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Sample records for antagonists minimum safety

  1. Screening computer-assisted dosage programs for anticoagulation with warfarin and other vitamin K antagonists: minimum safety requirements for individual programs

    DEFF Research Database (Denmark)

    Poller, L; Roberts, C; Ibrahim, S;

    2009-01-01

    Based on the results of the previous European Action on Anticoagulation (EAA) multicenter study, a simplified minimum procedure is described for screening the safety and effectiveness of marketed programs for dosage of oral anticoagulant drugs (vitamin K antagonists). The aim was to demonstrate non...

  2. Minimum staff complement: safety in numbers

    International Nuclear Information System (INIS)

    Adequate staffing is an essential safety barrier for event mitigation. For this reason, Canadian nuclear power plant (NPP) licences specify the minimum staff complement (MSC), which is the number and qualifications of staff always required on-site. A systematic analysis and its validation form the basis of the MSC. The analysis and validation demonstrate a licensee is able to control, cool and contain the reactor after any credible event. The CNSC published regulatory guidelines for analyzing the basis for essential staff levels, monitoring compliance with these levels, and controlling MSC changes (G-323). Lessons learned from a full-scale MSC analysis are discussed. (author)

  3. Physics and safety aspects of the minimum attention plant

    International Nuclear Information System (INIS)

    The Minimum Attention Plant design is based on a self-pressured, indirect-cycle light water reactor with multiple once-through steam generators located within the reactor vessel. Primary coolant flow is initiated and maintained solely by natural circulation. The design of the reactor system provides major operational and safety advantages compared to conventional designs rated at 500 MWe or less, as well as major simplifications and plant equipment reduction, without requiring significant departure from existing LWR technology. Reactor power changes throughout lifetime are accommodated through primary system pressure and temperature changes without requirement for soluble boron or control rod motion. The absence of external coolant loops and large pipe connections to the reactor vessel eliminates or limits major classes of potential accidents, including loss of flow, loss of coolant, and steam line break

  4. The safety of interleukin-1 receptor antagonist (anakinra in the treatment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    L. Riente

    2011-09-01

    Full Text Available The safety profile of interleukin-1 receptor antagonist (anakinra has been studied with randomised, placebo-controlled trials involving 2932 patients affected by rheumatoid arthritis. The most frequently reported adverse events were represented by injection site reactions (71% and headache (13.6%. No statistically significant difference in the incidence of infections was observed among the patients treated with the interleukin-1 receptor antagonist and the patients receiving placebo. In particular, the incidence of serious infections was 1,8% in rheumatoid arthritis patients on anakinra therapy and 0,7% in patients on placebo. The reported serious infections consisted of pneumonia, cellulitis, bone and joint infections, bursitis. No case of opportunistic infections or tubercolosis was observed. The results of clinical studies suggest that anakinra is a new well-tolerated drug for the treatment of patients affected by rheumatoid arthritis.

  5. 38 CFR 17.155 - Minimum standards of safety and quality for automotive adaptive equipment.

    Science.gov (United States)

    2010-07-01

    ... safety and quality for automotive adaptive equipment. 17.155 Section 17.155 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Automotive Equipment and Driver Training § 17.155 Minimum standards of safety and quality for automotive adaptive equipment. (a) The Under Secretary...

  6. Safety of long acting muscarinic antagonists: are all these drugs always and equally safe?

    Science.gov (United States)

    Melani, Andrea S; Sestini, Piersante

    2016-05-01

    Inhaled bronchodilators - such as long-acting muscarinic receptor antagonists (LAMAs) - are central to the pharmacological management of symptomatic chronic obstructive pulmonary disease. LAMAs are considered to be safe drugs at recommended dosages. In the present issue of the Journal safety of umeclidinium, a recently marketed LAMA, at twice the recommended dosage, has been evaluated with good results in a Japanese, COPD population. However, because muscarinic receptors are expressed not only in the lungs but also at the level of heart, digestive and urinary apparatus, the potential exists for LAMAs to cause adverse events related to stimulation of receptors in these organs. Head-to-head and post-marketing vigilance studies are required to determine the profile risk of these drugs, ultimately, and whether differences exist between currently available LAMAs. PMID:26789695

  7. Antihypertensive Efficiency and Safety of L- & N- type Ca2+ Antagonists -cilnidipine

    Institute of Scientific and Technical Information of China (English)

    张向阳; 刘国树

    2003-01-01

    Objectives To evaluate antihypertensive efficiency and safety of a new domesticof L - & N - type Ca2+ antagonist - cilnidipine withimidapril as a positive control. Methods After 2weeks' placebo washingout, 22 patients were treatedwith cilnidipine 5 mg daily and 27 patients were treatedwith imidapril 5 mg daily. 4 weeks later, if patient'ssitting diastolic blood pressure is over 90 mmHg, his/her dosage was doubled for another 4 weeks, the othersmeasuring up remained their dosage unchanged foranother 4 weeks. Blood pressure, heart rate, blood andurine routine examination, serum glucose, serumchemical examination including total cholesterol,triglyceride, HDL, LDL, transaminase, creatine etcand side reactions were recorded before and after thetrial. Data were analyzed statistically. Results After8 weeks' treatment, blood pressure was significantlydecreased (P < 0.05) in both groups, and the twomedicines had similar antihypertensive effects. Fur-thermore, the reducing of heart rate was statisticallysignificant compared with baseline ( P < 0.01 ) in thecilnidipine group, but not in the imidapril group. Thenegative chronotropic effect of cilnidipine had little ef-fect on continuing the therapy. There were no changeson blood and urine routine examination and serumlipid, serum glucose, creatine, transaminase and etcin both groups. Their side reactions were mild and well-tolerated. Conclusions Cilnidipine has a con-vincing antihypertensive effect similar to that of imi-dapril. Especially cilnidipine may be administered topatients with relatively mild tachycardia.

  8. Radiation safety culture for developing country. Adoption of the minimum operational radiation protection programme in developing country

    International Nuclear Information System (INIS)

    The purpose for this document was to present some Itemization about the Minimum Radiation safety Requirements and an Integrated strategy Aiming at Establishing an Adequate Infrastructure for developing country, non major power reactor programme. The capacity for its implementation will allow these countries, about 50% of the IAEA's Member States, to improve marginal radiation protection, specially those recipients of technical assistance and do not meet the minimum requirements of the IAEA's Basic Safety Standards for Radiation Protection, reasonably progress in the implementation of safety regulations depends on the concept of priority of the government and its understanding and conviction about the basic requirements for protection against the risks associated with exposure to ionizing radiation. Considering the above assumption, there is no doubt to conclude that reasons for the deficiency of sources control and dose limitation in many countries, are related to the lack of an appropriate legal and regulatory framework, specially considering the establishment of: an adequate legislation; a minimum legal infrastructure; a minimum operational radiation safety programme; alternatives for a point of optimum contact among competent authorities in the country, dealing with similar type of licensing and inspection. (author)

  9. Optimization of chromone-2-carboxamide melanin concentrating hormone receptor 1 antagonists: assessment of potency, efficacy, and cardiovascular safety.

    Science.gov (United States)

    Lynch, John K; Freeman, Jennifer C; Judd, Andrew S; Iyengar, Rajesh; Mulhern, Mathew; Zhao, Gang; Napier, James J; Wodka, Dariusz; Brodjian, Sevan; Dayton, Brian D; Falls, Doug; Ogiela, Christopher; Reilly, Regina M; Campbell, Thomas J; Polakowski, James S; Hernandez, Lisa; Marsh, Kennan C; Shapiro, Robin; Knourek-Segel, Victoria; Droz, Brian; Bush, Eugene; Brune, Michael; Preusser, Lee C; Fryer, Ryan M; Reinhart, Glenn A; Houseman, Kathryn; Diaz, Gilbert; Mikhail, Ann; Limberis, James T; Sham, Hing L; Collins, Christine A; Kym, Philip R

    2006-11-01

    Evaluation of multiple structurally distinct series of melanin concentrating hormone receptor 1 antagonists in an anesthetized rat cardiovascualar assay led to the identification of a chromone-2-carboxamide series as having excellent safety against the chosen cardiovascular endpoints at high drug concentrations in the plasma and brain. Optimization of this series led to considerable improvements in affinity, functional potency, and pharmacokinetic profile. This led to the identification of a 7-fluorochromone-2-carboxamide (22) that was orally efficacious in a diet-induced obese mouse model, retained a favorable cardiovascular profile in rat, and demonstrated dramatic improvement in effects on mean arterial pressure in our dog cardiovascular model compared to other series reported by our group. However, this analogue also led to prolongation of the QT interval in the dog that was linked to affinity for hERG channel and unexpectedly potent functional blockade of this ion channel. PMID:17064075

  10. The Safety of an Adenosine A(1)-Receptor Antagonist, Rolofylline, in Patients with Acute Heart Failure and Renal Impairment Findings from PROTECT

    NARCIS (Netherlands)

    Teerlink, John R.; Iragui, Vicente J.; Mohr, Jay P.; Carson, Peter E.; Hauptman, Paul J.; Lovett, David H.; Miller, Alan B.; Pina, Ileana L.; Thomson, Scott; Varosy, Paul D.; Zile, Michael R.; Cleland, John G. F.; Givertz, Michael M.; Metra, Marco; Ponikowski, Piotr; Voors, Adriaan A.; Davison, Beth A.; Cotter, Gad; Wolko, Denise; DeLucca, Paul; Salerno, Christina M.; Mansoor, George A.; Dittrich, Howard; O'Connor, Christopher M.; Massi, Barry M.

    2012-01-01

    Background: Adenosine exerts actions in multiple organ systems, and adenosine receptors are a therapeutic target in many development programmes. Objective: The aim of this analysis was to evaluate the safety of rolofylline, an adenosine A(1)-receptor antagonist, in patients with acute heart failure.

  11. Efficacy and safety of monotherapy by pegvisomant, a growth hormone receptor antagonist, in Japanese patients with acromegaly.

    Science.gov (United States)

    Shimatsu, Akira; Nagashima, Masahito; Hashigaki, Satoshi; Ohki, Nobuhiko; Chihara, Kazuo

    2016-04-25

    Pegvisomant is a GH receptor antagonist and strong inhibitor of insulin-like growth factor I (IGF-I) production. The treatment goal for acromegaly is to normalize serum IGF-I levels and attenuate associated symptoms. The efficacy and safety of pegvisomant as treatment for acromegaly have been reported in Caucasians, but not in Japanese. Here we report the clinical experience of using pegvisomant in Japanese patients with acromegaly. The efficacy and safety data for pegvisomant from two open-labeled clinical studies in Japan, conducted from 2004 to 2007, were re-analyzed using the new Japanese age- and sex-matched normative ranges for IGF-I. Eighteen patients with active acromegaly were enrolled in an initial pivotal study, and 16 of them were moved to a long-term (max 168 weeks) extension study. The dose of pegvisomant in the extension study was adjusted to 10-30 mg per day according to IGF-I levels. IGF-I normalization was observed in 81.3% (13/16 patients) during the extension study. The mean percentage decrease from baseline in serum IGF-I level was 64.7% at the time of last observation. The clinical symptoms and overall health status were improved, and the ring size was reduced over time until Week 12 and maintained. For safety, no clinically significant changes were observed both in the pituitary tumor size and the anti-GH antibody level. Three subjects were withdrawn from the studies due to an abnormal elevation of liver enzymes which resolved after discontinuation. Pegvisomant demonstrated excellent clinical efficacy and was well tolerated in Japanese patients with acromegaly. PMID:26796763

  12. Minimum requirements for safety-relevant computers in railway and nuclear engineering

    International Nuclear Information System (INIS)

    Safety-relevant computers basically have to satisfy the requirements of their field of application. These requirements are based on the respectively valid regulation also governing laws and standards. The two fields of application, railway and nuclear engineering, require separate regulations. For this reason, the requirements for these two fields of application are handled separately. Four safety classes were introduced for the nuclear engineering applications within the research project 210 (see also chapter 2, partial TUeV (Technical Surveyance Association) report, TUeV, northern Germany). Regulations valid in railway engineering and also common-day praxis do not allow safety classes to be subdivided. As far as an application is considered relevant in regard to safety, the technical signal safety must be guaranteed for this application. From the safety level, this includes safety-relevant applications of the railway engineering, basically in safety class 1 of the classification mentioned above. Note, however, that the requirements explicitly stated in the regulation are always to be satisfied. Essential aspects of computers used in safety applications are independent of the field of application. This especially applies for the application areas of railway and nuclear engineering, since computer applications with the highest safety class occur in these two fields of application. This was also the reason for VdTUeV Research Project 210 to handle the two fields of application jointly, when possible. In regard to this application-independent section, the two report volumes of TUeV northern Germany and TUeV Rhineland refer to the differences which reflect a corresponding division of work in Research Group 210. The partial report of TUeV northern Germany covers the theme in complete detail with the depths limited by the research material. (orig.)

  13. Psychomotor effects, pharmacokinetics and safety of the orexin receptor antagonist suvorexant administered in combination with alcohol in healthy subjects.

    Science.gov (United States)

    Sun, Hong; Yee, Ka Lai; Gill, Sean; Liu, Wen; Li, Xiaodong; Panebianco, Deborah; Mangin, Eric; Morrison, Dennis; McCrea, Jacqueline; Wagner, John A; Troyer, Matthew D

    2015-11-01

    A double-blind crossover study investigated psychomotor effects, pharmacokinetics, and safety of the orexin receptor antagonist suvorexant with and without alcohol. Healthy adults (n=31) were randomized to receive placebo or suvorexant (40 mg) plus placebo solution or alcohol (0.7 g/kg) in each of four treatments (single doses; morning administration). The US Food and Drug Administration approved suvorexant dose is 10 mg (up to 20 mg) daily. Pharmacodynamic effects were assessed using tests of digit vigilance (DVT; primary endpoint), choice reaction time, digit symbol substitution, numeric working memory, immediate/delayed word recall, body sway and subjective alertness. Suvorexant alone did not significantly affect DVT reaction time, but did impact some pharmacodynamic tests. Suvorexant with alcohol increased reaction time versus either alone (mean difference at 2 h: 44 ms versus suvorexant, p<0.001; 24 ms, versus alcohol, p<0.05) and had additive negative effects on tests of vigilance, working/episodic memory, postural stability and alertness. No effects of suvorexant alone or with alcohol were observed by 9 h. No important changes in pharmacokinetic parameters were observed upon co-administration. All treatments were generally well tolerated without serious adverse events. In conclusion, co-administration of 40 mg suvorexant and 0.7 g/kg alcohol had additive negative psychomotor effects. Patients are advised not to consume alcohol with suvorexant. PMID:26464455

  14. Psychomotor effects, pharmacokinetics and safety of the orexin receptor antagonist suvorexant administered in combination with alcohol in healthy subjects.

    Science.gov (United States)

    Sun, Hong; Yee, Ka Lai; Gill, Sean; Liu, Wen; Li, Xiaodong; Panebianco, Deborah; Mangin, Eric; Morrison, Dennis; McCrea, Jacqueline; Wagner, John A; Troyer, Matthew D

    2015-11-01

    A double-blind crossover study investigated psychomotor effects, pharmacokinetics, and safety of the orexin receptor antagonist suvorexant with and without alcohol. Healthy adults (n=31) were randomized to receive placebo or suvorexant (40 mg) plus placebo solution or alcohol (0.7 g/kg) in each of four treatments (single doses; morning administration). The US Food and Drug Administration approved suvorexant dose is 10 mg (up to 20 mg) daily. Pharmacodynamic effects were assessed using tests of digit vigilance (DVT; primary endpoint), choice reaction time, digit symbol substitution, numeric working memory, immediate/delayed word recall, body sway and subjective alertness. Suvorexant alone did not significantly affect DVT reaction time, but did impact some pharmacodynamic tests. Suvorexant with alcohol increased reaction time versus either alone (mean difference at 2 h: 44 ms versus suvorexant, palcohol, peffects on tests of vigilance, working/episodic memory, postural stability and alertness. No effects of suvorexant alone or with alcohol were observed by 9 h. No important changes in pharmacokinetic parameters were observed upon co-administration. All treatments were generally well tolerated without serious adverse events. In conclusion, co-administration of 40 mg suvorexant and 0.7 g/kg alcohol had additive negative psychomotor effects. Patients are advised not to consume alcohol with suvorexant.

  15. Calcium antagonist antihypertensive treatment of non-insulin-dependent diabetics: efficacy and safety of lacidipine versus nifedipine SR.

    Science.gov (United States)

    Gulizia, M; Valenti, R; Platania, F; D'Onofrio, V; Rizzini, P; Circo, A

    1994-01-01

    Arterial hypertension is a chronic condition regarded as one of the main risk factors for development of coronary atherosclerosis. As dyslipidemia and reduced glucose tolerance are also risk factors for coronary disease, it is considered important to use antihypertensive drugs having no negative effects on lipid and glucose metabolism when diabetic patients are treated for hypertension. Lacidipine, a new dihydropyridine-like calcium antagonist, has been shown in in vivo and in vitro preclinical studies to possess potent, long-lasting antihypertensive activity. The present study compared the efficacy and safety of once-daily treatment with lacidipine versus nifedipine SR given twice-daily in non-insulin-dependent diabetic patients. Results have shown a similar efficacy of the two treatments: 6 months later, both drugs had reduced blood pressure values [lacidipine from 184.8/105.2 mm Hg to 144.4/87.1 mm Hg; nifedipine slow-release (SR) from 182.3/106.8 mm Hg to 143.6/89.4 mmHg]. However, lacidipine exhibited a lower incidence of adverse events (particularly ankle edema and tachycardia) than nifedipine SR. Finally, both treatments showed no negative effect on metabolic parameters (total cholesterol, high-density lipoprotein cholesterol, triglycerides, and blood glucose). PMID:7609494

  16. 12 CFR Appendix A to Part 1720 - Policy Guidance; Minimum Safety and Soundness Requirements

    Science.gov (United States)

    2010-01-01

    ... business activities that, at a minimum, provide for: i. An organizational structure and assignment of... of the supervisory requirements set forth in the Policy Guidance may not warrant a formal supervisory... function appropriate to the Enterprise's size, structure and scope of operations; ii. Independence of...

  17. Effectiveness of In-Vessel Retention Strategies and Minimum Safety Injection Flow over Postulated Severe Accidents of OPR1000

    International Nuclear Information System (INIS)

    The objective of this study is first to evaluate various serious severe accident scenarios of OPR1000 with and without in-vessel retention strategies using MELCOR code. Second is to develop a mechanistic model of minimum safety injection flow using the thermal-hydraulic parameters of CET and collapsed water level obtained from the MELCOR simulation results. Effectiveness of RCS depressurization of OPR1000 is investigated for postulated severe accidents of SBLOCA, SBO, and TLOF. It is seen that timely operator action is important to achieve the best mitigation. Also The MELCOR simulation results of SBLOCA, SBO, and TLOFW are utilized to develop a model for minimum safety injection flow. The model suggests that if HPSI is available with RCS pressure lower than 120 bars, the core coolability can be guaranteed. In this study, several MELCOR simulations are conducted in search for effective in-vessel retention strategies over postulated severe accidents of SBLOCA, SBO, and TLOFW of OPR1000. Detailed accident sequences are presented and indicative parameters diagnosing the reactor thermal-hydraulic state are interrogated to provide useful information to the operator actions. To properly assist operator's action during the severe accident, the thermal-hydraulic parameters should be virtual, intuitive, and reliable. In addition, the parameters should be collected through the instrumentations close to the reactor core. In this regard, Core Exit Temperature (CET) and collapsed core water level are deemed as the commensurate parameters

  18. Comparative efficacy and safety of the non-vitamin K antagonist oral anticoagulants for patients with nonvalvular atrial fibrillation.

    Science.gov (United States)

    Senoo, Keitaro; Lip, Gregory Y H

    2015-03-01

    The non-vitamin K antagonist oral anticoagulants (NOACs), such as the thrombin inhibitor (dabigatran) and the direct factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), have been shown to be at least as efficacious and safe as conventional oral anticoagulants, such as the vitamin K antagonists (VKAs) (e.g., warfarin), for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Each NOAC has various advantages and specific features, and therefore decisions regarding appropriate stroke prevention require individual assessment of stroke and bleeding risk on anticoagulation with VKA therapy and NOACs when starting on any of these drugs. This review briefly describes the results of the four NOACs clinical randomized trials and discusses how they might impact clinical practice and choice of anticoagulants in atrial fibrillation patients. Moreover, this review discusses the differences of the proposed management of antithrombotic therapy in several international guidelines and pragmatic issues of NOACs for stroke prophylaxis. PMID:25682085

  19. Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers.

