylation that have been found to arise following dietary restrictions during the peri-conceptional period, the effects of paternal nutritional status on epigenetic programming through the germline, and transgenerational studies where, in future, greater emphasis in domesticated ruminants should be placed on traits of agricultural importance.

  13. Chloroplasts activity and PAP-signaling regulate programmed cell death in Arabidopsis

    KAUST Repository

    Bruggeman, Quentin

    2016-01-09

    Programmed cell death (PCD) is a crucial process both for plant development and responses to biotic and abiotic stress. There is accumulating evidence that chloroplasts may play a central role during plant PCD as for mitochondria in animal cells, but it is still unclear whether they participate in PCD onset, execution, or both. To tackle this question, we have analyzed the contribution of chloroplast function to the cell death phenotype of the myoinositol phosphate synthase1 (mips1) mutant that forms spontaneous lesions in a light-dependent manner. We show that photosynthetically active chloroplasts are required for PCD to occur in mips1, but this process is independent of the redox state of the chloroplast. Systematic genetic analyses with retrograde signaling mutants reveal that 3’-phosphoadenosine 5’-phosphate, a chloroplast retrograde signal that modulates nuclear gene expression in response to stress, can inhibit cell death and compromises plant innate immunity via inhibition of the RNA-processing 5’-3’ exoribonucleases. Our results provide evidence for the role of chloroplast-derived signal and RNA metabolism in the control of cell death and biotic stress response. © 2016 American Society of Plant Biologists. All Rights Reserved.

  14. Lives saved by laws and regulations that resulted from the Bloomberg road safety program.

    Science.gov (United States)

    Miller, Ted R; Levy, David T; Swedler, David I

    2018-04-01

    To estimate lives saved during 2008-2023 by traffic safety laws passed in six developing countries while participating in the Bloomberg Road Safety Program (BRSP). BRSP-funded local staff identified relevant laws and described enforcement to the study team. We analyzed road crash death estimates for 2004-2013 from the Global Burden of Disease and projected estimates absent intervention forward to 2023. We amalgamated developing country and US literature to estimate crash death reductions by country resulting from laws governing drink driving, motorcycle helmets, safety belt use, and traffic fines. BRSP helped win approval of traffic safety laws in Brazil, China, Kenya, Mexico, Turkey, and Vietnam. In 2008-2013, those laws saved an estimated 19,000 lives. Many laws only took effect in 2014. The laws will save an estimated 90,000 lives in 2014-2023. Of the 109,000 lives saved, drink driving laws will account for 84%, increased motorcyclist protection for 13%, increased fines and penalty points for 2%, and safety belt usage mandates for 1%. Drink driving reductions in China will account for 56% of the savings and reduced drink driving and motorcycling deaths in Vietnam for 35%. The savings in China will result from a narrow intervention with just 4% estimated effectiveness against drink driving deaths. As a percentage of deaths anticipated without BRSP effort, the largest reductions will be 11% in Vietnam and 5% in Kenya. Viewed as a public health measure, improving traffic safety provided large health gains in developing nations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Moving beyond non-engagement on regulated needle-syringe exchange programs in Australian prisons

    Directory of Open Access Journals (Sweden)

    Levy Michael

    2009-05-01

    Full Text Available Abstract Background Australia is at a fork in the road with the possibility of a needle-syringe exchange program (NSP to be introduced at the new prison in the ACT. However, the current situation is characterised by non-engagement from major stakeholders. We explore why informed discussion will not be enough to convince prison officers, policy makers and the wider community of the benefits of prison-based NSPs. Other methods of engagement and communication will be proposed – in that may provide avenues for "breakthrough". Methods A review of the literature on needle-syringe exchanges and harm reduction strategies within the context of prisons and prisoner health was conducted. Literature on strategies to change attitudes and move beyond intractable situations was also consulted. In addition, one author, DM, conducted a two-hour interview with an ex-prison officer. Results No studies were found which investigated the potential efficacy of interventions to modify attitudes or behaviours in the specific context of introducing an NSP into a prison. Nonetheless, several theories were identified which may explain the failure of informed discussion alone to create change in this situation and may therefore lead to suggestions for engagement and communication to move towards a resolution Discussion Cognitive-behavioural therapy highlights the importance of individual cognitions and how they shape behaviours in any change campaign. Social identity theory emphasizes changes to social processes that may open the prison officer workforce to change. Peace studies also suggests socialization strategies such as observing an established and effective prison-based needle-syringe exchange. Social marketing provides suggestions on how to sell an exchange to ensuring the benefits are framed to outweigh the costs. Conclusion Psychology, peace studies and social marketing all agree people's views must be carefully collected and analysed if people are going to be

  16. Mesenchymal Stromal Cell-Derived Microvesicles Regulate an Internal Pro-Inflammatory Program in Activated Macrophages

    Directory of Open Access Journals (Sweden)

    Juan S. Henao Agudelo

    2017-07-01

    Full Text Available Mesenchymal stromal cells (MSCs are multipotent cells with abilities to exert immunosuppressive response promoting tissue repair. Studies have shown that MSCs can secrete extracellular vesicles (MVs-MSCs with similar regulatory functions to the parental cells. Furthermore, strong evidence suggesting that MVs-MSCs can modulate several immune cells (i.e., Th1, Th17, and Foxp3+ T cells. However, their precise effect on macrophages (Mϕs remains unexplored. We investigated the immunoregulatory effect of MVs-MSCs on activated M1-Mϕs in vitro and in vivo using differentiated bone marrow Mϕs and an acute experimental model of thioglycollate-induced peritonitis, respectively. We observed that MVs-MSCs shared surface molecules with MSCs (CD44, CD105, CD90, CD73 and expressed classical microvesicle markers (Annexin V and CD9. The in vitro treatment with MVs-MSCs exerted a regulatory-like phenotype in M1-Mϕs, which showed higher CD206 level and reduced CCR7 expression. This was associated with decreased levels of inflammatory molecules (IL-1β, IL-6, nitric oxide and increased immunoregulatory markers (IL-10 and Arginase in M1-Mϕs. In addition, we detected that MVs-MSCs promoted the downregulation of inflammatory miRNAs (miR-155 and miR-21, as well as, upregulated its predicted target gene SOCS3 in activated M1-Mϕs. In vivo MVs-MSCs treatment reduced the Mϕs infiltrate in the peritoneal cavity inducing a M2-like regulatory phenotype in peritoneal Mϕs (higher arginase activity and reduced expression of CD86, iNOS, IFN-γ, IL-1β, TNF-α, IL-1α, and IL-6 molecules. This in vivo immunomodulatory effect of MVs-MSCs on M1-Mϕs was partially associated with the upregulation of CX3CR1 in F4/80+/Ly6C+/CCR2+ Mϕs subsets. In summary, our findings indicate that MVs-MSCs can modulate an internal program in activated Mϕs establishing an alternative regulatory-like phenotype.

  17. Untangling the Roles of Anti-Apoptosis in Regulating Programmed Cell Death using Humanized Yeast Cells

    International Nuclear Information System (INIS)

    Clapp, Caitlin; Portt, Liam; Khoury, Chamel; Sheibani, Sara; Eid, Rawan; Greenwood, Matthew; Vali, Hojatollah; Mandato, Craig A.; Greenwood, Michael T.

    2012-01-01

    Genetically programmed cell death (PCD) mechanisms, including apoptosis, are important for the survival of metazoans since it allows, among things, the removal of damaged cells that interfere with normal function. Cell death due to PCD is observed in normal processes such as aging and in a number of pathophysiologies including hypoxia (common causes of heart attacks and strokes) and subsequent tissue reperfusion. Conversely, the loss of normal apoptotic responses is associated with the development of tumors. So far, limited success in preventing unwanted PCD has been reported with current therapeutic approaches despite the fact that inhibitors of key apoptotic inducers such as caspases have been developed. Alternative approaches have focused on mimicking anti-apoptotic processes observed in cells displaying increased resistance to apoptotic stimuli. Hormesis and pre-conditioning are commonly observed cellular strategies where sub-lethal levels of pro-apoptotic stimuli lead to increased resistance to higher or lethal levels of stress. Increased expression of anti-apoptotic sequences is a common mechanism mediating these protective effects. The relevance of the latter observation is exemplified by the observation that transgenic mice overexpressing anti-apoptotic genes show significant reductions in tissue damage following ischemia. Thus strategies aimed at increasing the levels of anti-apoptotic proteins, using gene therapy or cell penetrating recombinant proteins are being evaluated as novel therapeutics to decrease cell death following acute periods of cell death inducing stress. In spite of its functional and therapeutic importance, more is known regarding the processes involved in apoptosis than anti-apoptosis. The genetically tractable yeast Saccharomyces cerevisiae has emerged as an exceptional model to study multiple aspects of PCD including the mitochondrial mediated apoptosis observed in metazoans. To increase our knowledge of the process of anti

  18. National Bureau of Standards health physics radioactive material shipment survey, packaging, and labelling program under ICAO/IATA and DOT regulations

    International Nuclear Information System (INIS)

    Sharp, D.R.; Slaback, L.A.

    1984-01-01

    NBS routinely ships many radionuclides in small to moderate activities, with many shipments containing mixtures of radionuclides in a variety of combinations. The ICAO/IATA shipping regulations (and the new DoT regulations on their model) specify individual shipping parameters for every radionuclide. As a result, quality control in the shipment of these radioactive packages has become difficult to maintain. The authors have developed a computer program that will guide a Health Physics technician through package surveys and give exact packaging and labelling instructions. The program is a 27 kilobyte user-friendly BASIC program that runs on an Epson-HX20 notebook computer with microcassette drive and 16 kilobyte memory expansion unit. This small computer is more manageable than the regulation books for which it will be substituted and will be used in routine radioactive shipments

  19. Ion channels involved in cell volume regulation: effects on migration, proliferation, and programmed cell death in non adherent EAT cells and adherent ELA cells.

    Science.gov (United States)

    Hoffmann, Else Kay

    2011-01-01

    This mini review outlines studies of cell volume regulation in two closely related mammalian cell lines: nonadherent Ehrlich ascites tumour cells (EATC) and adherent Ehrlich Lettre ascites (ELA) cells. Focus is on the regulatory volume decrease (RVD) that occurs after cell swelling, the volume regulatory ion channels involved, and the mechanisms (cellular signalling pathways) that regulate these channels. Finally, I shall also briefly review current investigations in these two cell lines that focuses on how changes in cell volume can regulate cell functions such as cell migration, proliferation, and programmed cell death. Copyright © 2011 S. Karger AG, Basel.

  20. Interval-parameter chance-constraint programming model for end-of-life vehicles management under rigorous environmental regulations.

    Science.gov (United States)

    Simic, Vladimir

    2016-06-01

    As the number of end-of-life vehicles (ELVs) is estimated to increase to 79.3 million units per year by 2020 (e.g., 40 million units were generated in 2010), there is strong motivation to effectively manage this fast-growing waste flow. Intensive work on management of ELVs is necessary in order to more successfully tackle this important environmental challenge. This paper proposes an interval-parameter chance-constraint programming model for end-of-life vehicles management under rigorous environmental regulations. The proposed model can incorporate various uncertainty information in the modeling process. The complex relationships between different ELV management sub-systems are successfully addressed. Particularly, the formulated model can help identify optimal patterns of procurement from multiple sources of ELV supply, production and inventory planning in multiple vehicle recycling factories, and allocation of sorted material flows to multiple final destinations under rigorous environmental regulations. A case study is conducted in order to demonstrate the potentials and applicability of the proposed model. Various constraint-violation probability levels are examined in detail. Influences of parameter uncertainty on model solutions are thoroughly investigated. Useful solutions for the management of ELVs are obtained under different probabilities of violating system constraints. The formulated model is able to tackle a hard, uncertainty existing ELV management problem. The presented model has advantages in providing bases for determining long-term ELV management plans with desired compromises between economic efficiency of vehicle recycling system and system-reliability considerations. The results are helpful for supporting generation and improvement of ELV management plans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope specificity, T-cell receptor clonotype usage and antigen load

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N; McGregor, Reuben; McLaren, James E

    2014-01-01

    of differentiation on HIV-1-specific CD8+ T-cell populations(n = 128) spanning 11 different epitope targets. RESULTS: Expression levels of PD-1, but not CD244 or LAG-3, varied substantially across epitope specificities both within and between individuals. Differential expression of PD-1 on T-cell receptor (TCR...

  2. Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Lei [Dana-Farber Cancer Institute, Department of Imaging, Boston, MA (United States); Harvard Medical School, Department of Radiology, Boston, MA (United States); Li, Xiang; Qu, Jinrong [Affiliated Cancer Hospital of Zhengzhou University, Department of Radiology, Zhengzhou, Henan (China); Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Stroiney, Amanda [Dana-Farber Cancer Institute, Department of Imaging, Boston, MA (United States); Northeastern University, Department of Behavioral Neuroscience, College of Sciences, Boston, MA (United States); Helgager, Jeffrey [Brigham and Women' s Hospital, Department of Pathology, Boston, MA (United States); Reardon, David A. [Dana-Farber Cancer Institute, CenterforNeuro-Oncology, Boston, MA (United States); Department of Medicine, Boston, MA (United States); Young, Geoffrey S. [Harvard Medical School, Department of Radiology, Boston, MA (United States); Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States)

    2017-02-15

    We describe the imaging findings encountered in GBM patients receiving immune checkpoint blockade and assess the potential of quantitative MRI biomarkers to differentiate patients who derive therapeutic benefit from those who do not. A retrospective analysis was performed on longitudinal MRIs obtained on recurrent GBM patients enrolled on clinical trials. Among 10 patients with analyzable data, bidirectional diameters were measured on contrast enhanced T1 (pGd-T1WI) and volumes of interest (VOI) representing measurable abnormality suggestive of tumor were selected on pGdT1WI (pGdT1 VOI), FLAIR-T2WI (FLAIR VOI), and ADC maps. Intermediate ADC (IADC) VOI represented voxels within the FLAIR VOI having ADC in the range of highly cellular tumor (0.7-1.1 x 10{sup -3} mm{sup 2}/s) (IADC VOI). Therapeutic benefit was determined by tissue pathology and survival on trial. IADC VOI, pGdT1 VOI, FLAIR VOI, and RANO assessment results were correlated with patient benefit. Five patients were deemed to have received therapeutic benefit and the other five patients did not. The average time on trial for the benefit group was 194 days, as compared to 81 days for the no benefit group. IADC VOI correlated well with the presence or absence of clinical benefit in 10 patients. Furthermore, pGd VOI, FLAIR VOI, and RANO assessment correlated less well with response. MRI reveals an initial increase in volumes of abnormal tissue with contrast enhancement, edema, and intermediate ADC suggesting hypercellularity within the first 0-6 months of immunotherapy. Subsequent stabilization and improvement in IADC VOI appear to better predict ultimate therapeutic benefit from these agents than conventional imaging. (orig.)

  3. CD8+ T cells undergo activation and programmed death-1 repression in the liver of aged Ae2a,b-/- mice favoring autoimmune cholangitis

    NARCIS (Netherlands)

    Concepcion, Axel R.; Salas, January T.; Sáez, Elena; Sarvide, Sarai; Ferrer, Alex; Portu, Ainhoa; Uriarte, Iker; Hervás-Stubbs, Sandra; Oude Elferink, Ronald P. J.; Prieto, Jesús; Medina, Juan F.

    2015-01-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic disease of unknown etiopathogenesis showing progressive autoimmune-mediated cholangitis. In PBC patients, the liver and lymphocytes exhibit diminished expression of AE2/SLC4A2, a Cl-/HCO3- anion exchanger involved in biliary bicarbonate

  4. Combination of Interleukin-11Rα chimeric antigen receptor T-cells and programmed death-1 blockade as an approach to targeting osteosarcoma cells In vitro

    Directory of Open Access Journals (Sweden)

    Hatel Rana Moonat

    2017-01-01

    Conclusion: This combination of IL-11Rα-CAR T-cells and an anti-PD-1 antibody did not provide any additional cytotoxic benefit over IL-11Rα-CAR T-cell therapy alone in this setting. Further studies are needed as simple interference with surface PD-1 expression alone may not be sufficient to inhibit this immune checkpoint pathway to then enhance IL-11Rα-CAR T-cell therapeutic effects.

  5. 31 CFR 103.120 - Anti-money laundering program requirements for financial institutions regulated by a Federal...

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Anti-money laundering program... Laundering Programs Anti-Money Laundering Programs § 103.120 Anti-money laundering program requirements for... anti-money laundering program that complies with the requirements of §§ 103.176 and 103.178 and the...

  6. The Effectiveness of a Self Regulated Learning-Based Training Program on Improving Cognitive and Metacognitive EFL Reading Comprehension of 9th Graders with Reading Disabilities

    Science.gov (United States)

    Eissa, Mourad Ali

    2015-01-01

    The purpose of this study was to explore the effect of a self regulated learning intervention program on cognitive and metacognitive EFL reading comprehension of 9th graders with reading disabilities. The participants in this study were 40 9th Graders with reading disabilities, selected from two schools located in Baltim Educational Edara. A…

  7. Neuro Emotional Literacy Program: Does Teaching the Function of Affect and Affect Regulation Strategies Improve Affect Management and Well-Being?

    Science.gov (United States)

    Patten, Kathryn E.; Campbell, Stephen R.

    2016-01-01

    Although research on Emotion Regulation (ER) is developing at a rapid rate, much of it lacks a clear theoretical framework and most focuses on a narrow set of ER strategies. This work presents the details of a pilot project, the Neuro Emotional Literacy Program (NELP), designed for parents and based on the Somatic Appraisal Model of Affect (SAMA).…

  8. The histone demethylase Kdm6b regulates a mature gene expression program in differentiating cerebellar granule neurons.

    Science.gov (United States)

    Wijayatunge, Ranjula; Liu, Fang; Shpargel, Karl B; Wayne, Nicole J; Chan, Urann; Boua, Jane-Valeriane; Magnuson, Terry; West, Anne E

    2018-03-01

    The histone H3 lysine 27 (H3K27) demethylase Kdm6b (Jmjd3) can promote cellular differentiation, however its physiological functions in neurons remain to be fully determined. We studied the expression and function of Kdm6b in differentiating granule neurons of the developing postnatal mouse cerebellum. At postnatal day 7, Kdm6b is expressed throughout the layers of the developing cerebellar cortex, but its expression is upregulated in newborn cerebellar granule neurons (CGNs). Atoh1-Cre mediated conditional knockout of Kdm6b in CGN precursors either alone or in combination with Kdm6a did not disturb the gross morphological development of the cerebellum. Furthermore, RNAi-mediated knockdown of Kdm6b in cultured CGN precursors did not alter the induced expression of early neuronal marker genes upon cell cycle exit. By contrast, knockdown of Kdm6b significantly impaired the induction of a mature neuronal gene expression program, which includes gene products required for functional synapse maturation. Loss of Kdm6b also impaired the ability of Brain-Derived Neurotrophic Factor (BDNF) to induce expression of Grin2c and Tiam1 in maturing CGNs. Taken together, these data reveal a previously unknown role for Kdm6b in the postmitotic stages of CGN maturation and suggest that Kdm6b may work, at least in part, by a transcriptional mechanism that promotes gene sensitivity to regulation by BDNF. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. NRC Task Force report on review of the federal/state program for regulation of commercial low-level radioactive waste burial grounds

    International Nuclear Information System (INIS)

    1977-01-01

    The underlying issue explored in this report is that of Federal vs State regulation of commercial radioactive waste burial grounds. The need for research and development, a comprehensive set of standards and criteria, a national plan for low-level waste management, and perpetual care funding are closely related to the central issue and are also discussed. Five of the six commercial burial grounds are regulated by Agreement States; the sixth is regulated solely by the NRC (NRC also regulates Special Nuclear Material at the sites). The sites are operated commercially. The operators contribute to the perpetual care funds for the sites at varying rates. The States have commitments for the perpetual care of the decommissioned sites except for one site, located on Federally owned land. Three conclusions are reached. Federal control over the disposal of low-level waste should be increased by requiring joint Federal/State site approval, NRC licensing, Federal ownership of the land, and a Federally administered perpetual care program. The NRC should accelerate the development of its regulatory program for the disposal of low-level waste. The undisciplined proliferation of low-level burial sites must be avoided. NRC should evaluate alternative disposal methods, conduct necessary studies, and develop a comprehensive low-level waste regulatory program (i.e., accomplish the above recommendations) prior to the licensing of new disposal sites

  10. Structures and short linear motif of disordered transcription factor regions provide clues to the interactome of the cellular hub radical-induced cell death1

    DEFF Research Database (Denmark)

    O'Shea, Charlotte; Staby, Lasse; Bendsen, Sidsel Krogh

    2017-01-01

    Intrinsically disordered protein regions (IDRs) lack a well-defined three-dimensional structure, but often facilitate key protein functions. Some interactions between IDRs and folded protein domains rely on short linear motifs (SLiMs). These motifs are challenging to identify, but once found can...... point to larger networks of interactions, such as with proteins that serve as hubs for essential cellular functions. The stress-associated plant protein Radical-Induced Cell Death1 (RCD1) is one such hub, interacting with many transcription factors via their flexible IDRs. To identify the SLiM bound......046 formed different structures or were fuzzy in the complexes. These findings allow us to present a model of the stress-associated RCD1-transcription factor interactome and to contribute to the emerging understanding of the interactions between folded hubs and their intrinsically disordered partners....

  11. 45 CFR 660.6 - What procedures apply to the selection of programs and activities under these regulations?

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false What procedures apply to the selection of programs... Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION INTERGOVERNMENTAL REVIEW OF THE NATIONAL SCIENCE FOUNDATION PROGRAMS AND ACTIVITIES § 660.6 What procedures apply to the selection of programs and activities...

  12. Programming

    International Nuclear Information System (INIS)

    Jackson, M.A.

    1982-01-01

    The programmer's task is often taken to be the construction of algorithms, expressed in hierarchical structures of procedures: this view underlies the majority of traditional programming languages, such as Fortran. A different view is appropriate to a wide class of problem, perhaps including some problems in High Energy Physics. The programmer's task is regarded as having three main stages: first, an explicit model is constructed of the reality with which the program is concerned; second, this model is elaborated to produce the required program outputs; third, the resulting program is transformed to run efficiently in the execution environment. The first two stages deal in network structures of sequential processes; only the third is concerned with procedure hierarchies. (orig.)

  13. Programming

    OpenAIRE

    Jackson, M A

    1982-01-01

    The programmer's task is often taken to be the construction of algorithms, expressed in hierarchical structures of procedures: this view underlies the majority of traditional programming languages, such as Fortran. A different view is appropriate to a wide class of problem, perhaps including some problems in High Energy Physics. The programmer's task is regarded as having three main stages: first, an explicit model is constructed of the reality with which the program is concerned; second, thi...

  14. NRC Task Force report on review of the Federal/State program for regulation of commercial low-level radioactive waste burial grounds. Analysis of public comments

    International Nuclear Information System (INIS)

    1977-09-01

    Correspondence after publication of NUREG-0217 in the Federal Register is listed by docket. A summary of the comments is given. Comments on the task force conclusions on federal/state roles, comprehensive regulator program, and need to study alternatives, provide adequate capacity, and avoid proliferation are analyzed. A breakdown of the comments of states, industry, and others on the task force conclusions and recommendations is tabulated

  15. The need for a public information program to promote understanding of the validity of the safety of IAEA transport regulations for shipment of radioactive material

    International Nuclear Information System (INIS)

    Kubo, M.

    2004-01-01

    It is important to convey basic knowledge that demonstrates to the general public and public officials that transport of radioactive materials is safe. Data, analysis, and testing for certification in member states of the IAEA as well as experience with packages involved in accidents demonstrate the margin of safety when radioactive material material is transported. In addition, the experience of TranSAS activity has shown it to be an effective and transparent means to the public people for Member States to demonstrate their commitment to the safe transport of RAM. Therefore, in the future, the IAEA must continue and expand its public efforts to make the public aware of the very high certainty of safe transport that is the consequence of following the regulations. I would like to ask IAEA to have the transportation specialist groups designated by each Member State. These transportation specialist groups, working with the IAEA transport regulations in each country, should have as a central activity an information program that conveys the margin of safety inherent in the IAEA transport regulations. Finally I would like to ask IAEA to produce a program relating to public perception of RAM transport for the public throughout the world. And also I would like to ask IAEA to send the transportation specialist groups to Member States and many concerned countries to explain and demonstrate the adequacy of the IAEA Regulations

  16. The need for a public information program to promote understanding of the validity of the safety of IAEA transport regulations for shipment of radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, M. [Japan Nuclear Cycle Development Inst., Ibaraki (Japan)

    2004-07-01

    It is important to convey basic knowledge that demonstrates to the general public and public officials that transport of radioactive materials is safe. Data, analysis, and testing for certification in member states of the IAEA as well as experience with packages involved in accidents demonstrate the margin of safety when radioactive material material is transported. In addition, the experience of TranSAS activity has shown it to be an effective and transparent means to the public people for Member States to demonstrate their commitment to the safe transport of RAM. Therefore, in the future, the IAEA must continue and expand its public efforts to make the public aware of the very high certainty of safe transport that is the consequence of following the regulations. I would like to ask IAEA to have the transportation specialist groups designated by each Member State. These transportation specialist groups, working with the IAEA transport regulations in each country, should have as a central activity an information program that conveys the margin of safety inherent in the IAEA transport regulations. Finally I would like to ask IAEA to produce a program relating to public perception of RAM transport for the public throughout the world. And also I would like to ask IAEA to send the transportation specialist groups to Member States and many concerned countries to explain and demonstrate the adequacy of the IAEA Regulations.

  17. The C. elegans tailless/Tlx homolog nhr-67 regulates a stage-specific program of linker cell migration in male gonadogenesis.

    Science.gov (United States)

    Kato, Mihoko; Sternberg, Paul W

    2009-12-01

    Cell migration is a common event during organogenesis, yet little is known about how migration is temporally coordinated with organ development. We are investigating stage-specific programs of cell migration using the linker cell (LC), a migratory cell crucial for male gonadogenesis of C. elegans. During the L3 and L4 larval stages of wild-type males, the LC undergoes changes in its position along the migratory route, in transcriptional regulation of the unc-5 netrin receptor and zmp-1 zinc matrix metalloprotease, and in cell morphology. We have identified the tailless homolog nhr-67 as a cell-autonomous, stage-specific regulator of timing in LC migration programs. In nhr-67-deficient animals, each of the L3 and L4 stage changes is either severely delayed or never occurs, yet LC development before the early L3 stage or after the mid-L4 stage occurs with normal timing. We propose that there is a basal migration program utilized throughout LC migration that is modified by stage-specific regulators such as nhr-67.

  18. 76 FR 3046 - Farmers' Market Promotion Program Regulation; Notice of Request for Approval of a New Information...

    Science.gov (United States)

    2011-01-19

    ... does not meet the definition of a Federal mandate because the resulting annual State expenditures would..., roadside stands, community-supported agriculture programs, agri-tourism activities, and other direct...' markets, roadside stands, community-supported agriculture programs, agri-tourism activities, and other...

  19. Effect of the Children's Health Activity Motor Program on Motor Skills and Self-Regulation in Head Start Preschoolers: An Efficacy Trial.

    Science.gov (United States)

    Robinson, Leah E; Palmer, Kara K; Bub, Kristen L

    2016-01-01

    Self-regulatory skills are broadly defined as the ability to manage emotions, focus attention, and inhibit some behaviors while activating others in accordance with social expectations and are an established indicator of academic success. Growing evidence links motor skills and physical activity to self-regulation. This study examined the efficacy of a motor skills intervention (i.e., the Children's Health Activity Motor Program, CHAMP) that is theoretically grounded in Achievement Goal Theory on motor skill performance and self-regulation in Head Start preschoolers. A sample of 113 Head Start preschoolers (Mage = 51.91 ± 6.5 months; 49.5% males) were randomly assigned to a treatment (n = 68) or control (n = 45) program. CHAMP participants engaged in 15, 40-min sessions of a mastery climate intervention that focused on the development of motor skills over 5 weeks while control participants engaged in their normal outdoor recess period. The Delay of Gratification Snack Task was used to measure self-regulation and the Test of Gross Motor Development-2nd Edition was used to assess motor skills. All measures were assessed prior to and following the intervention. Linear mixed models were fit for both self-regulation and motor skills. Results revealed a significant time × treatment interaction (p motor skills, post hoc comparisons found that all children improved their motor skills (p skills associated with healthy development in children (i.e., motor skills and self-regulation). This efficacy trial provided evidence that CHAMP helped maintain delay of gratification in preschool age children and significantly improved motor skills while participating in outdoor recess was not effective. CHAMP could help contribute to children's learning-related skills and physical development and subsequently to their academic success.

  20. Effect of the Children’s Health Activity Motor Program on Motor Skills and Self-Regulation in Head Start Preschoolers: An Efficacy Trial

    Science.gov (United States)

    Robinson, Leah E.; Palmer, Kara K.; Bub, Kristen L.

    2016-01-01

    Self-regulatory skills are broadly defined as the ability to manage emotions, focus attention, and inhibit some behaviors while activating others in accordance with social expectations and are an established indicator of academic success. Growing evidence links motor skills and physical activity to self-regulation. This study examined the efficacy of a motor skills intervention (i.e., the Children’s Health Activity Motor Program, CHAMP) that is theoretically grounded in Achievement Goal Theory on motor skill performance and self-regulation in Head Start preschoolers. A sample of 113 Head Start preschoolers (Mage = 51.91 ± 6.5 months; 49.5% males) were randomly assigned to a treatment (n = 68) or control (n = 45) program. CHAMP participants engaged in 15, 40-min sessions of a mastery climate intervention that focused on the development of motor skills over 5 weeks while control participants engaged in their normal outdoor recess period. The Delay of Gratification Snack Task was used to measure self-regulation and the Test of Gross Motor Development-2nd Edition was used to assess motor skills. All measures were assessed prior to and following the intervention. Linear mixed models were fit for both self-regulation and motor skills. Results revealed a significant time × treatment interaction (p motor skills, post hoc comparisons found that all children improved their motor skills (p skills associated with healthy development in children (i.e., motor skills and self-regulation). This efficacy trial provided evidence that CHAMP helped maintain delay of gratification in preschool age children and significantly improved motor skills while participating in outdoor recess was not effective. CHAMP could help contribute to children’s learning-related skills and physical development and subsequently to their academic success. PMID:27660751

  1. Molecular cloning and responsive expression to injury stimulus of a defender against cell death 1 (DAD1) gene from bay scallops Argopecten irradians.

    Science.gov (United States)

    Zhu, Ling; Song, Linsheng; Zhang, Huan; Zhao, Jianmin; Li, Chenghua; Xu, Wei

    2008-06-01

    Apoptosis is an active process of cell death, which is an integral part of growth and development in multicellular organisms. The defender against cell death 1 (DAD1), the regulatory protein to inhibit the apoptosis process, was first cloned from the bay scallop Argopecten irradians by randomly sequencing a whole tissue cDNA library and rapid amplification of cDNA end (RACE). The full-length cDNA of the A. irradians DAD1 was 607 bp, consist of a 5'-terminal untranslated region (UTR) of 63 bp, a 3'-terminal UTR of 205 bp with a canonical polyadenylation signal sequence AATAAA and a poly (A) tail, and an open reading frame of 339 bp. The deduced amino acid sequence of the A. irradians DAD1 showed 75.5% identity to Araneus ventricosus, 74.5% to Drosophila melanogaster, and 73.6% to Homo sapiens, Sus scrofa, Mesocricetus auratus, Rattus norvegicus and Mus musculus. Excluding the Saccharomyces cerevisiae DAD1 homologue, all animal DAD1 including A. irradians DAD1 homologue formed a subgroup and all plant DAD1 proteins formed another subgroup in the phylogenetic analysis. The A. irradians DAD1 was expressed in all examined tissues including adductor muscle, mantle, gills, digestive gland, gonad and hemolymph, suggesting that A. irradians DAD1 is expressed in most body tissues. Furthermore, the mRNA expression levels of A. irradians DAD1 gene of hemolymph were particularly high after injury, suggesting that the gene is responsive to injury stimuli.

  2. Programmed Death-Ligand 1 Immunohistochemistry Testing

    DEFF Research Database (Denmark)

    Büttner, Reinhard; Gosney, John R; Skov, Birgit Guldhammer

    2017-01-01

    Purpose Three programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of non-small-cell lung cancer (NSCLC). Treatment with pembrolizumab in NSCLC requires PD-L1 immunohistochemistry (IHC) testing. Nivolumab and atezolizumab are approved without PD-L1...

  3. Effect of the Children’s Health Activity Motor Program on Motor Skills and Self-Regulation in Head Start Preschoolers: An Efficacy Trial

    Directory of Open Access Journals (Sweden)

    Leah Elizabeth Robinson

    2016-09-01

    Full Text Available Self-regulatory skills are broadly defined as the ability to manage emotions, focus attention, and inhibit some behaviors while activating others in accordance with social expectations and are an established indicator of academic success. Growing evidence links motor skills and physical activity to self-regulation. This study examined the efficacy of a motor skills intervention (i.e., the Children’s Health Activity Motor Program, CHAMP that is theoretically grounded in Achievement Goal Theory on motor skill performance and self-regulation in Head Start preschoolers. A sample of 113 Head Start preschoolers (Mage = 51.91 + 6.5 months; 49.5% males were randomly assigned to a treatment (n = 68 or control (n = 45 program. CHAMP participants engaged in 15, 40-minute sessions of a mastery climate intervention that focused on the development of motor skills over 5 weeks while control participants engaged in their normal outdoor recess period. The Delay of Gratification Snack Task was used to measure self-regulation and the Test of Gross Motor Development - 2nd Edition was used to assess motor skills. All measures were assessed prior to and following the intervention. Linear mixed models were fit for both self-regulation and motor skills. Results revealed a significant time*treatment interaction (p < .001. In regards to motor skills, post hoc comparisons found that all children improved their motor skills (p < .05, but the CHAMP group improved significantly more than the control group (p < .001. Children in CHAMP maintained their self-regulation scores across time while children in the control group scored significantly lower than the CHAMP group at the posttest (p < .05. CHAMP is a mastery climate movement program that may be an approach to enhance skills associated with healthy development in children (i.e., motor skills and self-regulation. This efficacy trial provided evidence that CHAMP helped maintain delay of gratification in preschool age

  4. Peningkatan Prestasi Belajar CAD Mahasiswa Teknik Otomotif Non-Reguler FT UNY melalui Pembuatan “Pohon Kata” Perintah dalam Program AutoCAD

    Directory of Open Access Journals (Sweden)

    Martubi Martubi

    2010-05-01

    Full Text Available Penelitian ini bertujuan meningkatkan prestasi belajar mata kuliah Computer Aided Design (CAD mahasiswa prodi Teknik Otomotif Non-Reguler yang dinyatakan dalam bentuk rerata nilai akhir semester yang berasal dari komponen nilai tugas harian, nilai ujian tengah semester dan nilai ujian akhir semester. Penelitian quasi-eksperimen ini terdiri dari tahapan penelitian diawali dengan penyusunan materi pembelajaran sejumlah pokok bahasan tertentu dalam satu job sheet (lembar kerja, dilanjutkan dengan pembuatan bantuan “Pohon Kata” perintah dalam Auto CAD kepada kelas eksperimen yang ditentukan secara random dari dua kelas peserta kuliah Auto CAD pada Semester Genap 2008/2009. Kedua kelas diamati prestasinya, baik kecepatan penyelesaiannya maupun kualitas kebenaran gambarnya. Prestasi belajar kedua kelas juga diukur melalui pemberian ujian tengah semester dan ujian akhir semester. Setelah data prestasi kedua kelas terkumpul dilanjutkan dengan analisis statistik melalui uji beda (t-test setelah sebelumnya dilakukan uji persyaratan analisis yang ternyata dapat dipenuhi. Hasil penelitian ini disimpulkan bahwa: prestasi belajar CAD mahasiswa pada kelas yang diberi perlakuan strategi pembelajaran menggunakan “Pohon Kata” perintah dalam Program Auto CAD lebih baik dibanding prestasi belajar CAD mahasiswa pada kelas yang tidak diberi perlakuan (75,41>70,89, dengan demikian pembelajaran CAD menggunakan media “Pohon Kata” perintah dalam Program Auto CAD dapat meningkatkan prestasi belajar mahasiswa Teknik Otomotif Program Non-Reguler.

  5. User's guide for PRISIM (Plant Risk Status Information Management System) Arkansas Nuclear One--Unit 1: Volume 2, Program for regulators

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, D.J.; Guthrie, V.H.; Kirchner, J.R.; Kirkman, J.Q.; Paula, H.M.; Ellison, B.C.; Dycus, F.M.; Farquharson, J.A.; Flanagan, G.F.

    1988-03-01

    This user's guide is a two-volume document designed to teach NRC inspectors and NRC regulators how to access probabilistic risk assessment information from the two Plant Risk Status Information Management System (PRISIM) programs developed for Arkansas Nuclear One--Unit One (ANA-1). This document, Volume 2, describes how the PRA information available in Version 2.0 of PRISIM is useful as an evaluation tool for regulatory activities. Using PRISIM is useful as an evaluation tool for regulatory activities. Using PRISIM, regulators can both access PRA information and modify the information to assess the impact these changes may have on plant safety. Each volume is a stand-alone document.

  6. Online Coaching of Emotion-Regulation Strategies for Parents: Efficacy of the Online Rational Positive Parenting Program and Attention Bias Modification Procedures.

    Science.gov (United States)

    David, Oana A; Capris, David; Jarda, Alexandra

    2017-01-01

    Parenting programs are currently treatment of choice for behavioral disorders in children and one of their main components is reducing the negativity bias in the child-parent dyad. The Rational Positive Parenting Program (rPPP) is a program with a special focus on parent emotion-regulation functional reappraisal strategies, which has recently received consistent support for reducing child externalizing and internalizing disorders. In the last years, online interventions were proliferated and the Attention Bias Modification (ABM) becoming a promising implicit therapeutic intervention based on attention deployment emotion-regulation strategy, or adjunctive module to usual treatments, with results in multiple domains, varying from pain to self-esteem and emotional disorders (e.g., anxiety). We conducted two studies to investigate (1) the efficacy of the ABM procedures applied to parents and (2) the efficacy of the online version of the rPPP augmented with an ABM module. A total of 42 parents of children aged 2-12 years old participated in the first study, being allocated either to the ABM training or wait-list. Positive results were reported by the parents participating in the ABM group for own distress, satisfaction, positive interactions with the child, and child's strengths. In the second study, 53 parents and their children were allocated either in the rPPP group or in the rPPP + ABM group. Results show that ABM training can boost the effects of the rPPP on the strengths of children reported by the parents after the intervention. Findings are discussed in the light of limited research on using online tools for coaching effective emotion-regulation strategies for parents.

  7. Drug Pricing Program Ceiling Price and Manufacturer Civil Monetary Penalties Regulation. Final rule; further delay of effective date.

    Science.gov (United States)

    2017-09-29

    The Health Resources and Services Administration (HRSA) administers section 340B of the Public Health Service Act (PHSA), known as the "340B Drug Pricing Program" or the "340B Program." HRSA published a final rule on January 5, 2017, that set forth the calculation of the ceiling price and application of civil monetary penalties. The final rule applied to all drug manufacturers that are required to make their drugs available to covered entities under the 340B Program. On August 21, 2017, HHS solicited comments on further delaying the effective date of the January 5, 2017, final rule to July 1, 2018 (82 FR 39553). HHS proposed this action to allow a more deliberate process of considering alternative and supplemental regulatory provisions and to allow for sufficient time for additional rulemaking. After consideration of the comments received on the proposed rule, HHS is delaying the effective date of the January 5, 2017, final rule, to July 1, 2018.

  8. 75 FR 59100 - Removal of Regulations That Implement and Administer a Coupon Program for Digital-to-Analog...

    Science.gov (United States)

    2010-09-27

    .... Consumers had the option to apply by mail, over the phone, via fax, or online. Consumers had 90 days to... at Sec. 3005, 120 Stat. at 23. \\4\\ 72 FR 12,097 (Mar. 15, 2007). The regulations were codified at 47 CFR part 301. \\5\\ 47 CFR 301.4(e). \\6\\ 72 FR 12,118-12,121 (Mar. 15, 2007). \\7\\ 47 CFR 301.6(b)(2)(E...

  9. Effects of a culturally tailored physical activity promotion program on selected self-regulation skills and attitudes in adolescents of an underserved, multiethnic milieu.

    Science.gov (United States)

    Laberge, Suzanne; Bush, Paula Louise; Chagnon, Miguel

    2012-01-01

    To implement a culturally tailored physical activity (PA) promotion program (FunAction) and to assess its impact on five self-regulation skills and attitudes in adolescents. Design . The design and implementation of the FunAction program were informed by social marketing principles. The study used a quasi-experimental approach to assess the impact of the program on specific outcome variables. A multiethnic, underserved middle school in Montreal, Quebec, Canada. The intervention group was made up of grade 8 students (n  =  165) and the control group was made up of grade 7 students (n  =  137). During the 16-week intervention, adolescents were able to choose from a variety of 45-minute cardiovascular PAs offered daily during their school lunch period. Adolescents participated in the activities on a voluntary basis. A self-report questionnaire was administered preintervention and postintervention to measure adolescents' scores on the following self-regulation skills and attitudes: self-control, self-esteem, attention/concentration, social competence, and interethnic relationships. Three-way repeated measures analyses of variance and correlational analyses were used. Results . A significant improvement was observed only in attention/concentration. Girls' attention/concentration scores improved significantly in the intervention group compared to the control group (F(1,127)  =  16.26, p marketing principles can help encourage adolescents from underserved, multiethnic milieus to participate in PA during their school lunch hour. Furthermore, voluntary participation in a culturally tailored PA program can improve youths' attention/concentration.

  10. 34 CFR 79.3 - What programs and activities of the Department are subject to these regulations?

    Science.gov (United States)

    2010-07-01

    ... Metropolitan Development Act. (b) If a program or activity of the Department that provides Federal financial.... (5) Direct payments to individuals. (6) Financial transfers for which the Department has no funding... the Education Consolidation and Improvement Act of 1981). (7) Research and development national in...

  11. Regulative environmental policy. Regulative Umweltpolitik

    Energy Technology Data Exchange (ETDEWEB)

    Goerlitz, A; Voigt, R [Universitaet der Bundeswehr Muenchen, Neubiberg (Germany, F.R.). Fakultaet fuer Sozialwissenschaften; eds.

    1991-01-01

    Regulative policy means those governmental attempts to steer the course of things which can fall back on a certain repertoire of instruments for actions in order to warrant the causal and temporal connection between the making available and the employment of means. The fact that environmental protection needs regulative policy is substantiated by the thesis that the market has failed; consequently only government can manage the public goods 'environment' in a suitable way, and it is a matter of fact that environmental protection at present is operated preferably via regulative policy. The problems of regulative enviromental policy are manifold. Its implementation often miscarries because of limited administrative resources on the one hand - making sufficient control impossible for instance -, and because of poor quality regulative instruments on the other hand. One way out would be to increase the efficiency of regulative policy by sophisticating judicial techniques. Other ways out point to the executing level and aim at improving implementation strategies or are concerned with post-regulative law. The latter refers to a new legal quality which demonstrates itself already in corporatistical crisis regulation or in induction programs such as pollution limits. A final way out favours deregulation strategies which includes the introduction of environmental levies or the allocation of environmental licences. An interdisciplinary discourse is to find out what would happen if these ways were taken. Pointers to solutions from varying scientific disciplines resulting from this discourse are to be found in this volume. (orig./HSCH).

  12. Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function

    Directory of Open Access Journals (Sweden)

    Xin Sun

    2018-01-01

    Full Text Available How chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example, Baf60c (Smarcd3 encodes a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex, but its role in heart development is not fully understood. We found that constitutive loss of Baf60c leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of Baf60c in cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function. Baf60c regulates a gene expression program that includes genes encoding contractile proteins, modulators of sarcomere function, and cardiac metabolic genes. Many of the genes deregulated in Baf60c null embryos are targets of the MEF2/SRF co-factor Myocardin (MYOCD. In a yeast two-hybrid screen, we identified MYOCD as a BAF60c interacting factor; we showed that BAF60c and MYOCD directly and functionally interact. We conclude that Baf60c is essential for coordinating a program of gene expression that regulates the fundamental functional properties of cardiomyocytes.

  13. Clean/alternative fueled fleet programs - 1990 Amendments to the Clean Air Act, the Colorado Air Pollution Prevention and Control Act, and Denver City and County regulations

    International Nuclear Information System (INIS)

    Bowles, S.L.; Manderino, L.A.

    1993-01-01

    Despite substantial regulations for nearly two decades, attainment of this ambient standards for ozone and carbon monoxide (CO) remain difficult goals to achieve, Even with of ozone precursors and CO. The 1990 Amendments to the Clean Air Act (CAA90) prescribe further reductions of mobile source emissions. One such reduction strategy is using clean fuels, such as methanol, ethanol, or other alcohols (in blends of 85 percent or more alcohol with gasoline or other fuel), reformulated gasoline or diesel, natural gas, liquified petroleum gas, hydrogen, or electricity. There are regulatory measures involving special fuels which will be required in areas heavily polluted with ozone and CO. The state of Colorado recently passed the 1992 Air Pollution Prevention and Control Act which included provisions for the use of alternative fuels which will be implemented in 1994. In addition to adhering to the Colorado state regulations, the city and county of Denver also have regulations pertaining to the use of alternative fuels in fleets of 10 or more vehicles. Denver's program began in 1992. This paper will address the issue of fleet conversion and its impact on industry in Colorado, and Denver in particular

  14. Effects of the Self-Regulation Empowerment Program (SREP) on middle school students' strategic skills, self-efficacy, and mathematics achievement.

    Science.gov (United States)

    Cleary, Timothy J; Velardi, Brittany; Schnaidman, Bracha

    2017-10-01

    The current study examined the effectiveness of an applied self-regulated learning intervention (Self-Regulation Empowerment Program (SREP)) relative to an existing, school-based remedial mathematics intervention for improving the motivation, strategic skills, and mathematics achievement of academically at-risk middle school students. Although significant group differences in student self-regulated learning (SRL) were not observed when using self-report questionnaires, medium to large and statistically significant group differences were observed across several contextualized, situation-specific measures of strategic and regulatory thinking. The SREP group also exhibited a statistically significant and more positive trend in achievement scores over two years in middle school relative to the comparison condition. Finally, SREP students and coaches reported SREP to be a socially-valid intervention, in terms of acceptability and importance. The importance of this study and critical areas for future research are highlighted and discussed. Copyright © 2017 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  15. 340B Drug Pricing Program Ceiling Price and Manufacturer Civil Monetary Penalties Regulation. Final rule; further delay of effective date.

    Science.gov (United States)

    2017-05-19

    The Health Resources and Services Administration (HRSA) administers section 340B of the Public Health Service Act (PHSA), referred to as the "340B Drug Pricing Program" or the "340B Program." HRSA published a final rule on January 5, 2017, that set forth the calculation of the ceiling price and application of civil monetary penalties. The final rule applied to all drug manufacturers that are required to make their drugs available to covered entities under the 340B Program. In accordance with a January 20, 2017, memorandum from the Assistant to the President and Chief of Staff, entitled "Regulatory Freeze Pending Review," HRSA issued an interim final rule that delayed the effective date of the final rule published in the Federal Register (82 FR 1210, (January 5, 2017)) to May 22, 2017. HHS invited commenters to provide their views on whether a longer delay of the effective date to October 1, 2017, would be more appropriate. After consideration of the comments received on the interim final rule, HHS is delaying the effective date of the January 5, 2017 final rule, to October 1, 2017.

  16. TCR Signal Strength Regulates Akt Substrate Specificity To Induce Alternate Murine Th and T Regulatory Cell Differentiation Programs.

    Science.gov (United States)

    Hawse, William F; Boggess, William C; Morel, Penelope A

    2017-07-15

    The Akt/mTOR pathway is a key driver of murine CD4 + T cell differentiation, and induction of regulatory T (Treg) cells results from low TCR signal strength and low Akt/mTOR signaling. However, strong TCR signals induce high Akt activity that promotes Th cell induction. Yet, it is unclear how Akt controls alternate T cell fate decisions. We find that the strength of the TCR signal results in differential Akt enzymatic activity. Surprisingly, the Akt substrate networks associated with T cell fate decisions are qualitatively different. Proteomic profiling of Akt signaling networks during Treg versus Th induction demonstrates that Akt differentially regulates RNA processing and splicing factors to drive T cell differentiation. Interestingly, heterogeneous nuclear ribonucleoprotein (hnRNP) L or hnRNP A1 are Akt substrates during Treg induction and have known roles in regulating the stability and splicing of key mRNAs that code for proteins in the canonical TCR signaling pathway, including CD3ζ and CD45. Functionally, inhibition of Akt enzymatic activity results in the dysregulation of splicing during T cell differentiation, and knockdown of hnRNP L or hnRNP A1 results in the lower induction of Treg cells. Together, this work suggests that a switch in substrate specificity coupled to the phosphorylation status of Akt may lead to alternative cell fates and demonstrates that proteins involved with alternative splicing are important factors in T cell fate decisions. Copyright © 2017 by The American Association of Immunologists, Inc.

  17. Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth.

    Science.gov (United States)

    McMillen, I C; Muhlhausler, B S; Duffield, J A; Yuen, B S J

    2004-08-01

    Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the 'unilocular' component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a 'lipostatic' role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.

  18. Strategies for Effective Eating Development-SEEDS: Design of an obesity prevention program to promote healthy food preferences and eating self-regulation in children from low-income families

    Science.gov (United States)

    To develop a scientifically based childhood obesity prevention program supporting child eating self-regulation and taste preferences. This article describes the research methods for the Strategies for Effective Eating Development program. A logic model is provided that depicts a visual presentation ...

  19. The role of long-term geologic changes in the regulation of the Canadian nuclear fuel waste management program

    International Nuclear Information System (INIS)

    Flavelle, P.

    1996-01-01

    It is recognized that the geosphere is a dynamic system over the long time frames of nuclear fuel waste disposal. This paper describes how consideration of a dynamic geosphere has impacted upon the evolving regulatory environment in Canada, and how the approach taken to comply with the regulatory requirements can affect the evaluation of long-term geologic changes. AECB staff opinion is that if the maximum possible effect of geologic changes can be demonstrated to have negligible impact on the safety of a nuclear fuel waste repository, then further consideration of a dynamic geosphere is unnecessary for the current review of the Canadian Nuclear Fuel Waste Management Program. (authors). 7 refs., 4 figs

  20. Regulation of Dynamical Systems to Optimal Solutions of Semidefinite Programs: Algorithms and Applications to AC Optimal Power Flow

    Energy Technology Data Exchange (ETDEWEB)

    Dall' Anese, Emiliano; Dhople, Sairaj V.; Giannakis, Georgios B.

    2015-07-01

    This paper considers a collection of networked nonlinear dynamical systems, and addresses the synthesis of feedback controllers that seek optimal operating points corresponding to the solution of pertinent network-wide optimization problems. Particular emphasis is placed on the solution of semidefinite programs (SDPs). The design of the feedback controller is grounded on a dual e-subgradient approach, with the dual iterates utilized to dynamically update the dynamical-system reference signals. Global convergence is guaranteed for diminishing stepsize rules, even when the reference inputs are updated at a faster rate than the dynamical-system settling time. The application of the proposed framework to the control of power-electronic inverters in AC distribution systems is discussed. The objective is to bridge the time-scale separation between real-time inverter control and network-wide optimization. Optimization objectives assume the form of SDP relaxations of prototypical AC optimal power flow problems.

  1. Applying human factors engineering program to the modernization project of NPP Control Room in accordance with U.S.NRC and KTA regulations

    International Nuclear Information System (INIS)

    Avellar, Renato Koga de; Schirru, Roberto

    2017-01-01

    Application of Human Factors Engineering (HFE) in the design and implementation of such a project is essential to ensure that the new man-machine interface outcoming from the modernization does not have any negative impacts on human performance and plant safety. This paper analyzes the applicability of the Human Factors Engineering Program in the licensing and certification of Konvoi Nucleoelectric Power Plant Control Room Modernization Project using digital instrumentation and control in accordance with U.S.NRC and KTA regulations. The results of the analyses show that although regulatory bodies adopt different methodology in the process of licensing the modernization of control rooms, the engineering aspects are being developed based on the principles of engineering. (author)

  2. Applying human factors engineering program to the modernization project of NPP Control Room in accordance with U.S.NRC and KTA regulations

    Energy Technology Data Exchange (ETDEWEB)

    Avellar, Renato Koga de, E-mail: rkoga@eletronuclear.gov.br [Eletrobrás Termonuclear S.A. (ELETRONUCLEAR), Rio de Janeiro, RJ (Brazil). Assessoria de Licenciamento Nuclear e Ambiental; Schirru, Roberto, E-mail: schirru@lmp.ufrj.br [Coordenacao de Pos-Graduacao e Pesquisa de Engenharia (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear

    2017-07-01

    Application of Human Factors Engineering (HFE) in the design and implementation of such a project is essential to ensure that the new man-machine interface outcoming from the modernization does not have any negative impacts on human performance and plant safety. This paper analyzes the applicability of the Human Factors Engineering Program in the licensing and certification of Konvoi Nucleoelectric Power Plant Control Room Modernization Project using digital instrumentation and control in accordance with U.S.NRC and KTA regulations. The results of the analyses show that although regulatory bodies adopt different methodology in the process of licensing the modernization of control rooms, the engineering aspects are being developed based on the principles of engineering. (author)

  3. Differences in regulation and efficiency on the electricity market. A preliminary study in the Market Design program

    International Nuclear Information System (INIS)

    Bergendahl, Goeran; Lindblom, Ted; Olsson, Sven-Olof; Sandoff, Anders

    2001-05-01

    This paper reports the outcome of a pilot study focusing on corporate governance and mechanism design issues concerning the electricity industry. With respect to the on-going deregulation, enlargement and internationalisation of electricity markets, especial emphasis is put on exploring the importance of the regulatory environment for accomplishing overall market efficiency. Throughout this preliminary study a central assumption has been that the actors on electricity markets are trying to maximise profits under conditions of uncertainty and asymmetric information. This means that transaction costs should be taken into consideration when studying and analysing the efficiency of electricity markets. Accordingly, the theoretical framework of this paper is resting largely on information theories, like 'Transaction Cost Economics', 'Agency Theory', 'Public Choice and Regulation' and 'Information Economics'. The pilot study consists of three parts. The first part is focusing on the development of a relevant theoretical framework. This part is demonstrating important pricing principles and regulatory incentives for accomplishing an efficient electricity market and, thus, a fair competition between electricity actors, i.e. power companies and other traders of electricity. In such a market design we have distinguished three cornerstones: 1. Marginal cost based electricity pricing, both for energy and capacity. 2. Long-range planning of production and transmission expansions. 3. Transparent transmission pricing and open access to all regional and local transmission grids. The following areas are examples of theoretical research issues that are of a particular interest in practice: The production and transmission of electricity is characterised by considerable economies of scale. The financing of new production and transmission capacity is, however, hard to manage with internal funding when electricity prices are based on marginal costs. What methods or (pricing) strategies

  4. The cysteine protease CEP1, a key executor involved in tapetal programmed cell death, regulates pollen development in Arabidopsis.

    Science.gov (United States)

    Zhang, Dandan; Liu, Di; Lv, Xiaomeng; Wang, Ying; Xun, Zhili; Liu, Zhixiong; Li, Fenglan; Lu, Hai

    2014-07-01

    Tapetal programmed cell death (PCD) is a prerequisite for pollen grain development in angiosperms, and cysteine proteases are the most ubiquitous hydrolases involved in plant PCD. We identified a papain-like cysteine protease, CEP1, which is involved in tapetal PCD and pollen development in Arabidopsis thaliana. CEP1 is expressed specifically in the tapetum from stages 5 to 11 of anther development. The CEP1 protein first appears as a proenzyme in precursor protease vesicles and is then transported to the vacuole and transformed into the mature enzyme before rupture of the vacuole. cep1 mutants exhibited aborted tapetal PCD and decreased pollen fertility with abnormal pollen exine. A transcriptomic analysis revealed that 872 genes showed significantly altered expression in the cep1 mutants, and most of them are important for tapetal cell wall organization, tapetal secretory structure formation, and pollen development. CEP1 overexpression caused premature tapetal PCD and pollen infertility. ELISA and quantitative RT-PCR analyses confirmed that the CEP1 expression level showed a strong relationship to the degree of tapetal PCD and pollen fertility. Our results reveal that CEP1 is a crucial executor during tapetal PCD and that proper CEP1 expression is necessary for timely degeneration of tapetal cells and functional pollen formation. © 2014 American Society of Plant Biologists. All rights reserved.