    Science.gov (United States)

    Erpenbeck, Veit J; Vets, Eva; Gheyle, Lien; Osuntokun, Wande; Larbig, Michael; Neelakantham, Srikanth; Sandham, David; Dubois, Gerald; Elbast, Walid; Goldsmith, Paul; Weiss, Markus

    2016-07-01

    We evaluated the pharmacokinetics (PK), safety, and tolerability of a novel oral CRTh2 antagonist, fevipiprant (QAW039), in healthy subjects. Peak concentrations of fevipiprant in plasma were observed 1-3 hours postdosing. Concentrations declined in a multiexponential manner, followed by an apparent terminal phase (t1/2 , ∼20 hours). Steady state was achieved in 4 days with <2-fold accumulation. Elimination was partly by renal excretion (≤30% of the dose) and glucuronidation. Food had minimal impact on the PK of fevipiprant, and it was well tolerated at single and multiple oral doses up to 500 mg/day. No dose-dependent adverse events were observed, and all the events were mild or moderate in severity. Systemic concentrations were sufficiently high to achieve relevant target occupancy, considering in vitro pharmacology data. In summary, the data support further development as a once-daily oral therapy for allergic diseases. PMID:27310331

  20. Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants versus Vitamin K Antagonist Oral Anticoagulants in Patients Undergoing Radiofrequency Catheter Ablation of Atrial Fibrillation: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Giuseppe Santarpia

    Full Text Available Use of the non-vitamin K antagonist oral anticoagulants (NOACs is endorsed by current guidelines for stroke prevention in patients with atrial fibrillation (AF. However efficacy and safety of NOACs in patients undergoing catheter ablation (RFCA of AF has not been well established yet.To perform a meta-analysis of all studies comparing NOACs and vitamin K antagonist oral anticoagulants (VKAs in patients undergoing RFCA.Studies were searched for in PubMed and Google Scholar databases.Studies were considered eligible if: they evaluated the clinical impact of NOACs versus VKAs; they specifically analyzed the use of anticoagulants during periprocedural phase of RFCA; they reported clinical outcome data.25 studies were selected, including 9881 cases. The summary measure used was the risk ratio (RR with 95% confidence interval (CI. The random-effects or the fixed effect model were used to synthesize results from the selected studies.There was no significant difference in thromboembolic complications (RR 1.39; p=0.13. Bleeding complications were significantly lower in the NOACs-treated arm as compared to VKAs (RR=0.67, p<0.001. Interestingly, a larger number of thromboembolic events was found in the VKAs-treated arm in those studies where VKAs had been interrupted during the periprocedural phase (RR=0.68; p=ns. In this same subgroup a significantly higher incidence of both minor (RR=0.54; p=0.002 and major bleeding (RR=0.41; p=0.01 events was recorded. Conversely, the incidence of thromboembolic events in the VKAs-treated arm was significantly lower in those studies with uninterrupted periprocedural anticoagulation treatment (RR=1.89; p=0.02.As with every meta-analysis, no patients-level data were available.The use of NOACs in patients undergoing RFCA is safe, given the lower incidence of bleedings observed with NOACs. On the other side, periprocedural interruption of VKAs and bridging with heparin is associated with a higher bleeding rate with no

  1. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial

    DEFF Research Database (Denmark)

    Cannon, Christopher P; Husted, Steen; Harrington, Robert A;

    2007-01-01

    OBJECTIVES: Our goal was to compare the safety and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, with clopidogrel in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: AZD6140 achieves higher mean levels of p...

  2. Treatment of allergic rhinitis in infants and children: efficacy and safety of second-generation antihistamines and the leukotriene receptor antagonist montelukast.

    Science.gov (United States)

    Phan, Hanna; Moeller, Matthew L; Nahata, Milap C

    2009-01-01

    Allergic rhinitis (AR) affects a large percentage of paediatric patients. With the wide array of available agents, it has become a challenge to choose the most appropriate treatment for patients. Second-generation antihistamines have become increasingly popular because of their comparable efficacy and lower incidence of adverse effects relative to their first-generation counterparts, and the safety and efficacy of this drug class are established in the adult population. Data on the use of the second-generation antihistamines oral cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, and the leukotriene receptor antagonist montelukast as well as azelastine nasal spray in infants and children are evaluated in this review. These agents have been found to be relatively safe and effective in reducing symptoms associated with AR in children. Alternative dosage forms such as liquids or oral disintegrating tablets are available for most agents, allowing ease of administration to most young children and infants; however, limited data are available regarding use in infants for most agents, except desloratadine, cetirizine and montelukast. Unlike their predecessors, such as astemizole and terfenadine, the newer second-generation antihistamines and montelukast appear to be well tolerated, with absence of cardiotoxicities. Comparative studies are limited to cetirizine versus ketotifen, oxatomide and/or montelukast. Although second-generation antihistamines and montelukast are deemed relatively safe for use in paediatric patients, there are some noteworthy drug interactions to consider when selecting an agent. Given the wide variety of available agents for treatment of AR in paediatric patients, the safety and efficacy data available for specific age groups, type of AR, dosage form availability and cost should be considered when selecting treatment for AR in infants and children. PMID:19943707

  3. Biologics in the management of ulcerative colitis – comparative safety and efficacy of TNF-α antagonists

    Directory of Open Access Journals (Sweden)

    Fausel R

    2015-01-01

    Full Text Available Rebecca Fausel,1 Anita Afzali1,2 1Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, USA; 2Inflammatory Bowel Disease Program, UW Medicine – Harborview Medical Center, Seattle, WA, USA Abstract: Ulcerative colitis can cause debilitating symptoms and complications such as colonic strictures, colonic dysplasia, colorectal cancer, and toxic megacolon or perforation. Goals of treatment in ulcerative colitis include resolution of gastrointestinal symptoms, healing of colonic mucosa, and prevention of disease complications. Our treatment armamentarium has expanded dramatically over the past 10 years, and we now have multiple biologic agents approved for the treatment of moderate-severe disease, in addition to conventional therapies such as 5-aminosalicylates, thiopurines, and corticosteroids. In this review, we will provide a detailed discussion of the three tumor necrosis factor-alpha (TNF-α inhibitors currently approved for treatment of ulcerative colitis: infliximab, adalimumab, and golimumab. All three agents are effective for inducing and maintaining clinical response and remission in patients with ulcerative colitis, and they have comparable safety profiles. There are no head-to-head trials comparing their efficacy, and the choice of agent is most often based on insurance coverage, route of administration, and patient preference. Combination therapy with an immunomodulator is proven to be more effective than anti-TNF monotherapy, and patients who lose response to an anti-TNF agent should undergo dose intensification in order to regain clinical response. Despite therapeutic optimization, a significant percentage of patients will not achieve clinical remission with anti-TNF agents, and so newer therapies are on the horizon. Keywords: ulcerative colitis, inflammatory bowel disease, infliximab, adalimumab, golimumab

  4. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial

    OpenAIRE

    Pitt, Bertram; Kober, Lars; Ponikowski, Piotr; Gheorghiade, Mihai; Filippatos, Gerasimos; Krum, Henry; Nowack, Christina; Kolkhof, Peter; Kim, So-Young; Zannad, Faiez

    2013-01-01

    Aims Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD). Methods and results This randomized, controlled, phase II ...

  5. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease

    DEFF Research Database (Denmark)

    Pitt, Bertram; Kober, Lars; Ponikowski, Piotr;

    2013-01-01

    Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroida......Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non......-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD)....

  6. GABAB antagonists

    DEFF Research Database (Denmark)

    Frydenvang, Karla Andrea; Hansen, J J; Krogsgaard-Larsen, P;

    1994-01-01

    Phaclofen, which is the phosphonic acid analogue of the GABAB agonist (RS)-3-(4-chlorophenyl)-4-aminobutyric acid (baclofen), is a GABAB antagonist. As part of our studies on the structural requirements for activation and blockade of GABAB receptors, we have resolved phaclofen using chiral...... chromatographic techniques. The absolute stereochemistry of (-)-(R)-phaclofen was established by X-ray crystallographic analysis. (-)-(R)-Phaclofen was shown to inhibit the binding of [3H]-(R)-baclofen to GABAB receptor sites on rat cerebellar membranes (IC50 = 76 +/- 13 microM), whereas (+)-(S)-phaclofen was...... inactive in this binding assay (IC50 > 1000 microM). (-)-(R)-Phaclofen (200 microM) was equipotent with (RS)-phaclofen (400 microM) in antagonizing the action of baclofen in rat cerebral cortical slices, while (+)-(S)-phaclofen (200 microM) was inactive. The structural similarity of the agonist (R)-baclofen...

  7. Pharmacodynamics and safety of lefradafiban, an oral platelet glycoprotein IIb/IIIa receptor antagonist, in patients with stable coronary artery disease undergoing elective angioplasty

    NARCIS (Netherlands)

    K.M. Akkerhuis (Martijn); M.L. Simoons (Maarten); C. van der Zwaan (Coen); H. Suryapranata (Harry); J. Stibbe (Jeanne); J. Hoffmann; T. Baardman (Taco); M.J.B.M. van den Brand (Marcel); J.W. Deckers (Jaap); L.R. van der Wieken (Ron); H.O.J. Peels

    2001-01-01

    textabstractOBJECTIVE: Lefradafiban is the orally active prodrug of fradafiban, a glycoprotein IIb/IIIa receptor antagonist. The present phase II study aimed to determine the dose of lefradafiban that provides 80% blockade of the glycoprotein IIb/IIIa receptors by fradafiban, and to study the pharma

  8. ACTH Antagonists

    Science.gov (United States)

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing’s disease and ectopic ACTH syndrome – especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role. PMID:27547198

  9. ACTH antagonists

    Directory of Open Access Journals (Sweden)

    Adrian John Clark

    2016-08-01

    Full Text Available ACTH acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1 Cushing’s disease and ectopic ACTH syndrome – especially whilst preparing for definitive treatment of a causative tumour, or in refractory cases, or (2 congenital adrenal hyperplasia – as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role.

  10. ACTH Antagonists.

    Science.gov (United States)

    Clark, Adrian John; Forfar, Rachel; Hussain, Mashal; Jerman, Jeff; McIver, Ed; Taylor, Debra; Chan, Li

    2016-01-01

    Adrenocorticotropin (ACTH) acts via a highly selective receptor that is a member of the melanocortin receptor subfamily of type 1 G protein-coupled receptors. The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and high degree of ligand specificity suggests that antagonism of this receptor could provide a useful therapeutic aid and a potential investigational tool. Clinical situations in which this could be useful include (1) Cushing's disease and ectopic ACTH syndrome - especially while preparing for definitive treatment of a causative tumor, or in refractory cases, or (2) congenital adrenal hyperplasia - as an adjunct to glucocorticoid replacement. A case for antagonism in other clinical situations in which there is ACTH excess can also be made. In this article, we will explore the scientific and clinical case for an ACTH antagonist, and will review the evidence for existing and recently described peptides and modified peptides in this role. PMID:27547198

  11. Non-vitamin K antagonist oral anticoagulants and the treatment of venous thromboembolism in cancer patients: a semi systematic review and meta-analysis of safety and efficacy outcomes.

    Directory of Open Access Journals (Sweden)

    Torben Bjerregaard Larsen

    Full Text Available This study sought to investigate the relative efficacy and safety of non-vitamin K oral anticoagulants (NOACs for the treatment of venous thromboembolism (VTE in cancer patients.A systematic search of the PubMed, EMBASE, and ClinicalTrials.gov databases identified all multicentre, randomised phase III trials investigating the initial use of NOAC against a vitamin K antagonist (VKA together with subcutaneous heparin or low molecular weight heparin (upstart for treatment of VTE. Outcomes of interest were recurrent VTE (deep venous thrombosis or pulmonary embolism, and clinically relevant bleeding.Four randomised controlled phase III trials were included, comprising a total of 19,060 patients randomised to either NOAC or VKA. For patients with active cancer (N = 759, the analysis on the efficacy outcomes demonstrated a trend in favour of NOAC (OR 0.56, 95% CI 0.28-1.13. Similar, analyses on the safety outcomes comparing NOAC to VKA and enoxaparin demonstrated a trend in favour of NOAC (OR 0.88, 95% CI 0.57-1.35.Point estimates of the effect size suggest an important estimated beneficial effect of NOAC in the treatment of VTE in cancer, in terms of efficacy and safety, but given the small numbers of patients with cancer in the randomised trials, statistical significance was not achieved.

  12. SAFETY

    CERN Multimedia

    Niels Dupont

    2013-01-01

    CERN Safety rules and Radiation Protection at CMS The CERN Safety rules are defined by the Occupational Health & Safety and Environmental Protection Unit (HSE Unit), CERN’s institutional authority and central Safety organ attached to the Director General. In particular the Radiation Protection group (DGS-RP1) ensures that personnel on the CERN sites and the public are protected from potentially harmful effects of ionising radiation linked to CERN activities. The RP Group fulfils its mandate in collaboration with the CERN departments owning or operating sources of ionising radiation and having the responsibility for Radiation Safety of these sources. The specific responsibilities concerning "Radiation Safety" and "Radiation Protection" are delegated as follows: Radiation Safety is the responsibility of every CERN Department owning radiation sources or using radiation sources put at its disposition. These Departments are in charge of implementing the requi...

  13. Safety

    CERN Multimedia

    2003-01-01

    Please note that the safety codes A9, A10 AND A11 (ex annexes of SAPOCO/42) entitled respectively "Safety responsibilities in the divisions" "The safety policy committee (SAPOCO) and safety officers' committees" and "Administrative procedure following a serious accident or incident" are available on the web at the following URLs: Code A9: http://edms.cern.ch/document/337016/LAST_RELEASED Code A10: http://edms.cern.ch/document/337019/LAST_RELEASED Code A11: http://edms.cern.ch/document/337026/LAST_RELEASED Paper copies can also be obtained from the TIS divisional secretariat, e-mail: tis.secretariat@cern.ch. TIS Secretariat

  14. Safety, tolerability, pharmacokinetics, and effects on human experimental pain of the selective ionotropic glutamate receptor 5 (iGluR5) antagonist LY545694 in healthy volunteers.

    Science.gov (United States)

    Petersen, Karin L; Iyengar, Smriti; Chappell, Amy S; Lobo, Evelyn D; Reda, Haatem; Prucka, William R; Verfaille, Steven J

    2014-05-01

    The objective of this study was to establish in healthy volunteers the maximally tolerated multiple dose (MTMD) of the ionotropic glutamate receptor 5 antagonist LY545694 (part A), and to investigate whether that dose had analgesic or antihyperalgesic effects in the brief thermal stimulation (BTS) pain model (Part B). Part A was a double-blind, placebo-controlled study in 3 groups of 10 healthy men. To simulate an extended-release formulation, study drug was administered orally over 6hours (12 equally divided aliquots at 30-minute intervals). Part B was a double-blind, placebo-controlled, double-dummy, 3-way crossover study in 27 healthy men. At each of the 3 study periods, subjects received either LY545694 (MTMD; as determined during part A) as a simulated, twice daily extended-release formulation for 4 doses over 3days, gabapentin (600mg 8hours apart; 6 doses over 3days; positive control), or matching placebo. The BTS model was induced twice with a 1-hour interval on each of the 2 study days, before drug administration and at the time of expected peak analgesia of LY545694. Plasma exposure for LY545694 was approximately linear over the 25- to 75-mg dose range. The MTMD of LY545694 was 25mg twice daily. Areas of secondary hyperalgesia were significantly smaller after administration of LY545694 and gabapentin compared with placebo (Ppainfulness of skin heating during BTS model induction. The most common treatment-emergent adverse event was dizziness. The results of this study suggest that LY545694 should be explored further as a potential treatment for chronic pain involving neuronal sensitization.

  15. Safety of Aldosterone Receptor Antagonists in Heart Failure%醛固酮受体拮抗剂在心力衰竭患者中应用的安全性

    Institute of Scientific and Technical Information of China (English)

    戴士鹏(综述); 徐泽升(审校)

    2015-01-01

    Although the benefits of aldosterone receptor antagonists have been confirmed with multiple randomized,controlled studies and recommended by heart failure guideline,only a fraction of the patients with heart failure who are eligible for the indications receive this medication .This maybe, in part, concerns of adverse events-hyperkalemia and deteriorated renal function known to occur with using of these drugs.Here is to make a review of the safety of aldosterone receptor antagonists in heart failure , in order to improve the knowledge of this kind of drugs.%尽管应用醛固酮受体拮抗剂治疗心力衰竭的益处被多个大型临床随机对照试验所证实,并被临床治疗指南所推荐,但仅有一小部分适合应用醛固酮受体拮抗剂治疗的心力衰竭患者应用了这一药物,其部分原因是临床医师对醛固酮受体拮抗剂的主要不良反应———高钾血症和肾功能恶化的担心。该文对醛固酮受体拮抗剂在心力衰竭患者中应用的安全性做一综述,以提高人们对于这类药物的认识。

  16. Patient self-management of oral anticoagulation with vitamin K antagonists in everyday practice: efficacy and safety in a nationwide long-term prospective cohort study.

    Directory of Open Access Journals (Sweden)

    Michael Nagler

    Full Text Available Patient self-management (PSM of oral anticoagulation is under discussion, because evidence from real-life settings is missing. Using data from a nationwide, prospective cohort study in Switzerland, we assessed overall long-term efficacy and safety of PSM and examined subgroups. Data of 1140 patients (5818.9 patient-years were analysed and no patient were lost to follow-up. Median follow-up was 4.3 years (range 0.2-12.8 years. Median age at the time of training was 54.2 years (range 18.2-85.2 and 34.6% were women. All-cause mortality was 1.4 per 100 patient-years (95% CI 1.1-1.7 with a higher rate in patients with atrial fibrillation (2.5; 1.6-3.7; p50 years of age (2.0; 1.6-2.6; p<0.001, and men (1.6; 1.2-2.1; p = 0.036. The rate of thromboembolic events was 0.4 (0.2-0.6 and independent from indications, sex and age. Major bleeding were observed in 1.1 (0.9-1.5 per 100 patient-years. Efficacy was comparable to standard care and new oral anticoagulants in a network meta-analysis. PSM of properly trained patients is effective and safe in a long-term real-life setting and robust across clinical subgroups. Adoption in various clinical settings, including those with limited access to medical care or rural areas is warranted.

  17. SAFETY

    CERN Multimedia

    C. Schaefer and N. Dupont

    2013-01-01

      “Safety is the highest priority”: this statement from CERN is endorsed by the CMS management. An interpretation of this statement may bring you to the conclusion that you should stop working in order to avoid risks. If the safety is the priority, work is not! This would be a misunderstanding and misinterpretation. One should understand that “working safely” or “operating safely” is the priority at CERN. CERN personnel are exposed to different hazards on many levels on a daily basis. However, risk analyses and assessments are done in order to limit the number and the gravity of accidents. For example, this process takes place each time you cross the road. The hazard is the moving vehicle, the stake is you and the risk might be the risk of collision between both. The same principle has to be applied during our daily work. In particular, keeping in mind the general principles of prevention defined in the late 1980s. These principles wer...

  18. SAFETY

    CERN Multimedia

    M. Plagge, C. Schaefer and N. Dupont

    2013-01-01

    Fire Safety – Essential for a particle detector The CMS detector is a marvel of high technology, one of the most precise particle measurement devices we have built until now. Of course it has to be protected from external and internal incidents like the ones that can occur from fires. Due to the fire load, the permanent availability of oxygen and the presence of various ignition sources mostly based on electricity this has to be addressed. Starting from the beam pipe towards the magnet coil, the detector is protected by flooding it with pure gaseous nitrogen during operation. The outer shell of CMS, namely the yoke and the muon chambers are then covered by an emergency inertion system also based on nitrogen. To ensure maximum fire safety, all materials used comply with the CERN regulations IS 23 and IS 41 with only a few exceptions. Every piece of the 30-tonne polyethylene shielding is high-density material, borated, boxed within steel and coated with intumescent (a paint that creates a thick co...

  19. Minimum wage careers?

    OpenAIRE

    William J. Carrington; Bruce C. Fallick

    1999-01-01

    This paper investigates the extent to which people spend careers on minimum wage jobs. We find that a small but non-trivial number of NLSY respondents spend 25%, 50%, or even 75% of the first ten years of their career on minimum or near-minimum wage jobs. Workers with these minimum wage careers tend to be drawn from groups such as women, blacks, and the less-educated that are generally overrepresented in the low-wage population. The results indicate that lifetime incomes of some workers may b...

  20. 42 CFR 86.31 - Eligibility; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ....31 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES GRANTS FOR EDUCATION PROGRAMS IN OCCUPATIONAL SAFETY AND HEALTH Occupational Safety and Health Direct Traineeships § 86.31 Eligibility; minimum requirements....

  1. Studies on antagonistic marine streptomycetes

    Digital Repository Service at National Institute of Oceanography (India)

    Chandramohan, D.; Nair, S.

    Sixty nine strains of Streptomyces sp. isolated from the sediments of Andaman and Nicobar islands (Bay of Bengal) were screened for their antagonistic property against a number of test cultures (Vibrio sp., Klebsiella sp., Escherichia coli, Shigella...

  2. Setting the minimum wage

    OpenAIRE

    Boeri, Tito

    2009-01-01

    The process leading to the setting of the minimum wage so far has been fairly overlooked by economists. This paper suggests that this is a serious limitation as the setting regime contributes to explain cross-country variation in the fine-tuning of the minimum wage, hence in the way in which the trade-off between reducing poverty among working people and shutting down low productivity jobs is addressed. There are two common ways of setting national minimum wages: they are either government le...

  3. Development of transdermal therapeutic formulation of CNS5161, a novel NMDA receptor antagonist, by utilizing pressure-sensitive adhesives II: improved transdermal absorption and evaluation of efficacy and safety.

    Science.gov (United States)

    Naruse, Mamoru; Ogawara, Ken-ichi; Kimura, Toshikiro; Konishi, Ryoji; Higaki, Kazutaka

    2014-02-14

    The aim of this study was to prepare a transdermal therapeutic formulation of CNS5161, an NMDA receptor antagonist developed as a drug for neuropathic pain. Since a silicone pressure-sensitive adhesive (PSA) was found to be the best PSA for CNS5161 among six different PSAs examined in our previous study, the effects of the loading concentration of CNS5161 on release and rat skin permeability were investigated using silicone PSAs. The release of CNS5161 was elevated with an increase in the drug concentration from 1% to 14%. The transdermal flux at the steady state reached a plateau at 8% and over, while crystallization of CNS5161 was not observed for any formulation even at high drug concentrations. The drug concentration in rat skin at the steady state was also saturated at 8% and over, which correlated well with the transdermal flux at the steady state. Therefore, skin permeation clearance defined to the skin concentration at the steady state was almost constant at 0.21/h from 2% to 14% of CNS5161, which suggests that drug concentrations in the skin would be a driving force for transport of the drug to the receptor side. Since increasing the concentration of CNS5161 in the PSA patch was not able to elevate the transdermal flux, 12 formulations containing several permeation enhancers were examined to improve the transdermal transport of CNS5161. Among them, the formulation containing propylene glycol, diisopropyl adipate, and polyvinylpyrrolidone significantly increased the transdermal flux by approximately 1.8-fold by improving the diffusivity of CNS5161 in the skin, and also significantly enhanced the analgesic effect of CNS5161. This formulation caused only slight skin irritation, which indicated that it would be a promising transdermal therapeutic system for CNS5161.

  4. Minimum wages in Kenya

    OpenAIRE

    Andalón, Mabel; Pagés, Carmen

    2008-01-01

    This paper examines the performance of minimum wage legislation in Kenya, both in terms of its coverage and enforcement as well as in terms of their implications for wages and employment. Our findings based on the 1998/99 labor force data – the last labor force survey available – indicate that minimum wages, which, in principle, apply to all salaried employees, were better enforced and had stronger effects in the non-agricultural industry than in the agricultural one. More specifically, our r...

  5. Minimum variance geographic sampling

    Science.gov (United States)

    Terrell, G. R. (Principal Investigator)

    1980-01-01

    Resource inventories require samples with geographical scatter, sometimes not as widely spaced as would be hoped. A simple model of correlation over distances is used to create a minimum variance unbiased estimate population means. The fitting procedure is illustrated from data used to estimate Missouri corn acreage.

  6. ARGUMENTS AGAINST MINIMUM TAX

    OpenAIRE

    Mitu, Narcis Eduard

    2009-01-01

    This article seeks to debate from a critical perspective the opportunity and legality of introducing the minimum tax system introduced in Romania by the Emergency Ordinance on the budget rectification for the year 2009 and the regulation of some financial and fiscal measures.

  7. A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Morris Peter E

    2012-02-01

    Full Text Available Abstract Background The tissue factor (TF-dependent extrinsic pathway has been suggested to be a central mechanism by which the coagulation cascade is locally activated in the lungs of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS and thus represents an attractive target for therapeutic intervention. This study was designed to determine the pharmacokinetic and safety profiles of ALT-836, an anti-TF antibody, in patients with ALI/ARDS. Methods This was a prospective, randomized, placebo-controlled, dose-escalation Phase I clinical trial in adult patients who had suspected or proven infection, were receiving mechanical ventilation and had ALI/ARDS (PaO2/FiO2 ≤ 300 mm. Eighteen patients (6 per cohort were randomized in a 5:1 ratio to receive ALT-836 or placebo, and were treated within 48 hours after meeting screening criteria. Cohorts of patients were administered a single intravenously dose of 0.06, 0.08 or 0.1 mg/kg ALT-836 or placebo. Blood samples were taken for pharmacokinetic and immunogenicity measurements. Safety was assessed by adverse events, vital signs, ECGs, laboratory, coagulation and pulmonary function parameters. Results Pharmacokinetic analysis showed a dose dependent exposure to ALT-836 across the infusion range of 0.06 to 0.1 mg/kg. No anti-ALT-836 antibody response was observed in the study population during the trial. No major bleeding episodes were reported in the ALT-836 treated patients. The most frequent adverse events were anemia, observed in both placebo and ALT-836 treated patients, and ALT-836 dose dependent, self-resolved hematuria, which suggested 0.08 mg/kg as an acceptable dose level of ALT-836 in this patient population. Conclusions Overall, this study showed that ALT-836 could be safely administered to patients with sepsis-induced ALI/ARDS. Trial registration ClinicalTrials.gov: NCT01438853

  8. Antagonistic Interfa(e)ces

    DEFF Research Database (Denmark)

    Cox, Geoff; Jackson, Robert

    2011-01-01

    "lingering stink" so that it became purer and closer to authority. The paper will further link the purification of code to the structure of ideology inherent in Zizek’s psychoanalytical model between Symbolic reality, the antagonistic Real and ideological concealment. The purification is technical in so far...

  9. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

    Johansen, T N; Frydenvang, Karla Andrea; Ebert, B;

    1997-01-01

    We have previously shown that (RS)-2-amino-2-(5-tert-butyl-3-hydroxyisoxazol-4-yl)acetic acid (ATAA) is an antagonist at N-methyl-D-aspartic acid (NMDA) and (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors. We have now resolved ATAA via diastereomeric salt formation......)-phenylethylamine salt of N-BOC-(R)-ATAA. Like ATAA, neither (R)- nor (S)-ATAA significantly affected (IC50 > 100 microM) the receptor binding of tritiated AMPA, kainic acid, or (RS)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, the latter being a competitive NMDA antagonist. Electrophysiological experiments......, using the rat cortical wedge preparation, showed the NMDA antagonist effect as well as the AMPA antagonist effect of ATAA to reside exclusively in the (R)-enantiomer (Ki = 75 +/- 5 microM and 57 +/- 1 microM, respectively). Neither (R)- nor (S)-ATAA significantly reduced kainic acid-induced excitation...

  10. Synthesis of potential mescaline antagonists.

    Science.gov (United States)

    DeSantis, F; Nieforth, K A

    1976-10-01

    1-[2-(3,4,5-Trimethoxyphenyl)ethyl]-3-pyrroline, 2-(3,4,5-trimethoxybenzyl)-1,2,3,6-tetrahydropyridine, N-n-propylmescaline, N-cyclopropylmethylmescaline, and N-allylmescaline were synthesized as potential mescaline antagonists. The ability of these compounds to antagonize mescaline-induced disruption of swim behavior is also given.

  11. Minimum Entropy Orientations

    CERN Document Server

    Cardinal, Jean; Joret, Gwenaël

    2008-01-01

    We study graph orientations that minimize the entropy of the in-degree sequence. The problem of finding such an orientation is an interesting special case of the minimum entropy set cover problem previously studied by Halperin and Karp [Theoret. Comput. Sci., 2005] and by the current authors [Algorithmica, to appear]. We prove that the minimum entropy orientation problem is NP-hard even if the graph is planar, and that there exists a simple linear-time algorithm that returns an approximate solution with an additive error guarantee of 1 bit. This improves on the only previously known algorithm which has an additive error guarantee of log_2 e bits (approx. 1.4427 bits).

  12. DILEMATIKA PENETAPAN UPAH MINIMUM

    Directory of Open Access Journals (Sweden)

    . Pitaya

    2015-02-01

    Full Text Available In the effort of creating appropiate wage for employees, it is necessary to determine the wages by considering the increase of poverty without ignoring the increase of productivity, the progressivity of companies and the growth of economic. The new minimum wages in the provincial level and the regoinal/municipality level have been implemented per 1st January in Indonesia since 2001. The determination of minimum wage for provinvial level should be done 30 days before 1st January, whereas the determination of minimumwage for regional/municipality level should be done 40 days before 1st January. Moreover,there is an article which governs thet the minimumwage will be revised annually. By considering the time of determination and the time of revision above,it can be predicted that before and after the determination date will be crucial time. This is because the controversy among parties in industrial relationships will arise. The determination of minimum wage will always become a dilemmatic step which has to be done by the Government. Through this policy, on one side the government attempts to attract many investors, however, on the other side the government also has to protect the employees in order to have the appropiate wage in accordance with the standard of living.

  13. Effective use of TNF antagonists

    OpenAIRE

    Yocum, David

    2004-01-01

    Tumor necrosis factor (TNF) antagonists are biologic response modifiers that have significantly improved functional outcomes in patients with rheumatoid arthritis (RA). RA is a progressive disease in which structural joint damage can continue to develop even in the face of symptomatic relief. Before the introduction of biologic agents, the management of RA involved the use of disease-modifying antirheumatic drugs (DMARDs) early in the course of disease. This focus on early treatment, combined...

  14. Minimum Error Entropy Classification

    CERN Document Server

    Marques de Sá, Joaquim P; Santos, Jorge M F; Alexandre, Luís A

    2013-01-01

    This book explains the minimum error entropy (MEE) concept applied to data classification machines. Theoretical results on the inner workings of the MEE concept, in its application to solving a variety of classification problems, are presented in the wider realm of risk functionals. Researchers and practitioners also find in the book a detailed presentation of practical data classifiers using MEE. These include multi‐layer perceptrons, recurrent neural networks, complexvalued neural networks, modular neural networks, and decision trees. A clustering algorithm using a MEE‐like concept is also presented. Examples, tests, evaluation experiments and comparison with similar machines using classic approaches, complement the descriptions.

  15. Minimum wage noncompliance and the sub-minimum wage rate

    OpenAIRE

    Joachim Rosenmüller

    2004-01-01

    The present note examines the effect of minimum wage noncompliance on the sub-minimum wage rate in a competitive labor market. The note shows that noncompliance shifts leftward the demand curve of labor and shifts rightward the supply curve of labor, unambiguously leading to a fall in the equilibrium sub-minimum wage rate. Two implications follow: first, contrary to a major result in the minimum wage literature, noncompliance must not necessarily reduce employment (as compared to the pre-law ...

  16. Minimum fuel mode evaluation

    Science.gov (United States)

    Orme, John S.; Nobbs, Steven G.

    1995-01-01

    The minimum fuel mode of the NASA F-15 research aircraft is designed to minimize fuel flow while maintaining constant net propulsive force (FNP), effectively reducing thrust specific fuel consumption (TSFC), during cruise flight conditions. The test maneuvers were at stabilized flight conditions. The aircraft test engine was allowed to stabilize at the cruise conditions before data collection initiated; data were then recorded with performance seeking control (PSC) not-engaged, then data were recorded with the PSC system engaged. The maneuvers were flown back-to-back to allow for direct comparisons by minimizing the effects of variations in the test day conditions. The minimum fuel mode was evaluated at subsonic and supersonic Mach numbers and focused on three altitudes: 15,000; 30,000; and 45,000 feet. Flight data were collected for part, military, partial, and maximum afterburning power conditions. The TSFC savings at supersonic Mach numbers, ranging from approximately 4% to nearly 10%, are in general much larger than at subsonic Mach numbers because of PSC trims to the afterburner.

  17. Are peripheral opioid antagonists the solution to opioid side effects?

    LENUS (Irish Health Repository)

    Bates, John J

    2012-02-03

    Opioid medication is the mainstay of therapy for severe acute and chronic pain. Unfortunately, the side effects of these medications can affect patient comfort and safety, thus limiting their proven therapeutic potential. Whereas the main analgesic effects of opioids are centrally mediated, many of the common side effects are mediated via peripheral receptors. Novel peripheral opioid antagonists have been recently introduced that can block the peripheral actions of opioids without affecting centrally mediated analgesia. We review the clinical and experimental evidence of their efficacy in ameliorating opioid side effects and consider what further information might be useful in defining their role. IMPLICATIONS: The major analgesic effects of opioid medication are mediated within the brain and spinal cord. Many of the side effects of opioids are caused by activation of receptors outside these areas. Recently developed peripherally restricted opioid antagonists have the ability to block many opioid side effects without affecting analgesia.

  18. Minimum Wages and Training Revisited

    OpenAIRE

    1998-01-01

    Theory predicts that minimum wages will reduce employer-provided on-the-job training designed to improve workers' skills on the current job, but may increase the amount of training that workers obtain to qualify for a job. We estimate the effects of minimum wages on the amount of both types of training received by young workers by exploiting cross-state variation in minimum wage increases. The evidence provides considerable support for the hypothesis that higher minimum wages reduce training ...

  19. Minimum Complexity Pursuit

    CERN Document Server

    Jalali, Shirin

    2011-01-01

    The fast growing field of compressed sensing is founded on the fact that if a signal is 'simple' and has some 'structure', then it can be reconstructed accurately with far fewer samples than its ambient dimension. Many different plausible structures have been explored in this field, ranging from sparsity to low-rankness and to finite rate of innovation. However, there are important abstract questions that are yet to be answered. For instance, what are the general abstract meanings of 'structure' and 'simplicity'? Do there exist universal algorithms for recovering such simple structured objects from fewer samples than their ambient dimension? In this paper, we aim to address these two questions. Using algorithmic information theory tools such as Kolmogorov complexity, we provide a unified method of describing 'simplicity' and 'structure'. We then explore the performance of an algorithm motivated by Ocam's Razor (called MCP for minimum complexity pursuit) and show that it requires $O(k\\log n)$ number of samples...

  20. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

    Krall, Jacob; Balle, Thomas; Krogsgaard-Larsen, Niels;

    2015-01-01

    antagonists and describes the development of potent antagonists from partial agonists originally derived from the potent GABAAR agonist muscimol. In this process, several heterocyclic aromatic systems have been used in combination with structural models in order to map the orthosteric binding site...... and to reveal structural details to be used for obtaining potency and subtype selectivity. The challenges connected to functional characterization of orthosteric GABAAR partial agonists and antagonists, especially with regard to GABAAR stoichiometry and alternative binding sites are discussed. GABAAR...

  1. Social Security's special minimum benefit.

    Science.gov (United States)

    Olsen, K A; Hoffmeyer, D

    Social Security's special minimum primary insurance amount (PIA) provision was enacted in 1972 to increase the adequacy of benefits for regular long-term, low-earning covered workers and their dependents or survivors. At the time, Social Security also had a regular minimum benefit provision for persons with low lifetime average earnings and their families. Concerns were rising that the low lifetime average earnings of many regular minimum beneficiaries resulted from sporadic attachment to the covered workforce rather than from low wages. The special minimum benefit was seen as a way to reward regular, low-earning workers without providing the windfalls that would have resulted from raising the regular minimum benefit to a much higher level. The regular minimum benefit was subsequently eliminated for workers reaching age 62, becoming disabled, or dying after 1981. Under current law, the special minimum benefit will phase out over time, although it is not clear from the legislative history that this was Congress's explicit intent. The phaseout results from two factors: (1) special minimum benefits are paid only if they are higher than benefits payable under the regular PIA formula, and (2) the value of the regular PIA formula, which is indexed to wages before benefit eligibility, has increased faster than that of the special minimum PIA, which is indexed to inflation. Under the Social Security Trustees' 2000 intermediate assumptions, the special minimum benefit will cease to be payable to retired workers attaining eligibility in 2013 and later. Their benefits will always be larger under the regular benefit formula. As policymakers consider Social Security solvency initiatives--particularly proposals that would reduce benefits or introduce investment risk--interest may increase in restoring some type of special minimum benefit as a targeted protection for long-term low earners. Two of the three reform proposals offered by the President's Commission to Strengthen

  2. New antagonist agents of neuropeptide y receptors

    Directory of Open Access Journals (Sweden)

    Ignacio Aldana

    2000-12-01

    Full Text Available In the CNS, NPY has been implicated in obesity and feeding, endocrine function and metabolism. Potent and selective rNPY antagonists will be able to probe the merits of this approach for the treatment of obesity. We report the synthesis and preliminary evaluation of some hydrazide derivatives as antagonists of rNPY.

  3. Client Perceptions of Two Antagonist Programs.

    Science.gov (United States)

    Capone, Thomas A.; And Others

    1980-01-01

    Reports results of a questionnaire administered to participants in an antagonist drug outpatient clinic and an antagonist drug work-release program to obtain awareness of acceptance of the program participants. Naltrexone patients recommended an alternative method of administering the drug and changing the money system to award deserving inmates…

  4. A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate

    OpenAIRE

    Cohen, S.; Moreland, L; Cush, J; Greenwald, M.; Block, S; Shergy, W.; Hanrahan, P; Kraishi, M; Patel, A; Sun, G; Bear, M

    2004-01-01

    Objective: To assess the efficacy and safety of 100 mg daily anakinra (Kineret), a recombinant form of the naturally occurring interleukin 1 receptor antagonist, plus methotrexate (MTX) in reducing the signs and symptoms of rheumatoid arthritis (RA).

  5. Vaccine Safety

    Science.gov (United States)

    ... the safety of Tdap, Meningococcal, and HPV vaccines Human Papillomavirus (HPV) Vaccine is Very Safe Read about the safety of ... Hepatitis A Vaccine Safety Hepatitis B Vaccine Safety Human Papillomavirus (HPV) Vaccine Safety FAQs about HPV Safety Influenza (Flu) Vaccine ...

  6. 75 FR 6151 - Minimum Capital

    Science.gov (United States)

    2010-02-08

    ... Cease and Desist Order, as amended. See 74 FR 5597 (January 30, 2009). As a result, the definition of... AGENCY 12 CFR Part 1225 RIN 2590-AA01 Minimum Capital AGENCY: Federal Housing Finance Agency. ACTION... Soundness Act that provides for a temporary increase in the minimum capital level for entities regulated...

  7. Minimum signals in classical physics

    Institute of Scientific and Technical Information of China (English)

    邓文基; 许基桓; 刘平

    2003-01-01

    The bandwidth theorem for Fourier analysis on any time-dependent classical signal is shown using the operator approach to quantum mechanics. Following discussions about squeezed states in quantum optics, the problem of minimum signals presented by a single quantity and its squeezing is proposed. It is generally proved that all such minimum signals, squeezed or not, must be real Gaussian functions of time.

  8. Venus ionopause during solar minimum

    Science.gov (United States)

    Mahajan, K. K.; Mayr, H. G.

    1989-01-01

    Pioneer Venus ion composition measurements are used to study the Venus ionosphere during solar minimum. It is suggested that the topside electron density profile at Venus during solar minimum has two distinct regimes. One beween 140 and 180 km is dominated by O2(+) ions which are in photochemical equilibrium. The other regime is above 180 km and is dominated by O(+) ions which are disturbed by the solar wind induced plasma transport. For Pioneer Venus, Mariner 10, and Venera 9 and 10 data, it is found that Venus exhibits a photodynamical type of ionopause during solar minimum.

  9. Antagonistic formation motion of cooperative agents

    Institute of Scientific and Technical Information of China (English)

    卢婉婷; 代明香; 薛方正

    2015-01-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonis-tic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all agents make an antagonistic formation motion in a distributed manner. It is shown that all agents can be spontaneously divided into several groups, and agents in the same group collab-orate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results.

  10. Safe Minimum Internal Temperature Chart

    Science.gov (United States)

    ... JSR 286) Actions ${title} Loading... Safe Minimum Internal Temperature Chart Safe steps in food handling, cooking, and ... from other foods. Cook —Cook to the right temperature. Chill —Refrigerate food promptly. Cook all food to ...

  11. Minimum wage in economic context

    OpenAIRE

    Kratochvíl, Martin

    2014-01-01

    The thesis analyzes how minimum wage influences unemployment in the Czech Republic. Firstly, the economic theory is researched and the conclusion is that the Czech labour market is very similar to a monopsony market due to the low mobility of the workforce and the low rate of immigration. Another result is that the level of wages in developed economies does not depend on the productivity of the workforce anymore, so minimum wage laws have psychological impacts rather than economical. The foll...