  5. Activity-Dependent NPAS4 Expression and the Regulation of Gene Programs Underlying Plasticity in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    José Fernando Maya-Vetencourt

    2013-01-01

    Full Text Available The capability of the brain to change functionally in response to sensory experience is most active during early stages of development but it decreases later in life when major alterations of neuronal network structures no longer take place in response to experience. This view has been recently challenged by experimental strategies based on the enhancement of environmental stimulation levels, genetic manipulations, and pharmacological treatments, which all have demonstrated that the adult brain retains a degree of plasticity that allows for a rewiring of neuronal circuitries over the entire life course. A hot spot in the field of neuronal plasticity centres on gene programs that underlie plastic phenomena in adulthood. Here, I discuss the role of the recently discovered neuronal-specific and activity-dependent transcription factor NPAS4 as a critical mediator of plasticity in the nervous system. A better understanding of how modifications in the connectivity of neuronal networks occur may shed light on the treatment of pathological conditions such as brain damage or disease in adult life, some of which were once considered untreatable.

  6. Programming of stress-related behavior and epigenetic neural gene regulation in mice offspring through maternal exposure to predator odor

    Science.gov (United States)

    St-Cyr, Sophie; McGowan, Patrick O.

    2015-01-01

    Perinatal stress mediated through the mother can lead to long-term alterations in stress-related phenotypes in offspring. The capacity for adaptation to adversity in early life depends in part on the life history of the animal. This study was designed to examine the behavioral and neural response in adult offspring to prenatal exposure to predator odor: an ethologically-relevant psychological stressor. Pregnant mice were exposed daily to predator odors or distilled water control over the second half of the pregnancy. Predator odor exposure lead to a transient decrease in maternal care in the mothers. As adults, the offspring of predator odor-exposed mothers showed increased anti-predator behavior, a predator-odor induced decrease in activity and, in female offspring, an increased corticosterone (CORT) response to predator odor exposure. We found a highly specific response among stress-related genes within limbic brain regions. Transcript abundance of Corticotropin-releasing hormone receptor 1 (CRHR1) was elevated in the amygdala in adult female offspring of predator odor-exposed mothers. In the hippocampus of adult female offspring, decreased Brain-derived neurotrophic factor (BDNF) transcript abundance was correlated with a site-specific decrease in DNA methylation in Bdnf exon IV, indicating the potential contribution of this epigenetic mechanism to maternal programming by maternal predator odor exposure. These data indicate that maternal predator odor exposure alone is sufficient to induce an altered stress-related phenotype in adulthood, with implications for anti-predator behavior in offspring. PMID:26082698

  7. Lace plant ethylene receptors, AmERS1a and AmERS1c, regulate ethylene-induced programmed cell death during leaf morphogenesis.

    Science.gov (United States)

    Rantong, Gaolathe; Evans, Rodger; Gunawardena, Arunika H L A N

    2015-10-01

    The lace plant, Aponogeton madagascariensis, is an aquatic monocot that forms perforations in its leaves as part of normal leaf development. Perforation formation occurs through developmentally regulated programmed cell death (PCD). The molecular basis of PCD regulation in the lace plant is unknown, however ethylene has been shown to play a significant role. In this study, we examined the role of ethylene receptors during perforation formation. We isolated three lace plant ethylene receptors AmERS1a, AmERS1b and AmERS1c. Using quantitative PCR, we examined their transcript levels at seven stages of leaf development. Through laser-capture microscopy, transcript levels were also determined in cells undergoing PCD and cells not undergoing PCD (NPCD cells). AmERS1a transcript levels were significantly lower in window stage leaves (in which perforation formation and PCD are occurring) as compared to all other leaf developmental stages. AmERS1a and AmERS1c (the most abundant among the three receptors) had the highest transcript levels in mature stage leaves, where PCD is not occurring. Their transcript levels decreased significantly during senescence-associated PCD. AmERS1c had significantly higher transcript levels in NPCD compared to PCD cells. Despite being significantly low in window stage leaves, AmERS1a transcripts were not differentially expressed between PCD and NPCD cells. The results suggested that ethylene receptors negatively regulate ethylene-controlled PCD in the lace plant. A combination of ethylene and receptor levels determines cell fate during perforation formation and leaf senescence. A new model for ethylene emission and receptor expression during lace plant perforation formation and senescence is proposed.

  8. The polyadenylation factor subunit CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30: A key factor of programmed cell death and a regulator of immunity in arabidopsis

    KAUST Repository

    Bruggeman, Quentin

    2014-04-04

    Programmed cell death (PCD) is essential for several aspects of plant life, including development and stress responses. Indeed, incompatible plant-pathogen interactions are well known to induce the hypersensitive response, a localized cell death. Mutational analyses have identified several key PCD components, and we recently identified the mips1 mutant of Arabidopsis (Arabidopsis thaliana), which is deficient for the key enzyme catalyzing the limiting step of myoinositol synthesis. One of the most striking features of mips1 is the light-dependent formation of lesions on leaves due to salicylic acid (SA)-dependent PCD, revealing roles for myoinositol or inositol derivatives in the regulation of PCD. Here, we identified a regulator of plant PCD by screening for mutants that display transcriptomic profiles opposing that of the mips1 mutant. Our screen identified the oxt6 mutant, which has been described previously as being tolerant to oxidative stress. In the oxt6 mutant, a transfer DNA is inserted in the CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30 (CPSF30) gene, which encodes a polyadenylation factor subunit homolog. We show that CPSF30 is required for lesion formation in mips1 via SA-dependent signaling, that the prodeath function of CPSF30 is not mediated by changes in the glutathione status, and that CPSF30 activity is required for Pseudomonas syringae resistance. We also show that the oxt6 mutation suppresses cell death in other lesion-mimic mutants, including lesion-simulating disease1, mitogen-activated protein kinase4, constitutive expressor of pathogenesis-related genes5, and catalase2, suggesting that CPSF30 and, thus, the control of messenger RNA 3′ end processing, through the regulation of SA production, is a key component of plant immune responses. © 2014 American Society of Plant Biologists. All rights reserved.

  9. Heat shock instructs hESCs to exit from the self-renewal program through negative regulation of OCT4 by SAPK/JNK and HSF1 pathway.

    Science.gov (United States)

    Byun, Kyunghee; Kim, Taek-Kyun; Oh, Jeehyun; Bayarsaikhan, Enkhjargal; Kim, Daesik; Lee, Min Young; Pack, Chan-Gi; Hwang, Daehee; Lee, Bonghee

    2013-11-01

    Environmental factors affect self-renewal of stem cells by modulating the components of self-renewal networks. Heat shock, an environmental factor, induces heat shock factors (HSFs), which up-regulate stress response-related genes. However, the link of heat shock to self-renewal of stem cells has not been elucidated yet. Here, we present the direct link of heat shock to a core stem cell regulator, OCT4, in the self-renewal network through SAPK/JNK and HSF1 pathway. We first showed that heat shock initiated differentiation of human embryonic stem cells (hESCs). Gene expression analysis revealed that heat shock increased the expression of many genes involved in cellular processes related to differentiation of stem cells. We then examined the effects of HSFs induced by heat shock on core self-renewal factors. Among HSFs, heat shock induced mainly HSF1 in hESCs. The HSF1 repressed the expression of OCT4, leading to the differentiation of hESCs and the above differentiation-related gene expression change. We further examined the effects of the upstream MAP (mitogen-activated protein) kinases of HSF1 on the repression of OCT4 expression by HSF1. Among the MAP kinases, SAPK/JNK controlled predominantly the repression of the OCT4 expression by HSF1. The direct link of heat shock to the core self-renewal regulator through SAPK/JNK and HSF1 provides a fundamental basis for understanding the effect of heat and other stresses involving activation of HSF1 on the self-renewal program and further controlling differentiation of hESCs in a broad spectrum of stem cell applications using these stresses. © 2013.

  10. A user-friendly robotic sample preparation program for fully automated biological sample pipetting and dilution to benefit the regulated bioanalysis.

    Science.gov (United States)

    Jiang, Hao; Ouyang, Zheng; Zeng, Jianing; Yuan, Long; Zheng, Naiyu; Jemal, Mohammed; Arnold, Mark E

    2012-06-01

    Biological sample dilution is a rate-limiting step in bioanalytical sample preparation when the concentrations of samples are beyond standard curve ranges, especially when multiple dilution factors are needed in an analytical run. We have developed and validated a Microsoft Excel-based robotic sample preparation program (RSPP) that automatically transforms Watson worklist sample information (identification, sequence and dilution factor) to comma-separated value (CSV) files. The Freedom EVO liquid handler software imports and transforms the CSV files to executable worklists (.gwl files), allowing the robot to perform sample dilutions at variable dilution factors. The dynamic dilution range is 1- to 1000-fold and divided into three dilution steps: 1- to 10-, 11- to 100-, and 101- to 1000-fold. The whole process, including pipetting samples, diluting samples, and adding internal standard(s), is accomplished within 1 h for two racks of samples (96 samples/rack). This platform also supports online sample extraction (liquid-liquid extraction, solid-phase extraction, protein precipitation, etc.) using 96 multichannel arms. This fully automated and validated sample dilution and preparation process has been applied to several drug development programs. The results demonstrate that application of the RSPP for fully automated sample processing is efficient and rugged. The RSPP not only saved more than 50% of the time in sample pipetting and dilution but also reduced human errors. The generated bioanalytical data are accurate and precise; therefore, this application can be used in regulated bioanalysis.

  11. Food Reformulation, Responsive Regulation, and “Regulatory Scaffolding”: Strengthening Performance of Salt Reduction Programs in Australia and the United Kingdom

    Directory of Open Access Journals (Sweden)

    Roger Magnusson

    2015-06-01

    Full Text Available Strategies to reduce excess salt consumption play an important role in preventing cardiovascular disease, which is the largest contributor to global mortality from non-communicable diseases. In many countries, voluntary food reformulation programs seek to reduce salt levels across selected product categories, guided by aspirational targets to be achieved progressively over time. This paper evaluates the industry-led salt reduction programs that operate in the United Kingdom and Australia. Drawing on theoretical concepts from the field of regulatory studies, we propose a step-wise or “responsive” approach that introduces regulatory “scaffolds” to progressively increase levels of government oversight and control in response to industry inaction or under-performance. Our model makes full use of the food industry’s willingness to reduce salt levels in products to meet reformulation targets, but recognizes that governments remain accountable for addressing major diet-related health risks. Creative regulatory strategies can assist governments to fulfill their public health obligations, including in circumstances where there are political barriers to direct, statutory regulation of the food industry.

  12. Differential tissue distribution, developmental programming, estrogen regulation and promoter characteristics of cyp19 genes in teleost fish.

    Science.gov (United States)

    Callard, G V; Tchoudakova, A V; Kishida, M; Wood, E

    2001-12-01

    Teleost fish are characterized by exceptionally high levels of brain estrogen biosynthesis when compared to the brains of other vertebrates or to the ovaries of the same fish. Goldfish (Carassius auratus) and zebrafish (Danio rerio) have utility as complementary models for understanding the molecular basis and functional significance of exaggerated neural estrogen biosynthesis. Multiple cytochrome P450 aromatase (P450arom) cDNAs that derive from separate gene loci (cyp19a and cyp19b) are differentially expressed in brain (P450aromB>A) and ovary (P450aromA>B) and have a different developmental program (B>A) and response to estrogen upregulation (B only). As measured by increased P450aromB mRNA, a functional estrogen response system is first detected 24-48 h post-fertilization (hpf), consistent with the onset of estrogen receptor (ER) expression (alpha, beta, and gamma). The 5'-flanking region of the cyp19b gene has a TATA box, two estrogen response elements (EREs), an ERE half-site (ERE1/2), a nerve growth factor inducible-B protein (NGFI-B)/Nur77 responsive element (NBRE) binding site, and a sequence identical to the zebrafish GATA-2 gene neural specific enhancer. The cyp19a promoter region has TATA and CAAT boxes, a steroidogenic factor-1 (SF-1) binding site, and two aryl hydrocarbon receptor (AhR)/AhR nuclear translocator factor (ARNT) binding motifs. Both genes have multiple potential SRY/SOX binding sites (16 and 8 in cyp19b and cyp19a, respectively). Luciferase reporters have basal promoter activity in GH3 cells, but differences (a>b) are opposite to fish pituitary (b>a). When microinjected into fertilized zebrafish eggs, a cyp19b promoter-driven green fluorescent protein (GFP) reporter (but not cyp19a) is expressed in neurons of 30-48 hpf embryos, most prominently in retinal ganglion cells (RGCs) and their projections to optic tectum. Further studies are required to identify functionally relevant cis-elements and cellular factors, and to determine the

  13. Tight regulation between cell survival and programmed cell death in GBM stem-like cells by EGFR/GSK3b/PP2A signaling.

    Science.gov (United States)

    Gürsel, Demirkan B; Banu, Matei A; Berry, Nicholas; Marongiu, Roberta; Burkhardt, Jan-Karl; Kobylarz, Keith; Kaplitt, Michael G; Rafii, Shahin; Boockvar, John A

    2015-01-01

    Malignant gliomas represent one of the most aggressive forms of cancer, displaying high mortality rates and limited treatment options. Specific subpopulations of cells residing in the tumor niche with stem-like characteristics have been postulated to initiate and maintain neoplasticity while resisting conventional therapies. The study presented here aims to define the role of glycogen synthase kinase 3 beta (GSK3b) in patient-derived glioblastoma (GBM) stem-like cell (GSC) proliferation, apoptosis and invasion. To evaluate the potential role of GSK3b in GBM, protein profiles from 68 GBM patients and 20 normal brain samples were analyzed for EGFR-mediated PI3kinase/Akt and GSK3b signaling molecules including protein phosphatase 2A (PP2A). To better understand the function of GSK3b in GBM, GSCs were isolated from GBM patient samples. Blocking GSK3b phosphorylation at Serine 9 attenuated cell proliferation while concomitantly stimulating apoptosis through activation of Caspase-3 in patient-derived GSCs. Increasing GSK3b protein content resulted in the inhibition of cell proliferation, colony formation and stimulated programmed cell death. Depleting GSK3b in GSCs down regulated PP2A. Furthermore, knocking down PP2A or blocking its activity by okadaic acid inactivated GSK3b by increasing GSK3b phosphorylation at Serine 9. Our data suggests that GSK3b may function as a regulator of apoptosis and tumorigenesis in GSCs. Therapeutic approaches targeting GSK3b in glioblastoma stem-like cells may be a useful addition to our current therapeutic armamentarium.

  14. The "déjà vu effect:" evaluation of United States medical device legislation, regulation, and the Food and Drug Administration's contentious 510(k) program.

    Science.gov (United States)

    Bauman, Jordan

    2012-01-01

    With the Medical Device Amendments of 1976, Congress granted FDA authority to regulate medical devices by implementing a risk-based regulatory framework. Several years prior to this legislation, the Cooper Committee reviewed the medical device regulatory landscape and uncovered weaknesses that could be detrimental to public health. However, only after several high-profile incidents involving unsafe medical devices did Congress respond with strong legislation. Since 1976, additional medical device legislative revisions have been enacted to address deficiencies highlighted by various groups representing Congress, FDA, and industry. A repetitive conclusion from these groups has been that the 510(k) program is incapable of serving as a premarket evaluation of safety and effectiveness under the existing statutory framework. However, these legislative revisions did not change the statutory framework despite these repeated findings. In 2009, CDRH convened separate groups to again review the 510(k) program. While more comprehensive than previous initiatives, the observed deficiencies and the proposed recommendations are remarkably similar to those identified by their predecessors. This cyclical review of the medical device regulatory landscape whereby the same observations and recommendations are repeated yet the output of such review does not yield major legislative revision of the existing statutory framework can be described as the "déjà vu effect." This will continue unless Congress enacts legislation that implements a new statutory framework with a different standard other than substantial equivalence. In the past, Congress has implemented major legislation only after a public health crisis. Hopefully this will not be the driving force in the future.

  15. Effectiveness of an Attachment-Based Intervention Program in Promoting Emotion Regulation and Attachment in Adolescent Mothers and their Infants: A Pilot Study

    Science.gov (United States)

    Riva Crugnola, Cristina; Ierardi, Elena; Albizzati, Alessandro; Downing, George

    2016-01-01

    This pilot study examined the effectiveness of an attachment-based intervention program, PRERAYMI, based on video technique, psychological counseling and developmental guidance in improving the style of interaction and emotion regulation of adolescent mothers and their infants after 3 and 6 months of intervention. Analyses revealed that adolescent mothers who participated in the intervention (vs. control group adolescent mothers) increased their Sensitivity and reduced their Controlling style after both 3 and 6 months of treatment. Infants who participated in the intervention (vs. control group infants) increased their Cooperative style and reduced their Passive style from 3 to 9 months. Moreover, the intervention group dyads (vs. control group dyads) increased the amount of time spent in affective positive coordination states (matches), decreased the amount of time spent in affective mismatches, and had a greater ability to repair mismatches from 3 to 9 months. Furthermore, the intervention group dyads (vs. control group dyads) increased the amount of time spent in reciprocal involvement in play with objects from 3 to 9 months. The quality of maternal attachment did not affect the intervention effect. PMID:26941673

  16. Effectiveness of an attachment-based intervention program in promoting emotion regulation and attachment in adolescent mothers and their infants: a pilot study

    Directory of Open Access Journals (Sweden)

    Cristina eRiva Crugnola

    2016-02-01

    Full Text Available This pilot study examined the effectiveness of an attachment-based intervention program, PRERAYMI, based on video technique, psychological counseling and developmental guidance in improving the style of interaction and emotion regulation of adolescent mothers and their infants after 3 and 6 months of intervention. Analyses revealed that adolescent mothers who participated in the intervention (vs. control group adolescent mothers increased their Sensitivity and reduced their Controlling style after both 3 and 6 months of treatment. Infants who participated in the intervention (vs. control group infants increased their Cooperative style and reduced their Passive style from 3 to 9 months. Moreover, the intervention group dyads (vs. control group dyads increased the amount of time spent in affective positive coordination states (matches, decreased the amount of time spent in affective mismatches, and had a greater ability to repair mismatches from 3 to 9 months. Furthermore, the intervention group dyads (vs. control group dyads increased the amount of time spent in reciprocal involvement in play with objects from 3 to 9 months. The quality of maternal attachment did not affect the intervention effect.

  17. Fostering Self-Regulated Learning through Distance Education: A Case Study of M.Phil Secondary Teacher Education Program of Allama Iqbal Open University

    Science.gov (United States)

    Ambreen, Munazza; Haqdad, Ambreen; Saleem, Wajid A.

    2016-01-01

    Self-regulated learning (SLR) has been recognized as a pivotal antecedent of students' effective learning and academic achievement. A self-regulated learner can independently and effectively plan for learning, choose and use appropriate learning strategies and reflect and monitor learning progress. Self-regulated learning, for learners in general…

  18. The release of cytochrome c and the regulation of the programmed cell death progress in the endosperm of winter wheat (Triticum aestivum L.) under waterlogging.

    Science.gov (United States)

    Qi, Yuan-Hong; Mao, Fang-Fang; Zhou, Zhu-Qing; Liu, Dong-Cheng; Min-Yu; Deng, Xiang-Yi; Li, Ji-Wei; Mei, Fang-Zhu

    2018-05-02

    It has been shown in mammalian systems that the mitochondria can play a key role in the regulation of apoptosis by releasing intermembrane proteins (such as cytochrome c) into the cytosol. Cytochrome c released from the mitochondria to the cytoplasm activates proteolytic enzyme cascades, leading to specific nuclear DNA degradation and cell death. This pathway is considered to be one of the important regulatory mechanisms of apoptosis. Previous studies have shown that endosperm cell development in wheat undergoes specialized programmed cell death (PCD) and that waterlogging stress accelerates the PCD process; however, little is known regarding the associated molecular mechanism. In this study, changes in mitochondrial structure, the release of cytochrome c, and gene expression were studied in the endosperm cells of the wheat (Triticum aestivum L.) cultivar "huamai 8" during PCD under different waterlogging durations. The results showed that waterlogging aggravated the degradation of mitochondrial structure, increased the mitochondrial permeability transition (MPT), and decreased mitochondrial transmembrane potential (ΔΨm), resulting in the advancement of the endosperm PCD process. In situ localization and western blotting of cytochrome c indicated that with the development of the endosperm cell, cytochrome c was gradually released from the mitochondria to the cytoplasm, and waterlogging stress led to an advancement and increase in the release of cytochrome c. In addition, waterlogging stress resulted in the increased expression of the voltage-dependent anion channel (VDAC) and adenine nucleotide translocator (ANT), suggesting that the mitochondrial permeability transition pore (MPTP) may be involved in endosperm PCD under waterlogging stress. The MPTP inhibitor cyclosporine A effectively suppressed cell death and cytochrome c release during wheat endosperm PCD. Our results indicate that the mitochondria play important roles in the PCD of endosperm cells and that

  19. Administration: Army Congressional Fellowship Program

    National Research Council Canada - National Science Library

    2000-01-01

    This printing publishes a new Army Regulation. This regulation presents the policies and procedures under which the Army manages the Army Congressional Fellowship Program and supplements applicable Department...

  20. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in the United States. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D.A.; Weaver, C.L.; Gallagher, K.C.; Hejna, D.; Rielley, K.J.

    1980-01-01

    This report is one of a series of preliminary reports describing the laws and regulatory programs of the United States and each of the 50 states affecting the siting and operation of energy generating facilities likely to be used in Integrated Community Energy Systems (ICES). Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES. This report describes laws and regulatory programs in the United States. Subsequent reports will (1) describe public utility rate regulatory procedures and practices as they might affect an ICES, (2) analyze each of the aforementioned regulatory programs to identify impediments to the development of ICES, and (3) recommend potential changes in legislation and regulatory practices and procedures to overcome such impediments.

  1. Regulating the Regulator

    Energy Technology Data Exchange (ETDEWEB)

    1992-08-26

    The article reports on a challenge to the UK electricity regulator to defend his record by the Coalition for Fair Electricity Regulation (COFFER). The challenge centres on whether the obligation for the regional electric companies (REC) to purchase power from the cheapest source is being enforced. This is related to the wider issue of whether the REC's support of combined-cycle gas turbine (CCGT) is economic. COFFER considers that uneconomic gas-fired power plants are being allowed to displace economic coal-fired stations. Aspects discussed include the background to the dispute and the costs of CCGT and coal fired power generation. 1 fig., 1 tab.

  2. Government regulation of forestry practices on private forest land in the United States: an assessment of state government responsibilities and program performance

    Science.gov (United States)

    Paul V. Ellefson; Michael A. Kilgore; James E. Granskog

    2006-01-01

    In 2003, a comprehensive assessment of state government, forest practice regulatory programs in the United States was undertaken. Involved was an extensive review of the literature and information gathering h m program administration in all 50 states. The assessment determined that regulatory programs focus on a wide range of forestry practices applied to private...

  3. The polyadenylation factor subunit CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR30: A key factor of programmed cell death and a regulator of immunity in arabidopsis

    KAUST Repository

    Bruggeman, Quentin; Garmier, Marie; De Bont, Linda; Soubigou-Taconnat, Ludivine; Mazubert, Christelle; Benhamed, Moussa; Raynaud, Cé cile; Bergounioux, Catherine; Delarue, Marianne

    2014-01-01

    striking features of mips1 is the light-dependent formation of lesions on leaves due to salicylic acid (SA)-dependent PCD, revealing roles for myoinositol or inositol derivatives in the regulation of PCD. Here, we identified a regulator of plant PCD

  4. Benefits from flywheel energy storage for area regulation in California - demonstration results : a study for the DOE Energy Storage Systems program.

    Energy Technology Data Exchange (ETDEWEB)

    Eyer, James M. (Distributed Utility Associates, Livermore, CA)

    2009-10-01

    This report documents a high-level analysis of the benefit and cost for flywheel energy storage used to provide area regulation for the electricity supply and transmission system in California. Area regulation is an 'ancillary service' needed for a reliable and stable regional electricity grid. The analysis was based on results from a demonstration, in California, of flywheel energy storage developed by Beacon Power Corporation (the system's manufacturer). Demonstrated was flywheel storage systems ability to provide 'rapid-response' regulation. Flywheel storage output can be varied much more rapidly than the output from conventional regulation sources, making flywheels more attractive than conventional regulation resources. The performance of the flywheel storage system demonstrated was generally consistent with requirements for a possible new class of regulation resources - 'rapid-response' energy-storage-based regulation - in California. In short, it was demonstrated that Beacon Power Corporation's flywheel system follows a rapidly changing control signal (the ACE, which changes every four seconds). Based on the results and on expected plant cost and performance, the Beacon Power flywheel storage system has a good chance of being a financially viable regulation resource. Results indicate a benefit/cost ratio of 1.5 to 1.8 using what may be somewhat conservative assumptions. A benefit/cost ratio of one indicates that, based on the financial assumptions used, the investment's financial returns just meet the investors target.

  5. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Missouri. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate public utilities in Missouri is vested in the Public Service Commission. The Commission is composed of five members who are appointed by the governor with the advice and consent of the senate. Commissioners are appointed for a term of six years. Commissioners must be free from any employment or pecuniary interests incompatible with the duties of the Commission. The Commission is charged with the general supervision of public utilities. The Public Service Commission Law passed in 1913, makes no provision for the regulation of public utilities by municipalities. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  6. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had......This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  7. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Illinois. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate public utilities is vested generally in the Illinois Commerce Commission, comprised of five members appointed by the governor with the advice and consent of the senate and appointed for five year terms. They must be free from any employment or pecuniary interests in any business subject to regulation by the Commission. Local governments may exercise a large degree of regulatory authority over public utilities providing services within a municipality. The question of whether a municipality will exercise regulatory control over local public utilities must be put to the voters of the city. If the proposition is approved by a majority of the voters, the municipality may regulate services and rates and exercise most of the regulatory functions otherwise assigned to the Commission. If any public utility is dissatisfied with any action of a municipality, the utility is entitled to apply to the Commission for review of the action. On review, the Commission may take any determination which it deems just and reasonable. In addition, municipally-owned utilities are excluded specifically from the definition of public utility. These utilities are not within the jurisdiction of the Commission and are regulated locally. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  8. Technical study of brazilian vehicular natural gas program and impact of normative regulators; Estudo tecnico do programa de gas natural veicular e o impacto das normas reguladoras

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Newton; Fragoso, Karine; Caselli, Bruno [Servicco Nacional de Aprendizagem Industrial (SENAI), Rio de Janeiro, RJ (Brazil); Burrowes, Mariana [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Dept. de Engenharia de Materiais

    2004-07-01

    This paper it concept to present the evaluation of the Brazilian natural gas program in the last decade, our technological aspects and use, as those economical implications of this program. Verification of environment advantages from this gas system and the relation between another fuel system from the bibliographic review. Discussions of future scenarios in this market share, those threats and opportunities. The impact of new stands from next years and it considerations. Finally will be present proposes for sustainable grow of this program with base in the relationship of market, stand and technology, in expose aspects. (author)

  9. Proposed Regulation of Fuels and Fuel Additives: Federal Volatility Control Program in the Denver-Boulder-Greeley-Ft. Collins-Loveland, Colorado, 1997 8-Hour Ozone Nonattainment Area

    Science.gov (United States)

    This notice proposes establishing an applicable standard of 7.8 pounds (psi) Reid vapor pressure under the federal volatility control program, in the Denver-Boulder-Greeley-Ft. Collins-Loveland, Colorado, 1997 8-hour ozone nonattainment area.