  12. Benzodiazepine receptor antagonists for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Gluud, L L; Gluud, C

    2004-01-01

    Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

  13. 23 CFR 1208.4 - Adoption of National Minimum Drinking Age.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Adoption of National Minimum Drinking Age. 1208.4 Section 1208.4 Highways NATIONAL HIGHWAY TRAFFIC SAFETY ADMINISTRATION AND FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION GUIDELINES NATIONAL MINIMUM DRINKING AGE § 1208.4 Adoption of National...

  14. 75 FR 44841 - Hazardous Materials: Special Permits and Approvals-Minimum Level of Fitness Determinations...

    Science.gov (United States)

    2010-07-29

    ...--Minimum Level of Fitness Determinations; Public Meeting AGENCY: Pipeline and Hazardous Materials Safety... persons that PHMSA will conduct a public meeting to discuss Special Permit and Approval applicant fitness... used when determining an applicant's minimum level of fitness. DATES: Public Meeting: August 19,...

  15. 78 FR 22798 - Hazardous Materials: Revision of Maximum and Minimum Civil Penalties

    Science.gov (United States)

    2013-04-17

    .... 5101 et seq.). Section 5123(a) of that law provides civil penalties for knowing violations of Federal... Materials: Revision of Maximum and Minimum Civil Penalties AGENCY: Pipeline and Hazardous Materials Safety... the maximum and minimum civil penalties for a knowing violation of the Federal hazardous...

  16. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data

    DEFF Research Database (Denmark)

    Sørensen, Rikke; Hansen, Morten L; Abildstrøm, Steen;

    2009-01-01

    BACKGROUND: Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens...... according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding...... was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios...

  17. Minimum Q Electrically Small Antennas

    DEFF Research Database (Denmark)

    Kim, O. S.

    2012-01-01

    Theoretically, the minimum radiation quality factor Q of an isolated resonance can be achieved in a spherical electrically small antenna by combining TM1m and TE1m spherical modes, provided that the stored energy in the antenna spherical volume is totally suppressed. Using closed-form expressions...... for the stored energies obtained through the vector spherical wave theory, it is shown that a magnetic-coated metal core reduces the internal stored energy of both TM1m and TE1m modes simultaneously, so that a self-resonant antenna with the Q approaching the fundamental minimum is created. Numerical results...

  18. Coupling between minimum scattering antennas

    DEFF Research Database (Denmark)

    Andersen, J.; Lessow, H; Schjær-Jacobsen, Hans

    1974-01-01

    Coupling between minimum scattering antennas (MSA's) is investigated by the coupling theory developed by Wasylkiwskyj and Kahn. Only rotationally symmetric power patterns are considered, and graphs of relative mutual impedance are presented as a function of distance and pattern parameters. Crossed......-dipoles and helices are considered in order to establish a correspondence with simple antenna structures....

  19. Minimum Wage Standard in China

    Institute of Scientific and Technical Information of China (English)

    Wang Ting

    2010-01-01

    @@ On July 1st,at least six Chinese provinces and cities would raise the minimum wages from today.In 2010,each province and city in China has begun to increase the lowest monthly salary for employers.Of them,Jiangsu province is leading the adjustment since Feb.

  20. Auto Safety

    Science.gov (United States)

    ... 5 Things to Know About Zika & Pregnancy Auto Safety KidsHealth > For Parents > Auto Safety Print A A ... by teaching some basic rules. Importance of Child Safety Seats Using a child safety seat (car seat) ...

  1. Risk of ischemic stroke, hemorrhagic stroke, bleeding, and death in patients switching from vitamin K antagonist to dabigatran after an ablation

    DEFF Research Database (Denmark)

    Pallisgaard, Jannik Langtved; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian;

    2016-01-01

    BACKGROUND: Safety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke...

  2. Auxin-Oxylipin Crosstalk: Relationship of Antagonists

    Institute of Scientific and Technical Information of China (English)

    Maik Hoffmann; Mathias Hentrich; Stephan Pollmann

    2011-01-01

    Phytohormones regulate a wide array of developmental processes throughout the life cycle of plants. Herein, the various plant hormones may interact additively, synergistically, or antagonistically. By their cooperation they create a delicate regulatory network whose net output largely depends on the action of specific phytohormone combinations rather than on the independent activities of separate hormones. While most classical studies of plant hormonal control have focused mainly on the action of single hormones or on the synergistic interaction of hormones in regulating various developmental processes, recent work is beginning to shed light on the crosstalk of nominally antagonistic plant hormones, such as gibberellins and auxins with oxylipins or abscisic acid. In this review, we summarize our current understanding of how two of the first sight antagonistic plant hormones, i.e. auxins and oxylipins,interact in controlling plant responses and development.

  3. Antagonistic formation motion of cooperative agents

    Science.gov (United States)

    Lu, Wan-Ting; Dai, Ming-Xiang; Xue, Fang-Zheng

    2015-02-01

    This paper investigates a new formation motion problem of a class of first-order multi-agent systems with antagonistic interactions. A distributed formation control algorithm is proposed for each agent to realize the antagonistic formation motion. A sufficient condition is derived to ensure that all of the agents make an antagonistic formation motion in a distributed manner. It is shown that all of the agents can be spontaneously divided into several groups and that agents in the same group collaborate while agents in different groups compete. Finally, a numerical simulation is included to demonstrate our theoretical results. Project supported by the National Natural Science Foundation of China (Grant Nos. 61203080 and 61473051) and the Natural Science Foundation of Chongqing City (Grant No. CSTC 2011BB0081).

  4. Risk assessment in contemporary outpatients with non-valvular atrial fibrillation recently on vitamin K antagonists

    OpenAIRE

    Abumuaileq, Rami Riziq Yousef

    2016-01-01

    Atrial Fibrillation increases the risk of embolic stroke by five fold. Vitamin K antagonists (VKAs) are still the most used oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF) and are highly effective for the prevention of thromboembolic (TE) complications in these patients. However, achieving the best benefit and safety from VKAs in the clinical practice remains a major challenge mainly because of their unpredictable anticoagulant response. In this thes...

  5. 77 FR 58707 - Minimum Internal Control Standards

    Science.gov (United States)

    2012-09-21

    ... Minimum Internal Control Standards. 64 FR 590. The rule added a new part to the Commission's regulations... minimum internal control standards for audit and accounting? 543.24 What are the minimum internal control... Minimum Internal Control Standards; Final Rule #0;#0;Federal Register / Vol. 77 , No. 184 /...

  6. 77 FR 32444 - Minimum Internal Control Standards

    Science.gov (United States)

    2012-06-01

    ... Minimum Internal Control Standards. 64 FR 590. The rule added a new part to the Commission's regulations... the minimum internal control standards for audit and accounting? 543.24 What are the minimum internal... National Indian Gaming Commission 25 CFR Part 543 RIN 3141-AA27 Minimum Internal Control Standards...

  7. Safety in paediatric imaging

    International Nuclear Information System (INIS)

    Those of us working in a dedicated paediatric environment are aware of the important safety issues with regard to paediatrics. Our goal when working with paediatric patients, the goal is to obtain the best quality images while keeping patients safe and their distress to a minimum. This article will discuss some of the issues regarding paediatric safety in a diagnostic imaging department, including radiation doses and the risk to paediatric patients, reducing medication errors, safe sedation practice and environmental safety. Also discussed are some conditions requiring special consideration to maintain patient safety such as epiglottitis and suspected child abuse. Promotion of a patient/family-centered care system will create an environment of trust where parents or guardians will know that their children are being well cared for in a safe, effective environment. (author)

  8. Safety in paediatric imaging

    Energy Technology Data Exchange (ETDEWEB)

    Carter, D.; Filice, I.; Murray, D.; Thomas, K. [The Hospital for Sick Children, Toronto, Ontario (Canada)

    2006-01-01

    Those of us working in a dedicated paediatric environment are aware of the important safety issues with regard to paediatrics. Our goal when working with paediatric patients, the goal is to obtain the best quality images while keeping patients safe and their distress to a minimum. This article will discuss some of the issues regarding paediatric safety in a diagnostic imaging department, including radiation doses and the risk to paediatric patients, reducing medication errors, safe sedation practice and environmental safety. Also discussed are some conditions requiring special consideration to maintain patient safety such as epiglottitis and suspected child abuse. Promotion of a patient/family-centered care system will create an environment of trust where parents or guardians will know that their children are being well cared for in a safe, effective environment. (author)

  9. Fingerprinting with Minimum Distance Decoding

    CERN Document Server

    Lin, Shih-Chun; Gamal, Hesham El

    2007-01-01

    This work adopts an information theoretic framework for the design of collusion-resistant coding/decoding schemes for digital fingerprinting. More specifically, the minimum distance decision rule is used to identify 1 out of t pirates. Achievable rates, under this detection rule, are characterized in two distinct scenarios. First, we consider the averaging attack where a random coding argument is used to show that the rate 1/2 is achievable with t=2 pirates. Our study is then extended to the general case of arbitrary $t$ highlighting the underlying complexity-performance tradeoff. Overall, these results establish the significant performance gains offered by minimum distance decoding as compared to other approaches based on orthogonal codes and correlation detectors. In the second scenario, we characterize the achievable rates, with minimum distance decoding, under any collusion attack that satisfies the marking assumption. For t=2 pirates, we show that the rate $1-H(0.25)\\approx 0.188$ is achievable using an ...

  10. Genetic factors influencing pyrimidine-antagonist chemotherapy

    NARCIS (Netherlands)

    Maring, JG; Groen, HJM; Wachters, FM; Uges, DRA; de Vries, EGE

    2005-01-01

    Pyrimidine antagonists, for example, 5-fluorouracil (5-FU), cytarabine (ara-C) and gemcitabine (dFdC), are widely used in chemotherapy regimes for colorectal, breast, head and neck, non-small-cell lung cancer, pancreatic cancer and leukaemias. Extensive metabolism is a prerequisite for conversion of

  11. Oxazolidinones as novel human CCR8 antagonists.

    Science.gov (United States)

    Jin, Jian; Wang, Yonghui; Wang, Feng; Kerns, Jeffery K; Vinader, Victoria M; Hancock, Ashley P; Lindon, Matthew J; Stevenson, Graeme I; Morrow, Dwight M; Rao, Parvathi; Nguyen, Cuc; Barrett, Victoria J; Browning, Chris; Hartmann, Guido; Andrew, David P; Sarau, Henry M; Foley, James J; Jurewicz, Anthony J; Fornwald, James A; Harker, Andy J; Moore, Michael L; Rivero, Ralph A; Belmonte, Kristen E; Connor, Helen E

    2007-03-15

    High-throughput screening of the corporate compound collection led to the discovery of a novel series of N-substituted-5-aryl-oxazolidinones as potent human CCR8 antagonists. The synthesis, structure-activity relationships, and optimization of the series that led to the identification of SB-649701 (1a), are described. PMID:17267215

  12. Why are mineralocorticoid receptor antagonists cardioprotective?

    NARCIS (Netherlands)

    W. Chai (Wenxia); A.H.J. Danser (Jan)

    2006-01-01

    textabstractTwo clinical trials, the Randomized ALdosterone Evaluation Study (RALES) and the EPlerenone HEart failure and SUrvival Study (EPHESUS), have recently shown that mineralocorticoid receptor (MR) antagonists reduce mortality in patients with heart failure on top of ACE inhibition. This effe

  13. Azines as histamine H4 receptor antagonists.

    Science.gov (United States)

    Lazewska, Dorota; Kiec-Kononowicz, Katarzyna

    2012-01-01

    Since 2000, when the histamine H4 receptor (H4R) was cloned, it has constituted an interesting target for drug development. Pharmacological studies suggest the potential utility of histamine H4R antagonists/inverse agonists in the treatment of inflammatory diseases, e.g. allergic rhinitis, asthma, atopic dermatitis, colitis, or pruritus. The first H4R ligands were non-selective compounds, but intensive chemical and pharmacological work has led to the discovery of highly potent and selective H4R antagonists (e.g. JNJ7777120, CZC-13788, PF-2988403, A-940894, A-987306). The first compound (UR-63325) has finally entered into clinical studies for the treatment of allergic respiratory diseases (completing the phase I ascending dose trial) and has been found to be safe and well tolerated. The number of scientific publications and patent applications in the H4 field is increasing annually. Among the diverse chemical structures of the H4R antagonists described a 2-aminopyrimidine scaffold is repeatedly found. This review looked at recent advances in the search for H4R antagonists as reflected in patent applications/patents and peer-reviewed publications over the last two years. The work concerns azines (mono-, di-, triazines) and their fused analogues. The chemistry and pharmacology has been described. PMID:22202103

  14. The substance P/NK-1 receptor system: NK-1 receptor antagonists as anti-cancer drugs

    Indian Academy of Sciences (India)

    Miguel Muñoz; Rafael Coveñas; Francisco Esteban; Maximino Redondo

    2015-06-01

    The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the proliferation of tumour cells, angiogenesis and the migration of tumour cells. We review the involvement of SP, the NK-1 receptor and NK-1 receptor antagonists in cancer. Tumour cells overexpress NK-1 receptors, which are involved in their viability. This overexpression suggests the possibility of specific treatment against tumour cells using NK-1 receptor antagonists, thus promoting a considerable decrease in the side effects of the treatment. This strategy opens up new approaches for cancer treatment, since these antagonists, after binding to their molecular target, induce the death of tumour cells by apoptosis, exert an antiangiogenic action and inhibit the migration of tumour cells. The use of NK-1 receptor antagonists such as aprepitant (used in clinical practice) as antitumour agents could be a promising innovation. The value of aprepitant as an antitumour agent could be determined faster than for less well-known compounds because many studies addressing its safety and characterization have already been completed. The NK-1 receptor may be a promising target in the treatment of cancer; NK-1 receptor antagonists could act as specific drugs against tumour cells; and these antagonists could be new candidate anti-cancer drugs.

  15. EFFECT OF ANGIOTENSIN II RECEPTOR ANTAGONIST AND ENDOTHELIN RECEPTOR ANTAGONIST ON NITROGLYCERIN TOLERANCE IN RATS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty-four rats were divided into 4 groups (n=6,each): Control group, Nitroglycerin (Nit) group, Nit+ bosentan group and Nit+ losartan group. Nitroglycerin tolerance was induced by 2-day treatment of nitroglycerin patch (0.05 mg/h). AngiotensinⅡ receptor antagonist losartan ( 10 mg· kg- 1· d- 1 ) and endothelin receptor antagonist bosentan ( 100 mg· kg- 1· d- 1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group . The effective percentages of hypotensive response to SNP were increased in both Nit+ losartan group and Nit+ bosentan group compared with Nit group [(31.95± 4.45 ) % vs (21.00± 3.69 ) % , P Conclusion. Endothelin receptor antagonist and angiotensin Ⅱ receptor antagonist could prevent against the Nit tolerance .

  16. Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study

    OpenAIRE

    Nicoletta Riva; Walter Ageno; Daniela Poli; Sophie Testa; Serena Rupoli; Rita Santoro; Teresa Lerede; Antonietta Piana; Monica Carpenedo; Alberto Nicolini; Piera Maria Ferrini; Giuliana Martini; Catello Mangione; Laura Contino; Carlo Bonfanti

    2015-01-01

    It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoa...

  17. High affinity retinoic acid receptor antagonists: analogs of AGN 193109.

    Science.gov (United States)

    Johnson, A T; Wang, L; Gillett, S J; Chandraratna, R A

    1999-02-22

    A series of high affinity retinoic acid receptor (RAR) antagonists were prepared based upon the known antagonist AGN 193109 (2). Introduction of various phenyl groups revealed a preference for substitution at the para-position relative to the meta-site. Antagonists with the highest affinities for the RARs possessed hydrophobic groups, however, the presence of polar functionality was also well tolerated.

  18. Nuclear safety

    International Nuclear Information System (INIS)

    The author proposes an overview of methods and concepts used in the nuclear industry, at the design level as well as at the exploitation level, to ensure an acceptable safety level, notably in the case of nuclear reactors. He first addresses the general objectives of nuclear safety and the notion of acceptable risk: definition and organisation of nuclear safety (relationships between safety authorities and operators), notion of acceptable risk, deterministic safety approach and main safety principles (safety functions and confinement barriers, concept of defence in depth). Then, the author addresses the safety approach at the design level: studies of operational situations, studies of internal and external aggressions, safety report, design principles for important-for-safety systems (failure criterion, redundancy, failure prevention, safety classification). The next part addresses safety during exploitation and general exploitation rules: definition of the operation domain and of its limits, periodic controls and tests, management in case of incidents, accidents or aggressions

  19. Minimum Bias Trigger in ATLAS

    International Nuclear Information System (INIS)

    Since the restart of the LHC in November 2009, ATLAS has collected inelastic pp collisions to perform first measurements on charged particle densities. These measurements will help to constrain various models describing phenomenologically soft parton interactions. Understanding the trigger efficiencies for different event types are therefore crucial to minimize any possible bias in the event selection. ATLAS uses two main minimum bias triggers, featuring complementary detector components and trigger levels. While a hardware based first trigger level situated in the forward regions with 2.2 < |η| < 3.8 has been proven to select pp-collisions very efficiently, the Inner Detector based minimum bias trigger uses a random seed on filled bunches and central tracking detectors for the event selection. Both triggers were essential for the analysis of kinematic spectra of charged particles. Their performance and trigger efficiency measurements as well as studies on possible bias sources will be presented. We also highlight the advantage of these triggers for particle correlation analyses. (author)

  20. Safety culture

    Energy Technology Data Exchange (ETDEWEB)

    Keen, L.J. [Canadian Nuclear Safety Commission, Ottawa, Ontario (Canada)

    2003-07-01

    Safety culture has become a topic of increasing interest for industry and regulators as issues are raised on safety problems around the world. The keys to safety culture are organizational effectiveness, effective communications, organizational learning, and a culture that encourages the identification and resolution of safety issues. The necessity of a strong safety culture places an onus on all of us to continually question whether the safety measures already in place are sufficient, and are being applied. (author)

  1. Effectiveness and safety of dabigatran versus acenocoumarol in 'real-world' patients with atrial fibrillation

    NARCIS (Netherlands)

    Korenstra, Jennie; Wijtvliet, E. Petra J.; Veeger, Nic J.G.M.; Geluk, Christiane A.; Bartels, G. Louis; Posma, Jan L.; Piersma-Wichers, Margriet; van Gelder, Isabelle C.; Rienstra, Michiel; Tieleman, Robert G.

    2016-01-01

    AIMS: Randomized trials showed non-inferior or superior results of the non-vitamin-K-antagonist oral anticoagulants (NOACs) compared with warfarin. The aim of this study was to assess the effectiveness and safety of dabigatran (direct thrombin inhibitor) vs. acenocoumarol (vitamin K antagonist) in p

  2. [Cutaneous adverse effects of TNFalpha antagonists].

    Science.gov (United States)

    Failla, V; Sabatiello, M; Lebas, E; de Schaetzen, V; Dezfoulian, B; Nikkels, A F

    2012-01-01

    The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

  3. New set of Chemical Safety rules

    CERN Multimedia

    HSE Unit

    2011-01-01

    A new set of four Safety Rules was issued on 28 March 2011: Safety Regulation SR-C ver. 2, Chemical Agents (en); General Safety Instruction GSI-C1, Prevention and Protection Measures (en); General Safety Instruction GSI-C2, Explosive Atmospheres (en); General Safety Instruction GSI-C3, Monitoring of Exposure to Hazardous Chemical Agents in Workplace Atmospheres (en). These documents form part of the CERN Safety Rules and are issued in application of the “Staff Rules and Regulations” and of document SAPOCO 42. These documents set out the minimum requirements for the protection of persons from risks to their occupational safety and health arising, or likely to arise, from the effects of hazardous chemical agents that are present in the workplace or used in any CERN activity. Simultaneously, the HSE Unit has published seven Safety Guidelines and six Safety Forms. These documents are available from the dedicated Web page “Chemical, Cryogenic and Biological Safety&...

  4. The Optimal Minimum Wage for Poverty Minimization

    OpenAIRE

    Goto, Hideaki

    2008-01-01

    The effects of a minimum wage on employment and on poverty have been studied in the literature. This paper characterizes the poverty minimizing minimum wage, and shows how it depends on productivity, inequality and the degree of labor market competitiveness.