  10. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in North Dakota. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The North Dakota Public Service Commission (PSC) is a constitutional body responsible for the regulation of all public utilities. The PSC is composed of three elected commissioners who serve for six year terms. Section 83 of the state's Constitution gives the legislature the power to prescribe the powers and duties of the PCS. Pursuant to this authorization, the legislature adopted Title 49 of the North Dakota Century Code prescribing the jurisdiction as well as the powers and duties of the PSC. It also prescribes various rules and regulations pertaining to electric, gas, and other public utilities. All authority over public utilities is vested in the PSC. Local governments, except for the powers inherent in their franchising and zoning authority, are not given any control over utility regulation. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  11. Construct Validation of a Program to Increase Use of Self-Regulation for Physical Activity among Overweight and Obese Adults with Type 2 Diabetes Mellitus

    Science.gov (United States)

    Petosa, R. Lingyak; Silfee, Valerie

    2016-01-01

    Background: Studies have revealed that overweight adults with type 2 diabetes have low rates of physical activity and are resistant to change. Purpose: The purpose of this study was to use construct validation of intervention methods to examine the impact of a 4-week behavioral intervention on the use of self-regulation skills for physical…

  12. PACE. A Program for Acquiring Competence in Entrepreneurship. Part II: Becoming an Entrepreneur. Unit D: Government Regulations and Small Businesses. Research and Development Series No. 194 B-4.

    Science.gov (United States)

    Ohio State Univ., Columbus. National Center for Research in Vocational Education.

    This three-part curriculum for entrepreneurship education is primarily for postsecondary level, including four-year colleges and adult education, but it can be adapted for special groups or vocational teacher education. The emphasis of the seven instructional units in Part II is establishing a business. Unit D focuses on business regulations at…

  13. 48 CFR 3019.705 - Responsibilities for the contracting officer under the subcontracting program.

    Science.gov (United States)

    2010-10-01

    ... Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS The Small Business Subcontracting Program 3019.705...

  14. Austria; Financial Sector Assessment Program Update Technical Note: Factual Update and Analysis of the IOSCO Objectives and Principles of Securities Regulation

    OpenAIRE

    International Monetary Fund

    2008-01-01

    This technical note focuses on the International Organization of Securities Commissions objectives and principles of securities regulations of Austria. The 2003 assessment found that Austria had fully broadly implemented a large majority of principles. The human resources of the Securities Supervision Department of the Financial Market Authority (FMA) should be increased, especially to conduct on-site inspections, in addition to the 14 planned appointments. Administrative fines should be rais...

  15. No evidence for dualism in function and receptors: PD-L2/B7-DC is an inhibitory regulator of human T cell activation.

    Science.gov (United States)

    Pfistershammer, Katharina; Klauser, Christoph; Pickl, Winfried F; Stöckl, Johannes; Leitner, Judith; Zlabinger, Gerhard; Majdic, Otto; Steinberger, Peter

    2006-05-01

    The B7 family member programmed-death-1-ligand 2 (PD-L2/B7-DC) is a ligand for programmed-death-receptor 1 (PD-1), a receptor involved in negative regulation of T cell activation. Several independent studies have reported that PD-L2, however, can also potently costimulate murine T cells via an additional yet unidentified receptor. In this study, we evaluated the contribution of PD-L2 to the activation of human T cells using a novel system of engineered T cell stimulators that expresses membrane-bound anti-CD3 antibodies. Analyzing early activation markers, cytokine production and proliferation, we found PD-L2 to consistently inhibit T cell activation. PD-L2 inhibition affected CD4+ and CD8+ T cells and was not abrogated by costimulation via CD28. Blocking PD-1 reverted the inhibitory effect of PD-L2, demonstrating involvement of this pathway. In human T cells, we found no evidence for any of the costimulatory effects described for PD-L2 in murine systems. In line with our functional data that do not point to stimulatory PD-L2-ligands, we show that binding of PD-L2-immunoglobulin to activated human T cells is abrogated by PD-1 antibodies. Our results demonstrate that PD-L2 negatively regulates human T cell activation and thus might be a candidate molecule for immunotherapeutic approaches aimed to attenuate pathological immune responses.

  16. Incentive policies for promoting wind power production in Brazil: Scenarios for the Alternative Energy Sources Incentive Program (PROINFA) under the New Brazilian electric power sector regulation

    International Nuclear Information System (INIS)

    Dutra, Ricardo Marques; Szklo, Alexandre Salem

    2008-01-01

    The Alternative Energy Sources Incentive Program (PROINFA) was designed in 2002 to stimulate the electricity generation from three energy sources (wind, biomass and small-scale hydro) in Brazil. The Program was divided into two phases. The first one uses feed-in tariffs for promoting the development of 3300 MW. The second one that was originally based on feed-in tariffs was modified in 2003, in order to be based on biddings for renewables. These biddings are capped to limit their impact on the final electricity tariff. Due to this bound, the highest-cost power option promoted by PROINFA (wind power generation) might have development problems. Simulating different scenarios for the biddings, it was verified that the only way to reach the original goal set by PROINFA (10% of the annual electricity consumption provided by alternative sources up to 2020) and, simultaneously, not overcome the bidding bound is to promote biomass-fired power generation alone, during the Program's second phase. However, this action contradicts one of the targets of the Program, which is to diversify the energy matrix. An alternative option could be biddings for renewables according to specific criteria (complementarities, industrial and technological development and cost), based not only on their cost-effectiveness. (author)

  17. Endogenous programmed death ligand-1 restrains the development and onset of Sjӧgren's syndrome in non-obese diabetic mice.

    Science.gov (United States)

    Zhou, Jing; Jin, Jun-O; Kawai, Toshihisa; Yu, Qing

    2016-12-14

    Programmed death-ligand 1 (PD-L1) down-modulates various immune responses by engaging the co-inhibitory receptor programmed death-1. Expression of PD-L1 and programmed death-1 is elevated in the salivary glands of patients with Sjögren's syndrome (SS). The objective of this study is to define the role of endogenous PD-L1 in SS pathogenesis in non-obese diabetic (NOD) mouse model of this disease. We inhibited endogenous PD-L1 function by intraperitoneal administration of a blocking antibody to 6 week-old female NOD/ShiLtJ mice repeatedly during a 9-day period. PD-L1 blockade accelerated leukocyte infiltration and caspase-3 activation in the submandibular gland (SMG), production of antinuclear and anti-M3 muscarinic acetylcholine receptor (M3R) autoantibodies and impairment of saliva secretion, indicative of accelerated development and onset of SS. The effect of PD-L1 blockade was associated with increased T- and B cells and T helper 1 cytokine IFN-γ in the SMG. Local administration of exogenous IFN-γ to the SMG led to impaired salivary secretion accompanied by down-regulation of aquaporin 5 and an increase in anti-M3R autoantibodies. Conversely, neutralization of IFN-γ markedly improved salivary secretion and aquaporin 5 expression in anti-PD-L1-treated NOD/ShiLtJ mice. Hence, endogenous PD-L1 hinders the development and onset of SS in NOD mice, in part by suppressing IFN-γ production.

  18. The new renewable energy regulation of the European Union of 2009. Is there a reorientation in te question of the promotional programs since the regulation of 2001?; Die neue erneuerbare Energie-Richtlinie der EU von 2009. Zeigt sich seit der Richtlinie von 2001 ein Umdenken bei der Frage der Foerdersysteme?

    Energy Technology Data Exchange (ETDEWEB)

    Lauber, Volkmar; Schenner, Elisa [Salzburg Univ. (Austria). Fachbereich Politikwissenschaft und Soziologie

    2009-12-15

    The authors of the contribution under consideration report on the new renewable energy regulation of the European Union of the year 2009. In particular, it is examined whether there is a reorientation with the question of promotional programs since the regulation of 2001. The first chapter of this contribution is an introduction to the problem and formulates hypotheses. In the second chapter, the analytic framework for the research is described which orientates itself at the interpretive methods of the politics field analysis. The third chapter fills the theoretical framework with experience and lights up the structural preconditions of the political controversies as well as the two politics processes (1996-2001 and 2007-2009).

  19. Foxo1 and Foxp1 play opposing roles in regulating the differentiation and antitumor activity of TH9 cells programmed by IL-7

    Science.gov (United States)

    Bi, Enguang; Ma, Xingzhe; Lu, Yong; Yang, Maojie; Wang, Qiang; Xue, Gang; Qian, Jianfei; Wang, Siqing; Yi, Qing

    2018-01-01

    Tumor-specific CD4+ T helper 9 (TH9) cells, so-called because of their production of the cytokine interleukin-9 (IL-9), are a powerful effector T cell subset for cancer immunotherapy. We found that pretreatment of naïve CD4+ T cells with IL-7 further enhanced their differentiation into TH9 cells and augmented their antitumor activity. IL-7 markedly increased the abundance of the histone acetyltransferase p300 by activating the STAT5 and PI3K-AKT-mTOR signaling pathways and promoting the acetylation of histones at the Il9 promoter. As a result, the transcriptional regulator Foxo1 was dephosphorylated and translocated to the nucleus, bound to the Il9 promoter, and induced the production of IL-9 protein. In contrast, Foxp1, which bound to the Il9 promoter in naïve CD4+ T cells and inhibited Il9 expression, was outcompeted for binding to the Il9 promoter by Foxo1 and translocated to the cytoplasm. Furthermore, forced expression of Foxo1 or a deficiency in Foxp1 in CD4+ T cells markedly increased the production of IL-9, whereas a deficiency in Foxo1 inhibited the ability of IL-7 to enhance the differentiation and antitumor activity of TH9 cells. Thus, we identified the roles of Foxo1 as a positive regulator and Foxp1 as a negative regulator of TH9 cell differentiation and antitumor activity, which may provide potential targets for cancer immunotherapy. PMID:29018172

  20. Simulation of Darlington shutdown and regulation systems

    International Nuclear Information System (INIS)

    1986-10-01

    This report describes the development of a simulation of the Darlington Nuclear Generating Station shutdown and regulating systems, DARSIM. The DARSIM program simulates the spatial neutron dynamics, the regulation of the reactor power, and Shutdown System 1, SDS1, and Shutdown System 2, SDS2, software. The DARSIM program operates in the interactive simulation (INSIM) program environment

  1. Comparison of national programs and regulations for the management of spent fuel and disposal of high-level waste in seven countries

    International Nuclear Information System (INIS)

    Numark, N.J.; Mattson, R.J.; Gaunt, J.

    1986-01-01

    This paper describes programs and regulatory requirements affecting the management of spent fuel and disposal of high-level radioactive waste in seven nations with large nuclear power programs. The comparison is intended to illustrate that the range of spent fuel management options is influenced by certain technical and political constraints. It begins by providing overall nuclear fuel cycle facts for each country, including nuclear generating capacities, rates of spent fuel discharge, and policies on spent fuel reprocessing. Spent fuel storage techniques and reprocessing activities are compared in light of constraints such as fuel type. Waste disposal investigations are described, including a summary of the status of regulatory developments affecting repository siting and disposal. A timeline is provided to illustrate the principle milestones in spent fuel management and waste disposal in each country. Finally, policies linking nuclear power licensing and development to nuclear waste management milestones and RandD progress are discussed

  2. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Massachusetts. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate public utilities is vested generally in the Department of Public Utilities. The Department is under the supervision and control of a commission consisting of three members appointed by the governor for terms of four years. No more than two of the commissioners may be members of the same political party. Commissioners must be freee from any employment or financial interests which are incompatible with the duties of the Department. The Department is responsible for regulating public utilities. The Department is specifically granted general supervisory authority over all gas and electric companies. Specific provisions for the appeal of local decisions exist only in the case of a municipality's approval or disapproval of new operaions by an electric or gas company in a municipality already being served by another such utility. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  3. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in New York. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate public utilities is vested generally in the New York Public Service Commission. The Commission is composed of five members appointed by the governor with the advice and consent of the senate. Commissioners are appointed for six-year terms. Commissioners may not have any pecuniary or financial interest in any public utility. Local governing bodies are authorized to exercise such power, jurisdiction and authority in enforcing the laws of the state and the orders, rules, and regulations of the commission as may be prescribed by statute or by the commission with respect to public utilities. A Commission spokesman confirmed that no statutes have been passed pursuant to this provision and the Commission has not ceded any of its regulatory powers to local governments. With the exception of the granting of franchises and permits to use public ways, local governments exercise no regulatory powers over public utilities. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  4. Nigeria; Publication of Financial Sector Assessment Program Documentation––Detailed Assessment of Implementation of IOSCO Objectives and Principles of Securities Regulation

    OpenAIRE

    International Monetary Fund

    2013-01-01

    An assessment of the level of implementation of the International Organization of Securities Commissions (IOSCO) Principles in Nigeria was conducted as part of the International Monetary Fund (IMF)-World Bank Financial Sector Assessment Program (FSAP). The ongoing global financial crisis has reinforced the need for assessors to make a judgment about supervisory practices and to determine whether they are sufficiently effective. The assessment methodology provides a set of assessment criteria ...

  5. Regulations in radiation protection

    International Nuclear Information System (INIS)

    1986-01-01

    On the occasion of the twenty fifth anniversary of the Dutch Society for Radiation Protection, a symposium was held about Regulations in Radiation Protection. The program consisted of six contributions of which four are included in this publication. The posters presented are published in NVS-nieuws, 1985, vol. 11(5). (G.J.P.)

  6. A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jihui; Lin, Coney Pei-Chen; Pathak, Manish C.; Temple, Brenda R.S.; Nile, Aaron H.; Mousley, Carl J.; Duncan, Mara C.; Eckert, Debra M.; Leiker, Thomas J.; Ivanova, Pavlina T.; Myers, David S.; Murphy, Robert C.; Brown, H. Alex; Verdaasdonk, Jolien; Bloom, Kerry S.; Ortlund, Eric A.; Neiman, Aaron M.; Bankaitis, Vytas A. [Emory-MED; (SBU); (TAM); (UNC); (Vanderbilt-MED); (Utah); (UCHSC)

    2014-07-11

    Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumed during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and phosphoinositide) biology that are invisible to contemporary haploid-centric cell biological, proteomic, and functional genomics approaches.

  7. A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jihui; Lin, Coney Pei-Chen; Pathak, Manish C.; Temple, Brenda R.S.; Nile, Aaron H.; Mousley, Carl J.; Duncan, Mara C.; Eckert, Debra M.; Leiker, Thomas J.; Ivanova, Pavlina T.; Myers, David S.; Murphy, Robert C.; Brown, H. Alex; Verdaasdonk, Jolien; Bloom, Kerry S.; Ortlund, Eric A.; Neiman, Aaron M.; Bankaitis, Vytas A. (Emory-MED); (UNCSM); (UNC); (UCHSC); (TAM); (Vanderbilt-MED); (SBU); (Utah)

    2016-07-06

    Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumed during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and phosphoinositide) biology that are invisible to contemporary haploid-centric cell biological, proteomic, and functional genomics approaches.

  8. Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA interaction network regulating intestinal epithelial cellular pathways using R programming.

    Science.gov (United States)

    Robinson, J M; Henderson, W A

    2018-01-12

    We report a method using functional-molecular databases and network modelling to identify hypothetical mRNA-miRNA interaction networks regulating intestinal epithelial barrier function. The model forms a data-analysis component of our cell culture experiments, which produce RNA expression data from Nanostring Technologies nCounter ® system. The epithelial tight-junction (TJ) and actin cytoskeleton interact as molecular components of the intestinal epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is effected by the Rac/Rock/Rho signaling pathway and other associated pathways which may be activated or suppressed by extracellular signaling from growth factors, hormones, and immune receptors. Pathway activations affect epithelial homeostasis, contributing to degradation of the epithelial barrier associated with osmotic dysregulation, inflammation, and tumor development. The complexity underlying miRNA-mRNA interaction networks represents a roadblock for prediction and validation of competing-endogenous RNA network function. We developed a network model to identify hypothetical co-regulatory motifs in a miRNA-mRNA interaction network related to epithelial function. A mRNA-miRNA interaction list was generated using KEGG and miRWalk2.0 databases. R-code was developed to quantify and visualize inherent network structures. We identified a sub-network with a high number of shared, targeting miRNAs, of genes associated with cellular proliferation and cancer, including c-MYC and Cyclin D.

  9. Fluoroorotic acid-selected Nicotiana plumbaginifolia cell lines with a stable thymine starvation phenotype have lost the thymine-regulated transcriptional program.

    Science.gov (United States)

    Santoso, D; Thornburg, R

    2000-08-01

    We have selected 143 independent Nicotiana plumbaginifolia cell lines that survive in the presence of 5-fluoroorotic acid. These lines show several diverse phenotypes. The majority of these cell lines showed reduced levels of UMP synthase. However, one particular phenotype, which represents 14% of the total independent lines (20 cell lines), showed an unexpected, high level of UMP synthase and was therefore analyzed in detail. The selected cell lines showed no differences with wild-type cells with respect to uptake of orotic acid, affinity of UMP synthase for its substrates, or UMP synthase gene-copy number. Alternative detoxification mechanisms were also excluded. The elevated enzyme activity was correlated with elevated UMP synthase protein levels as well as elevated UMP synthase mRNA levels. In contrast to wild-type cell lines, the fluoroorotic acid-selected cell lines did not respond to thymine or to other biochemicals that affect thymine levels. In addition, there was also a concomitant up-regulation of aspartate transcarbamoylase, however, dihydroorotase and dihydroorotate dehydrogenase are not up-regulated in these cell lines.

  10. Fluoroorotic Acid-Selected Nicotiana plumbaginifolia Cell Lines with a Stable Thymine Starvation Phenotype Have Lost the Thymine-Regulated Transcriptional Program1

    Science.gov (United States)

    Santoso, Djoko; Thornburg, Robert

    2000-01-01

    We have selected 143 independent Nicotiana plumbaginifolia cell lines that survive in the presence of 5-fluoroorotic acid. These lines show several diverse phenotypes. The majority of these cell lines showed reduced levels of UMP synthase. However, one particular phenotype, which represents 14% of the total independent lines (20 cell lines), showed an unexpected, high level of UMP synthase and was therefore analyzed in detail. The selected cell lines showed no differences with wild-type cells with respect to uptake of orotic acid, affinity of UMP synthase for its substrates, or UMP synthase gene-copy number. Alternative detoxification mechanisms were also excluded. The elevated enzyme activity was correlated with elevated UMP synthase protein levels as well as elevated UMP synthase mRNA levels. In contrast to wild-type cell lines, the fluoroorotic acid-selected cell lines did not respond to thymine or to other biochemicals that affect thymine levels. In addition, there was also a concomitant up-regulation of aspartate transcarbamoylase, however, dihydroorotase and dihydroorotate dehydrogenase are not up-regulated in these cell lines. PMID:10938367

  11. Endogenous programmed death ligand-1 restrains the development and onset of Sjӧgren’s syndrome in non-obese diabetic mice

    OpenAIRE

    Jing Zhou; Jun-O. Jin; Toshihisa Kawai; Qing Yu

    2016-01-01

    Programmed death-ligand 1 (PD-L1) down-modulates various immune responses by engaging the co-inhibitory receptor programmed death-1. Expression of PD-L1 and programmed death-1 is elevated in the salivary glands of patients with Sj?gren?s syndrome (SS). The objective of this study is to define the role of endogenous PD-L1 in SS pathogenesis in non-obese diabetic (NOD) mouse model of this disease. We inhibited endogenous PD-L1 function by intraperitoneal administration of a blocking antibody to...

  12. Regulations and instructions; Propisi i uputstva

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1960-07-01

    Regulations and instructions for operating the RA reactor consist of the following chapters: general regulations with the fundamental RA reactor characteristics, operating regulations and instructions for the personnel on duty, regulations for accidental conditions, training program for the staff of the Laboratory for reactor operation. Propisi i uputstva za rad reaktora RA sadrze sledeca poglavlja: opsti deo sa kratkim opisom karakteristika reaktora RA, propisi za rad dezurnog osoblja, propisi za slucaj udesa, program obuke osoblja Laboratorije za eksploataciju reaktora RA.

  13. Radiation regulation

    International Nuclear Information System (INIS)

    Braithwaite, J.; Grabosky, P.

    1985-01-01

    The five main areas of radiation regulation considered are radiation exposure in the mining of uranium and other minerals, exposure in the use of uranium in nuclear reactors, risks in the transport of radioactive materials and hazards associated with the disposal of used materials. In Australia these problems are regulated by mines departments, the Australian Atomic Energy Commission and radiation control branches in state health departments. Each of these instutional areas of regulation is examined

  14. Risk-informed regulation

    International Nuclear Information System (INIS)

    Hoffman, D.R.

    2003-01-01

    In assessing safety for nuclear facilities, regulators have traditionally used a deterministic approach. New techniques for assessing nuclear or radiological risks make it possible for regulators to incorporate risk insights into their regulations. By 'risk-informing' the regulatory processes, independent bodies tasked with protecting the health and safety of the public can focus on those design and operational issues most important to safety. Such an approach is a move away from prescriptive regulations that were based on conservative engineering judgments toward regulations focused on issues that contribute significantly to safety. Despite the availability of probabilistic risk assessment (PRA) tools, organisations often struggle with how to best use this capability. Most international regulations are still based largely on deterministic analyses that were developed without the benefit of quantitative or measurable estimates of risk. PRA considers issues of risk in a more comprehensive manner by examining a wider spectrum of initiating events and their frequency, and considers the likelihood of events in a rigorous and comprehensive manner. In some countries, nuclear regulators are actively moving toward increasing the use of risk insights in a variety of strategic arenas, including risk-informed technical specifications (operating limits and conditions), in-service inspection and testing, programs, and assessment and enforcement actions. A risk-informed approach enhances the traditional deterministic approach by explicitly considering a broader range of safety challenges, focusing resources on the basis of risk significance, considering a broader range of counter measures to mitigate challenges, and explicitly identifying and quantifying uncertainties in analyses. (author)

  15. 48 CFR 519.7016 - Program review.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Program review. 519.7016 Section 519.7016 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7016 Program review. At the conclusion of...

  16. Phosphorylation state of a Tob/BTG protein, FOG-3, regulates initiation and maintenance of the Caenorhabditis elegans sperm fate program.

    Science.gov (United States)

    Lee, Myon-Hee; Kim, Kyung Won; Morgan, Clinton T; Morgan, Dyan E; Kimble, Judith

    2011-05-31

    FOG-3, the single Caenorhabditis elegans Tob/BTG protein, directs germ cells to adopt the sperm fate at the expense of oogenesis. Importantly, FOG-3 activity must be maintained for the continued production of sperm that is typical of the male sex. Vertebrate Tob proteins have antiproliferative activity and ERK phosphorylation of Tob proteins has been proposed to abrogate "antiproliferative" activity. Here we investigate FOG-3 phosphorylation and its effect on sperm fate specification. We found both phosphorylated and unphosphorylated forms of FOG-3 in nematodes. We then interrogated the role of FOG-3 phosphorylation in sperm fate specification. Specifically, we assayed FOG-3 transgenes for rescue of a fog-3 null mutant. Wild-type FOG-3 rescued both initiation and maintenance of sperm fate specification. A FOG-3 mutant with its four consensus ERK phosphorylation sites substituted to alanines, called FOG-3(4A), rescued partially: sperm were made transiently but not continuously in both sexes. A different FOG-3 mutant with its sites substituted to glutamates, called FOG-3(4E), had no rescuing activity on its own, but together with FOG-3(4A) rescue was complete. Thus, when FOG-3(4A) and FOG-3(4E) were both introduced into the same animals, sperm fate specification was not only initiated but also maintained, resulting in continuous spermatogenesis in males. Our findings suggest that unphosphorylated FOG-3 initiates the sperm fate program and that phosphorylated FOG-3 maintains that program for continued sperm production typical of males. We discuss implications of our results for Tob/BTG proteins in vertebrates.

  17. The Cysteine Protease CEP1, a Key Executor Involved in Tapetal Programmed Cell Death, Regulates Pollen Development in Arabidopsis[W][OPEN

    Science.gov (United States)

    Zhang, Dandan; Liu, Di; Lv, Xiaomeng; Wang, Ying; Xun, Zhili; Liu, Zhixiong; Li, Fenglan; Lu, Hai

    2014-01-01

    Tapetal programmed cell death (PCD) is a prerequisite for pollen grain development in angiosperms, and cysteine proteases are the most ubiquitous hydrolases involved in plant PCD. We identified a papain-like cysteine protease, CEP1, which is involved in tapetal PCD and pollen development in Arabidopsis thaliana. CEP1 is expressed specifically in the tapetum from stages 5 to 11 of anther development. The CEP1 protein first appears as a proenzyme in precursor protease vesicles and is then transported to the vacuole and transformed into the mature enzyme before rupture of the vacuole. cep1 mutants exhibited aborted tapetal PCD and decreased pollen fertility with abnormal pollen exine. A transcriptomic analysis revealed that 872 genes showed significantly altered expression in the cep1 mutants, and most of them are important for tapetal cell wall organization, tapetal secretory structure formation, and pollen development. CEP1 overexpression caused premature tapetal PCD and pollen infertility. ELISA and quantitative RT-PCR analyses confirmed that the CEP1 expression level showed a strong relationship to the degree of tapetal PCD and pollen fertility. Our results reveal that CEP1 is a crucial executor during tapetal PCD and that proper CEP1 expression is necessary for timely degeneration of tapetal cells and functional pollen formation. PMID:25035401

  18. Study of Risk Assessment Programs at Federal Agencies and Commercial Industry Related to the Conduct or Regulation of High Hazard Operations

    International Nuclear Information System (INIS)

    Bari, R.; Rosenbloom, S.; O'Brien, J.

    2011-01-01

    In the Department of Energy (DOE) Implementation Plan (IP) for Defense Nuclear Facilities Safety Board's Recommendation 2009-1, the DOE committed to studying the use of quantitative risk assessment methodologies at government agencies and industry. This study consisted of document reviews and interviews of senior management and risk assessment staff at six organizations. Data were collected and analyzed on risk assessment applications, risk assessment tools, and controls and infrastructure supporting the correct usage of risk assessment and risk management tools. The study found that the agencies were in different degrees of maturity in the use of risk assessment to support the analysis of high hazard operations and to support decisions related to these operations. Agencies did not share a simple, 'one size fits all' approach to tools, controls, and infrastructure needs. The agencies recognized that flexibility was warranted to allow use of risk assessment tools in a manner that is commensurate with the complexity of the application. The study also found that, even with the lack of some data, agencies application of the risk analysis structured approach could provide useful insights such as potential system vulnerabilities. This study, in combination with a companion study of risk assessment programs in the DOE Offices involved in high hazard operations, is being used to determine the nature and type of controls and infrastructure needed to support risk assessments at the DOE.

  19. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in New Jersey. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate the operations of public utilities in New Jersey is generally vested in the Board of Public Utilities. The Board is subsumed within the Department of Energy for administrative purposes, but functions largely independently of supervision or control by that agency. The Board is composed of three members who serve for six-year terms. They are appointed by the governor with the advice and consent of the senate. Within the purview of its powers, the authority of the Board supersedes that of local governments. The Board, for example, may grant exemptions from local zoning provisions, and has approving authority over privileges or franchises granted by municipalities to public utilities. The Board, however, cannot override the refusal of a municipality to grant consent to the initiation of operations by a public utility. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  20. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Maryland. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D A; Weaver, C L; Gallagher, K C; Hejna, D; Rielley, K J

    1980-01-01

    The authority to regulate public utilities in Maryland is vested in the Public Service Commission under the authority of the Public Service Commission Law. The Commission consists of five commissioners who are appointed by the governor with the advice and consent of the Senate. Commissioners must be or become citizens of Maryland, at least three are to serve full time, and one of the commissioners is to be nominated as chairman. The tenure of each commissioner is six years and their terms are on a staggered schedule. Commissioners are eligible for reappointment. The Public Service Commission Law provides that the Commission's powers an jurisdiction shall extend to the full extent permitted by the Constitution and laws of the United States. Local governments in Maryland are not given regulatory power over public service companies. The only power that local governments have over the operations of utilities is the power to grant franchises. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  1. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in California. Preliminary background report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, D.A.; Weaver, C.L.; Gallagher, K.C.; Hejna, D.; Rielley, K.J.

    1980-01-01

    The Constitution of the State of California grants to the Legislature control over persons and private corporations that own or operate a line, plant, or system for the production, generation, or transmission of heat, light, water, or power to be furnished either directly or indirectly to or for the public. The Constitution establishes the Public Utilities Commission and grants certain specific powers to the PUC, including the power to fix rates, establish rules and prescribe a uniform system of accounts. The Constitution also recognizes that the Legislature has plenary power to confer additional authority and jurisdiction upon the PUC. The Constitution prohibits regulation by a city, county, or other municipal body of matters over which the Legislature has granted regulatory power to the PUC. This provision does not, however, impair the right of any city to grant franchises for public utilities. The California legislature has enacted the California Public Utilities Code and has designated the PUC as the agency to implement the regulatory provisions of the Code. The Public Utilities Commission consists of five members appointed by the governor and approved by the senate, a majority of the membership concurring, for staggered 6-year terms. Certain limited powers over the conduct of public utilities may still be exercised by municipalities. Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES.