  5. Antagonistic parent-offspring co-adaptation.

    Directory of Open Access Journals (Sweden)

    Mathias Kölliker

    Full Text Available BACKGROUND: In species across taxa, offspring have means to influence parental investment (PI. PI thus evolves as an interacting phenotype and indirect genetic effects may strongly affect the co-evolutionary dynamics of offspring and parental behaviors. Evolutionary theory focused on explaining how exaggerated offspring solicitation can be understood as resolution of parent-offspring conflict, but the evolutionary origin and diversification of different forms of family interactions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In contrast to previous theory that largely uses a static approach to predict how "offspring individuals" and "parental individuals" should interact given conflict over PI, we present a dynamic theoretical framework of antagonistic selection on the PI individuals obtain/take as offspring and the PI they provide as parents to maximize individual lifetime reproductive success; we analyze a deterministic and a stochastic version of this dynamic framework. We show that a zone for equivalent co-adaptation outcomes exists in which stable levels of PI can evolve and be maintained despite fast strategy transitions and ongoing co-evolutionary dynamics. Under antagonistic co-adaptation, cost-free solicitation can evolve as an adaptation to emerging preferences in parents. CONCLUSIONS/SIGNIFICANCE: We show that antagonistic selection across the offspring and parental life-stage of individuals favors co-adapted offspring and parental behavior within a zone of equivalent outcomes. This antagonistic parent-offspring co-adaptation does not require solicitation to be costly, allows for rapid divergence and evolutionary novelty and potentially explains the origin and diversification of the observed provisioning forms in family life.

  6. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    OpenAIRE

    Kleynhans, Janke

    2013-01-01

    Aims of this project - The aim of this study was to design and synthesise novel 2-aminopyrimidine derivatives as potential adenosine A1 and A2A receptor antagonists. Background and rationale - Parkinson’s disease is the second most common neurodegenerative disorder (after Alzheimer’s disease) and is characterised by the selective death of the dopaminergic neurons of the nigro-striatal pathway. Distinctive motor symptoms include bradykinesia, muscle rigidity and tremor, while non-m...

  7. Personalized medicine: theranostics (therapeutics diagnostics) essential for rational use of tumor necrosis factor-alpha antagonists.

    Science.gov (United States)

    Bendtzen, Klaus

    2013-04-01

    With the discovery of the central pathogenic role of tumor necrosis factor (TNF)-alpha in many immunoinflammatory diseases, specific inhibition of this pleiotropic cytokine has revolutionized the treatment of patients with several non-infectious inflammatory disorders. As a result, genetically engineered anti-TNF-alpha antibody constructs now constitute one of the heaviest medicinal expenditures in many countries. All currently used TNF antagonists may dramatically lower disease activity and, in some patients, induce remission. Unfortunately, however, not all patients respond favorably, and safety can be severely impaired by immunogenicity, i.e., the ability of a drug to induce anti-drug antibodies (ADA). Assessment of ADA is therefore an important component of the evaluation of drug safety in both pre-clinical and clinical studies and in the process of developing less immunogenic and safer biopharmaceuticals. Therapeutics diagnostics, also called theranostics, i.e., monitoring functional drug levels and neutralizing ADA in the circulation, is central to more effective use of biopharmaceuticals. Hence, testing-based strategies rather than empirical dose-escalation may provide more cost-effective use of TNF antagonists as this allows therapies tailored according to individual requirements rather than the current universal approach to diagnosis. The objective of the present review is to discuss the reasons for recommending theranostics to implement an individualized use of TNF antagonists and to highlight some of the methodological obstacles that have obscured cost-effective ways of using these therapies.

  8. Biological Control of Patulin by Antagonistic Yeast: A case study and possible model.

    Science.gov (United States)

    Mahunu, Gustav Komla; Zhang, Hongyin; Yang, Qiya; Li, Chaolan; Zheng, Xiangfeng

    2016-08-01

    The occurrence of patulin in fresh apples and apple products is a great burden from health, safety and economic perspectives. Attempts to prevent patulin accumulation in fruits might lead to the excessive use of fungicides. Therefore, guaranteeing the safety of apple foods is crucial for the international apple industry. Recently, literature revealed that application of antagonistic yeasts and other BCAs have been able to disrupt the process of fungal infection and patulin production in apples. Although, over the years the effect of interaction between BCAs and fungi on patulin production has been reported, the exact mechanism(s) of their action remain unclear. Here, the review focused on toxicology and occurrence of PAT; research advances made over the past few years on the interaction between antagonistic yeast, fruits and patulin-producing fungi; the prevalence of patulin in apple fruits and products and the implications of synthetic-fungicide applications. In addition, attention was focused on the mechanism(s) and the enhancement of the biocontrol efficacy of antagonistic for patulin control. PMID:25845381

  9. Medicinal chemistry of competitive kainate receptor antagonists.

    Science.gov (United States)

    Larsen, Ann M; Bunch, Lennart

    2011-02-16

    Kainic acid (KA) receptors belong to the group of ionotropic glutamate receptors and are expressed throughout in the central nervous system (CNS). The KA receptors have been shown to be involved in neurophysiological functions such as mossy fiber long-term potentiation (LTP) and synaptic plasticity and are thus potential therapeutic targets in CNS diseases such as schizophrenia, major depression, neuropathic pain and epilepsy. Extensive effort has been made to develop subtype-selective KA receptor antagonists in order to elucidate the physiological function of each of the five subunits known (GluK1-5). However, to date only selective antagonists for the GluK1 subunit have been discovered, which underlines the strong need for continued research in this area. The present review describes the structure-activity relationship and pharmacological profile for 10 chemically distinct classes of KA receptor antagonists comprising, in all, 45 compounds. To the medicinal chemist this information will serve as reference guidance as well as an inspiration for future effort in this field. PMID:22778857

  10. MINIMUM WAGE VIOLATION IN SOUTH AFRICA

    OpenAIRE

    Haroon Bhorat; Ravi Kanbur; Natasha Mayet

    2011-01-01

    Minimum wage legislation is central in South African policy discourse, with both strong support and strong opposition. The validity of either position depends, however, on the effectiveness of minimum wage enforcement. Using detailed matching of occupational, sectoral and locational codes in the 2007 Labour Force Survey to the gazetted minimum wages, this paper presents, we believe for the first time, estimates of minimum wage violation in South Africa. Our results give considerable cause for...

  11. Irradiance Variations During This Solar Cycle Minimum

    OpenAIRE

    Woods, Thomas N.

    2010-01-01

    The current cycle minimum appears to be deeper and broader than recent cycle minima, and this minimum appears similar to the minima in the early 1900s. With the best-ever solar irradiance measurements from several different satellite instruments, this minimum offers a unique opportunity to advance our understanding of secular (long-term) changes in the solar irradiance. Comparisons of the 2007-2009 irradiance results to the irradiance levels during the previous minimum in 1996 suggest that th...

  12. 78 FR 63873 - Minimum Internal Control Standards

    Science.gov (United States)

    2013-10-25

    ... NIGC published a final rule in the Federal Register called Minimum Internal Control Standards. 64 FR... National Indian Gaming Commission 25 CFR Part 543 RIN 3141-AA27 Minimum Internal Control Standards AGENCY... Commission (NIGC) amends its minimum internal control standards for Class II gaming under the Indian...

  13. Minimum income protection in the Netherlands

    NARCIS (Netherlands)

    T. van Peijpe

    2009-01-01

    This article offers an overview of the Dutch legal system of minimum income protection through collective bargaining, social security, and statutory minimum wages. In addition to collective agreements, the Dutch statutory minimum wage offers income protection to a small number of workers. Its effect

  14. Minimum wage development in the Russian Federation

    OpenAIRE

    Bolsheva, Anna

    2012-01-01

    The aim of this paper is to analyze the effectiveness of the minimum wage policy at the national level in Russia and its impact on living standards in the country. The analysis showed that the national minimum wage in Russia does not serve its original purpose of protecting the lowest wage earners and has no substantial effect on poverty reduction. The national subsistence minimum is too low and cannot be considered an adequate criterion for the setting of the minimum wage. The minimum wage d...

  15. Prothrombin complex concentrate for reversal of vitamin K antagonist treatment in bleeding and non-bleeding patients

    DEFF Research Database (Denmark)

    Johansen, Mathias; Wikkelsø, Anne; Lunde, Jens;

    2015-01-01

    BACKGROUND: Treatment with vitamin K antagonists is associated with increased morbidity and mortality. Reversal therapy with prothrombin complex concentrate (PCC) is used increasingly and is recommended in the treatment of patients with bleeding complications undertaking surgical interventions......, as well as patients at high risk of bleeding. Evidence is lacking regarding indication, dosing, efficacy and safety. OBJECTIVES: We assessed the benefits and harms of PCC compared with fresh frozen plasma in the acute medical and surgical setting involving vitamin K antagonist-treated bleeding and non...... finding a beneficial effect of PCC in reducing the volume of fresh frozen plasma (FFP) transfused to reverse the effect of vitamin K antagonist treatment. The number of new occurrences of transfusion of red blood cells (RBCs) did not seem to be associated with the use of PCC (RR 1.08, 95% CI 0.82 to 1...

  16. EFFECT OF ANGIOTENSIN II RECEPTOR ANTAGONIST AND ENDOTHELIN RECEPTOR ANTAGONIST ON NITROGLYCERIN TOLERANCE IN RATS

    Institute of Scientific and Technical Information of China (English)

    张建梅; 陈永红; 王晓红; 唐朝枢

    2001-01-01

    Objective. To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo. Methods. Twenty-four rats were divided into 4 groups (n =6, each): Control group, Nitroglycerin (Nit) group, Nit + bosentan group and Nit + losartan group. Nitroglycerin tolerance was induced by 2-day treatment ofnitroglycerin patch (0. 05mg/h). Angiotensin I1 receptor antagonist losartan (10mg ·kg-1·d-1) and endothe-lin receptor antagonist bosentan ( 100 mg·kg-1· d-1 ) were given by gavage for 2 days respectively. Results. The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group. The effec-tive percentages of hypotensive response to SNP were increased in both Nit + losartan group and Nit + bosentangroup compared with Nit group [(31.95±4.45) % vs (21.00±3.69) %, P <0.01and (33. 18±6. 16)% vs (21.00±3.69 ) %, P < 0. 01 , respectivelyl. The maximal vessel relaxation induced by SNP was thesame in 4 different groups but the highest EC50 (concentration which produces 50% of the maximal response toSNP) was found in tolerant group[ (34 ±10) nmol/L, P < 0. 01 ]. The ET-1 amounts in plasma and vasculartissue were markedly increased by 54% and 60% in Nit group compared with those in control group( P<0. 01). The ET-1 amounts in plasma and vascular tissue were decreased by 30% and 37% in Nit + losartangroup compared with those in Nit group ( P < 0.01 ). Conclusion. Endothelin receptor antagonist and angiotensin Ⅱ receptor antagonist could prevent against the Nit tolerance.

  17. 16 CFR Table 2 to Part 1512 - Minimum Candlepower per Incident Foot-Candle for Clear Reflector 1

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Minimum Candlepower per Incident Foot-Candle for Clear Reflector 1 2 Table 2 to Part 1512 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... 1512—Minimum Candlepower per Incident Foot-Candle for Clear Reflector 1 Observation angle Front,...

  18. 16 CFR Table 1 to Part 1512 - Minimum Candlepower per Incident Foot-Candle for Clear Reflector 1

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Minimum Candlepower per Incident Foot-Candle for Clear Reflector 1 1 Table 1 to Part 1512 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... 1512—Minimum Candlepower per Incident Foot-Candle for Clear Reflector 1 Observation angle Front,...

  19. Theoretical analysis of the cost of antagonistic activity for aquatic bacteria in oligotrophic environments

    Directory of Open Access Journals (Sweden)

    Eneas eAguirre-Von-Wobeser

    2015-05-01

    Full Text Available Many strains of bacteria produce antagonistic substances that restrain the growth of others, and potentially give them a competitive advantage. These substances are commonly released to the surrounding environment, involving metabolic costs in terms of energy and nutrients. The rate at which these molecules need to be produced to maintain a certain amount of them close to the producing cell before they are diluted into the environment has not been explored so far. To understand the potential cost of production of antagonistic substances in water environments, we used two different theoretical approaches. Using a probabilistic model, we determined the rate at which a cell needs to produce individual molecules in order to keep on average a single molecule in its vicinity at all times. For this minimum protection, a cell would need to invest 3.92X10-22 kg s-1 of organic matter, which is 9 orders of magnitude lower than the estimated expense for growth. Next, we used a continuous model, based on Fick’s laws, to explore the production rate needed to sustain minimum inhibitory concentrations around a cell, which would provide much more protection from competitors. In this scenario, cells would need to invest 1.20X10-11 kg s-1, which is 2 orders of magnitude higher than the estimated expense for growth, and thus not sustainable. We hypothesize that the production of antimicrobial compounds by bacteria in aquatic environments lies between these two extremes.

  20. Theoretical analysis of the cost of antagonistic activity for aquatic bacteria in oligotrophic environments.

    Science.gov (United States)

    Aguirre-von-Wobeser, Eneas; Eguiarte, Luis E; Souza, Valeria; Soberón-Chávez, Gloria

    2015-01-01

    Many strains of bacteria produce antagonistic substances that restrain the growth of others, and potentially give them a competitive advantage. These substances are commonly released to the surrounding environment, involving metabolic costs in terms of energy and nutrients. The rate at which these molecules need to be produced to maintain a certain amount of them close to the producing cell before they are diluted into the environment has not been explored so far. To understand the potential cost of production of antagonistic substances in water environments, we used two different theoretical approaches. Using a probabilistic model, we determined the rate at which a cell needs to produce individual molecules in order to keep on average a single molecule in its vicinity at all times. For this minimum protection, a cell would need to invest 3.92 × 10(-22) kg s(-1) of organic matter, which is 9 orders of magnitude lower than the estimated expense for growth. Next, we used a continuous model, based on Fick's laws, to explore the production rate needed to sustain minimum inhibitory concentrations around a cell, which would provide much more protection from competitors. In this scenario, cells would need to invest 1.20 × 10(-11) kg s(-1), which is 2 orders of magnitude higher than the estimated expense for growth, and thus not sustainable. We hypothesize that the production of antimicrobial compounds by bacteria in aquatic environments lies between these two extremes.

  1. Linear Minimum variance estimation fusion

    Institute of Scientific and Technical Information of China (English)

    ZHU Yunmin; LI Xianrong; ZHAO Juan

    2004-01-01

    This paper shows that a general mulitisensor unbiased linearly weighted estimation fusion essentially is the linear minimum variance (LMV) estimation with linear equality constraint, and the general estimation fusion formula is developed by extending the Gauss-Markov estimation to the random paramem of distributed estimation fusion in the LMV setting.In this setting ,the fused estimator is a weighted sum of local estimatess with a matrix quadratic optimization problem subject to a convex linear equality constraint. Second, we present a unique solution to the above optimization problem, which depends only on the covariance matrixCK. Third, if a priori information, the expectation and covariance, of the estimated quantity is unknown, a necessary and sufficient condition for the above LMV fusion becoming the best unbiased LMV estimation with dnown prior information as the above is presented. We also discuss the generality and usefulness of the LMV fusion formulas developed. Finally, we provied and off-line recursion of Ck for a class of multisensor linear systems with coupled measurement noises.

  2. Dose variation during solar minimum

    Energy Technology Data Exchange (ETDEWEB)

    Gussenhoven, M.S.; Mullen, E.G.; Brautigam, D.H. (Phillips Lab., Geophysics Directorate, Hanscom Air Force Base, MA (US)); Holeman, E. (Boston Univ., MA (United States). Dept. of Physics)

    1991-12-01

    In this paper, the authors use direct measurement of dose to show the variation in inner and outer radiation belt populations at low altitude from 1984 to 1987. This period includes the recent solar minimum that occurred in September 1986. The dose is measured behind four thicknesses of aluminum shielding and for two thresholds of energy deposition, designated HILET and LOLET. The authors calculate an average dose per day for each month of satellite operation. The authors find that the average proton (HILET) dose per day (obtained primarily in the inner belt) increased systematically from 1984 to 1987, and has a high anticorrelation with sunspot number when offset by 13 months. The average LOLET dose per day behind the thinnest shielding is produced almost entirely by outer zone electrons and varies greatly over the period of interest. If any trend can be discerned over the 4 year period it is a decreasing one. For shielding of 1.55 gm/cm{sup 2} (227 mil) Al or more, the LOLET dose is complicated by contributions from {gt} 100 MeV protons and bremsstrahlung.

  3. Operating pumps on minimum flow

    International Nuclear Information System (INIS)

    The Nuclear Regulatory Commission (NRC) regulations in Appendix A to 10 CFR 50 require that components important to safety be designed and tested to quality standards commensurate with the importance of the safety functions to be performed. The NRC regulations in 10 CFR 50.55a reference the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code for criteria to conduct inservice testing of pumps. The ASME Code allows the performance of pump inservice testing using mini flow bypass loops. Operating experience and studies performed for the Nuclear Plant Aging Research Program (NUREG/ CR-4597, Vols. 1 and 2) showed that a leading cause of pump problems and failures is associated with hydraulic instability phenomena induced by low-flow operation. The NRC staff issued Information Notice (IN) 87-59 to alert all licensees to two miniflow design concerns identified by Westinghouse. The first potential problem discussed in this IN involves parallel pump operation. If the head/capacity curve of one of the parallel pumps is greater than the other, the weaker pump may be dead-headed when the pumps are operating at low-flow conditions. The other problem relates to potential pump damage as a result of hydraulic instability during low-flow operation. In NRC Bulletin 88-04, dated May 5, 1988, the staff requested all licensees to investigate and correct, as applicable, the two miniflow design concerns. The staff also developed a Temporary Instruction, TI 2515/105, dated January 29, 1990, to inspect for the adequacy of licensee response and follow-up actions to NRC Bulletin 88-04. Oak Ridge National Laboratory has reviewed utility responses to Bulletin 88-04 under the auspices of the NRC's Nuclear Plant Aging Research Program, and participated in several NRC inspections. Examples of actions that have been taken, an assessment of the overall industry response, and resultant conclusions and recommendations are presented

  4. Job safety in magnetic particle inspection

    International Nuclear Information System (INIS)

    Safety in the workplace is utmost importance to both employees and employers. It is a shared responsibility to make safety a way of life. General precautions to be exercised when performing magnetic particle inspection include consideration of exposure to oils, paste, and electrical current. It is important that the following minimum safety requirement to be observed when performing magnetic particle inspection. Always consult the Material Safety Data Sheet (MSDS) for the specific product or products you will be using to insure all necessary safety precautions are taken for potential health effects, first aid, fire hazard, accidental release measures, exposure controls, personal protection, physical properties,stability, reactivity toxicological information, disposal and transportation. (author)

  5. Orexin receptor antagonists as therapeutic agents for insomnia

    Directory of Open Access Journals (Sweden)

    Ana Clementina Equihua

    2013-12-01

    Full Text Available Insomnia is a common clinical condition characterized by difficulty initiating or maintaining sleep, or non-restorative sleep with impairment of daytime functioning.Currently, treatment for insomnia involves a combination of cognitive behavioral therapy and pharmacological therapy. Among pharmacological interventions, the most evidence exists for benzodiazepine receptor agonist drugs (GABAA receptor, although concerns persist regarding their safety and their limited efficacy. The use of these hypnotic medications must be carefully monitored for adverse effects.Orexin (hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep by promoting cholinergic/monoaminergic neural pathways. This has led to the development of a new class of pharmacological agents that antagonize the physiological effects of orexin. The development of these agents may lead to novel therapies for insomnia without the side effect profile of hypnotics (e.g. impaired cognition, disturbed arousal, and motor balance difficulties. However, antagonizing a system that regulates the sleep-wake cycle may create an entirely different side effect profile. In this review, we discuss the role of orexin and its receptors on the sleep-wake cycle and that of orexin antagonists in the treatment of insomnia.

  6. Balancing safety and economics

    International Nuclear Information System (INIS)

    The safety requirements of NPPs have always aimed at limiting societal risks. This risk approach initially resulted in deterministic design criteria and concepts. In the 1980s the paradigm 'safety at all costs' arose and often led to questionable backfitting measures. Conflicts between new requirements, classical design concepts and operational demands were often ignored. The design requirements for advanced reactors ensure enhanced protection against severe accidents. Still, it is questionable whether the 'no-damage-outside-the-fence' criteria can be achieved deterministically and at competitive costs. Market deregulation and utility privatisation call for a balance between safety and costs, without jeopardising basic safety concepts. An ideal approach must be risk-based and imply modern PSAs and new methods for cost-benefit and ALARA analyses, embed nuclear risks in a wider risk spectrum, but also make benefits transparent within the context of a broader life experience. Governments should define basic requirements, minimum standards and consistent comparison criteria, and strengthen operator responsibility. Internationally sufficient and binding safety requirements must be established and nuclear technology transfer handled in a responsible way, while existing plants, with their continuous backfitting investments, should receive particular attention. (orig.)