  2. Program of environmental radiological monitoring

    International Nuclear Information System (INIS)

    2005-11-01

    This Regulation refers to the requirement of the Regulation CNEN-NN.3.01, 'Basic Act of Radiological Protection', as expressed in the section 5.14, related to the Program of Environmental Radiological Monitoring (PMRA)

  3. Incentive regulation of nuclear power plants by state regulators

    International Nuclear Information System (INIS)

    Martin, R.L.; Baker, K.; Olson, J.

    1991-02-01

    The Nuclear Regulatory Commission (NRC) monitors incentive programs established by state regulators in order to obtain current information and to consider the potential safety effects of the incentive programs as applied to nuclear units. The current report is an update of NUREG/CR-5509, Incentive Regulation of Nuclear Power Plants by State Public Utility Commissions, published in December 1989. The information in this report was obtained from interviews conducted with each state regulator and each utility with a minimum entitlement of 10%. The agreements, orders, and settlements from which each incentive program was implemented were reviewed as required. The interviews and supporting documentation form the basis for the individual state reports describing the structure and financial impact of each incentive program. The programs currently in effect represent the adoption of an existing nuclear performance incentive program proposal and one new program. In addition, since 1989 a number of nuclear units have been included in one existing program; while one program was discontinued and another one concluded. 6 refs., 27 tabs

  4. Army Programs: Army Finance and Accounting Quality Assurance Program

    National Research Council Canada - National Science Library

    1988-01-01

    This regulation discusses the primary responsibilities of commanders and staff officers at installation and higher levels for execution of the Army Finance and Accounting Quality Assurance (QA) Program...

  5. 48 CFR 3019.705-1 - General support for the program.

    Science.gov (United States)

    2010-10-01

    ... SECURITY, HOMELAND SECURITY ACQUISITION REGULATION (HSAR) SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS The Small Business Subcontracting Program 3019.705-1 General support for the program. In any...

  6. Regulation of the O-glycan-type Sialyl-Lewis X (sLex) Bio-synthesis Pathway during Cell Transformation Programs: Epithelial-Mesenchymal Transition (EMT) and Molecular Subtypes in Breast Carcinoma and Human T Cell Activation

    KAUST Repository

    AbuElela, Ayman

    2017-12-01

    During tumor progression and development of distant metastases, a subset of cancer cells undergoes transformation programs, such as epithelial-mesenchymal transition (EMT), to acquire enhanced migratory attributes to commence the metastatic cascade with the intension of achieving an active cell adhesion molecule-mediated organ-specific homing. Similarly, naive T cells reform the assemblage of their surface adhesion molecules during differentiation to activated T cells in order to successfully home to sites of inflammation and other extra-lymphoid organs for surveillance purposes. Sialyl-Lewis X (sLex) is well-known for mediating the homing of epithelial circulating tumor cellss (CTCs) and activated T cells to target sites through the interaction with endothelial selectins. Since glycan structures are not directly encoded by the genome, their expression is dependent on the glycosyltransferase (GT) expression and activity. Yet, the modulation of GTs during breast cancer transformation and in different molecular subtypes is still unknown. In addition, although the regulation of GTs during T cell activation is well-understood, the regulation at the epigenetic level is lacking. O-glycan-type sLex expression and E-selectin binding under static and flow conditions varies among molecular subtypes of breast cancer and upon the induction of EMT which is linked to the expression patterns of GTs. GTs displayed a significant prognostic value of in the association with the patients\\' survival profiles and in the ability to predict the breast cancer molecular subtypes from the expression data of a random patient sample. Also, GTs were able to differentiate between tumor and their normal counterparts as well as cancer types and glioblastoma subtypes. On the other hand, we studied the regulation of GTs in human CD4+ memory T cells compared to the naive cells at the epigenetic level. Memory T cell subsets demonstrated differential chromatin accessibility and histone marks within

  7. The immune checkpoint regulator PD-L1 is a specific target for naturally occurring CD4(+) T cells

    DEFF Research Database (Denmark)

    Munir, Shamaila; Andersen, Gitte Holmen; Svane, Inge Marie

    2013-01-01

    Programmed cell death 1 ligand 1 (PD-L1) is an important regulator of T-cell responses and may consequently limit anticancer immunity. We have recently identified PD-L1-specific, cytotoxic CD8(+) T cells. In the present study, we develop these findings and report that CD4(+) helper T cells...... spontaneously recognize PD-L1. We examined the locality of a previously identified HLA-A*0201-restricted PD-L1-epitope for the presence of possible CD4(+) T-cell epitopes. Thus, we identified naturally occurring PD-L1-specific CD4(+) T cells among the peripheral blood lymphocytes of cancer patients...... and - to lesser extents - healthy donors, by means of ELISPOT assays. PD-L1-specific CD4(+) T cells appeared to be TH17 cells exhibiting an effector T-cell cytokine profile. Hence, PD-L1-specific CD4(+) T cells released interferon γ (IFNγ), tumor necrosis factor α (TNFα) and interleukin-17 (IL-17) in response...

  8. Child Care Program Office

    Science.gov (United States)

    Information Medicaid Public Health Centers Temporary "Cash" Assistance Senior Benefits Program the proposed regulation changes, including the potential costs to private persons of complying with Heating Assistance Medicaid Senior Benefits Temporary Assistance Get Help Food Health Care Cash Child Care

  9. 78 FR 40651 - Regulated Navigation Area; Special Buzzards Bay Vessel Regulation, Buzzards Bay, MA

    Science.gov (United States)

    2013-07-08

    ... Carrier Program RNA Regulated Navigation Area RA Technical Risk Assessment VMRS Vessel Movement Reporting... avoid the fragmentation of regulatory regimes as a vessel transits across State [[Page 40652

  10. 25 CFR 275.4 - Implementing regulations.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Implementing regulations. 275.4 Section 275.4 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR INDIAN SELF-DETERMINATION AND EDUCATION ASSISTANCE ACT PROGRAM STAFFING § 275.4 Implementing regulations. Regulations to implement section 105 of the Act...

  11. NORM regulations

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

    The author reviews the question of regulation for naturally occuring radioactive material (NORM), and the factors that have made this a more prominent concern today. Past practices have been very relaxed, and have often involved very poor records, the involvment of contractors, and the disposition of contaminated equipment back into commercial service. The rationale behind the establishment of regulations is to provide worker protection, to exempt low risk materials, to aid in scrap recycling, to provide direction for remediation and to examine disposal options. The author reviews existing regulations at federal and state levels, impending legislation, and touches on the issue of site remediation and potential liabilities affecting the release of sites contaminated by NORM.

  12. Fisheries regulation

    DEFF Research Database (Denmark)

    Jensen, Frank; Frost, Hans Staby; Abildtrup, Jens

    2017-01-01

    Economists normally claim that a stock externality arises within fisheries because each individual fisherman does not take the effect on stock size into account when making harvest decisions. Due to the stock externality, it is commonly argued that fisheries regulation is necessary, but regulatory...... decisions are complicated by a tremendous amount of uncertainty and asymmetric information. This paper provides an overview of selected parts of the literature on the regulation of fisheries under uncertainty and asymmetric information, and possible areas for future research are identified. Specifically...

  13. Environmental Regulation

    Data.gov (United States)

    Kansas Data Access and Support Center — KR305b 1994 coverage, used to support water quality programs, references water quality use designations and support levels. The KR305b 1994 coverage is available for...

  14. Apoptotic Regulation

    National Research Council Canada - National Science Library

    Thress, Kenneth

    2000-01-01

    ... for implementation of the cell death program. In an extensive analysis of chromosomal deletion mutants in the fly, Drosophila Melanogaster, Steller and colleagues identified a chromosomal region containing a number of genes critical...

  15. French regulations

    International Nuclear Information System (INIS)

    Ballereau, P.

    1998-01-01

    In this issue are given the new French regulations relative to radiation protection of temporary personnel, the licensing to release gaseous and liquid wastes and the licensing granted to thirty two laboratories using beta and gamma decay radioisotopes. (N.C.)

  16. Pilot Program for the implementation of the Regulation Doc. nr. 453 of the Ministry of Health in the Image Service of the Hospital Municipal Cardoso Fontes, Rio de Janeiro, Brazil - preliminary results

    International Nuclear Information System (INIS)

    Almeida, Claudio Domingues; Ferreira, Rubemar de Souza; Marechal, Maria Helena H.; Milano, Nelly Ester

    2000-01-01

    Overall quality in radiological protection and medical image depend largely on keeping certain safety standard and technical procedures in good levels. This way, In June 1998, the Ministry of Health published the document 453 - Guidelines of Radiological Protection to Medical and Dental practices defining different levels of actions and responsibility to radiological installation where the critical starting point was the necessity of a previous quality assurance program (QAP) into the radiological service. Preliminary results of a QAP realized in the Department of Radiology of a high complexity Hospital in Rio de Janeiro has showed that, although the importance of 453 regulation be recognizing, there is a few motivation for implementing it. Besides, during 1999 was possible identify losses of 14,9 % related only to the repetition of exposures in the patients, reflecting in terms of cost about of U$ 70,000 a year. Results suggest that loss of 54% of total film are due to under or over exposures and 20% are due to inadequate positioning either film or patient, evidencing the need of training the technical and medical staff. (author)

  17. Foxg1 regulates retinal axon pathfinding by repressing an ipsilateral program in nasal retina and by causing optic chiasm cells to exert a net axonal growth-promoting activity.

    Science.gov (United States)

    Tian, Natasha M; Pratt, Thomas; Price, David J

    2008-12-01

    Mammalian binocular vision relies on the divergence of retinal ganglion cell axons at the optic chiasm, with strictly controlled numbers projecting contralaterally and ipsilaterally. In mouse, contralateral projections arise from the entire retina, whereas ipsilateral projections arise from ventrotemporal retina. We investigate how development of these patterns of projection is regulated by the contralateral determinant Foxg1, a forkhead box transcription factor expressed in nasal retina and at the chiasm. In nasal retina, loss of Foxg1 causes increased numbers of ipsilateral projections and ectopic expression of the ipsilateral determinants Zic2, Ephb1 and Foxd1, indicating that nasal retina is competent to express an ipsilateral program that is normally suppressed by Foxg1. Using co-cultures that combine Foxg1-expressing with Foxg1-null retinal explants and chiasm cells, we provide functional evidence that Foxg1 promotes contralateral projections through actions in nasal retina, and that in chiasm cells, Foxg1 is required for the generation of a hitherto unrecognized activity supporting RGC axon growth.

  18. Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status.

    Science.gov (United States)

    Messai, Yosra; Gad, Sophie; Noman, Muhammad Zaeem; Le Teuff, Gwenael; Couve, Sophie; Janji, Bassam; Kammerer, Solenne Florence; Rioux-Leclerc, Nathalie; Hasmim, Meriem; Ferlicot, Sophie; Baud, Véronique; Mejean, Arnaud; Mole, David Robert; Richard, Stéphane; Eggermont, Alexander M M; Albiges, Laurence; Mami-Chouaib, Fathia; Escudier, Bernard; Chouaib, Salem

    2016-10-01

    Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene. To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression. A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene. The 786-O, A498, and RCC4 cell lines were used to investigate the mechanisms of PD-L1 regulation. Fisher's exact test was used for VHL mutation and Kruskal-Wallis test for PD-L1 expression. If no covariate accounted for the association of VHL and PD-L1, then a Kruskal-Wallis test was used; otherwise Cochran-Mantel-Haenzsel test was used. We also used the Fligner-Policello test to compare two medians when the distributions had different dispersions. We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells. Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. We investigated the relationship between von Hippel-Lindau mutations and programmed death-ligand 1 expression. We

  19. 75 FR 69009 - Acquisition Regulation: Socioeconomic Programs

    Science.gov (United States)

    2010-11-10

    ... 952.223-72, Radiation Protection and Nuclear Criticality. 12. Part 924 is a new part being added... Procurement and Assistance Management, or for the National Nuclear Security Administration (NNSA), to the... issue a Family Policymaking Assessment for any rulemaking or policy that may affect family well-being...

  20. Redox regulation in metabolic programming and inflammation

    Directory of Open Access Journals (Sweden)

    Helen R. Griffiths

    2017-08-01

    Resolution of inflammation is triggered by encounter with apoptotic membranes exposing oxidised phosphatidylserine that interact with the scavenger receptor, CD36. Downstream of CD36, activation of AMPK and PPARγ elicits mitochondrial biogenesis, arginase expression and a switch towards oxidative phosphorylation in the M2 macrophage. Proinflammatory cytokine production by M2 cells decreases, but anti-inflammatory and wound healing growth factor production is maintained to support restoration of normal function.

  1. Regulating Internalities

    OpenAIRE

    Sunstein, Cass Robert; Allcott, Hunt

    2015-01-01

    This paper offers a framework for regulating internalities. Using a simple economic model, we provide four principles for designing and evaluating behaviorally-motivated policy. We then outline rules for determining which contexts reliably reflect true preferences and discuss empirical strategies for measuring internalities. As a case study, we focus on energy efficiency policy, including Corporate Average Fuel Economy (CAFE) standards and appliance and lighting energy efficiency standards.

  2. 78 FR 79567 - National School Lunch Program and School Breakfast Program: Nutrition Standards for All Foods...

    Science.gov (United States)

    2013-12-31

    ... Program: Nutrition Standards for All Foods Sold in Schools as Required by the Healthy, Hunger-Free Kids... interim rule entitled National School Lunch Program and School Breakfast Program: Nutrition Standards for..., 2013 / Rules and Regulations [[Page 79567

  3. 77 FR 33456 - Public Water Supply Supervision Program; Program Revision for the State of Washington

    Science.gov (United States)

    2012-06-06

    ... ENVIRONMENTAL PROTECTION AGENCY [FRL-9682-4] Public Water Supply Supervision Program; Program... State Public Water Supply Supervision Primacy Program. Washington has adopted regulations analogous to... of Health--Office of Drinking Water, [[Page 33457

  4. Nuclear regulation

    International Nuclear Information System (INIS)

    1990-04-01

    Because of an accidental release in 1986 of low-level waste stored at the Wright-Patterson Air Force Base, Ohio, several individuals inhaled small amounts of a radioactive substance. GAO examined the Nuclear Regulatory Commission's oversight of the Department of Defense's use, handling, and disposal of radioactive material and found that no comprehensive DOD waste disposal program exists and none of the three services knows the full extent of its low-level radioactive waste disposal problems. Throughout the 1980s, the Army and the Air Force had, on occasion, been banned from disposal sites for failing to comply with federal and state requirements. By December 1992, two of the three sites now used by DOD to disposed of waste will close, and only a limited number of new sites may be available for several years. In the interim, DID will pay substantial surcharges to dispose of waste. After January 1993, DOD will have to comply with disposal requirements for as many as 16 sites or store waste on-site pending the availability of new sites. This report discusses how GAO believes DOD needs to take full advantage of the time between now and January 1993 to establish a low-level radioactive waste disposal program. DOD also needs to work with other federal agencies, compacts, and states to determine the feasibility of dedicating a portion of one or more disposal sites for the government's use

  5. 42 CFR 55a.107 - What other regulations apply?

    Science.gov (United States)

    2010-10-01

    ... FOR BLACK LUNG CLINICS General Provisions § 55a.107 What other regulations apply? Other regulations which apply to the Black Lung Clinics Program include, but are not limited to, the following: 42 CFR...

  6. 40 CFR 122.37 - Will the small MS4 storm water program regulations at §§ 122.32 through 122.36 and § 123.35 of...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Will the small MS4 storm water program... 122.37 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS EPA ADMINISTERED PERMIT PROGRAMS: THE NATIONAL POLLUTANT DISCHARGE ELIMINATION SYSTEM Permit Application and...

  7. Regulation of radiation sources in Canada

    International Nuclear Information System (INIS)

    Brown, W.R.

    1989-04-01

    This paper describes in general the Canadian program for the regulation of radiation sources, with particular emphasis on radioisotope licences. The Atomic Energy Control Board is described, as are the most significant parts of the Regulations. Licensing, which is the method chosen for control, is explained by describing the assessment of an application through the enforcement of the requirements, and the overall effectiveness of the program is measured by analyzing the incidents and overexposures that have occurred in recent years

  8. Functional Programming

    OpenAIRE

    Chitil, Olaf

    2009-01-01

    Functional programming is a programming paradigm like object-oriented programming and logic programming. Functional programming comprises both a specific programming style and a class of programming languages that encourage and support this programming style. Functional programming enables the programmer to describe an algorithm on a high-level, in terms of the problem domain, without having to deal with machine-related details. A program is constructed from functions that only map inputs to ...

  9. The regulations of the Nuclear Technology Committee

    International Nuclear Information System (INIS)

    Schwarzer, W.

    1984-01-01

    The work of the Nuclear Technology Committee (NTC) is characterised by the key words 'safety related regulations' and 'nuclear technology'. The rationalisation effect desired from regulations and the not unlimited number of experts qualified for working out regulations, make it necessary to establish priorities. The NTC has almost exclusively worked out regulations for nuclear powerstations and mainly for light water reactors. The program defined at present seems to cover the most important areas. Future developments can be foreseen in the execution of the part of the program not yet concluded, the maintenance of the regulations and, depending on the development of nuclear technology, the greater inclusion of the HTR and possibly the expansion of the regulations to fast breeder reactors and plant of the fuel circuit. (orig./HSCH) [de

  10. 77 FR 13009 - Regulation of Fuels and Fuel Additives: Identification of Additional Qualifying Renewable Fuel...

    Science.gov (United States)

    2012-03-05

    ... Regulation of Fuels and Fuel Additives: Identification of Additional Qualifying Renewable Fuel Pathways Under the Renewable Fuel Standard Program AGENCY: Environmental Protection Agency (EPA). ACTION: Withdrawal... Renewable Fuel Standard program regulations. Because EPA received adverse comment, we are withdrawing the...

  11. Idaho Chemical Processing Plant training program

    International Nuclear Information System (INIS)

    1975-01-01

    Objectives, regulations and requirements, training methods, certification and recertification, progression and incentives, and coverage of the ICPP operator training program are discussed in detail. (LK)

  12. 76 FR 6587 - Pennsylvania Regulatory Program

    Science.gov (United States)

    2011-02-07

    ... [PA-159-FOR; OSM 2010-0017] Pennsylvania Regulatory Program AGENCY: Office of Surface Mining... remove a required amendment to the Pennsylvania regulatory program (the ``Pennsylvania program'') under... program amendment codified in the Federal regulations, Pennsylvania has submitted information that it...

  13. 29 CFR 1470.25 - Program income.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Program income. 1470.25 Section 1470.25 Labor Regulations... Financial Administration § 1470.25 Program income. (a) General. Grantees are encouraged to earn income to defray program costs. Program income includes income from fees for services performed, from the use or...

  14. Retooling for new environmental regulations

    International Nuclear Information System (INIS)

    Levy, W.W.

    1997-01-01

    The petroleum industry is subject to regulations which require better management of emissions. This presentation discussed those regulations that dealt specifically with gasoline and diesel fuels and how they impact on vehicle emissions. The review showed that since 1975 the average fuel economy and improvements in tailpipe emissions for a light duty vehicle has increased significantly. Nitrogen oxide emissions were reduced by 94 per cent, carbon monoxide emissions were reduced by 96 per cent, and hydrocarbon emissions from tailpipes were reduced by 98 per cent. The phase-out of lead in fuel formulations, the controversy over the octane enhancing fuel additive MMT and a major study underway investigating the reduction of sulphur in gasoline, were also discussed. Future developments in regulations are likely to include capture of vapour emissions, mandatory inspection and maintenance programs, remote sensing of tailpipe emissions, and scrapping of old high emitting vehicles.5 figs

  15. Planned and proposed pipeline regulations

    International Nuclear Information System (INIS)

    De Leon, C.

    1992-01-01

    The Research and Special Programs Administration administers the Natural Gas Pipeline Safety Act of 1968 (NGPSA) and the Hazardous Liquid Pipeline Safety Act of 1979 (HLPSA). The RSPA issues and enforces design, construction, operation and maintenance regulations for natural gas pipelines and hazardous liquid pipelines. This paper discusses a number of proposed and pending safety regulations and legislative initiatives currently being considered by the RSPA and the US Congress. Some new regulations have been enacted. The next few years will see a great deal of regulatory activity regarding natural gas and hazardous liquid pipelines, much of it resulting from legislative requirements. The office of Pipeline Safety is currently conducting a study to streamline its operations. This study is analyzing the office's business, social and technical operations with the goal of improving overall efficiency, effectiveness, productivity and job satisfaction to meet the challenges of the future

  16. 22 CFR 139.4 - Responsibilities of the Program Administrator.

    Science.gov (United States)

    2010-04-01

    ... of living, support infrastructure, and other relevant factors. The Program Administrator, from time... program regulations, including rules of the Program Administrator and the code of code of conduct; or the...

  17. General RMP Guidance - Chapter 8: Emergency Response Program

    Science.gov (United States)

    If you have a Program 2 or 3 process at your facility, 40 CFR Part 68 (risk management program) requires an emergency response program in place if employees respond to some releases involving regulated toxic or flammable substances.

  18. Fact Sheet: Risk Management Plan (RMP) Audit Program

    Science.gov (United States)

    Risk management programs, which consist of a hazard assessment, a prevention program, and an emergency response program; must be periodically audited to assess whether the plans are adequate or need to be revised to comply with the regulation.

  19. 49 CFR 381.400 - What is a pilot program?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false What is a pilot program? 381.400 Section 381.400... PILOT PROGRAMS Initiation of Pilot Programs § 381.400 What is a pilot program? (a) A pilot program is a... that would be subject to the regulations. (b) During a pilot program, the participants would be given...

  20. Regulation of the O-glycan-type Sialyl-Lewis X (sLex) Bio-synthesis Pathway during Cell Transformation Programs: Epithelial-Mesenchymal Transition (EMT) and Molecular Subtypes in Breast Carcinoma and Human T Cell Activation

    KAUST Repository

    AbuElela, Ayman

    2017-01-01

    During tumor progression and development of distant metastases, a subset of cancer cells undergoes transformation programs, such as epithelial-mesenchymal transition (EMT), to acquire enhanced migratory attributes to commence the metastatic cascade

  1. Removal of regulations on black lung benefits. Final rule.

    Science.gov (United States)

    2012-03-30

    This final rule removes regulations on the Black Lung program from the Social Security Administration's (SSA) chapter of the Code of Federal Regulations (CFR). The Black Lung Consolidation of Administrative Responsibility Act transferred the responsibility for administering Part B of the Black Lung benefits program from SSA to the Department of Labor (DOL), and we are removing the regulations in recognition of the fact that we are no longer responsible for administering any aspect of the Part B Black Lung program. DOL concurs with this final rule removing the regulations.

  2. 76 FR 70220 - New Jersey Regulations on Transportation of Regulated Medical Waste

    Science.gov (United States)

    2011-11-10

    ...., Director, Healthcare Waste Institute, 4301 Connecticut Avenue NW., Suite 300, Washington, DC 20008, and (2... Hazardous Waste Management Program, Mail Code 401-02C, P.O. Box 420, Trenton, NJ 08625-0420. A certification.... PHMSA-2011-0294 (PDA-35(R)] New Jersey Regulations on Transportation of Regulated Medical Waste AGENCY...

  3. Russian programs

    International Nuclear Information System (INIS)

    Heywood, A.

    1993-01-01

    Lawrence Livermore National Laboratory (LLNL) initiated several projects with the Boreskov Institute of Catalysis to develop innovative process technologies for the treatment of mixed and hazardous wastes containing a high percentage of organic material. Each of these processes involves the use of catalysts for oxidation (or initial reduction) of the hazardous organic constituents. Because of their commitment to a national mixed waste treatment program, both the Department of Energy/Office of Environmental Management (DOE/EM) and LLNL Environmental Restoration and Waste Management/Applied Technologies (ER-WM/AT) programs have a considerable interest in innovative/alternative flowsheets for organic mixed waste treatment. Selective Catalytic Reduction (SCR) using ammonia as a reducing agent is current a preferred method of treating NO x in off-gases. The advantages of SCR over methods, such as wet scrubbing, include compact design, low maintenance, and the absence of gas cooling requirements and secondary wastes. Any further improvements in catalyst design would lower costs, improve their resistance to poisons, expand their ability to promote oxidation/reduction in mixtures such as NO x /CO, and increase their mechanical strength. An additional requirement of catalysts to be used in California is that the catalyst formulations must meet the California Land Ban disposal restrictions. A monitoring network is needed in Russia to coordinate the environmental monitoring activities of government (including military establishments and facilities) and commercial entities. The network shall incorporate existing as well as proposed monitoring stations. It will comply with all toxic substance control regulations and include analyses for all priority radiochemical and chemical substances. A database compatible with the Environmental Technologies for Remedial Actions Data Exchange (EnviroTRADE) database will ultimately be compiled

  4. Description of the DLL regulation interface in HAWC

    DEFF Research Database (Denmark)

    Larsen, Torben J.

    2001-01-01

    This report contains a description of the external regulation interface between the aeroelastic code HAWC and a separate regulation unit programmed as a DLL (Dynamic Link Library). Specific HAWC commands used with the regulation as well as simple DLLexamples written in Delphi, Fortran and C...

  5. 34 CFR 660.3 - What regulations apply?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What regulations apply? 660.3 Section 660.3 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION THE INTERNATIONAL RESEARCH AND STUDIES PROGRAM General § 660.3 What regulations apply...

  6. 34 CFR 656.6 - What regulations apply?

    Science.gov (United States)

    2010-07-01

    ..., DEPARTMENT OF EDUCATION NATIONAL RESOURCE CENTERS PROGRAM FOR FOREIGN LANGUAGE AND AREA STUDIES OR FOREIGN LANGUAGE AND INTERNATIONAL STUDIES General § 656.6 What regulations apply? The following regulations apply... 34 Education 3 2010-07-01 2010-07-01 false What regulations apply? 656.6 Section 656.6 Education...

  7. 76 FR 28193 - Amendments to Material Control and Accounting Regulations

    Science.gov (United States)

    2011-05-16

    ...] Amendments to Material Control and Accounting Regulations AGENCY: Nuclear Regulatory Commission. ACTION... amendments to the material control and accounting (MC&A) regulations. These regulations apply to NRC... ``accounting,'' and thus does not fully describe the accounting aspects that MC&A programs must include...

  8. Intrinsic and Extrinsic Regulation of PD-L2 Expression in Oncogene-Driven Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Shibahara, Daisuke; Tanaka, Kentaro; Iwama, Eiji; Kubo, Naoki; Ota, Keiichi; Azuma, Koichi; Harada, Taishi; Fujita, Jiro; Nakanishi, Yoichi; Okamoto, Isamu

    2018-03-27

    The interaction of programmed cell death ligand 2 (PD-L2) with programmed cell death 1 is implicated in tumor immune escape. The regulation of PD-L2 expression in tumor cells has remained unclear, however. We here examined intrinsic and extrinsic regulation of PD-L2 expression in NSCLC. PD-L2 expression was evaluated by reverse transcription and real-time polymerase chain reaction analysis and by flow cytometry. BEAS-2B cells stably expressing an activated mutant form of EGFR or the echinoderm microtubule associated protein like 4 (EML4)-ALK receptor tyrosine kinase fusion oncoprotein manifested increased expression of PD-L2 at both the mRNA and protein levels. Furthermore, treatment of NSCLC cell lines that harbor such driver oncogenes with corresponding EGFR or ALK tyrosine kinase inhibitors or depletion of EGFR or ALK by small interfering RNA transfection suppressed expression of PD-L2, demonstrating that activating EGFR mutations or echinoderm microtubule associated protein like 4 gene (EML4)-ALK receptor tyrosine kinase gene (ALK) fusion intrinsically induce PD-L2 expression. We also found that interferon gamma (IFN-γ) extrinsically induced expression of PD-L2 through signal transducer and activator of transcription 1 signaling in NSCLC cells. Oncogene-driven expression of PD-L2 in NSCLC cells was inhibited by knockdown of the transcription factors signal transducer and activator of transcription 3 (STAT3) or c-FOS. IFN-γ also activated STAT3 and c-FOS, suggesting that these proteins may also contribute to the extrinsic induction of PD-L2 expression. Expression of PD-L2 is induced intrinsically by activating EGFR mutations or EML4-ALK fusion and extrinsically by IFN-γ, with STAT3 and c-FOS possibly contributing to both intrinsic and extrinsic pathways. Our results thus provide insight into the complexity of tumor immune escape in NSCLC. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  9. 75 FR 49432 - Impact Aid Programs

    Science.gov (United States)

    2010-08-13

    ... Government Writing'' require each agency to write regulations that are easy to understand. The Secretary... Education Act of 1965, as amended (ESEA). Through this program, the Department provides competitive grants... administration and distribution of funds under this program. The proposed regulations would apply to the grant...

  10. Environmental radioactive intercomparison program and radioactive standards program

    Energy Technology Data Exchange (ETDEWEB)

    Dilbeck, G. [Environmental Monitoring Systems Laboratory, Las Vegas, NV (United States)

    1993-12-31

    The Environmental Radioactivity Intercomparison Program described herein provides quality assurance support for laboratories involved in analyzing public drinking water under the Safe Drinking Water Act (SDWA) Regulations, and to the environmental radiation monitoring activities of various agencies. More than 300 federal and state nuclear facilities and private laboratories participate in some phase of the program. This presentation describes the Intercomparison Program studies and matrices involved, summarizes the precision and accuracy requirements of various radioactive analytes, and describes the traceability determinations involved with radioactive calibration standards distributed to the participants. A summary of program participants, sample and report distributions, and additional responsibilities of this program are discussed.

  11. Site Support Program Plan Infrastructure Program

    International Nuclear Information System (INIS)

    1995-01-01

    The Fiscal Year 1996 Infrastructure Program Site Support Program Plan addresses the mission objectives, workscope, work breakdown structures (WBS), management approach, and resource requirements for the Infrastructure Program. Attached to the plan are appendices that provide more detailed information associated with scope definition. The Hanford Site's infrastructure has served the Site for nearly 50 years during defense materials production. Now with the challenges of the new environmental cleanup mission, Hanford's infrastructure must meet current and future mission needs in a constrained budget environment, while complying with more stringent environmental, safety, and health regulations. The infrastructure requires upgrading, streamlining, and enhancement in order to successfully support the site mission of cleaning up the Site, research and development, and economic transition

  12. Site Support Program Plan Infrastructure Program

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-26

    The Fiscal Year 1996 Infrastructure Program Site Support Program Plan addresses the mission objectives, workscope, work breakdown structures (WBS), management approach, and resource requirements for the Infrastructure Program. Attached to the plan are appendices that provide more detailed information associated with scope definition. The Hanford Site`s infrastructure has served the Site for nearly 50 years during defense materials production. Now with the challenges of the new environmental cleanup mission, Hanford`s infrastructure must meet current and future mission needs in a constrained budget environment, while complying with more stringent environmental, safety, and health regulations. The infrastructure requires upgrading, streamlining, and enhancement in order to successfully support the site mission of cleaning up the Site, research and development, and economic transition.

  13. GROUNDWATER PROTECTION MANAGEMENT PROGRAM DESCRIPTION.

    Energy Technology Data Exchange (ETDEWEB)

    PAQUETTE,D.E.; BENNETT,D.B.; DORSCH,W.R.; GOODE,G.A.; LEE,R.J.; KLAUS,K.; HOWE,R.F.; GEIGER,K.

    2002-05-31

    THE DEPARTMENT OF ENERGY ORDER 5400.1, GENERAL ENVIRONMENTAL PROTECTION PROGRAM, REQUIRES THE DEVELOPMENT AND IMPLEMENTATION OF A GROUNDWATER PROTECTION PROGRAM. THE BNL GROUNDWATER PROTECTION MANAGEMENT PROGRAM DESCRIPTION PROVIDES AN OVERVIEW OF HOW THE LABORATORY ENSURES THAT PLANS FOR GROUNDWATER PROTECTION, MONITORING, AND RESTORATION ARE FULLY DEFINED, INTEGRATED, AND MANAGED IN A COST EFFECTIVE MANNER THAT IS CONSISTENT WITH FEDERAL, STATE, AND LOCAL REGULATIONS.

  14. Program specialization

    CERN Document Server

    Marlet, Renaud

    2013-01-01

    This book presents the principles and techniques of program specialization - a general method to make programs faster (and possibly smaller) when some inputs can be known in advance. As an illustration, it describes the architecture of Tempo, an offline program specializer for C that can also specialize code at runtime, and provides figures for concrete applications in various domains. Technical details address issues related to program analysis precision, value reification, incomplete program specialization, strategies to exploit specialized program, incremental specialization, and data speci

  15. Nutrition Program Quality Assurance through a Formalized Process of On-Site Program Review

    Science.gov (United States)

    Paddock, Joan Doyle; Dollahite, Jamie

    2012-01-01

    A protocol for a systematic onsite review of the Expanded Food and Nutrition Education Program and Supplemental Nutrition Assistance Program-Education was developed to support quality programming and ensure compliance with state guidelines and federal regulations. Onsite review of local nutrition program operations is one strategy to meet this…

  16. 75 FR 70083 - Emergency Forest Restoration Program and Emergency Conservation Program

    Science.gov (United States)

    2010-11-17

    ... Restoration Program and Emergency Conservation Program AGENCY: Farm Service Agency, USDA. ACTION: Interim rule. SUMMARY: The Farm Service Agency (FSA) is amending regulations as required by the Food, Conservation, and... as follows: PART 701--EMERGENCY CONSERVATION PROGRAM, EMERGENCY FOREST RESTORATION PROGRAM, AND...

  17. 76 FR 27986 - Funding for the Conservation Loan Program; Farm Loan Programs

    Science.gov (United States)

    2011-05-13

    ... for the Conservation Loan Program; Farm Loan Programs AGENCY: Farm Service Agency, USDA. ACTION... or guaranteed loan applications for the Conservation Loan (CL) Program because of lack of program... provisions to the existing direct and guaranteed loan regulations found in 7 CFR parts 761, 762, 764, 765...

  18. Competition between bank regulators

    OpenAIRE

    Schindler, Dirk; Eggert, Wolfgang

    2004-01-01

    This paper examines competition between bank regulators in open economies. We use a model where credit demand of firms is endogenous and show any tendency for downward competition in regulation policy is limited by the effect of regulation on profits of nonfinancial firms. Moreover, perfect mobility on loans and deposit markets fully eliminates the incentives of regulators to set bank regulation at ine±cient low levels.

  19. 78 FR 3848 - Fisheries Off West Coast States; Pacific Coast Groundfish Fishery; Trawl Rationalization Program...

    Science.gov (United States)

    2013-01-17

    ... Rationalization Program; Emergency Rule Extension AGENCY: National Marine Fisheries Service (NMFS), National... Coast Groundfish Fishery Trawl Rationalization Program (program) regulations. This emergency rule... trawl rationalization program. Background on this rule was provided in the proposed rule, published on...

  20. Regulating through leverage: Civil regulation in China

    NARCIS (Netherlands)

    Fürst, K.

    2016-01-01

    The overarching goal of this study is to examine the efforts of Chinese NGOs to prevent and/or control industrial pollution risks and then use the findings of this research to study the nature of civil regulation in, and beyond, China’s authoritarian setting. It first argues that 'regulation through

  1. New technologies to meet regulations

    International Nuclear Information System (INIS)

    Frank, C.; Harmon, L.

    1991-01-01

    The US Department of Energy's (DOE's) Office of Environmental Restoration and Waste Management has set the ambitious goal of having all of its facilities cleaned up and in compliance with applicable environmental laws and regulations by the year 2019. This goal is ambitious both because of the magnitude of the effort required and because, in many cases, the means for attaining the goal do not now exist. The DOE's strategy for reaching its goal is based on applied research and development, education, and cooperation with regulators. The Office of Technology Development (OTD) within the Office of Environmental Restoration and Waste Management has instituted a program to assess the magnitude of the cleanup effort and to evaluate the potential technologies to be used. The OTD has program responsibility for providing new and more effective technologies for meeting DOE's goal for compliance and cleanup. Included are research and development of new technologies; demonstration, testing, and evaluation of technologies developed elsewhere; transportation; and educational programs to produce the scientists and engineers needed to maintain the momentum of research, development, demonstration, testing, and evaluation (RDDT and E) until the job is complete

  2. Regulation of online pharmacy: an Australian perspective.

    Science.gov (United States)

    Bernath, Paul

    2003-02-01

    This article argues that existing Australian regulations do not adequately cover online pharmacies or Internet advertising of medicines and that existing penalties and sanctions are often ineffective, potentially placing public health and safety at risk. Suggestions are made for future regulatory approaches. It is concluded that as well as an effective program of public education, cautious domestic legislative reform is necessary to ensure specific regulation of Australian online pharmacy practice and Internet advertising of medicines. In addition, the global nature of the Internet demands international co-operation and increased regulator and consumer vigilance.

  3. 77 FR 76414 - William D. Ford Federal Direct Loan Program

    Science.gov (United States)

    2012-12-28

    ... Federal Direct Loan Program AGENCY: Department of Education. ACTION: Final regulations; correction... Loan (Perkins Loan) Program; the Federal Family Education Loan (FFEL) Program; and the William D. Ford Federal Direct Loan (Direct Loan) Program, including the Public Service Loan Forgiveness (PSLF) Program...

  4. 49 CFR 613.100 - Metropolitan transportation planning and programming.

    Science.gov (United States)

    2010-10-01

    ... programming. 613.100 Section 613.100 Transportation Other Regulations Relating to Transportation (Continued... Metropolitan Transportation Planning and Programming § 613.100 Metropolitan transportation planning and programming. The regulations in 23 CFR 450, subpart C, shall be followed in complying with the requirements of...

  5. 75 FR 5697 - Employee Protection Program; Removal

    Science.gov (United States)

    2010-02-04

    ... DEPARTMENT OF TRANSPORTATION Office of the Secretary 14 CFR Part 314 RIN 2105-AD94 Employee... Employee Protection Program. These regulations are removed because the underlying program was repealed by... Employee Protection Program, to be administered by the U.S. Department of Transportation. Section 43 of the...

  6. 48 CFR 212.7002 - Pilot program.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Pilot program. 212.7002... OF DEFENSE ACQUISITION PLANNING ACQUISITION OF COMMERCIAL ITEMS Pilot Program for Transition to Follow-On Contracting After Use of Other Transaction Authority 212.7002 Pilot program. ...

  7. 7 CFR 227.5 - Program funding.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS NUTRITION EDUCATION AND TRAINING PROGRAM General § 227.5 Program funding. (a... related support personnel costs including fringe benefits and travel expenses, (ii) Undertaking a needs...

  8. 75 FR 73911 - Grassland Reserve Program

    Science.gov (United States)

    2010-11-29

    ... the program are being achieved; (4) To track participation by crop and livestock type; and (5) To... regulations in Sec. 1415.4 ``Program requirements,'' Sec. 1415.11 ``Restoration agreements,'' and Sec. 1415.17...://ias.sc.egov.usda.gov/PRSHOME/ . Program performance also is reported annually to Congress and the...

  9. 48 CFR 2019.705 - Responsibilities of the contracting officer under the subcontracting assistance program.

    Science.gov (United States)

    2010-10-01

    ... Regulations System NUCLEAR REGULATORY COMMISSION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Subcontracting With Small Business, Small Disadvantaged Business, and Women-Owned Small Business Concerns 2019.705...

  10. 48 CFR 319.705 - Responsibilities of the Contracting Officer under the subcontracting assistance program.

    Science.gov (United States)

    2010-10-01

    ... Regulations System HEALTH AND HUMAN SERVICES SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS Subcontracting With Small Business, Small Disadvantaged Business, and Women-Owned Small Business Concerns 319.705...

  11. Spent fuels program

    International Nuclear Information System (INIS)

    Shappert, L.B.

    1983-01-01

    The goal of this task is to support the Domestic Spent Fuel Storage Program through studies involving the transport of spent fuel. A catalog was developed to provide authoritative, timely, and accessible transportation information for persons involved in the transport of irradiated reactor fuel. The catalog, drafted and submitted to the Transportation Technology Center, Sandia National Laboratories, for their review and approval, covers such topics as federal, state, and local regulations, spent fuel characteristics, cask characteristics, transportation costs, and emergency response information

  12. Atomic Energy Control Regulations

    International Nuclear Information System (INIS)

    1992-01-01

    This is the consolidated text of the Atomic Energy Control Regulations of 17 March 1960, with amendments to 27 August 1992. The Regulations cover the licensing of nuclear facilities, radiation sources, including uranium mining, radiation protection questions, etc. (NEA)

  13. Environmental regulation and competitiveness

    NARCIS (Netherlands)

    Mulatu, A.; Florax, R.J.G.M.; Withagen, C.A.A.M.

    2001-01-01

    The potential relationship between domestic environmental regulation and international competitiveness has evoked various speculations. The common neoclassical train of thought is that strict environmental regulation is detrimental to the competitiveness of industry, and that it induces phenomena

  14. Ocean Dumping Control Regulations

    International Nuclear Information System (INIS)

    1978-01-01

    These Regulations were made further to the Ocean Dumping Control Act which provides for restrictions in dumping operations. The Regulations contain model applications for permits to dump or load a series of materials. (NEA)

  15. Regulation of Genetic Tests

    Science.gov (United States)

    ... for Genomics Research Intellectual Property Issues in Genetics Archive Online Bioethics Resources Privacy in Genomics Regulation of ... are not regulated, meaning that they go to market without any independent analysis to verify the claims ...

  16. Trout Stream Special Regulations

    Data.gov (United States)

    Minnesota Department of Natural Resources — This layer shows Minnesota trout streams that have a special regulation as described in the 2006 Minnesota Fishing Regulations. Road crossings were determined using...

  17. 48 CFR 217.7506 - Spare parts breakout program.

    Science.gov (United States)

    2010-10-01

    ..., DoD Supply Chain Materiel Management Regulation, Chapter 8, Section C8.3, for spare parts breakout... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Spare parts breakout program. 217.7506 Section 217.7506 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS...

  18. PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5-Dependent Mechanism.

    Science.gov (United States)

    McKay, Jerome T; Haro, Marcela A; Daly, Christina A; Yammani, Rama D; Pang, Bing; Swords, W Edward; Haas, Karen M

    2017-09-15

    B-1 cells produce natural Abs which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate that programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural Abs against phosphorylcholine (PC). Naive PD-L2-deficient (PD-L2 -/- ) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2 -/- mice with selectively enhanced protection against PC-expressing nontypeable Haemophilus influenzae , but not PC-negative nontypeable Haemophilus influenzae , relative to wild-type mice. PD-L2 -/- mice had significantly increased PC-specific CD138 + splenic plasmablasts bearing a B-1a phenotype, and produced PC-reactive Abs largely of the T15 Id. Importantly, PC-reactive B-1 cells expressed PD-L2 and irradiated chimeras demonstrated that B cell-intrinsic PD-L2 expression regulated PC-specific Ab production. In addition to increased PC-specific IgM, naive PD-L2 -/- mice and irradiated chimeras reconstituted with PD-L2 -/- B cells had significantly higher levels of IL-5, a potent stimulator of B-1 cell Ab production. PD-L2 mAb blockade of wild-type B-1 cells in culture significantly increased CD138 and Blimp1 expression and PC-specific IgM, but did not affect proliferation. PD-L2 mAb blockade significantly increased IL-5 + T cells in culture. Both IL-5 neutralization and STAT5 inhibition blunted the effects of PD-L2 mAb blockade on B-1 cells. Thus, B-1 cell-intrinsic PD-L2 expression inhibits IL-5 production by T cells and thereby limits natural Ab production by B-1 cells. These findings have broad implications for the development of therapeutic strategies aimed at altering natural Ab levels critical for protection against infectious disease, autoimmunity, allergy, cancer, and atherosclerosis. Copyright © 2017 by The American Association of Immunologists, Inc.

  19. Program History

    Science.gov (United States)

    Learn how the National Cancer Institute transitioned the former Cooperative Groups Program to the National Clinical Trials Network (NCTN) program. The NCTN gives funds and other support to cancer research organizations to conduct cancer clinical trials.

  20. Program auto

    International Nuclear Information System (INIS)

    Rawool-Sullivan, M.W.; Plagnol, E.

    1990-01-01

    The program AUTO was developed to be used in the analysis of dE vs E type spectra. This program is written in FORTRAN and calculates dE vs E lines in MeV. The provision is also made in the program to convert these lines from MeV to ADC channel numbers to facilitate the comparison with the raw data from the experiments. Currently the output of this program can be plotted with the display program, called VISU, but it can also be used independent of the program VISU, with little or no modification in the actual fortran code. The program AUTO has many useful applications. In this article the program AUTO is described along with its applications

  1. Culture and emotion regulation.

    Science.gov (United States)

    Ford, Brett Q; Mauss, Iris B

    2015-06-01

    While anthropological research has long emphasized cultural differences in whether emotions are viewed as beneficial versus harmful, psychological science has only recently begun to systematically examine those differences and their implications for emotion regulation and well-being. Underscoring the pervasive role of culture in people's emotions, we summarize research that has examined links between culture, emotion regulation, and well-being. Specifically, we focus on two questions. First, how does culture lead individuals to regulate their emotions? And second, how does culture modulate the link between emotion regulation and well-being? We finish by suggesting directions for future research to advance the study of culture and emotion regulation.

  2. Radiation Control Regulation 1993

    International Nuclear Information System (INIS)

    1993-01-01

    This Regulation (No. 434-1993) was made in pursuance of the Radiation Control Act 1990 and replaces the Active Substances Regulations 1959 repealed by the Act. It entered into force on 1 September 1993. The Regulation specifies that the technical radiation protection definitions have the same meaning as in the 1990 recommendations. The Regulation provides for the licensing of persons to use radioactive substances and radiation apparatus. It prescribes activities which may only be carried out by an accredited radiation expert and regulates the use of radiation apparatus and radioactive substances as well as the disposal and transport of radiation apparatus and radioactive substances. (NEA)

  3. Load regulating expansion fixture

    International Nuclear Information System (INIS)

    Wagner, L.M.; Strum, M.J.

    1998-01-01

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located there between. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig

  4. Volume regulation in epithelia

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Hoffmann, Else Kay

    2016-01-01

    to amphibian skin and mammalian cortical collecting tubule of low and intermediate osmotic permeability. Crosstalk between entrance and exit mechanisms interferes with volume regulation both at aniso-osmotic and iso-osmotic volume perturbations. It has been proposed that cell volume regulation is an intrinsic...... regulation are cloned. The volume-regulated anion channel (VRAC) exhibiting specific electrophysiological characteristics seems exclusive to serve cell volume regulation. This is contrary to K+ channels as well as cotransporters and exchange mechanisms that may serve both transepithelial transport and cell...... volume regulation. In the same cell, these functions may be maintained by different ion pathways that are separately regulated. RVD is often preceded by increase in cytosolic free Ca2+, probably via influx through TRP channels, but Ca2+ release from intracellular stores has also been observed. Cell...

  5. Voltage regulator for generator

    Energy Technology Data Exchange (ETDEWEB)

    Naoi, K

    1989-01-17

    It is an object of this invention to provide a voltage regulator for a generator charging a battery, wherein even if the ambient temperature at the voltage regulator rises abnormally high, possible thermal breakage of the semiconductor elements constituting the voltage regulator can be avoided. A feature of this invention is that the semiconductor elements can be protected from thermal breakage, even at an abnormal ambient temperature rise at the voltage regulator for the battery charging generator, by controlling a maximum conduction ratio of a power transistor in the voltage regulator in accordance with the temperature at the voltage regulator. This is achieved through a switching device connected in series to the field coil of the generator and adapted to be controlled in accordance with an output voltage of the generator and the ambient temperature at the voltage regulator. 6 figs.

  6. A Qualitative Exploration of Self-Kindness and “Treating Oneself” in Contexts of Eating, Weight Regulation and Other Health Behaviors: Implications for Mindfulness-Based Eating Programs

    Directory of Open Access Journals (Sweden)

    Helen Egan

    2018-05-01

    Full Text Available Background: Caring for oneself through mindfulness and compassion to improve or enhance health behaviors, and specifically eating behaviors has come to the forefront of scientific inquiry. The experiences and challenges for people in decision making around food within the context of self-kindness for body and mind care have not been previously explored.Aims: This study explored the experiences of eating behaviors in a community sample and examined the understanding of self-kindness and its relationship to eating behaviors and wellbeing of body and mind.Methods: A phenomenological theoretical position was taken; data were collected using individual semi-structured interviews. The sample was twenty-five members of the wider community in the West Midlands in England. The data were analyzed using Braun and Clarke’s (2006 procedural steps for thematic analysis.Results: Two overarching themes were inductively formulated: ‘Thinking about eating’ and ‘Caring for body and mind’. Five themes were constructed: (a Treat food is exceptional eating, (b The proof of the pudding is in the planning, (c Dieting is a dirty word, which are subsumed under Thinking about eating, and (d Self-kindness is a disavowed abstract noun, and (e Self-kindness: A rose by any other name; under Caring for body and mind. Participants described a number of ways of treating themselves both with food and with other activities and pleasure in eating was discussed in terms of social aspects of eating rather than food. Two clear contradictions within narratives around eating and health behaviors were shown. Participants largely eschewed the concept of dieting, but described engaging in highly regulated and restrained eating. There was a lack of connection with the notion of self-kindness; although positive eating and exercise health behaviors were undertaken, they were described as necessary self-regulation, not construed as acts of self-kindness.Conclusion: The results

  7. State child health; revisions to the regulations implementing the State Children's Health Insurance Program. Interim final rule with comment period; revisions, delay of effective date, and technical amendments to final rule.

    Science.gov (United States)

    2001-06-25

    Title XXI authorizes the State Children's Health Insurance Program (SCHIP) to assist State efforts to initiate and expand the provision of child health assistance to uninsured, low-income children. On January 11, 2001 we published a final rule in the Federal Register to implement SCHIP that has not gone into effect. This interim final rule further delays the effective date, revises certain provisions and solicits public comment, and makes technical corrections and clarifications to the January 2001 final rule based on further review of the comments received and applicable law. Only the provisions set forth in this document have changed. All other provisions set forth in the January 2001 final rule will be implemented without change.

  8. Chromatin Regulation of Neuronal Maturation and Plasticity.

    Science.gov (United States)

    Gallegos, David A; Chan, Urann; Chen, Liang-Fu; West, Anne E

    2018-05-01

    Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives. The structural and functional plasticity of neurons requires the regulated transcription of new gene products, and dysregulation of transcription in either the developing or adult brain impairs cognition. We discuss how mechanisms of chromatin regulation help to orchestrate the transcriptional programs that underlie the maturation of developing neurons and the plasticity of adult neurons. We review how chromatin regulation acts locally to modulate the expression of specific genes and more broadly to coordinate gene expression programs during transitions between cellular states. These data highlight the importance of epigenetic transcriptional mechanisms in postmitotic neurons. We suggest areas where emerging methods may advance understanding in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Marine biosurfaces research program

    Science.gov (United States)

    The Office of Naval Research (ONR) of the U.S. Navy is starting a basic research program to address the initial events that control colonization of surfaces by organisms in marine environments. The program “arises from the Navy's need to understand and ultimately control biofouling and biocorrosion in marine environments,” according to a Navy announcement.The program, “Biological Processes Controlling Surface Modification in the Marine Environment,” will emphasize the application of in situ techniques and modern molecular biological, biochemical, and biophysical approaches; it will also encourage the development of interdisciplinary projects. Specific areas of interest include sensing and response to environmental surface (physiology/physical chemistry), factors controlling movement to and retention at surfaces (behavior/hydrodynamics), genetic regulation of attachment (molecular genetics), and mechanisms of attachment (biochemistry/surface chemistry).

  10. WIPP radiation dosimetry program

    International Nuclear Information System (INIS)

    Wu, C.F.

    1991-01-01

    Radiation dosimetry is the process by which various measurement results and procedures are applied to quantify the radiation exposure of an individual. Accurate and precise determination of radiation dose is a key factor to the success of a radiation protection program. The Waste Isolation Pilot Plant (WIPP), a Department of Energy (DOE) facility designed for permanent repository of transuranic wastes in a 2000-foot-thick salt bed 2150 feet underground, has established a dosimetry program developed to meet the requirements of DOE Order 5480.11, ''Radiation Protection for Occupational Workers''; ANSI/ASME NQA-1, ''Quality Assurance Program Requirements for Nuclear Facilities''; DOE Order 5484.1, ''Environmental Protection, Safety, and Health Protection Information Reporting Requirements''; and other applicable regulations

  11. Functional Expression of Programmed Death-Ligand 1 (B7-H1 by Immune Cells and Tumor Cells

    Directory of Open Access Journals (Sweden)

    Rachel M. Gibbons Johnson

    2017-08-01

    Full Text Available The programmed death-1 (PD-1 and its ligand PD-L1 (B7-H1 signaling pathway has been the focus of much enthusiasm in the fields of tumor immunology and oncology with recent FDA approval of the anti-PD-1 antibodies pembrolizumab and nivolumab and the anti-PD-L1 antibodies durvalumab, atezolimuab, and avelumab. These therapies, referred to here as PD-L1/PD-1 checkpoint blockade therapies, are designed to block the interaction between PD-L1, expressed by tumor cells, and PD-1, expressed by tumor-infiltrating CD8+ T cells, leading to enhanced antitumor CD8+ T cell responses and tumor regression. The influence of PD-L1 expressed by tumor cells on antitumor CD8+ T cell responses is well characterized, but the impact of PD-L1 expressed by immune cells has not been well defined for antitumor CD8+ T cell responses. Although PD-L1 expression by tumor cells has been used as a biomarker in selection of patients for PD-L1/PD-1 checkpoint blockade therapies, patients whose tumor cells lack PD-L1 expression often respond positively to PD-L1/PD-1 checkpoint blockade therapies. This suggests that PD-L1 expressed by non-malignant cells may also contribute to antitumor immunity. Here, we review the functions of PD-L1 expressed by immune cells in the context of CD8+ T cell priming, contraction, and differentiation into memory populations, as well as the role of PD-L1 expressed by tumor cells in regulating antitumor CD8+ T cell responses.

  12. Comprehensive quality management program for radiation oncology

    International Nuclear Information System (INIS)

    Dawson, J.; Roy, T.; Abrath, F.; Wu, T.; Gu, J.; McDonald, R.; Kim, H.; Haenchen, M.

    1994-01-01

    A quality management program for both external beam irradiation (electron and photon modes) and brachytherapy (high dose rate (HDR) and low dose rate (LDR) has been developed. The program follows current USA federal regulations for therapeutic administration of by-product materials. After implementation of the program, 54 HDR patients, 36 LDR brachytherapy patients and 311 external beam patients (including 30 stereotactic radiosurgery cases) were treated. The results of this program are presented

  13. 34 CFR 425.4 - What regulations apply?

    Science.gov (United States)

    2010-07-01

    ..., DEPARTMENT OF EDUCATION DEMONSTRATION PROJECTS FOR THE INTEGRATION OF VOCATIONAL AND ACADEMIC LEARNING... Projects for the Integration of Vocational and Academic Learning Program: (a) The regulations in this part...

  14. 42 CFR 64.9 - Other HHS regulations that apply.

    Science.gov (United States)

    2010-10-01

    ..., TRAINING NATIONAL LIBRARY OF MEDICINE TRAINING GRANTS § 64.9 Other HHS regulations that apply. Several...) and requirements for drug-free workplace (grants). 45 CFR part 80—Nondiscrimination under programs...

  15. NRC - regulator of nuclear safety

    International Nuclear Information System (INIS)

    1997-01-01

    The U.S. Nuclear Regulatory Commission (NRC) was formed in 1975 to regulate the various commercial and institutional uses of nuclear energy, including nuclear power plants. The agency succeeded the Atomic Energy Commission, which previously had responsibility for both developing and regulating nuclear activities. Federal research and development work for all energy sources, as well as nuclear weapons production, is now conducted by the U.S. Department of Energy. Under its responsibility to protect public health and safety, the NRC has three principal regulatory functions: (1) establish standards and regulations, (2) issue licenses for nuclear facilities and users of nuclear materials, and (3) inspect facilities and users of nuclear materials to ensure compliance with the requirements. These regulatory functions relate to both nuclear power plants and to other uses of nuclear materials - like nuclear medicine programs at hospitals, academic activities at educational institutions, research work, and such industrial applications as gauges and testing equipment. The NRC places a high priority on keeping the public informed of its work. The agency recognizes the interest of citizens in what it does through such activities as maintaining public document rooms across the country and holding public hearings, public meetings in local areas, and discussions with individuals and organizations

  16. [The Influence of the Functional State of Brain Regulatory Structures on the Programming, Selective Regulation and Control of Cognitive Activity in Children. Report I: Neuropsychological and EEG Analysis of Age-Related Changes in Brain Regulatory Functions in Children Aged 9-12 Years].