  7. Minimum Additive Waste Stabilization (MAWS)

    International Nuclear Information System (INIS)

    In the Minimum Additive Waste Stabilization(MAWS) concept, actual waste streams are utilized as additive resources for vitrification, which may contain the basic components (glass formers and fluxes) for making a suitable glass or glassy slag. If too much glass former is present, then the melt viscosity or temperature will be too high for processing; while if there is too much flux, then the durability may suffer. Therefore, there are optimum combinations of these two important classes of constituents depending on the criteria required. The challenge is to combine these resources in such a way that minimizes the use of non-waste additives yet yields a processable and durable final waste form for disposal. The benefit to this approach is that the volume of the final waste form is minimized (waste loading maximized) since little or no additives are used and vitrification itself results in volume reduction through evaporation of water, combustion of organics, and compaction of the solids into a non-porous glass. This implies a significant reduction in disposal costs due to volume reduction alone, and minimizes future risks/costs due to the long term durability and leach resistance of glass. This is accomplished by using integrated systems that are both cost-effective and produce an environmentally sound waste form for disposal. individual component technologies may include: vitrification; thermal destruction; soil washing; gas scrubbing/filtration; and, ion-exchange wastewater treatment. The particular combination of technologies will depend on the waste streams to be treated. At the heart of MAWS is vitrification technology, which incorporates all primary and secondary waste streams into a final, long-term, stabilized glass wasteform. The integrated technology approach, and view of waste streams as resources, is innovative yet practical to cost effectively treat a broad range of DOE mixed and low-level wastes

  8. Evaluation of H2 receptor antagonists in chronic idiopathic urticaria

    Directory of Open Access Journals (Sweden)

    Minocha Y

    1995-01-01

    Full Text Available H1-antagonist (hydroxyzine hydrochloride in dosage of 10 mg-25 mg thrice a day failed to elicit satisfactory response in 60 out of 170 patients of chronic idiopathic urticaria. Additional administration of H2-antagonist (cimetidine in dosage of 200 mg four times a day, in patients not responding earlier to H1-antagonist alones exhibited moderate to good improvement of various parameters of urticaria in approximately 85% patients

  9. Sexually antagonistic selection in human male homosexuality.

    Science.gov (United States)

    Camperio Ciani, Andrea; Cermelli, Paolo; Zanzotto, Giovanni

    2008-01-01

    Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness), accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait. PMID:18560521

  10. Sexually antagonistic selection in human male homosexuality.

    Directory of Open Access Journals (Sweden)

    Andrea Camperio Ciani

    Full Text Available Several lines of evidence indicate the existence of genetic factors influencing male homosexuality and bisexuality. In spite of its relatively low frequency, the stable permanence in all human populations of this apparently detrimental trait constitutes a puzzling 'Darwinian paradox'. Furthermore, several studies have pointed out relevant asymmetries in the distribution of both male homosexuality and of female fecundity in the parental lines of homosexual vs. heterosexual males. A number of hypotheses have attempted to give an evolutionary explanation for the long-standing persistence of this trait, and for its asymmetric distribution in family lines; however a satisfactory understanding of the population genetics of male homosexuality is lacking at present. We perform a systematic mathematical analysis of the propagation and equilibrium of the putative genetic factors for male homosexuality in the population, based on the selection equation for one or two diallelic loci and Bayesian statistics for pedigree investigation. We show that only the two-locus genetic model with at least one locus on the X chromosome, and in which gene expression is sexually antagonistic (increasing female fitness but decreasing male fitness, accounts for all known empirical data. Our results help clarify the basic evolutionary dynamics of male homosexuality, establishing this as a clearly ascertained sexually antagonistic human trait.

  11. Activins and activin antagonists in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Alev Deli; Emanuel Kreidl; Stefan Santifaller; Barbara Trotter; Katja Seir; Walter Berger; Rolf Schulte-Hermann; Chantal Rodgarkia-Dara; Michael Grusch

    2008-01-01

    In many parts of the world hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood. There is increasing evidence that activins, which are members of the transforming growth factor β (TGFβ) superfamily of growth and differentiation factors, could play important roles in liver carcinogenesis. Activins are disulphide-linked homo-or heterodimers formed from four different β subunits termed βA, βB, βC, and βE, respectively. Activin A, the dimer of two βA subunits, is critically involved in the regulation of cell growth, apoptosis, and tissue architecture in the liver, while the hepatic function of other activins is largely unexplored so far. Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG, and at the cell membrane antagonistic co-receptors like Cripto or BAMBI. Additionally, in the intracellular space inhibitory Smads can modulate and control activin activity. Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation, fibrosis and development of cancer. The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.

  12. Smoking, calcium, calcium antagonists, and aging.

    Science.gov (United States)

    Nicita-Mauro, V

    1990-01-01

    Aging is characterized, besides other changes, by a progressive increase in calcium content in the arterial wall, which is enhanced by diabetes mellitus, osteoporosis, arterial hypertension, and tabagism. As to tabagism, experiments in animals have shown that nicotine can increase calcium content of the arterial wall, and clinical studies have demonstrated that cigarette smoking induces peripheral vasoconstriction, with consequent increase in blood pressure levels. In order to study the role of calcium ions in the pathogenesis of the vasoconstrictive lesions caused by "acute" smoking, the author has studied the peripheral vascular effects of the calcium-channel antagonist nifedipine, a dihydropyridine derivative, and calcitonin, a hypocalcemizing hormone which possess vasoactive actions on 12 elderly regular smokers (mean age 65.8 years). The results demonstrated that both nifedipine (10 mg sublingually 20 min before smoking) and salmon calcitonin (100 MRC U/daily intramuscularly for three days) are able to prevent peripheral vasoconstriction evaluated by Doppler velocimetry, as well as the increase of blood pressure induced by smoking. On the basis of our results, the author proposes that cigarette smoking-induced vasoconstriction is a calcium-mediated process, which can be hindered by drugs with calcium antagonist action. PMID:2226675

  13. Minimum wage increases under straightened circumstances

    OpenAIRE

    Addison, John T.; Blackburn, McKinley L.; Cotti, Chad

    2011-01-01

    Do apparently large minimum wage increases in an environment of recession produce clearer evidence of disemployment effects than is typically observed in the new minimum wage literature? This paper augments the sparse literature on the most recent increases in the U.S. minimum wage, using three different data sets and the two main estimation strategies for handling geographically-disparate trends. The evidence is generally unsupportive of negative employment effects, still less of a 'recessio...

  14. How Do Alternative Minimum Wage Variables Compare?

    OpenAIRE

    Sara Lemos

    2005-01-01

    Several minimum wage variables have been suggested in the literature. Such a variety of variables makes it difficult to compare the associated estimates across studies. One problem is that these estimates are not always calibrated to represent the effect of a 10% increase in the minimum wage. Another problem is that these estimates measure the effect of the minimum wage on the employment of different groups of workers. In this paper we critically compare employment effect estimates using five...

  15. Illegal Migration, Enforcement and Minimum Wage

    OpenAIRE

    Epstein, Gil S.; Heizler (Cohen), Odelia

    2007-01-01

    This paper examines the connection between illegal migration, minimum wages and enforcement policy. We first explore the employers' decision regarding the employment of illegal migrants in the presence of an effective minimum wage. We show that the employers' decision depends on the wage gap between those of the legal and illegal workers and on the penalty for employing illegal workers. We consider the effects a change in the minimum wage has on the employment of illegal immigrants and local ...

  16. A MODEL OF MINIMUM SIZE LIMIT REGULATIONS

    OpenAIRE

    Homans, Frances R.; Ruliffson, Jane A.

    1998-01-01

    Minimum size limits have become an increasingly popular management tool in recreational fisheries. This popularity stems from the potential of minimum size limits to accomplish the twin goals of limiting overfishing and improving fishing quality through increasing the average size of fish caught. The success of minimum size limits in achieving these objectives depends in a complicated way on both the behavior of anglers and the biological mechanisms that guide the growth of the fish populatio...

  17. Minimum wages, globalization and poverty in Honduras

    OpenAIRE

    Gindling, T. H.; Terrell, Katherine

    2008-01-01

    To be competitive in the global economy, some argue that Latin American countries need to reduce or eliminate labour market regulations such as minimum wage legislation because they constrain job creation and hence increase poverty. On the other hand, minimum wage increases can have a direct positive impact on family income and may therefore help to reduce poverty. We take advantage of a complex minimum wage system in a poor country that has been exposed to the forces of globalization to test...

  18. Does the Minimum Wage Cause Inefficient Rationing?

    OpenAIRE

    Luttmer, Erzo F. P.

    2007-01-01

    This paper investigates whether the minimum wage leads to inefficient job rationing. By not allowing wages to clear the labor market, the minimum wage could cause workers with low reservation wages to be rationed out while equally skilled workers with higher reservation wages are employed. This paper exploits the overlapping nature of the CPS panels to more precisely identify those most affected by the minimum wage, a group I refer to as the "unskilled." I test for inefficient rationing by ex...

  19. Safety Plan

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Swan Lake National Wildlife Refuge Safety Plan discusses policies for the safety of the station employees, volunteers, and public. This plan seeks to identify...

  20. ITER safety

    International Nuclear Information System (INIS)

    As part of the series of publications by the IAEA that summarize the results of the Conceptual Design Activities for the ITER project, this document describes the ITER safety analyses. It contains an assessment of normal operation effluents, accident scenarios, plasma chamber safety, tritium system safety, magnet system safety, external loss of coolant and coolant flow problems, and a waste management assessment, while it describes the implementation of the safety approach for ITER. The document ends with a list of major conclusions, a set of topical remarks on technical safety issues, and recommendations for the Engineering Design Activities, safety considerations for siting ITER, and recommendations with regard to the safety issues for the R and D for ITER. Refs, figs and tabs

  1. SAFETY FIRST

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Ensuring safety while peacefully utilizing nuclear energy is a top priority for China A fter a recent earthquake in Japan caused radioactive leaks at a nuclear power plant in Tokyo, the safety of nuclear energy has again aroused public attention.

  2. Effect of Pressure on Minimum Fluidization Velocity

    Institute of Scientific and Technical Information of China (English)

    Zhu Zhiping; Na Yongjie; Lu Qinggang

    2007-01-01

    Minimum fluidization velocity of quartz sand and glass bead under different pressures of 0.5, 1.0, 1.5 and 2.0 Mpa were investigated. The minimum fluidization velocity decreases with the increasing of pressure. The influence of pressure to the minimum fluidization velocities is stronger for larger particles than for smaller ones.Based on the test results and Ergun equation, an experience equation of minimum fluidization velocity is proposed and the calculation results are comparable to other researchers' results.

  3. Safety matters

    OpenAIRE

    Gelder, P. van

    1999-01-01

    Several events have transpired recently to underscore yet again how important the issue of safety is for the local construction industry. This month regular contributor J.A. McInnis takes a look at how some of these events relate to one major area of site safety: safety whilst working at a height.

  4. 75 FR 9018 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2010-02-26

    ... percent for calendar year 2010. ] On January 19, 2010, PHMSA published an Advisory Bulletin (75 FR 2926... Pipeline and Hazardous Materials Safety Administration Pipeline Safety: Random Drug Testing Rate AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT. ACTION: Notice of Minimum...

  5. Guidance for preparation of safety analysis reports

    International Nuclear Information System (INIS)

    Department of Energy (DOE) Order 5480.5, ''Safety of Nuclear Facilities,'' requires the preparation of appropriate safety analyses for each DOE operation and subsequent significant modifications including decommissioning, and independent review of each safety analysis. The purpose of this guide is to assist in the preparation and review of safety documentation for Oak Ridge Operations (ORO) nonreactor facilities and operations. This guide provides a narrative outline of the minimum information needed to prepare safety documentation for ORO moderate or high hazard facilities. Safety documentation is required for new, existing, and modified facilities. The basic purpose of the safety documentation process is to provide assurance that there is no significant increase in risk, as defined in DOE safety policy statements, to people or the environment from operation of ORO facilities

  6. Adjusting the Passing Scores for Gearing up for Safety: Production Agriculture Safety Training for Youth Curriculum Test Instruments

    Science.gov (United States)

    Hoover, William Brian; French, Brian F.; Field, William E.; Tormoehlen, Roger L.

    2012-01-01

    Minimum passing scores for the Gearing Up for Safety: Production Agriculture Safety Training for Youth curriculum (Gearing Up for Safety) were set in 2006 with widely used and established procedures by efforts of subject matter experts (French, Breidenbach et al., 2007; French, Field, and Tormoehlen, 2006, 2007). While providing a research-based…

  7. Safety handbook

    International Nuclear Information System (INIS)

    The purpose of the Australian Nuclear Science and Technology Organization's Safety Handbook is to outline simply the fundamental procedures and safety precautions which provide an appropriate framework for safe working with any potential hazards, such as fire and explosion, welding, cutting, brazing and soldering, compressed gases, cryogenic liquids, chemicals, ionizing radiations, non-ionising radiations, sound and vibration, as well as safety in the office. It also specifies the organisation for safety at the Lucas Heights Research Laboratories and the responsibilities of individuals and committees. It also defines the procedures for the scrutiny and review of all operations and the resultant setting of safety rules for them. ills

  8. Corticospinal control of antagonistic muscles in the cat.

    Science.gov (United States)

    Ethier, Christian; Brizzi, Laurent; Giguère, Dominic; Capaday, Charles

    2007-09-01

    We recently suggested that movement-related inter-joint muscle synergies are recruited by selected excitation and selected release from inhibition of cortical points. Here we asked whether a similar cortical mechanism operates in the functional linking of antagonistic muscles. To this end experiments were done on ketamine-anesthetized cats. Intracortical microstimulation (ICMS) and intramuscular electromyographic recordings were used to find and characterize wrist, elbow and shoulder antagonistic motor cortical points. Simultaneous ICMS applied at two cortical points, each evoking activity in one of a pair of antagonistic muscles, produced co-contraction of antagonistic muscle pairs. However, we found an obvious asymmetry in the strength of reciprocal inhibition; it was always significantly stronger on physiological extensors than flexors. Following intravenous injection of a single bolus of strychnine, a cortical point at which only a physiological flexor was previously activated also elicited simultaneous activation of its antagonist. This demonstrates that antagonistic corticospinal neurons are closely grouped, or intermingled. To test whether releasing a cortical point from inhibition allows it to be functionally linked with an antagonistic cortical point, one of three GABA(A) receptor antagonists, bicuculline, gabazine or picrotoxin, was injected iontophoretically at one cortical point while stimulation was applied to an antagonistic cortical point. This coupling always resulted in co-contraction of the represented antagonistic muscles. Thus, antagonistic motor cortical points are linked by excitatory intracortical connections held in check by local GABAergic inhibition, with reciprocal inhibition occurring at the spinal level. Importantly, the asymmetry of cortically mediated reciprocal inhibition would appear significantly to bias muscle maps obtained by ICMS in favor of physiological flexors. PMID:17880397

  9. Nuclear Safety

    International Nuclear Information System (INIS)

    In this short paper it has only been possible to deal in a rather general way with the standards of safety used in the UK nuclear industry. The record of the industry extending over at least twenty years is impressive and, indeed, unique. No other industry has been so painstaking in protection of its workers and in its avoidance of damage to the environment. Headings are: introduction; how a nuclear power station works; radiation and its effects (including reference to ICRP, the UK National Radiological Protection Board, and safety standards); typical radiation doses (natural radiation, therapy, nuclear power programme and other sources); safety of nuclear reactors - design; key questions (matters of concern which arise in the public mind); safety of operators; safety of people in the vicinity of a nuclear power station; safety of the general public; safety bodies. (U.K.)

  10. Minimum tube diameters for steady propagation of gaseous detonations

    Science.gov (United States)

    Gao, Y.; Ng, H. D.; Lee, J. H. S.

    2014-07-01

    Recent experimental results on detonation limits are reported in this paper. A parametric study was carried out to determine the minimum tube diameters for steady detonation propagation in five different hydrocarbon fuel-oxygen combustible mixtures and in five polycarbonate test tube diameters ranging from 50.8 mm down to a small scale of 1.5 mm. The wave propagation in the tube was monitored by optical fibers. By decreasing the initial pressure, hence the sensitivity of the mixture, the onset of limits is indicated by an abrupt drop in the steady detonation velocity after a short distance of travel. From the measured wave velocities inside the test tube, the critical pressure corresponding to the limit and the minimum tube diameters for the propagation of the detonation can be obtained. The present experimental results are in good agreement with previous studies and show that the measured minimum tube diameters can be reasonably estimated on the basis of the /3 rule over a wide range of conditions, where is the detonation cell size. These new data shall be useful for safety assessment in process industries and in developing and validating models for detonation limits.

  11. 78 FR 11793 - Minimum Internal Control Standards

    Science.gov (United States)

    2013-02-20

    ... Internal Control Standards. 64 FR 590. The rule added a new part to the Commission's regulations... National Indian Gaming Commission 25 CFR Part 543 RIN 3141-AA27 Minimum Internal Control Standards AGENCY... (NIGC) proposes to amend its minimum internal control standards for Class II gaming under the...

  12. Probable Value for the Next Sunspot Minimum

    OpenAIRE

    Virginia Mabel Silbergleit

    2014-01-01

    Gumbel’s first distribution is applied to smoothed monthly mean sunspot numbers for solar cycles 10 to 24. According to that, the next minimum for solar cycle 24-25 transition would be the deepest solar minimum of the last 150 years. This study provides an additional insight about changes in the Sun which are currently happening.

  13. Probable Value for the Next Sunspot Minimum

    Directory of Open Access Journals (Sweden)

    Virginia Mabel Silbergleit

    2014-01-01

    Full Text Available Gumbel’s first distribution is applied to smoothed monthly mean sunspot numbers for solar cycles 10 to 24. According to that, the next minimum for solar cycle 24-25 transition would be the deepest solar minimum of the last 150 years. This study provides an additional insight about changes in the Sun which are currently happening.

  14. Stochastic variational approach to minimum uncertainty states

    International Nuclear Information System (INIS)

    We introduce a new variational characterization of Gaussian diffusion processes as minimum uncertainty states. We then define a variational method constrained by kinematics of diffusions and Schroedinger dynamics to seek states of local minimum uncertainty for general non-harmonic potentials. (author)

  15. Stochastic variational approach to minimum uncertainty states

    Energy Technology Data Exchange (ETDEWEB)

    Illuminati, F.; Viola, L. [Dipartimento di Fisica, Padova Univ. (Italy)

    1995-05-21

    We introduce a new variational characterization of Gaussian diffusion processes as minimum uncertainty states. We then define a variational method constrained by kinematics of diffusions and Schroedinger dynamics to seek states of local minimum uncertainty for general non-harmonic potentials. (author)

  16. Stochastic variational approach to minimum uncertainty states

    CERN Document Server

    Illuminati, F; Illuminati, F; Viola, L

    1995-01-01

    We introduce a new variational characterization of Gaussian diffusion processes as minimum uncertainty states. We then define a variational method constrained by kinematics of diffusions and Schr\\"{o}dinger dynamics to seek states of local minimum uncertainty for general non-harmonic potentials.

  17. Stochastic Variational Approach to Minimum Uncertainty States

    OpenAIRE

    Illuminati, F.; Viola, L.

    1995-01-01

    We introduce a new variational characterization of Gaussian diffusion processes as minimum uncertainty states. We then define a variational method constrained by kinematics of diffusions and Schr\\"{o}dinger dynamics to seek states of local minimum uncertainty for general non-harmonic potentials.

  18. The Operational Risk – Minimum Capital Requirements

    OpenAIRE

    Gabriela Victoria Anghelache; Ana Cornelia Olteanu

    2009-01-01

    This paper aims to present how to quantify the minimum capital requirement for operational risk using three approaches proposed by the Basel Committee to identify optimal allocation of capital, given that until recently to this risk has been allocated a minimum attention, considering that it has a low impact on the business of financial institutions.

  19. Mutually-antagonistic interactions in baseball networks

    Science.gov (United States)

    Saavedra, Serguei; Powers, Scott; McCotter, Trent; Porter, Mason A.; Mucha, Peter J.

    2010-03-01

    We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit structural changes over time. We find interesting structure in the networks and examine their sensitivity to baseball’s rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to (1) compare the performance of players who competed under different conditions and (2) include information about which particular players a given player has faced. We find that a player’s position in the network does not correlate with his placement in the random walker ranking. However, network position does have a substantial effect on the robustness of ranking placement to changes in head-to-head matchups.

  20. Mutually-Antagonistic Interactions in Baseball Networks

    CERN Document Server

    Saavedra, Serguei; McCotter, Trent; Porter, Mason A; Mucha, Peter J

    2009-01-01

    We formulate the head-to-head matchups between Major League Baseball pitchers and batters from 1954 to 2008 as a bipartite network of mutually-antagonistic interactions. We consider both the full network and single-season networks, which exhibit interesting structural changes over time. We also find that these networks exhibit a significant network structure that is sensitive to baseball's rule changes. We then study a biased random walk on the matchup networks as a simple and transparent way to compare the performance of players who competed under different conditions. We find that a player's position in the network does not correlate with his success in the random walker ranking but instead has a substantial effect on its sensitivity to changes in his own aggregate performance.