    Science.gov (United States)

    Semenova, A; Machinskaya, R I; Lomakin, D I

    2015-01-01

    Age-related changes in brain regulatory functions in children aged from 9 to 12 years with typical development were studied by means of neuropsychological and EEG analysis. The participants of the study were 107 children without learning difficulties and behavior deviations; they were devided into three groups (9-10, 10-11 and 11-12 years). The neuropsychological tests revealed nonlinear age-related changes in different executive brain functions. The group of 10-11-year-old children showed better results in programming, in- hibition of impulsive reactions and in the perception of socially relevant information than the group of 9-10- year-old children. At the same time, these children had more difficulties with selective activity regulation as compared with the younger group. The difficulties were mainly caused by switching from one element of the program to another and by retention of learned sequence of actions. These children also showed a lower level of motivation for task performance. The children aged 11-12 years had less difficulties with selective activity regulation; however, impulsive behavior was more frequent; these children also had a higher level of task performance motivation than in children aged 10-11 years. The analysis of resting state EEG revealed age-related differences in deviated EEG patterns associated with non-optimal functioning of fronto-thalamic system and hypothalamic structures. The incidence of these two types of EEG patterns was significantly higher in children aged 10-11 years as compared with children aged 9-10 years. The EEG of the groups of 10-11 and 11-12-years-old children did not show any significant differences.

  17. TOWARD MORE EFFECTIVE REGULATION

    Energy Technology Data Exchange (ETDEWEB)

    J. GRAF

    2000-06-01

    This paper proposes a model relationship between the operator engaged in a hazardous activity, the regulator of that activity, and the general public. The roles and responsibilities of each entity are described in a way that allows effective communication flow. The role of the regulator is developed using the steam boiler as an example of a hazard subject to regulation; however, the model applies to any regulated activity. In this model the safety analyst has the extremely important role of communicating sometimes difficult technical information to the regulator in a way that the regulator can provide credible assurance to the general public as to the adequacy of the control of the hazardous activity. The conclusion asserts that acceptance of the model, understanding of the roles and responsibilities and definition of who communicates what information to whom will mitigate frustration on the part of each of the three entities.

  18. The development of regulations

    International Nuclear Information System (INIS)

    Slokan Dusic, D.; Levstek, M.F.; Stritar, A.

    2003-01-01

    In October 2002, The Act on Protection Against Ionising Radiation and Nuclear Safety which regulates all aspects of protection against ionising radiation and nuclear safety entered into force in Slovenia. The Slovenian government and its responsible ministries shall issue several governmental and ministerial regulations to support the above - mentioned act. The Slovenian Nuclear Safety Administration (SNSA) which acts within the Ministry of the Environment, Spatial Planing and Energy takes an active part in drafting the regulations which are defined in the act. Due to a very comprehensive and pretentious task, that is to be completed in a relatively short period of time, taking into consideration the involvement of stakeholders and all competent ministries, the SNSA within the Quality Management System developed a special procedure that insures the systematic approach to the preparation of regulations. The article will briefly represent the process that: defines the preparation, development, harmonisation, review, approval and issue of regulations and uniforms the format of developed regulations. (author)

  19. Federal radiation protection regulations: An industry viewpoint

    International Nuclear Information System (INIS)

    Harward, E.D.

    1987-01-01

    Regulations and standards to protect the public and workers from ionizing radiation have been in transition for a number of years, although most of the basic limits in use have remained essentially unchanged over the past 25 years or so. Legislation, political changes, new scientific data, advances in scientific concepts, and finally, public perception and resulting pressures have all been factors in the modifications that have been implemented or considered for radiation protection regulations in recent years. During this period, radiation exposures to both the public and the work force have been reduced through program management and improved technology. Based on activities of the AIF Subcommittee on Radiation Protection, this paper reviews pertinent NRC and EPA regulations, standards and guidance as well as NCRP recommendations and provide some analyses of these in terms of their potential effect on nuclear industry operations. Comments include suggestions where minor changes in Federal agency approaches to radiation regulation might be made for the public benefit

  20. Regulation of Stem Cell Differentiation by Histone Methyltransferases and Demethylases

    DEFF Research Database (Denmark)

    Pasini, D; Bracken, A P; Agger, K

    2008-01-01

    The generation of different cell types from stem cells containing identical genetic information and their organization into tissues and organs during development is a highly complex process that requires defined transcriptional programs. Maintenance of such programs is epigenetically regulated...... and the factors involved in these processes are often essential for development. The activities required for cell-fate decisions are frequently deregulated in human tumors, and the elucidation of the molecular mechanisms that regulate these processes is therefore important for understanding both developmental...

  1. 76 FR 5157 - Public Water Supply Supervision Program; Program Revision for the State of Alaska

    Science.gov (United States)

    2011-01-28

    ... ENVIRONMENTAL PROTECTION AGENCY [FRL-9259-6] Public Water Supply Supervision Program; Program... Water Supply Supervision Primacy Program. Alaska has adopted regulations analogous to EPA's Stage 2 Disinfectants and Disinfection Byproducts Rule; Long Term 2 Enhanced Surface Water Treatment Rule; and Lead and...

  2. 76 FR 366 - Public Water Supply Supervision Program; Program Revision for the State of Washington

    Science.gov (United States)

    2011-01-04

    ... ENVIRONMENTAL PROTECTION AGENCY [FRL-9247-4] Public Water Supply Supervision Program; Program... State Public Water Supply Supervision Primacy Program. Washington has adopted a definition for public water system that is analogous to EPA's definition of public water system, and has adopted regulations...

  3. 76 FR 45253 - Public Water Supply Supervision Program; Program Revision for the State of Alaska

    Science.gov (United States)

    2011-07-28

    ... ENVIRONMENTAL PROTECTION AGENCY [FRL-9444-8] Public Water Supply Supervision Program; Program... Water Supply Supervision Primacy Program. Alaska has adopted regulations analogous to the EPA's Ground Water Rule. The EPA has determined that these revisions are no less stringent than the corresponding...

  4. 78 FR 42945 - Public Water Supply Supervision Program; Program Revision for the State of Oregon

    Science.gov (United States)

    2013-07-18

    ... ENVIRONMENTAL PROTECTION AGENCY [FRL-9834-9] Public Water Supply Supervision Program; Program... Water Supply Supervision Primacy Program. Oregon has adopted regulations analogous to EPA's Stage 2 Disinfectants and Disinfection Byproducts Rule; Long Term 2 Enhanced Surface Water Treatment Rule; Ground Water...

  5. Regulating hedge funds.

    OpenAIRE

    Daníelsson, J.; Zigrand, JP.

    2007-01-01

    Due to the ever-increasing amounts under management and their unregulated and opaque nature, hedge funds have emerged as a key concern for policymakers. While until now, hedge funds have been left essentially unregulated, we are seeing increasing calls for regulation for both microprudential and macroprudential reasons. In our view, most calls for the regulation of hedge funds are based on a misperception of the effectiveness of financial regulations, perhaps coupled with a lack of understand...

  6. Regulating household financial advice

    Directory of Open Access Journals (Sweden)

    Benjamin F. Cummings

    2012-08-01

    Full Text Available This paper reviews economic theory related to investment advice. This theory explains 1 why financial advisors need to be carefully regulated for the benefit of both the investment advice industry and for consumers, 2 why principles-based regulation (e.g., a fiduciary standard is more efficient than rules-based regulation, 3 why dual regulation of financial professionals providing investment or insurance advice is inefficient and inequitable policy, and 4 why the application of a universal and uniform fiduciary standard will be difficult to implement.

  7. The regulation of hunting

    DEFF Research Database (Denmark)

    Abildtrup, Jens; Jensen, Frank

    Within hunting, wildlife populations are estimated to be too high in many countries which is assumed to be due to the market failure, that each hunter harvests too little compared to what the regulator wants. This may be due to the existing regulation which, among other things, requires knowledge...... by an individual, variable tax rate. The variable tax rate is, among other things, based on the difference in marginal value of the population between the hunter and the regulator. The paper shows that the population tax/subsidy secures a first-best optimum. Thus, the population tax is a good alternative...... to the existing regulation....

  8. Nuclear safety and regulation

    International Nuclear Information System (INIS)

    Kim, Hho Jung

    2000-03-01

    This book contains 12 chapters, which are atom and radiation, nuclear reactor and kinds of nuclear power plant, safeguard actuation system and stability evaluation for rock foundation of nuclear power plant, nuclear safety and principle, safety analysis and classification of incident, probabilistic safety assessment and major incident, nuclear safety regulation, system of nuclear safety regulation, main function and subject of safety regulation in nuclear facilities, regulation of fuel cycle and a nuclear dump site, protection of radiation and, safety supervision and, safety supervision and measurement of environmental radioactivity.

  9. Material Programming

    DEFF Research Database (Denmark)

    Vallgårda, Anna; Boer, Laurens; Tsaknaki, Vasiliki

    2017-01-01

    . Consequently we ask what the practice of programming and giving form to such materials would be like? How would we be able to familiarize ourselves with the dynamics of these materials and their different combinations of cause and effect? Which tools would we need and what would they look like? Will we program......, and color, but additionally being capable of sensing, actuating, and computing. Indeed, computers will not be things in and by themselves, but embedded into the materials that make up our surroundings. This also means that the way we interact with computers and the way we program them, will change...... these computational composites through external computers and then transfer the code them, or will the programming happen closer to the materials? In this feature we outline a new research program that floats between imagined futures and the development of a material programming practice....

  10. Effective Programming

    DEFF Research Database (Denmark)

    Frost, Jacob

    To investigate the use of VTLoE as a basis for formal derivation of functional programs with effects. As a part of the process, a number of issues central to effective formal programming are considered. In particular it is considered how to develop a proof system suitable for pratical reasoning......, how to implement this system in the generic proof assistant Isabelle and finally how to apply the logic and the implementation to programming....

  11. Program Fullerene

    DEFF Research Database (Denmark)

    Wirz, Lukas; Peter, Schwerdtfeger,; Avery, James Emil

    2013-01-01

    Fullerene (Version 4.4), is a general purpose open-source program that can generate any fullerene isomer, perform topological and graph theoretical analysis, as well as calculate a number of physical and chemical properties. The program creates symmetric planar drawings of the fullerene graph, an......-Fowler, and Brinkmann-Fowler vertex insertions. The program is written in standard Fortran and C++, and can easily be installed on a Linux or UNIX environment....

  12. 34 CFR 658.3 - What regulations apply?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What regulations apply? 658.3 Section 658.3 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION UNDERGRADUATE INTERNATIONAL STUDIES AND FOREIGN LANGUAGE PROGRAM General § 658.3 What...

  13. 34 CFR 461.4 - What regulations apply?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What regulations apply? 461.4 Section 461.4 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION ADULT EDUCATION STATE-ADMINISTERED BASIC GRANT PROGRAM General § 461.4 What...

  14. 34 CFR 350.4 - What regulations apply?

    Science.gov (United States)

    2010-07-01

    ... (IRB) reviews research that purposefully requires inclusion of children with disabilities or... REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION DISABILITY AND REHABILITATION RESEARCH PROJECTS AND CENTERS PROGRAM General § 350.4 What regulations apply? The following regulations apply to the Disability and...

  15. 77 FR 74347 - Freedom of Information Act Regulations

    Science.gov (United States)

    2012-12-14

    ... regulation, CIGIE adhered to the regulatory philosophy and the applicable principles of regulation as set... research (if the request is from an educational institution) or scientific research (if the request is from... operating one or more programs of scholarly research. (2) The term ``non-commercial scientific institution...

  16. Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...SUBTITLE 5a. CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM...blocked by the addition of Pim inhibitors. These results suggest that the Pim protein kinase can regulate stromal cell biology to modulate epithelial

  17. Does self-regulation of advertisement length improve consumer welfare?

    OpenAIRE

    Matsubae, Taisuke; Matsushima, Noriaki

    2012-01-01

    In Japan, TV platforms regulate themselves as to the length of the advertisements they air. Using modified Hotelling models, we investigate whether such self-regulation improves consumer and social welfare or not. When all consumers choose a single TV program (the utility functions of consumers satisfy the standard 'full-coverage' condition), self-regulation always reduces consumer welfare. It improves social welfare only if the advertisement revenue of each platform is not small and the cost...

  18. Programming F#

    CERN Document Server

    Smith, Chris

    2009-01-01

    Why learn F#? This multi-paradigm language not only offers you an enormous productivity boost through functional programming, it also lets you develop applications using your existing object-oriented and imperative programming skills. With Programming F#, you'll quickly discover the many advantages of Microsoft's new language, which includes access to all the great tools and libraries of the .NET platform. Learn how to reap the benefits of functional programming for your next project -- whether it's quantitative computing, large-scale data exploration, or even a pursuit of your own. With th

  19. PLC Programming

    International Nuclear Information System (INIS)

    Lee, Seong Jae; Wi, Seong Dong; Yoo, Jong Seon; Kim, Se Chan

    2001-02-01

    This book tells of PLC programming for KGL-WIN with summary of PLC, performance and function of PLC like characteristic of KGL-WIN, connection method with PLC, basic performance of K200S/K300S/K1000S, diagram of input and output H/W, writing project, staring the program, editing of program, on-line function, debugging and instructions like control, timer and counter, data transmission, comparison, rotation and moving, system, data operating data conversion and application program.

  20. Programming Interactivity

    CERN Document Server

    Noble, Joshua

    2009-01-01

    Make cool stuff. If you're a designer or artist without a lot of programming experience, this book will teach you to work with 2D and 3D graphics, sound, physical interaction, and electronic circuitry to create all sorts of interesting and compelling experiences -- online and off. Programming Interactivity explains programming and electrical engineering basics, and introduces three freely available tools created specifically for artists and designers: Processing, a Java-based programming language and environment for building projects on the desktop, Web, or mobile phonesArduino, a system t

  1. Medicare and Medicaid fraud and abuse regulations.

    Science.gov (United States)

    Liang, F Z; Black, B L

    1991-11-01

    Specific business arrangements that are protected under legislation and regulations governing parties doing business with Medicare or Medicaid are discussed. Regulations implementing the Medicare and Medicaid Patient Protection Act of 1987 specify practices and activities that are not subject to criminal penalties under the antikickback provisions of the Social Security Act or to exclusion from Medicare or state health-care programs. As of July 29, 1991, all organized health-care settings that receive payments from either Medicare or state health-care programs must comply with these regulations. The final rule sets forth "safe harbors"--exceptions to prohibitions against (1) kickbacks, bribes, rebates, and other illegal activities involving remunerations for patient referrals and (2) inducements to purchase or lease goods paid for by Medicare or state health-care programs. The safe harbors comprise 11 broad categories--investment interests, space rental, equipment rental, personal services and management contracts, purchase of a medical practice, referral services, warranties, discounts, employees, group purchasing organizations, and waiver of deductibles and coinsurance. Implications for pharmacy are discussed. These regulations will affect the purchase of pharmaceuticals by institutional pharmacies. Each institution should review its current practices to determine whether they are within the safe harbors.

  2. Economic regulation of ambulance services in California.

    Science.gov (United States)

    Narad, R A

    1997-01-01

    This study was intended to identify economic regulatory programs used by California counties (including ambulance franchising and rate setting), to inventory their foci and application, and to identify differences around the state. By studying the variety of programs used in one state, this study establishes a framework for evaluation of state and local regulatory programs elsewhere. This study surveyed all California local EMS agencies (LEMSAs); these are California's equivalent of regional EMS organizations. The survey achieved a 100% response rate, and all data involve population parameters obviating the need for inferential statistics. Seventy-three percent of California counties use economic regulations. Large-population counties and those that operate their own LEMSAs are more likely to use economic regulations than are small counties and those that participate in multicounty EMS agencies. Despite a preference for competition in the authorizing statute, most franchises were granted without competition to existing providers. The majority of franchises in the state were granted to public services. Most ambulance rate setting occurs outside of a competitive process. Economic regulations that were intended to provide a structured marketplace are often being used to protect existing providers, particularly public services, from competition. The growing interest by fire departments in entering the market for emergency ambulance service, along with the existing bias toward them in granting of franchises, does not bode well for use of the competitive process. The growth of managed care may change or eliminate the need for economic regulations but, if they are to continue, more state oversight should be considered.

  3. 78 FR 28953 - William D. Ford Federal Direct Loan Program

    Science.gov (United States)

    2013-05-16

    .... Ford Federal Direct Loan Program; Interim Final Rule #0;#0;Federal Register / Vol. 78, No. 95... [Docket ID ED-2013-OPE-0066] RIN 1840-AD13 William D. Ford Federal Direct Loan Program AGENCY: Office of... Secretary amends the William D. Ford Federal Direct Loan Program (Direct Loan Program) regulations to...

  4. 48 CFR 1552.219-70 - Mentor-Protege Program.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Mentor-Protege Program... Mentor-Protege Program. As prescribed in 1519.203(a), insert the following clause: Mentor-Protege Program OCT 2000 (a) The Contractor has been approved to participate in the EPA Mentor-Protege program. The...

  5. Peak regulation right

    International Nuclear Information System (INIS)

    Gao, Z. |; Ren, Z.; Li, Z.; Zhu, R.

    2005-01-01

    A peak regulation right concept and corresponding transaction mechanism for an electricity market was presented. The market was based on a power pool and independent system operator (ISO) model. Peak regulation right (PRR) was defined as a downward regulation capacity purchase option which allowed PRR owners to buy certain quantities of peak regulation capacity (PRC) at a specific price during a specified period from suppliers. The PRR owner also had the right to decide whether or not they would buy PRC from suppliers. It was the power pool's responsibility to provide competitive and fair peak regulation trading markets to participants. The introduction of PRR allowed for unit capacity regulation. The PRR and PRC were rated by the supplier, and transactions proceeded through a bidding process. PRR suppliers obtained profits by selling PRR and PRC, and obtained downward regulation fees regardless of whether purchases are made. It was concluded that the peak regulation mechanism reduced the total cost of the generating system and increased the social surplus. 6 refs., 1 tab., 3 figs

  6. Soft Regulators, though judges

    NARCIS (Netherlands)

    de Geest, G.G.A.; Dari Mattiacci, G.

    Judges have a tendency to be more demanding than regulators. In the United States, a majority of the courts has adopted the rule that the unexcused violation of a statutory standard is negligence per se. However, the converse does not hold: compliance with regulation does not relieve the injurer of

  7. Mortgage market regulation: Europe

    NARCIS (Netherlands)

    Aalbers, M.B.; Smith, S.J.

    2012-01-01

    Despite several European Union (EU) initiatives, there is only limited pan-European mortgage market regulation. The EU strategy can be characterised as one of parallel liberalisation and consolidation. This article highlights the key differences in regulation among European mortgage markets.

  8. Child Development Program Evaluation Scale.

    Science.gov (United States)

    Fiene, Richard J.

    The Child Development Program Evaluation Scale (CDPES) is actually two scales in one, a licensing scale and a quality scale. Licensing predictor items have been found to predict overall compliance of child day care centers with state regulations in four states. Quality scale items have been found to predict the overall quality of child day care…

  9. Regulation as Rhetoric

    DEFF Research Database (Denmark)

    Boll, Karen; Györy, Csaba

    This paper analyses the way regulatory agencies strategically use public ‘rhetoric’ and ‘management of appearance’ to strengthen their regulation. It reports a comparative study of the Securities and Exchange Commission (SEC) which is the US federal securities regulator and the Danish Tax...... and Customs Administration (SKAT) which is the national tax regulator in Denmark. SEC operates in a US context where the agency fights to get trust, while SKAT operates in a context where high trust in public agencies is a basic condition. We argue, however, that despite the radically different institutional...... engage reflectively in image promotion which serves two purposes: establishing and maintaining legitimacy in a particular social and political environment and producing compliance. Further, we argue that this regulation is a form of ‘post-bureaucratic’ regulation in which compliance is achieved...

  10. Reconceptualizing Civil Regulation

    DEFF Research Database (Denmark)

    Galang, Roberto Martin; Castello, Itziar

    2011-01-01

    This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility litera....... Finally, we argue that, in Asia, governments act as a structuration mechanism which challenges the current understanding of CSR.......This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility...... and environmental standards; but also that local, small and medium companies play a key role in the development of Asian civil regulation. We call this second finding the “CSR importation trap”. Our findings are supported by evidence on the limitations in the interchangeable properties of business and governments...

  11. Computer Programs.

    Science.gov (United States)

    Anderson, Tiffoni

    This module provides information on development and use of a Material Safety Data Sheet (MSDS) software program that seeks to link literacy skills education, safety training, and human-centered design. Section 1 discusses the development of the software program that helps workers understand the MSDSs that accompany the chemicals with which they…

  12. BASIC Programming.

    Science.gov (United States)

    Jennings, Carol Ann

    Designed for use by both secondary- and postsecondary-level business teachers, this curriculum guide consists of 10 units of instructional materials dealing with Beginners All-Purpose Symbol Instruction Code (BASIC) programing. Topics of the individual lessons are numbering BASIC programs and using the PRINT, END, and REM statements; system…

  13. Choreographic Programming

    DEFF Research Database (Denmark)

    Montesi, Fabrizio

    , as they offer a concise view of the message flows enacted by a system. For this reason, in the last decade choreographies have been used in the development of programming languages, giving rise to a programming paradigm that in this dissertation we refer to as Choreographic Programming. Recent studies show...... endpoint described in a choreography can then be automatically generated, ensuring that such implementations are safe by construction. However, current formal models for choreographies do not deal with critical aspects of distributed programming, such as asynchrony, mobility, modularity, and multiparty...... sessions; it remains thus unclear whether choreographies can still guarantee safety when dealing with such nontrivial features. This PhD dissertation argues for the suitability of choreographic programming as a paradigm for the development of safe distributed systems. We proceed by investigating its...

  14. 75 FR 13081 - Fisheries off West Coast States; Pacific Coast Groundfish Fishery; Trawl Rationalization Program

    Science.gov (United States)

    2010-03-18

    ... West Coast States; Pacific Coast Groundfish Fishery; Trawl Rationalization Program AGENCY: National... proposed Trawl Rationalization Program. We are interested in feedback concerning proposed regulations to... Pacific Fishery Management Council (Council) has been developing a trawl rationalization program that...

  15. 48 CFR 227.7204 - Contracts under the Small Business Innovative Research Program.

    Science.gov (United States)

    2010-10-01

    ... Business Innovative Research Program. 227.7204 Section 227.7204 Federal Acquisition Regulations System... under the Small Business Innovative Research Program. When contracting under the Small Business Innovative Research Program, follow the procedures at 227-7104. ...

  16. Industrial Energy Efficiency: Designing Effective State Programs for the Industrial Sector

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, Amelie [Institute for Industrial Productivity (United States); Taylor, Robert P. [Institute for Industrial Productivity (United States); Hedman, Bruce [Institute for Industrial Productivity (United States)

    2014-03-21

    This report provides state regulators, utilities, and other program administrators with an overview of U.S. industrial energy efficiency programs and assesses some of the key features of programs that have generated increased energy savings.

  17. 40 CFR 146.2 - Law authorizing these regulations.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Law authorizing these regulations. 146.2 Section 146.2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) UNDERGROUND INJECTION CONTROL PROGRAM: CRITERIA AND STANDARDS General Provisions § 146.2 Law...

  18. Computer programs as accounting object

    Directory of Open Access Journals (Sweden)

    I.V. Perviy

    2015-03-01

    Full Text Available Existing approaches to the regulation of accounting software as one of the types of intangible assets have been considered. The features and current state of the legal protection of computer programs have been analyzed. The reasons for the need to use patent law as a means of legal protection of individual elements of computer programs have been discovered. The influence of the legal aspects of the use of computer programs for national legislation to their accounting reflection has been analyzed. The possible options for the transfer of rights from computer programs copyright owners have been analyzed that should be considered during creation of software accounting system at the enterprise. Identified and analyzed the characteristics of computer software as an intangible asset under the current law. General economic characteristics of computer programs as one of the types of intangible assets have been grounded. The main distinguishing features of software compared to other types of intellectual property have been all ocated

  19. Icobj Programming

    OpenAIRE

    Boussinot , Frédéric

    1996-01-01

    A simple and fully graphical programming method is presented, using a powerful means to combine behaviors. This programming is based on the notion of an «icobj» which has a behavioral aspect («object» part), a graphical aspect («icon» part), with an «animation» aspect. Icobj programming provides parallelism, broadcast event communication and migration through the network. An experimental system based on this approach is described in details. Its implementation with reactive scripts is also pr...

  20. Programming Python

    CERN Document Server

    Lutz, Mark

    2011-01-01

    If you've mastered Python's fundamentals, you're ready to start using it to get real work done. Programming Python will show you how, with in-depth tutorials on the language's primary application domains: system administration, GUIs, and the Web. You'll also explore how Python is used in databases, networking, front-end scripting layers, text processing, and more. This book focuses on commonly used tools and libraries to give you a comprehensive understanding of Python's many roles in practical, real-world programming. You'll learn language syntax and programming techniques in a clear and co

  1. Epigenetic Regulation of Adipokines

    Directory of Open Access Journals (Sweden)

    Tho X. Pham

    2017-08-01

    Full Text Available Adipose tissue expansion in obesity leads to changes in the expression of adipokines, adipocyte-specific hormones that can regulate whole body energy metabolism. Epigenetic regulation of gene expression is a mechanism by which cells can alter gene expression through the modifications of DNA and histones. Epigenetic mechanisms, such as DNA methylation and histone modifications, are intimately tied to energy metabolism due to their dependence on metabolic intermediates such as S-adenosylmethionine and acetyl-CoA. Altered expression of adipokines in obesity may be due to epigenetic changes. The goal of this review is to highlight current knowledge of epigenetic regulation of adipokines.

  2. The power of regulation

    International Nuclear Information System (INIS)

    Lewis, M.G.

    1995-01-01

    Slides accompanying a presentation at The Power of Change Conference in Vancouver, BC in April 1995 about regulations affecting the power industry were presented. Issues addressed included customer choice, incentive regulation changes (price-caps, revenue sharing and pricing flexibility), the reactions of Canadian industry to regulatory changes, and anticipated reactions of the financial markets to changes in regulations. The potential effects of competition and changes that will create competition were discussed. The level of readiness of Canadian financial, ownership and regulatory bodies was discussed. The needs and expectations of investors from a new regulatory regime were quesstimated. Possible alternatives to the present regulatory framework were suggested

  3. Electrical installations and regulations

    CERN Document Server

    Whitfield, J F

    1966-01-01

    Electrical Installations and Regulations focuses on the regulations that apply to electrical installations and the reasons for them. Topics covered range from electrical science to alternating and direct current supplies, as well as equipment for providing protection against excess current. Cables, wiring systems, and final subcircuits are also considered, along with earthing, discharge lighting, and testing and inspection.Comprised of 12 chapters, this book begins with an overview of electrical installation work, traits of a good electrician, and the regulations governing installations. The r

  4. VA Dental Insurance Program--federalism. Direct final rule.

    Science.gov (United States)

    2013-10-22

    The Department of Veterans Affairs (VA) is taking direct final action to amend its regulations related to the VA Dental Insurance Program (VADIP), a pilot program to offer premium-based dental insurance to enrolled veterans and certain survivors and dependents of veterans. Specifically, this rule will add language to clarify the limited preemptive effect of certain criteria in the VADIP regulations.

  5. 17 CFR 270.0-11 - Customer identification programs.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Customer identification... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.0-11 Customer identification programs... implementing regulation at 31 CFR 103.131, which requires a customer identification program to be implemented...

  6. 48 CFR 1353.219 - Small business programs.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Small business programs. 1353.219 Section 1353.219 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE CLAUSES AND FORMS FORMS Prescription of Forms 1353.219 Small business programs. Use Form CD-570, Small Business Set...

  7. 48 CFR 653.219 - Small business programs.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Small business programs. 653.219 Section 653.219 Federal Acquisition Regulations System DEPARTMENT OF STATE CLAUSES AND FORMS FORMS Prescription of Forms 653.219 Small business programs. ...