  1. The Attractiveness of Opposites: Agonists and Antagonists.

    LENUS (Irish Health Repository)

    O'Brien, Tony

    2015-02-02

    ABSTRACT Opioid-induced bowel dysfunction, of which constipation is the most common aspect, is a major limiting factor in the use of opioids for pain management. The availability of an oral, long-acting formulation of oxycodone and naloxone represents a highly significant development in pain management. The combination of an opioid analgesic with an opioid antagonist offers reliable pain control with a significant reduction in the burden of opioid-induced constipation. This report is adapted from paineurope 2014; Issue 3, ©Haymarket Medical Publications Ltd, and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the website: http:\\/\\/www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.

  2. ETA-receptor antagonists or allosteric modulators?

    DEFF Research Database (Denmark)

    De Mey, Jo G R; Compeer, Matthijs G; Lemkens, Pieter;

    2011-01-01

    The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects. In resista......The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects......(A) and that ERAs and the physiological antagonist allosterically reduce ET(A) functions. Combining the two-state model and the two-domain model of GPCR function and considering receptor activation beyond agonist binding might lead to better anti-endothelinergic drugs. Future studies could lead to compounds...

  3. Antagonistic activity of marine sponges associated Actinobacteria

    Institute of Scientific and Technical Information of China (English)

    Selvakumar Dharmaraj; Dhevendaran Kandasamy

    2016-01-01

    Objective: To focus on the isolation and preliminary characterization of marine sponges associated Actinobacteria particularly Streptomyces species and also their antagonistic activities against bacterial and fungal pathogens. Methods: The sponges were collected from Kovalam and Vizhinjam port of south-west coast of Kerala, India. Isolation of strains was carried out from sponge extracts using international Streptomyces project media. For preliminary identification of the strains, morphological (mycelial colouration, soluble pigments, melanoid pigmentation, spore morphology), nutritional uptake (carbon utilisation, amonoacids influence, sodium chloride tolerance), physiological (pH, temperature) and chemotaxonomical characterization were done. Antimicrobial studies were also carried out for the selected strains. Results: With the help of the spicule structures, the collected marine sponges were identified as Callyspongia diffusa, Mycale mytilorum, Tedania anhelans and Dysidea fragilis. Nearly 94 strains were primarily isolated from these sponges and further they were sub-cultured using international Streptomyces project media. The strains exhibited different mycelial colouration (aerial and substrate), soluble and melanoid pigmentations. The strains possessed three types of sporophore morphology namely rectus flexibilis, spiral and retinaculiaperti. Among the 94 isolates, seven exhibited antibacterial and antifungal activities with maximal zone of inhibition of 30 mm. The nutritional, physiological and chemotaxonomical characteristic study helped in the conventional identification of the seven strains and they all suggest that the strains to be grouped under the genus Streptomyces. Conclusions: The present study clearly helps in the preliminary identification of the isolates associated with marine sponges. Antagonistic activities prove the production of antimicrobial metabolites against the pathogens. Marine sponges associated Streptomyces are universally well

  4. Optimisation of GnRH antagonist use in ART

    NARCIS (Netherlands)

    Hamdine, O.

    2014-01-01

    This thesis focuses on the optimisation of controlled ovarian stimulation for IVF using exogenous FSH and GnRH antagonist co-treatment, by studying the timing of the initiation of GnRH antagonist co-medication and the role of ovarian reserve markers in optimising ovarian response and reproductive ou

  5. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Rasmussen, Hans; Arnt, Jørn;

    2011-01-01

    receptor antagonists is evaluated. Moreover, the investigational pipeline of major pharmaceutical companies is examined and an Internet search conducted to identify other pharmaceutical companies investigating 5-HT2A receptor antagonists for the treatment of schizophrenia. Expert opinion: 5-HT2A receptor...

  6. Antagonistic and Bargaining Games in Optimal Marketing Decisions

    Science.gov (United States)

    Lipovetsky, S.

    2007-01-01

    Game theory approaches to find optimal marketing decisions are considered. Antagonistic games with and without complete information, and non-antagonistic games techniques are applied to paired comparison, ranking, or rating data for a firm and its competitors in the market. Mix strategy, equilibrium in bi-matrix games, bargaining models with…

  7. DEFICIENCY OF INTERLEUKIN-1 RECEPTOR ANTAGONIST RESPONSIVE TO ANAKINRA

    OpenAIRE

    SCHNELLBACHER, CHARLOTTE; CIOCCA, GIOVANNA; MENENDEZ, ROXANNA; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela; DUARTE, ANAM.; RIVAS-CHACON, RAFAEL

    2012-01-01

    We describe a 3-month-old infant who presented to our institution with interleukin (IL)-1 receptor antagonist deficiency (DIRA), which consists of neutrophilic pustular dermatosis, periostitis, aseptic multifocal osteomyelitis, and persistently high acutephase reactants. Skin findings promptly improved upon initiation of treatment with anakinra (recombinant human IL-1 receptor antagonist), and the bony lesions and systemic inflammation resolved with continued therapy.

  8. 42 CFR 84.140 - Air velocity and noise levels; hoods and helmets; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Air velocity and noise levels; hoods and helmets; minimum requirements. 84.140 Section 84.140 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Supplied-Air...

  9. 42 CFR 84.202 - Air velocity and noise levels; hoods and helmets; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Air velocity and noise levels; hoods and helmets; minimum requirements. 84.202 Section 84.202 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Chemical...

  10. 42 CFR 84.1139 - Air velocity and noise levels; hoods and helmets; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Air velocity and noise levels; hoods and helmets; minimum requirements. 84.1139 Section 84.1139 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Dust, Fume, and...

  11. Kinetic properties of 'dual' orexin receptor antagonists at OX1R and OX2R orexin receptors.

    Directory of Open Access Journals (Sweden)

    Gabrielle Elizabeth Callander

    2013-12-01

    Full Text Available Orexin receptor antagonists represent attractive targets for the development of drugs for the treatment of insomnia. Both efficacy and safety are crucial in clinical settings and thorough investigations of pharmacokinetics and pharmacodynamics can predict contributing factors such as duration of action and undesirable effects. To this end, we studied the interactions between various ‘dual’ orexin receptor antagonists and the orexin receptors, OX1R and OX2R, over time using saturation and competition radioligand binding with [3H]-BBAC ((S-N-([1,1'-biphenyl]-2-yl-1-(2-((1-methyl-1H-benzo[d]imidazol-2-ylthioacetylpyrrolidine-2-carboxamide. In addition, the kinetics of these compounds were investigated in cells expressing human, mouse and rat OX1R and OX2R using FLIPR® assays for calcium accumulation. We demonstrate that almorexant reaches equilibrium very slowly at OX2R, whereas SB-649868, suvorexant and filorexant may take hours to reach steady state at both orexin receptors. By contrast, compounds such as BBAC or the selective OX2R antagonist IPSU ((2-((1H-Indol-3-ylmethyl-9-(4-methoxypyrimidin-2-yl-2,9-diazaspiro[5.5]undecan-1-one bind rapidly and reach equilibrium very quickly in both binding and / or functional assays. Overall, the dual antagonists tested here tend to be rather unselective under non-equilibrium conditions and reach equilibrium very slowly. Once equilibrium is reached, each ligand demonstrates a selectivity profile that is however, distinct from the non-equilibrium condition. The slow kinetics of the dual antagonists tested suggest that in vitro receptor occupancy may be longer lasting than would be predicted. This raises questions as to whether pharmacokinetic studies measuring plasma or brain levels of these antagonists are accurate reflections of receptor occupancy in vivo.

  12. Pharmacokinetic interactions with calcium channel antagonists (Part I).

    Science.gov (United States)

    Schlanz, K D; Myre, S A; Bottorff, M B

    1991-11-01

    Calcium channel antagonists are a diverse class of drugs widely used in combination with other therapeutic agents. The potential exists for many clinically significant pharmacokinetic interactions between these and other concurrently administered drugs. The mechanisms of calcium channel antagonist-induced changes in drug metabolism include altered hepatic blood flow and impaired hepatic enzyme metabolising activity. Increases in serum concentrations and/or reductions in clearance have been reported for several drugs used with a number of calcium channel antagonists. A number of reports and studies of calcium channel antagonist interactions have yielded contradictory results and the clinical significance of pharmacokinetic changes seen with these agents is ill-defined. The first part of this article deals with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. PMID:1773549

  13. EXPERIMENTAL STUDY OF MINIMUM IGNITION TEMPERATURE

    Directory of Open Access Journals (Sweden)

    Igor WACHTER

    2015-12-01

    Full Text Available The aim of this scientific paper is an analysis of the minimum ignition temperature of dust layer and the minimum ignition temperatures of dust clouds. It could be used to identify the threats in industrial production and civil engineering, on which a layer of combustible dust could occure. Research was performed on spent coffee grounds. Tests were performed according to EN 50281-2-1:2002 Methods for determining the minimum ignition temperatures of dust (Method A. Objective of method A is to determine the minimum temperature at which ignition or decomposition of dust occurs during thermal straining on a hot plate at a constant temperature. The highest minimum smouldering and carbonating temperature of spent coffee grounds for 5 mm high layer was determined at the interval from 280 °C to 310 °C during 600 seconds. Method B is used to determine the minimum ignition temperature of a dust cloud. Minimum ignition temperature of studied dust was determined to 470 °C (air pressure – 50 kPa, sample weight 0.3 g.

  14. Safety; Avertissement

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This annual report of the Senior Inspector for the Nuclear Safety, analyses the nuclear safety at EDF for the year 1999 and proposes twelve subjects of consideration to progress. Five technical documents are also provided and discussed concerning the nuclear power plants maintenance and safety (thermal fatigue, vibration fatigue, assisted control and instrumentation of the N4 bearing, 1300 MW reactors containment and time of life of power plants). (A.L.B.)

  15. Visit safety

    CERN Multimedia

    2012-01-01

    Experiment areas, offices, workshops: it is possible to have co-workers or friends visit these places.     You already know about the official visits service, the VIP office, and professional visits. But do you know about the safety instruction GSI-OHS1, “Visits on the CERN site”? This is a mandatory General Safety Instruction that was created to assist you in ensuring safety for all your visits, whatever their nature—especially those that are non-official. Questions? The HSE Unit will be happy to answer them. Write to safety-general@cern.ch.   The HSE Unit

  16. Medication safety.

    Science.gov (United States)

    Keohane, Carol A; Bates, David W

    2008-03-01

    Patient safety is a state of mind, not a technology. The technologies used in the medical setting represent tools that must be properly designed, used well, and assessed on an on-going basis. Moreover, in all settings, building a culture of safety is pivotal for improving safety, and many nontechnologic approaches, such as medication reconciliation and teaching patients about their medications, are also essential. This article addresses the topic of medication safety and examines specific strategies being used to decrease the incidence of medication errors across various clinical settings.

  17. Does the Minimum Wage Cause Inefficient Rationing?

    Institute of Scientific and Technical Information of China (English)

    何满辉; 梁明秋

    2008-01-01

    By not allowing wages to dearthe labor market,the minimum wage could cause workers with low reservation wages to be rationed out while equally skilled woTkers with higher reservation wages are employed.I find that proxies for reservation wages of unskilled workers in high-impact stales did not rise relative to reservation wages in other states,suggesting that the increase in the minimum wage did not cause jobs to be allocated less efficiently.However,even if rationing is efficient,the minimum wage can still entail other efficiency costs.

  18. Restaurant prices and the minimum wage

    OpenAIRE

    Fougère, Denis; Gautier, Erwan; Le Bihan, Hervé

    2009-01-01

    In this paper, we examine the e¤ect of the minimum wage on restaurant prices.We contributeboth to the study of economic impact of the minimum wage and to the study of microeconomicpatterns of price stickiness. For this purpose, we use a unique dataset of individual price quotescollected to calculate the Consumer Price Index in France and we estimate a price rigidity modelbased on a ?exible (S; s) rule. We ?nd a positive and signi?cant impact of the minimum wageon prices. The e¤ect of the mini...

  19. Who Benefits from a Minimum Wage Increase?

    OpenAIRE

    John W. Lopresti; Mumford, Kevin J.

    2015-01-01

    This paper addresses the question of how a minimum wage increase affects the wages of low-wage workers. Most studies assume that there is a simple mechanical increase in the wage for workers earning a wage between the old and the new minimum wage, with some studies allowing for spillovers to workers with wages just above this range. Rather than assume that the wages of these workers would have remained constant, this paper estimates how a minimum wage increase impacts a low-wage worker's wage...

  20. The Negative Effects of the Minimum Wage

    OpenAIRE

    Henderson, David R.

    2006-01-01

    Various state legislators and interest groups around the United States are pushing for increases in the minimum wage. In California, for example, even Republican Gov. Arnold Schwarzenegger now advocates raising the state minimum wage from its current $6.75 an hour to $7.75 by July 2007. But when the minimum wage law confronts the law of demand, the law of demand wins every time. And the real losers are the most marginal workers — the ones who will be out of a job.

  1. Minimum emittance in TBA and MBA lattices

    Science.gov (United States)

    Xu, Gang; Peng, Yue-Mei

    2015-03-01

    For reaching a small emittance in a modern light source, triple bend achromats (TBA), theoretical minimum emittance (TME) and even multiple bend achromats (MBA) have been considered. This paper derived the necessary condition for achieving minimum emittance in TBA and MBA theoretically, where the bending angle of inner dipoles has a factor of 31/3 bigger than that of the outer dipoles. Here, we also calculated the conditions attaining the minimum emittance of TBA related to phase advance in some special cases with a pure mathematics method. These results may give some directions on lattice design.

  2. Rank 72 high minimum norm lattices

    CERN Document Server

    Griess, Robert L

    2009-01-01

    Given a polarization of an even unimodular lattice and integer $k\\ge 1$, we define a family of unimodular lattices $L(M,N,k)$. Of special interest are certain $L(M,N,3)$ of rank 72. Their minimum norms lie in $\\{4, 6, 8\\}$. Norms 4 and 6 do occur. Consequently, 6 becomes the highest known minimum norm for rank 72 even unimodular lattices. We discuss how norm 8 might occur for such a $L(M,N,3)$. We note a few $L(M,N,k)$ in dimensions 96, 120 and 128 with moderately high minimum norms.

  3. Workplace Safety and Health Topics: Safety & Prevention

    Science.gov (United States)

    ... and Healthy Jobs - Prevention through Design Hierarchy of Controls Industry and Occupation Coding and Support Logging Safety Machine Safety Motor Vehicle Safety Motor-Vehicle Safety of Law Enforcement Officers Nail Gun Safety National Occupational Mortality Surveillance (NOMS) Noise and ...

  4. Laser safety in the lab

    CERN Document Server

    Barat, Ken L

    2012-01-01

    There is no more challenging setting for laser use than a research environment. In almost every other setting the laser controls count on engineering controls, and human exposure is kept to a minimum. In research, however, the user often manipulates the optical layout and thereby places him or herself in peril, but this does not mean that accidents and injury are unavoidable. On the contrary, laser accidents can be avoided by following a number of simple approaches. [i]Laser Safety in the Lab[/i] provides the laser user and laser safety officer with practical guidelines from housekeeping to ey

  5. Update on leukotriene receptor antagonists in preschool children wheezing disorders

    Directory of Open Access Journals (Sweden)

    Montella Silvia

    2012-06-01

    Full Text Available Abstract Asthma is the most common chronic disease in young children. About 40% of all preschool children regularly wheeze during common cold infections. The heterogeneity of wheezing phenotypes early in life and various anatomical and emotional factors unique to young children present significant challenges in the clinical management of this problem. Anti-inflammatory therapy, mainly consisting of inhaled corticosteroids (ICS, is the cornerstone of asthma management. Since Leukotrienes (LTs are chemical mediators of airway inflammation in asthma, the leukotriene receptor antagonists (LTRAs are traditionally used as potent anti-inflammatory drugs in the long-term treatment of asthma in adults, adolescents, and school-age children. In particular, montelukast decreases airway inflammation, and has also a bronchoprotective effect. The main guidelines on asthma management have confirmed the clinical utility of LTRAs in children older than five years. In the present review we describe the most recent advances on the use of LTRAs in the treatment of preschool wheezing disorders. LTRAs are effective in young children with virus-induced wheeze and with multiple-trigger disease. Conflicting data do not allow to reach definitive conclusions on LTRAs efficacy in bronchiolitis or post-bronchiolitis wheeze, and in acute asthma. The excellent safety profile of montelukast and the possibility of oral administration, that entails better compliance from young children, represent the main strengths of its use in preschool children. Montelukast is a valid alternative to ICS especially in poorly compliant preschool children, or in subjects who show adverse effects related to long-term steroid therapy.

  6. How unprecedented a solar minimum was it?

    Science.gov (United States)

    Russell, C. T.; Jian, L. K.; Luhmann, J. G.

    2013-05-01

    The end of the last solar cycle was at least 3 years late, and to date, the new solar cycle has seen mainly weaker activity since the onset of the rising phase toward the new solar maximum. The newspapers now even report when auroras are seen in Norway. This paper is an update of our review paper written during the deepest part of the last solar minimum [1]. We update the records of solar activity and its consequent effects on the interplanetary fields and solar wind density. The arrival of solar minimum allows us to use two techniques that predict sunspot maximum from readings obtained at solar minimum. It is clear that the Sun is still behaving strangely compared to the last few solar minima even though we are well beyond the minimum phase of the cycle 23-24 transition.

  7. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  8. Economic evaluation of minimum flow at Rockton

    International Nuclear Information System (INIS)

    This paper reports that the Rockton Hydroelectric Project is a two-unit, 1,100 kW plant operated by South Beloit Water, Gas and Electric Company, a wholly owned subsidiary of Wisconsin Power and Light Company. The project's 1,000-foot spillway directs water from the main stem of the Rock River, down a 5,000-foot power canal to the project. During relicensing of the project, state and federal resource agencies directed the licensee to propose an operations scheme for providing a protected minimum flow in the main stem of the river. As the prime relicensing consultant to Wisconsin Power and Light, Mead and Hunt conducted field studies to assess the environmental impact of various minimum flows. Mead and Hunt then conducted economic analyses to determine the economic impact of various minimum flows. The economic and environmental analyses were combined to develop a recommended minimum flow, which will be provided in the Draft Application for Subsequent License

  9. Graph theory for FPGA minimum configurations

    Institute of Scientific and Technical Information of China (English)

    Ruan Aiwu; Li Wenchang; Xiang Chuanyin; Song Jiangmin; Kang Shi; Liao Yongbo

    2011-01-01

    A traditional bottom-up modeling method for minimum configuration numbers is adopted for the study of FPGA minimum configurations.This method is limited ifa large number of LUTs and multiplexers are presented.Since graph theory has been extensively applied to circuit analysis and test,this paper focuses on the modeling FPGA configurations.In our study,an internal logic block and interconnections of an FPGA are considered as a vertex and an edge connecting two vertices in the graph,respectively.A top-down modeling method is proposed in the paper to achieve minimum configuration numbers for CLB and IOB.Based on the proposed modeling approach and exhaustive analysis,the minimum configuration numbers for CLB and IOB are five and three,respectively.

  10. Minimum disparity estimation in controlled branching processes

    OpenAIRE

    Gonzalez, Miguel; Minuesa, Carmen; del Puerto, Ines

    2015-01-01

    Minimum disparity estimation in controlled branching processes is dealt with by assuming that the offspring law belongs to a general parametric family. Under some regularity conditions it is proved that the minimum disparity estimators proposed -based on the nonparametric maximum likelihood estimator of the offspring law when the entire family tree is observed- are consistent and asymptotic normally distributed. Moreover, it is discussed the robustness of the estimators proposed. Through a si...

  11. Minimum Dominating Tree Problem for Graphs

    Institute of Scientific and Technical Information of China (English)

    LIN Hao; LIN Lan

    2014-01-01

    A dominating tree T of a graph G is a subtree of G which contains at least one neighbor of each vertex of G. The minimum dominating tree problem is to find a dominating tree of G with minimum number of vertices, which is an NP-hard problem. This paper studies some polynomially solvable cases, including interval graphs, Halin graphs, special outer-planar graphs and others.

  12. What causes geomagnetic activity during sunspot minimum

    OpenAIRE

    Kirov, Boian; Asenovski, Simeon; GEORGIEVA, KATYA; Obridko, Vladimir

    2014-01-01

    The average geomagnetic activity during sunspot minimum has been continuously decreasing in the last four cycles. The geomagnetic activity is caused by both interplanetary disturbances - coronal mass ejections and high speed solar wind streams, and the background solar wind over which these disturbances ride. We show that the geomagnetic activity in cycle minimum does not depend on the number and parameters of coronal mass ejections or high speed solar wind streams, but on the background sola...