  8. 34 CFR 300.110 - Program options.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Program options. 300.110 Section 300.110 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND... DISABILITIES State Eligibility Other Fape Requirements § 300.110 Program options. The State must ensure that...

  9. 78 FR 32126 - VA Dental Insurance Program

    Science.gov (United States)

    2013-05-29

    ... secure reasonable premium and copayment pricing through multiple tier options to allow enrollees to... program that offers premium-based dental insurance to enrolled veterans and certain survivors and... regulations to establish VADIP, a pilot program that would offer premium-based dental insurance to enrolled...

  10. 77 FR 70409 - System Safety Program

    Science.gov (United States)

    2012-11-26

    ...-0060, Notice No. 2] 2130-AC31 System Safety Program AGENCY: Federal Railroad Administration (FRA... rulemaking (NPRM) published on September 7, 2012, FRA proposed regulations to require commuter and intercity passenger railroads to develop and implement a system safety program (SSP) to improve the safety of their...

  11. 76 FR 56262 - Community Advantage Pilot Program

    Science.gov (United States)

    2011-09-12

    ... SMALL BUSINESS ADMINISTRATION [Docket No. SBA 2011-0003] Community Advantage Pilot Program AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of change to Community Advantage Pilot... Community Advantage Pilot Program. In that notice, SBA modified or waived as appropriate certain regulations...

  12. 75 FR 6330 - North Dakota Regulatory Program

    Science.gov (United States)

    2010-02-09

    ... be consistent with the corresponding Federal regulations and to improve operational efficiency. This document gives the times and locations that the North Dakota program and proposed amendment to that program..., contact the person listed under FOR FURTHER INFORMATION CONTACT. We will arrange the location and time of...

  13. 77 FR 58056 - Mississippi Regulatory Program

    Science.gov (United States)

    2012-09-19

    ... its program to be no less effective than the Federal regulations and to improve operational efficiency. This document gives the times and locations of the Mississippi program and this proposed amendment to... hours at the following location: Mississippi Office of Geology, Department of Environmental Quality, 700...

  14. 7 CFR 3560.52 - Program objectives.

    Science.gov (United States)

    2010-01-01

    ... objectives. The Agency uses appropriated funds to finance the construction, rehabilitation of program... 7 Agriculture 15 2010-01-01 2010-01-01 false Program objectives. 3560.52 Section 3560.52 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF...

  15. 76 FR 20534 - Program Integrity Issues

    Science.gov (United States)

    2011-04-13

    ... Code of Federal Regulations is available via the Federal Digital System at: http://www.gpo.gov/fdsys... educational programs or those that provide marketing, advertising, recruiting, or admissions services. We have... the institution to provide services, such as food service, other than educational programs, marketing...

  16. 24 CFR 984.102 - Program objectives.

    Science.gov (United States)

    2010-04-01

    ... education, employment, and business and social skills necessary to achieve self-sufficiency, as defined in... 984.102 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... SECTION 8 AND PUBLIC HOUSING FAMILY SELF-SUFFICIENCY PROGRAM General § 984.102 Program objectives. The...

  17. 75 FR 30113 - Rural Microentrepreneur Assistance Program

    Science.gov (United States)

    2010-05-28

    ...)); Removing ``socially-disadvantaged'' and clarifying that the percentage of rural entrepreneurs that received... entrepreneurs that have not received a microloan from an MDO under this program would not be able to receive... the Agency is easier to implement and consistent with other program regulations. The Agency, therefore...

  18. 49 CFR 212.101 - Program principles.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Program principles. 212.101 Section 212.101 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... principles. (a) The purpose of the national railroad safety program is to promote safety in all areas of...

  19. Program overview

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    The program overview describes the following resources and facilities; laser facilities, main laser room, target room, energy storage, laboratory area, building support systems, general plant project, and the new trailer complex

  20. Linear programming

    CERN Document Server

    Solow, Daniel

    2014-01-01

    This text covers the basic theory and computation for a first course in linear programming, including substantial material on mathematical proof techniques and sophisticated computation methods. Includes Appendix on using Excel. 1984 edition.

  1. Science Programs

    Science.gov (United States)

    Laboratory Delivering science and technology to protect our nation and promote world stability Science & ; Innovation Collaboration Careers Community Environment Science & Innovation Facilities Science Pillars Research Library Science Briefs Science News Science Highlights Lab Organizations Science Programs Applied

  2. Operating Nuclear Power Stations in a Regulated Cyber Security Environment

    Energy Technology Data Exchange (ETDEWEB)

    Dorman, E.

    2014-07-01

    The United States Nuclear Regulatory Commission (NRC) issued 10CFR73.54 to implement a regulated Cyber Security Program at each operating nuclear reactor facility. Milestones were implemented December 31, 2012 to mitigate the attack vectors for the most critical digital assets acknowledged by the industry and the NR C. The NRC inspections have begun. The nuclear Cyber Security Plan, implemented by the site Cyber Security Program (Program), is an element of the operating license at each facility. (Author)

  3. Operating Nuclear Power Stations in a Regulated Cyber Security Environment

    International Nuclear Information System (INIS)

    Dorman, E.

    2014-01-01

    The United States Nuclear Regulatory Commission (NRC) issued 10CFR73.54 to implement a regulated Cyber Security Program at each operating nuclear reactor facility. Milestones were implemented December 31, 2012 to mitigate the attack vectors for the most critical digital assets acknowledged by the industry and the NR C. The NRC inspections have begun. The nuclear Cyber Security Plan, implemented by the site Cyber Security Program (Program), is an element of the operating license at each facility. (Author)

  4. [Regulation of terpene metabolism.] Progress report

    International Nuclear Information System (INIS)

    Croteau, R.

    1984-01-01

    This research program represents a very broad-based approach to understanding the biochemistry of the monoterpene and sesquiterpene constituents of the essential oils. This program includes basic research on the pathways, enzymes and mechanisms of terpene biosynthesis and catabolism, on the physiology of essential oil production, and on the morphology and development of oil glands, as well as practical approaches to manipulating essential oil composition and yield. As a natural extension of research on monoterpene biosynthesis and catabolism in sage and peppermint we have explored some aspects of possible regulatory mechanisms. Tentative evidence has been obtained for developmental regulation of the levels of biosynthetic and catabolic enzymes. 10 refs., 8 figs

  5. Legislation and regulation

    International Nuclear Information System (INIS)

    1998-01-01

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the nuclear and environmental licensing, and emergency preparedness legislation

  6. Benchmarking and Regulation

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    . The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  7. Legislation and regulation

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    This document presents the fulfilling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 3 of the document contains some details about the Brazilian legislation and regulation, the nuclear and environmental licensing, and emergency preparedness legislation.

  8. SPOT Program

    Science.gov (United States)

    Smith, Jason T.; Welsh, Sam J.; Farinetti, Antonio L.; Wegner, Tim; Blakeslee, James; Deboeck, Toni F.; Dyer, Daniel; Corley, Bryan M.; Ollivierre, Jarmaine; Kramer, Leonard; hide

    2010-01-01

    A Spacecraft Position Optimal Tracking (SPOT) program was developed to process Global Positioning System (GPS) data, sent via telemetry from a spacecraft, to generate accurate navigation estimates of the vehicle position and velocity (state vector) using a Kalman filter. This program uses the GPS onboard receiver measurements to sequentially calculate the vehicle state vectors and provide this information to ground flight controllers. It is the first real-time ground-based shuttle navigation application using onboard sensors. The program is compact, portable, self-contained, and can run on a variety of UNIX or Linux computers. The program has a modular objec-toriented design that supports application-specific plugins such as data corruption remediation pre-processing and remote graphics display. The Kalman filter is extensible to additional sensor types or force models. The Kalman filter design is also strong against data dropouts because it uses physical models from state and covariance propagation in the absence of data. The design of this program separates the functionalities of SPOT into six different executable processes. This allows for the individual processes to be connected in an a la carte manner, making the feature set and executable complexity of SPOT adaptable to the needs of the user. Also, these processes need not be executed on the same workstation. This allows for communications between SPOT processes executing on the same Local Area Network (LAN). Thus, SPOT can be executed in a distributed sense with the capability for a team of flight controllers to efficiently share the same trajectory information currently being computed by the program. SPOT is used in the Mission Control Center (MCC) for Space Shuttle Program (SSP) and International Space Station Program (ISSP) operations, and can also be used as a post -flight analysis tool. It is primarily used for situational awareness, and for contingency situations.

  9. Sprego programming

    OpenAIRE

    Csernoch, Mária; Biró, Piroska

    2015-01-01

    Spreadsheet management is a border-land between office applications and programming, however, it is rather communicated that spreadsheet is nothing more than an easily handled fun piece. Consequently, the complexity of spreadsheet handling, the unprepared end-users, their problem solving abilities and approaches do not match. To overcome these problems we have developed and introduced Sprego (Spreadsheet Lego). Sprego is a simplified functional programming language in spreadsheet environment,...

  10. Recombinant Programming

    OpenAIRE

    Pawlak , Renaud; Cuesta , Carlos; Younessi , Houman

    2004-01-01

    This research report presents a promising new approach to computation called Recombinant Programming. The novelty of our approach is that it separates the program into two layers of computation: the recombination and the interpretation layer. The recombination layer takes sequences as inputs and allows the programmer to recombine these sequences through the definition of cohesive code units called extensions. The output of such recombination is a mesh that can be used by the interpretation la...

  11. The regulation of appetite

    OpenAIRE

    Druce, M; Bloom, S R

    2006-01-01

    The worsening global obesity epidemic, particularly the increase in childhood obesity, has prompted research into the mechanisms of appetite regulation. Complex pathways modulate energy balance, involving appetite centres in the hypothalamus and brain stem, and hormonal signals of energy status released by the gut and by the periphery. Better understanding of appetite regulation improves understanding of the aetiology of obesity. Manipulation of this homoeostatic system offers potentially use...

  12. Corruption, Institutions and Regulation

    OpenAIRE

    Michael Breen; Robert Gillanders

    2011-01-01

    We analyze the effects of corruption and institutional quality on the quality of business regulation. Our key findings indicate that corruption negatively aspects the quality of regulation and that general institutional quality is insignificant once corruption is controlled for. These findings hold over a number of specifications which include additional exogenous historical and geographic controls. The findings imply that policy-makers should focus on curbing corruption to improve regulat...

  13. Regulating deregulated energy markets

    International Nuclear Information System (INIS)

    Jackson, M.

    2002-01-01

    The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

  14. Canadian hydrogen safety program

    International Nuclear Information System (INIS)

    MacIntyre, I.; Tchouvelev, A.V.; Hay, D.R.; Wong, J.; Grant, J.; Benard, P.

    2007-01-01

    The Canadian hydrogen safety program (CHSP) is a project initiative of the Codes and Standards Working Group of the Canadian transportation fuel cell alliance (CTFCA) that represents industry, academia, government, and regulators. The Program rationale, structure and contents contribute to acceptance of the products, services and systems of the Canadian Hydrogen Industry into the Canadian hydrogen stakeholder community. It facilitates trade through fair insurance policies and rates, effective and efficient regulatory approval procedures and accommodation of the interests of the general public. The Program integrates a consistent quantitative risk assessment methodology with experimental (destructive and non-destructive) failure rates and consequence-of-release data for key hydrogen components and systems into risk assessment of commercial application scenarios. Its current and past six projects include Intelligent Virtual Hydrogen Filling Station (IVHFS), Hydrogen clearance distances, comparative quantitative risk comparison of hydrogen and compressed natural gas (CNG) refuelling options; computational fluid dynamics (CFD) modeling validation, calibration and enhancement; enhancement of frequency and probability analysis, and Consequence analysis of key component failures of hydrogen systems; and fuel cell oxidant outlet hydrogen sensor project. The Program projects are tightly linked with the content of the International Energy Agency (IEA) Task 19 Hydrogen Safety. (author)

  15. Motor carrier evaluation program

    International Nuclear Information System (INIS)

    Portsmouth, James

    1992-01-01

    The U.S. Department of Energy-Headquarters (DOE-HQ), Transportation Management Program (TMP) has the overall responsibility to provide a well-managed transportation program for the safe, efficient, and economical transportation of DOE-owned materials. The DOE-TMP has established an excellent safety record in the transportation of hazardous materials including radioactive materials and radioactive wastes. This safety record can be maintained only through continued diligence and sustained effort on the part of the DOE-TMP, its field offices, and the contractors' organizations. Key elements in the DOE'S effective hazardous and radioactive materials shipping program are (1) integrity of packages, (2) strict adherence to regulations and procedures, (3) trained personnel, (4) complete management support, and (5) use of the best commercial carriers. The DOE Motor Carrier Evaluation Program was developed to better define the criteria and methodology needed to identify motor carriers for use in the transportation of Highway Route Controlled Quantities (HRCQ), Truck Load (TL) quantities of radioactive materials, hazardous materials and waste. (author)

  16. Environmental radiation exposure: Regulation, monitoring, and assessment

    International Nuclear Information System (INIS)

    Chen, S.Y.; Yu, C.; Hong, K.J.

    1991-01-01

    Radioactive releases to the environment from nuclear facilities constitute a public health concern. Protecting the public from such releases can be achieved through the establishment and enforcement of regulatory standards. In the United States, numerous standards have been promulgated to regulate release control at nuclear facilities. Most recent standards are more restrictive than those in the past and require that radioactivity levels be as low as reasonably achievable (ALARA). Environmental monitoring programs and radiological dose assessment are means of ensuring compliance with regulations. Environmental monitoring programs provide empirical information on releases, such as the concentrations of released radioactivity in environmental media, while radiological dose assessment provides the analytical means of quantifying dose exposures for demonstrating compliance

  17. Interpersonal emotion regulation.

    Science.gov (United States)

    Zaki, Jamil; Williams, W Craig

    2013-10-01

    Contemporary emotion regulation research emphasizes intrapersonal processes such as cognitive reappraisal and expressive suppression, but people experiencing affect commonly choose not to go it alone. Instead, individuals often turn to others for help in shaping their affective lives. How and under what circumstances does such interpersonal regulation modulate emotional experience? Although scientists have examined allied phenomena such as social sharing, empathy, social support, and prosocial behavior for decades, there have been surprisingly few attempts to integrate these data into a single conceptual framework of interpersonal regulation. Here we propose such a framework. We first map a "space" differentiating classes of interpersonal regulation according to whether an individual uses an interpersonal regulatory episode to alter their own or another person's emotion. We then identify 2 types of processes--response-dependent and response-independent--that could support interpersonal regulation. This framework classifies an array of processes through which interpersonal contact fulfills regulatory goals. More broadly, it organizes diffuse, heretofore independent data on "pieces" of interpersonal regulation, and identifies growth points for this young and exciting research domain.

  18. Examples of NRC research products used in regulation

    International Nuclear Information System (INIS)

    Anderson, N.R.

    1987-01-01

    The key to effective research is a close relationship between information needs and research results. This can only be achieved by close cooperation between the researchers and the regulators. At the NRC, this relationship has matured over the years until now the researchers participate in definition of the information needs and the regulators help define the research programs. The more formal means of ensuring a close match between needs and results include joint research groups, oversight working groups, and a system of Research Information Letters (RILs). On an informal basis there are many day to day discussions and meetings on the various programs which ensure effective program guidance and early identification of significant findings. This paper describes both the formal and informal researcher/regulation interface and discusses some examples of how specific research programs are utilized in the regulatory process. Specific programs described are the pressurized thermal shock program, the seismic margins program and the Category 1 structures program. Other examples cited are the aging and life extension programs

  19. Alternative Renewable Biomass Tracking Program Document under the Renewable Fuel Standard Program

    Science.gov (United States)

    The approval letters that EPA approves a company's biomass tracking program meeting all the requirements outlined in 40 CFR part 80.1454, including elements determined necessary to achieve the level of quality assurance required under the regulation list.

  20. Radiation protection for nurses. Regulations and guidelines

    International Nuclear Information System (INIS)

    Jankowski, C.B.

    1992-01-01

    Rules and regulations of federal agencies and state radiation protection programs provide the bases for hospital policy regarding radiation safety for nurses. Nursing administrators should work with the radiation safety officer at their institutions to ensure that radiation exposures to staff nurses will be as low as reasonably achievable and that special consideration will be given to pregnant nurses. Nurses' fears about their exposure to radiation can be greatly reduced through education

  1. Making Healthy Choices Easier: Regulation versus Nudging.

    Science.gov (United States)

    Hansen, Pelle Guldborg; Skov, Laurits Rohden; Skov, Katrine Lund

    2016-01-01

    In recent years, the nudge approach to behavior change has emerged from the behavioral sciences to challenge the traditional use of regulation in public health strategies to address modifiable individual-level behaviors related to the rise of noncommunicable diseases and their treatment. However, integration and testing of the nudge approach as part of more comprehensive public health strategies aimed at making healthy choices easier are being threatened by inadequate understandings of its scientific character, its relationship with regulation, and its ethical implications. This article reviews this character and its ethical implication with a special emphasis on the compatibility of nudging with traditional regulation, special domains of experience, and the need for a more nuanced approach to the ethical debate. The aim is to advance readers' understanding and give guidance to those who have considered working with or incorporating the nudge approach into programs or policies aimed at making healthful choices easier.

  2. Federal Aviation Regulations - National Aviation Regulations of Russia

    Science.gov (United States)

    Chernykh, O.; Bakiiev, M.

    2018-03-01

    Chinese Aerospace Engineering is currently developing cooperation with Russia on a wide-body airplane project that has directed the work towards better understanding of Russian airworthiness management system. The paper introduces national Aviation regulations of Russia, presents a comparison of them with worldwide recognized regulations, and highlights typical differences. They have been found to be: two general types of regulations used in Russia (Aviation Regulations and Federal Aviation Regulations), non-unified structure of regulations on Aircraft Operation management, various separate agencies responsible for regulation issuance instead of one national aviation authority, typical confusions in references. The paper also gives a list of effective Russian Regulations of both types.

  3. New regulations foster wellhead protection efforts

    International Nuclear Information System (INIS)

    Lennox, J.

    1993-01-01

    Groundwater contamination can have disastrous consequences: closed wellfields, insufficient temporary water supplies, and costly, prolonged clean-up. Realizing that it is more prudent to protect water wells than to wait for contamination to occur, many states are issuing regulations designed to protect the surface and subsurface areas surrounding public water system wells. The states have been prompted in part by the federal Safe Drinking Water Act Amendments of 1986, which provide grants and technical guidance to state wellhead protection programs. The Act does not impose regulations itself, but leaves it to the states to create and manage protection programs. Accordingly, regulations may differ dramatically from state to state, reflecting distinct hydrogeology and land uses. In every program, however, the starting point is the determination of wellhead protection areas. The protection area can range from a few hundred feet to several miles from a well. The characteristics of the aquifers surrounding the well and the amount of pumping are factors in delineating the protected area's boundaries. This article examines methods for determining the protection area

  4. 77 FR 9659 - General Services Administration Acquisition Regulation; Information Collection; GSA Mentor...

    Science.gov (United States)

    2012-02-17

    ... Services Administration Acquisition Regulation; Information Collection; GSA Mentor-Prot[eacute]g[eacute... collection concerning the GSA Mentor-Prot[eacute]g[eacute] Program, General Service Administration...- 0286, GSA Mentor-Prot[eacute]g[eacute] Program by any of the following methods: Regulations.gov : http...

  5. 77 FR 31016 - General Services Administration Acquisition Regulation; Submission for OMB Review; GSA Mentor...

    Science.gov (United States)

    2012-05-24

    ... Services Administration Acquisition Regulation; Submission for OMB Review; GSA Mentor-Prot[eacute]g[eacute... collection concerning the GSA Mentor-Prot[eacute]g[eacute] Program, General Service Administration... Collection 3090- 0286, GSA Mentor-Prot[eacute]g[eacute] Program by any of the following methods: Regulations...

  6. Nuclear regulation in transition

    International Nuclear Information System (INIS)

    Tomain, J.P.

    1986-01-01

    The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed. (author)

  7. Nuclear regulation in transition

    Energy Technology Data Exchange (ETDEWEB)

    Tomain, J.P. (Cincinnati Univ., OH, US. Coll. of Law)

    1986-01-01

    The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed.

  8. 75 FR 1685 - HOPE for Homeowners Program; Statutory Transfer of Program Authority to HUD and Conforming...

    Science.gov (United States)

    2010-01-12

    ... 90 percent, excluding the upfront premium, may not exceed 31 percent of the mortgagor's monthly gross... regulations for the program are codified in a chapter of the Code of Federal Regulations (CFR) reserved for... Treasury, the Federal Deposit Insurance Corporation, and the Federal Reserve Board. The Board will continue...

  9. Panel presentation: Should some type of incentive regulation replace traditional methods for regulating LDCs?

    International Nuclear Information System (INIS)

    Turner, J.L.

    1992-01-01

    This paper reviews the advantages and disadvantages of using incentive regulation to provide the best service and rates for natural gas consumers and compares it to the traditional rate-of-return regulation. It discusses some of the allegations used to prevent incentive regulation such as the rate-of-return regulation provides an incentive to over-build and pad rate base, thus creating inefficiencies. The author also feels that strict competition is not necessarily beneficial and that some form of regulation is necessary. The paper goes on to outline the author's ideas of how a successful incentive plan should work while emphasizing his preference for a rate-of-return regulation. From the ratepayers' view, the incentives granted should be rewards for improvement in a utility's performance. In other words, there must be clear goals set for management and the fulfillment or lack of fulfillment should result in rewards or penalties. The author feels that incentive regulation could prove to be appropriate in the areas of demand side management such as energy conservation programs

  10. Integer programming

    CERN Document Server

    Conforti, Michele; Zambelli, Giacomo

    2014-01-01

    This book is an elegant and rigorous presentation of integer programming, exposing the subject’s mathematical depth and broad applicability. Special attention is given to the theory behind the algorithms used in state-of-the-art solvers. An abundance of concrete examples and exercises of both theoretical and real-world interest explore the wide range of applications and ramifications of the theory. Each chapter is accompanied by an expertly informed guide to the literature and special topics, rounding out the reader’s understanding and serving as a gateway to deeper study. Key topics include: formulations polyhedral theory cutting planes decomposition enumeration semidefinite relaxations Written by renowned experts in integer programming and combinatorial optimization, Integer Programming is destined to become an essential text in the field.

  11. Canonical wnt signaling regulates atrioventricular junction programming and electrophysiological properties

    NARCIS (Netherlands)

    Gillers, Benjamin S.; Chiplunkar, Aditi; Aly, Haytham; Valenta, Tomas; Basler, Konrad; Christoffels, Vincent M.; Efimov, Igor R.; Boukens, Bastiaan J.; Rentschler, Stacey

    2015-01-01

    Proper patterning of the atrioventricular canal (AVC) is essential for delay of electrical impulses between atria and ventricles, and defects in AVC maturation can result in congenital heart disease. To determine the role of canonical Wnt signaling in the myocardium during AVC development. We used a

  12. [Walking in Crustacea: motor program and peripheral regulation (author's transl)].

    Science.gov (United States)

    Clarac, F; Ayers, J

    1977-01-01

    1. Rock lobsters can walk in all directions. In the present study, we report the organization of the motor output of the three muscles which control the mero-carpopodite joint (M-C): the extensor E, the flexor F and the accuracy flexor FA, during unrestrained locomotion (fig. 1). 2. During lateral walking, movements of the M-C joint provide most of the propulsive force, whereas during forward and backward walking this joint function more as a strut (fig. 2). Corresponding differences are observed in the motor discharge in the different walking modes. During lateral walking, discharge in the M-C extensor and M-C flexor alternates, whereas during forward and backward walking these antagonists are coactivated (fig. 3 and 4). 3. We have also examined the effects of alterations of proprioceptive feedback: the FA tendon has been cut to eliminate MCO afferents during walking. This ablation does not modify the burst period and the temporal structure of the output pattern is largely unaffected (fig. 5, 6 and 7). MCO may influence the motor output of a given muscle depending upon whether it participates in the return stroke or the power stroke.

  13. SECURITIES REGULATION: Improvements Needed in the Amex Listing Program

    National Research Council Canada - National Science Library

    2001-01-01

    .... The remaining markets had significantly fewer listings. For example, the fourth-largest market in terms of the number of companies listed was the Boston Stock Exchange, with 84 listings, 46 of which were also listed on Nasdaq...

  14. Regulation of Programmed Necrosis and Bone Marrow Failure

    Science.gov (United States)

    2017-03-01

    ORGANIZATION: Vanderbilt University Medical Center Nashville, TN 37203 REPORT DATE: March 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army...ABOVE ADDRESS. 1. REPORT DATE March 2017 2. REPORT TYPE Annual 3. DATES COVERED 03/01/2016-02/28/2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b...marrow damage by amplifying the pathological inflammatory response. We hypothesize that increased necrotic cell death initiates a feed forward

  15. 75 FR 77727 - Federal Acquisition Regulation; HUBZone Program Revisions

    Science.gov (United States)

    2010-12-13

    ... officer. Response: If the contracting officer is notified of possible contractor violations of Federal law...) * * * * * (d)(1) Contractors acting in good faith may rely on written representations by their subcontractors... award of a HUBZone contract, a HUBZone small business concern must be a HUBZone small business concern...

  16. 15 CFR 922.72 - Prohibited or otherwise regulated activities-Sanctuary-wide.

    Science.gov (United States)

    2010-01-01

    ... activities-Sanctuary-wide. 922.72 Section 922.72 Commerce and Foreign Trade Regulations Relating to Commerce... OCEAN AND COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Channel Islands National Marine Sanctuary § 922.72 Prohibited or otherwise regulated activities—Sanctuary-wide. (a) Except...

  17. 45 CFR 90.2 - What is the purpose of these regulations?

    Science.gov (United States)

    2010-10-01

    ... NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE General § 90.2 What is the purpose of these regulations? (a) The purpose of these regulations is to state general... 45 Public Welfare 1 2010-10-01 2010-10-01 false What is the purpose of these regulations? 90.2...

  18. 77 FR 29579 - Removing Unnecessary Office on Violence Against Women Regulations

    Science.gov (United States)

    2012-05-18

    ... now unnecessary STOP VAIW Program regulations. Higher Education Amendments of 1998 Violence against... Office on Violence Against Women Regulations AGENCY: Office on Violence Against Women, Justice. ACTION: Proposed rule. SUMMARY: This rule proposes to remove the regulations for the STOP Violence Against Indian...

  19. 76 FR 37703 - Regulation of Fuels and Fuel Additives: 2012 Renewable Fuel Standards; Public Hearing

    Science.gov (United States)

    2011-06-28

    ... Regulation of Fuels and Fuel Additives: 2012 Renewable Fuel Standards; Public Hearing AGENCY: Environmental... hearing to be held for the proposed rule ``Regulation of Fuels and Fuel Additives: 2012 Renewable Fuel... be proposing amendments to the renewable fuel standard program regulations to establish annual...

  20. To regulate or not to regulate?

    Energy Technology Data Exchange (ETDEWEB)

    Mason, G.; Wrixon, A. [IAEA, Vienna (Austria)

    2006-07-01

    Full text of publication follows: In Hamlet famous soliloquy to be or not to be, he wrestles with the perennial human problem of choosing the right course of action in difficult circumstances. In recent years, we have witnessed a cast of thousands playing out a long-running scene that seems to echo Hamlet dilemma on a rather more prosaic level. When is it necessary to apply regulations to the control of exposure to ionizing radiation and when is regulatory control not warranted? This seemingly straightforward question has brought out the philosopher, ethician, lawyer, pragmatist, orator in simple radiation protection folk and has led to passionate debate on numerous occasions. This paper attempts an answer based on a review of recent developments. For deciding when to apply regulatory controls, several concepts have evolved over time, including exemption of practices and sources, exclusion of exposures and clearance of materials. These have different origins, purposes and characteristics. Exemption and clearance have often been associated with triviality of risk, while exclusion has been related to un-amenability of control. For each concept, criteria have been developed to assist the regulator in reaching a decision, but there has much disputation over numerical values. This paper briefly reviews and analyses recent developments and attempts to clarify the problem from first principles. The conclusion is that the underlying issue in each case is to determine when regulatory controls become unwarranted: that is, when the societal resources expended in applying them and complying with them would be disproportionate to any benefit they might bring. This is a natural extension of the principle of optimization of protection to the regulatory control of protection, in the context of exposure to radiation at very low levels. It also reflects common expectations of good governance: wise management of finite societal resources and avoidance of unwarranted controls on