  13. The minimum wage and restaurant prices

    OpenAIRE

    Daniel Aaronson; Eric French; MacDonald, James M.

    2004-01-01

    Using both store-level and aggregated price data from the food away from home component of the Consumer Price Index survey, we show that restaurant prices rise in response to an increase in the minimum wage. These results hold up when using several different sources of variation in the data. We interpret these findings within a model of employment determination. The model implies that minimum wage hikes cause employment to fall and prices to rise if labor markets are competitive but potential...

  14. Safety Instructions

    CERN Multimedia

    2003-01-01

    Please note that the Safety Instructions N0 37 rev. 3 (IS 37 rev. 3) entitled ""LEVEL-3" SAFETY ALARMS AND ALARM SYSTEMS" Is available on the web at the following URL: http://edms.cern.ch/document/335802 Paper copies can also be obtained from the TIS divisional secretariat, e-mail: tis.secretariat@cern.ch TIS Secretariat

  15. Behavioural effects of histamine and its antagonists: a review.

    Science.gov (United States)

    White, J M; Rumbold, G R

    1988-01-01

    This review focuses on the behavioural effects of histamine and drugs which affect histaminergic function, particularly the H1- and H2-receptors antagonists. Research in this area has assumed considerable importance with increasing interest in the role of brain histamine, the clinical use of both H1 and H2 antagonists and evidence of nonmedical use of H1 antagonists. Results from a number of studies show that H1 and H2 antagonists have clear, but distinct subjective effects and that H1 antagonists have discriminative effects in animals. While H1 antagonists are reinforcers in certain conditions, histamine itself is a punisher. Moderate doses of H1 antagonists affect psychomotor performance in some situations, but the results are variable. The exceptions are terfenadine and astemizole, which do not seem to penetrate the blood-brain barrier readily. In studies of schedule-controlled behaviour, marked changes in response rate have been observed following administration of H1 antagonists, with the magnitude and direction dependent on the dose and the baseline behaviour. Histamine reduces avoidance responding, an effect mediated via H1-receptors. Changes in drinking and aggressive behaviour have also been observed following histamine administration and distinct roles for H1- and H2-receptors have been delineated. Separate H1- and H2-receptor mechanisms have also been suggested to account for changes in activity level. While the H2 antagonists do not always have strong behavioural effects when administered peripherally, there is evidence that cimetidine has a depressant effect on sexual function. These and other findings reveal an important role for histaminergic systems in a wide range of behaviour. PMID:3133686

  16. Effect of the selective vasopressin V2 receptor antagonists in hepatic cirrhosis patients with ascites: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Shao-hui TANG

    2013-07-01

    Full Text Available Objective To evaluate the efficacy and safety of selective vasopressin V2 receptor antagonists in the treatment of hepatic cirrhosis patients with ascites. Methods PubMed, EMBASE, Web of Science, The Cochrane Central Register of Controlled Trials, Database for Chinese Technical Periodical (VIP, Chinese Journal Full-Text Database (CNKI, and Wan Fang Digital Journal Full-text Database were retrieved to collect clinical randomized controlled trials of hepatic cirrhosis with ascites treated by selective vasopressin V2 receptor antagonists. Meta analysis was performed by using Review Manager 5.0. Results Nine randomized controlled trials including 1884 patients met the inclusion criteria. Meta-analysis showed that: 1 The selective vasopressin V2 receptor antagonists were associated with a significant reduction in body weight compared with placebo (WMD=–1.98kg, 95%CI:–3.24-–0.72kg, P=0.002. Treatment with selective vasopressin V2 receptor antagonists was associated with an improvement of low serum sodium concentration compared to placebo (WMD=3.74mmol/L, 95%CI: 0.91-6.58mmol/L, P=0.01. The percentage of patients with worsening ascites was higher in the group of patients treated with placebo (RR=0.51, 95%CI: 0.34-0.77, P=0.001. 2 The amplitude of increased urine volume was obviously higher in selective vasopressin V2 receptor antagonists group than in placebo group (WMD=1437.65ml, 95%CI: 649.01-2226.30ml, P=0.0004. The difference of serum creatinine in the selective vasopressin V2 receptor antagonists group was not statistically significant compared with the control group (WMD=–3.49μmol/L, 95%CI: –12.54¬5.56μmol/L, P=0.45. 3 There was no statistical significance between the two groups in the heart rate, systolic pressure, diastolic pressure and mortality (P>0.05. The rate of other adverse reactions was higher in the selective vasopressin V2 receptor antagonists group compared with that of placebo group (P=0.003. Conclusion

  17. Leukotriene Receptor Antagonists and Related Compounds

    Directory of Open Access Journals (Sweden)

    Sally E Wenzel

    1999-01-01

    Full Text Available Leukotrienes (LTs, lipid mediators of inflammation, have proved to be important biochemicals involved in the symptoms and physiological changes of asthma. In the past year and a half, the development of three new drugs that modulate the LT pathway has been completed. The first subclass of these drugs, leukotriene receptor antagonists (LTRA (zafirlukast and montelukast, blocks the interaction of the cysteinyl form of the LTs with the cell type bearing the receptor. The second subclass, the 5-lipoxygenase (5-LO inhibitors (zileuton inhibits the 5-LO enzyme, which prevents the formation of both cysteinyl LTs and LTB4. The LT modulators have shown efficacy in inhibiting the physiological changes occurring after allergen, acetylsalicylic acid and exercise challenge in asthmatics. In addition, they have shown efficacy in improving symptoms, beta-agonist use and forced expiratory volume in 1 s (FEV1 in chronic, ‘day-to-day’ asthma in patients with mild disease. Comparison studies with low doses of inhaled corticosteroids suggest that LT modulators may have similar effects on symptom scores and beta-agonist use, but have lesser effects on FEV1. Finally, emerging data suggest that these drugs are beneficial in decreasing the dose of inhaled corticosteroids necessary to control more moderate to severe asthma. While long term studies will be helpful in determining the ‘disease modifying’ effects of these drugs, data suggest that these drugs are useful in the treatment of a broad range of asthmatic patients.

  18. Identification of a novel conformationally constrained glucagon receptor antagonist.

    Science.gov (United States)

    Lee, Esther C Y; Tu, Meihua; Stevens, Benjamin D; Bian, Jianwei; Aspnes, Gary; Perreault, Christian; Sammons, Matthew F; Wright, Stephen W; Litchfield, John; Kalgutkar, Amit S; Sharma, Raman; Didiuk, Mary T; Ebner, David C; Filipski, Kevin J; Brown, Janice; Atkinson, Karen; Pfefferkorn, Jeffrey A; Guzman-Perez, Angel

    2014-02-01

    Identification of orally active, small molecule antagonists of the glucagon receptor represents a novel treatment paradigm for the management of type 2 diabetes mellitus. The present work discloses novel glucagon receptor antagonists, identified via conformational constraint of current existing literature antagonists. Optimization of lipophilic ligand efficiency (LLE or LipE) culminated in enantiomers (+)-trans-26 and (-)-trans-27 which exhibit good physicochemical and in vitro drug metabolism profiles. In vivo, significant pharmacokinetic differences were noted with the two enantiomers, which were primarily driven through differences in clearance rates. Enantioselective oxidation by cytochrome P450 was ruled out as a causative factor for pharmacokinetic differences.

  19. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Mohammad eKhanfar

    2016-05-01

    Full Text Available With the very recent market approval of pitolisant (Wakix®, the interest in clinical applications of novel multifunctional histamine H3 receptor antagonists has clearly increased. Since histamine H3 receptor antagonists in clinical development have been tested for a variety of different indications, the combination of pharmacological properties in one molecule for improved pharmacological effects and reduced unwanted side-effects is rationally based on the increasing knowledge on the complex neurotransmitter regulations. The polypharmacological approaches on histamine H3 receptor antagonists on different G-protein coupled receptors, transporters, enzymes as well as on NO-signaling mechanism are described, supported with some lead structures.

  20. The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3 receptors.

    Science.gov (United States)

    Lochner, Martin; Thompson, Andrew J

    2016-09-01

    Scopolamine is a high affinity muscarinic antagonist that is used for the prevention of post-operative nausea and vomiting. 5-HT3 receptor antagonists are used for the same purpose and are structurally related to scopolamine. To examine whether 5-HT3 receptors are affected by scopolamine we examined the effects of this drug on the electrophysiological and ligand binding properties of 5-HT3A receptors expressed in Xenopus oocytes and HEK293 cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09 μM. Competitive antagonism was shown by Schild plot (pA2 = 5.02) and by competition with the 5-HT3 receptor antagonists [(3)H]granisetron (Ki = 6.76 μM) and G-FL (Ki = 4.90 μM). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 μM, and competed with G-FL with a Ki of 7.94 μM. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki = 6.5 μM). In behavioural studies scopolamine is used to block muscarinic receptors and induce a cognitive deficit, and centrally administered concentrations can exceed the IC50 values found here. It is therefore possible that 5-HT3 receptors are also inhibited. Studies that utilise higher concentrations of scopolamine should be mindful of these potential off-target effects. PMID:27108935

  1. Random-start GnRH antagonist for emergency fertility preservation: a self-controlled trial

    Directory of Open Access Journals (Sweden)

    Checa MA

    2015-02-01

    Full Text Available Miguel A Checa,1,2 Mario Brassesco,2 Margalida Sastre,1 Manuel Gómez,2 Julio Herrero,3 Laura Marque,3 Arturo Brassesco,2 Juan José Espinós3 1Department of Obstetrics and Gynecology, Parc de Salut Mar, Universitat Autònoma de Barcelona, 2Centro de Infertilidad y Reproducción Humana (CIRH, 3Centro de Reproducción Asistida Sagrada Familia, Clínica Sagrada Familia, Barcelona, Spain Abstract: The aim of this study is to evaluate the feasibility and safety of random-start controlled ovarian hyperstimulation (COH for emergency fertility preservation, regardless of the phase of the menstrual cycle. A self-controlled pilot clinical trial (NCT01385332 was performed in an acute-care teaching hospital and in two private reproductive centers in Barcelona, Spain. Eleven egg donors participated in the study. Two random-start gonadotropin-releasing hormone (GnRH antagonist protocols were assessed in which ganirelix was initiated on either day 10 (protocol B or on day 20 (protocol C of the menstrual cycle and was continued until estradiol levels were below 60 pg/dL. These protocols were compared with a standard protocol (protocol A. The main outcome of interest was the number of metaphase 2 oocytes retrieved. Results from this study show that the number of mature oocytes retrieved was comparable across the different protocols (14.3±4.6 in the standard protocol versus 13.0±9.1 and 13.2±5.2 in protocols B and C, respectively; values expressed as mean ± standard deviation. The mean number of days needed for a GnRH antagonist to lower estradiol levels, as well as the ongoing pregnancy rates, were also similar when protocols B (stimulation in follicular phase and C (stimulation on luteal phase were compared with protocol A (standard stimulation. GnRH antagonists can be effectively used for random-start controlled ovarian hyperstimulation with an ovarian response similar to that of standard protocols, and the antagonists appear suitable for emergency

  2. Safety strategy

    International Nuclear Information System (INIS)

    The basis for safety strategy in nuclear industry and especially nuclear power plants is the prevention of radioactivity release inside or outside of the technical installation. Therefore either technical or administrative measures are combined to a general strategy concept. This introduction will explain in more detail the following topics: - basic principles of safety - lines of assurance (LOA) - defense in depth - deterministic and probabilistic methods. This presentation is seen as an introduction to the more detailed discussion following in this course, nevertheless some selected examples will be used to illustrate the aspects of safety strategy development although they might be repeated later on. (orig.)

  3. Secondary prevention with calcium antagonists after acute myocardial infarction

    DEFF Research Database (Denmark)

    Hansen, J F

    1992-01-01

    Experimental studies have demonstrated that the 3 calcium antagonists nifedipine, diltiazem, and verapamil have a comparable effect in the prevention of myocardial damage during ischaemia. Secondary prevention trials after acute myocardial infarction, which aimed at improving survival...

  4. Interleukin-2 receptor antagonists as induction therapy after heart transplantation

    DEFF Research Database (Denmark)

    Møller, Christian H; Gustafsson, Finn; Gluud, Christian;

    2008-01-01

    About half of the transplantation centers use induction therapy after heart transplantation. Interleukin-2 receptor antagonists (IL-2Ras) are used increasingly for induction therapy. We conducted a systematic review of randomized trials assessing IL-2Ras....

  5. A minimum attention control center for nuclear power plants

    International Nuclear Information System (INIS)

    Control Centers for Nuclear Power Plants have characteristically been designed for maximum attention by the operating staffs of these plants. Consequently, the monitoring, control and diagnostics oriented cognitive activities by these staffs, were mostly ''data-driven'' in nature. This paper addresses a control center concept, under development by Combustion Engineering, that promotes a more ''information-driven'' cognitive interaction process between the operator and the plant. The more ''intelligent'' and therefore less attentive nature of such interactive process utilizes computer implemented cognitive engineered algorithms. The underlying structure of these algorithms is based upon the Critical Function/Success Path monitoring principle. The paper highlights a typical implementation of the minimum attention concept for the handling of unfamiliar safety related events. (author)

  6. The Apolipoprotein E Antagonistic Pleiotropy Hypothesis: Review and Recommendations

    OpenAIRE

    Tuminello, Elizabeth R.; S Duke Han

    2011-01-01

    Research on apolipoprotein E (APOE) has consistently revealed a relationship between the gene's ε 4 allele and risk for development of Alzheimer's disease (AD). However, research with younger populations of ε 4 carriers has suggested that the APOE ε 4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an e...

  7. Bradykinin antagonists modified with dipeptide mimetic beta-turn inducers.

    Science.gov (United States)

    Alcaro, Maria C; Vinci, Valerio; D'Ursi, Anna M; Scrima, Mario; Chelli, Mario; Giuliani, Sandro; Meini, Stefania; Di Giacomo, Marcello; Colombo, Lino; Papini, Anna Maria

    2006-05-01

    Bradykinin (BK) is involved in a wide variety of pathophysiological processes. Potent BK peptide antagonists can be developed introducing constrained unnatural amino acids, necessary to force the secondary structure of the molecule. In this paper, we report a structure-activity relationship study of two peptide analogues of the potent B2 antagonist HOE 140 by replacing the D-Tic-Oic dipeptide with conformationally constrained dipeptide mimetic beta-turn inducers. PMID:16504505

  8. Identification of M-CSF agonists and antagonists

    Science.gov (United States)

    Pandit, Jayvardhan; Jancarik, Jarmila; Kim, Sung-Hou; Koths, Kirston; Halenbeck, Robert; Fear, Anna Lisa; Taylor, Eric; Yamamoto, Ralph; Bohm, Andrew

    2000-02-15

    The present invention is directed to methods for crystallizing macrophage colony stimulating factor. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.

  9. Nowcasting daily minimum air and grass temperature

    Science.gov (United States)

    Savage, M. J.

    2016-02-01

    Site-specific and accurate prediction of daily minimum air and grass temperatures, made available online several hours before their occurrence, would be of significant benefit to several economic sectors and for planning human activities. Site-specific and reasonably accurate nowcasts of daily minimum temperature several hours before its occurrence, using measured sub-hourly temperatures hours earlier in the morning as model inputs, was investigated. Various temperature models were tested for their ability to accurately nowcast daily minimum temperatures 2 or 4 h before sunrise. Temperature datasets used for the model nowcasts included sub-hourly grass and grass-surface (infrared) temperatures from one location in South Africa and air temperature from four subtropical sites varying in altitude (USA and South Africa) and from one site in central sub-Saharan Africa. Nowcast models used employed either exponential or square root functions to describe the rate of nighttime temperature decrease but inverted so as to determine the minimum temperature. The models were also applied in near real-time using an open web-based system to display the nowcasts. Extrapolation algorithms for the site-specific nowcasts were also implemented in a datalogger in an innovative and mathematically consistent manner. Comparison of model 1 (exponential) nowcasts vs measured daily minima air temperatures yielded root mean square errors (RMSEs) errors for grass minimum temperature and the 4-h nowcasts.

  10. Sun Safety

    Science.gov (United States)

    ... Links Buttons and Badges Stay Informed Cancer Home Sun Safety Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir The sun’s ultraviolet (UV) rays can damage your skin in ...

  11. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF)

    DEFF Research Database (Denmark)

    Pitt, Bertram; Anker, Stefan D; Böhm, Michael;

    2015-01-01

    AIMS: To investigate the safety and potential efficacy of the novel non-steroidal mineralocorticoid receptor antagonist finerenone in patients with worsening chronic heart failure and reduced left ventricular ejection fraction (HFrEF) and at high risk of hyperkalaemia and worsening renal...... with eplerenone. Other objectives are to assess the effects of finerenone on a composite clinical endpoint (death from any cause, cardiovascular hospitalizations, or emergency presentations for worsening chronic HF), and on changes in health-related quality of life from baseline. CONCLUSIONS: ARTS-HF is the first...... dysfunction. METHODS AND RESULTS: The MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF; NCT01807221) is a multicentre, randomized, double-blind, active-comparator-controlled, six-parallel-group, phase 2b dose-finding study. In total, 1060 patients with HFrEF and concomitant type...

  12. The new or non-vitamin K antagonist oral anticoagulants: what have we learned since their debut.

    Science.gov (United States)

    McMahon, Brandon J; Kwaan, Hau C

    2015-03-01

    One of the major advances in the management of thrombosis is arguably the introduction of the new non-vitamin K antagonist oral anticoagulants (NOACs). These are small molecules, designed to directly inhibit specific steps in the coagulation pathway, with dabigatran (Pradaxa), inhibiting thrombin and rivaroxaban (Xarelto), apixiban (Eliquis), edoxaban (Lixiana), and betrixaban being factor Xa inhibitors. They have several advantages over vitamin K antagonists such as warfarin, with more predictable bioavailability, fewer drug interactions, and improved safety, especially intracranial hemorrhage. Yet, since their debut, several issues have arisen with their increasing usage, with concerns over monitoring and reversal, being predominant. Issues addressed in this article include their efficacy, bleeding risk, and the recognition of a vulnerable population where monitoring is needed. The current approach to reversing the drug action is updated. The change in the approach to future drug design is also discussed. PMID:25682082

  13. Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial

    DEFF Research Database (Denmark)

    Bousser, M.G.; Bouthier, J.; Buller, H.R.;

    2008-01-01

    BACKGROUND: Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim...... of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists. METHODS: Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2.5 mg weekly) or adjusted-dose vitamin K...... to treat; the non-inferiority hazard ratio was set at 1.5. This trial is registered with ClinicalTrials.gov, number NCT00070655. FINDINGS: The trial was stopped after randomisation of 4576 patients (2283 to receive idraparinux, 2293 to receive vitamin K antagonists) and a mean follow-up period of 10.7 (SD...

  14. Safety first!

    CERN Document Server

    2016-01-01

    Among the many duties I assumed at the beginning of the year was the ultimate responsibility for Safety at CERN: the responsibility for the physical safety of the personnel, the responsibility for the safe operation of the facilities, and the responsibility to ensure that CERN acts in accordance with the highest standards of radiation and environmental protection.   The Safety Policy document drawn up in September 2014 is an excellent basis for the implementation of Safety in all areas of CERN’s work. I am happy to commit during my mandate to help meet its objectives, not least by ensuring the Organization makes available the necessary means to achieve its Safety objectives. One of the main objectives of the HSE (Occupational Health and Safety and Environmental Protection) unit in the coming months is to enhance the measures to minimise CERN’s impact on the environment. I believe CERN should become a role model for an environmentally-aware scientific research laboratory. Risk ...

  15. Deep solar minimum and global climate changes

    Directory of Open Access Journals (Sweden)

    Ahmed A. Hady

    2013-05-01

    Full Text Available This paper examines the deep minimum of solar cycle 23 and its potential impact on climate change. In addition, a source region of the solar winds at solar activity minimum, especially in the solar cycle 23, the deepest during the last 500 years, has been studied. Solar activities have had notable effect on palaeoclimatic changes. Contemporary solar activity are so weak and hence expected to cause global cooling. Prevalent global warming, caused by building-up of green-house gases in the troposphere, seems to exceed this solar effect. This paper discusses this issue.

  16. Minimum quality standards and non-compliance

    OpenAIRE

    Voßwinkel, Jan; Birg, Laura

    2015-01-01

    This paper studies the effect of non-compliance with a minimum quality standard on prices, quality, and welfare in a vertical differentiation model. Non-compliance with a minimum quality standard by a low-quality firm reduces quality levels of both firms, increases the price for the high-quality product, decreases the price for the low-quality product, and shifts demand from the low-quality to the high-quality firm. Under non-compliance, an increase in the standard increases the quality diffe...

  17. Entrepreneurship and Compliance With Minimum Wage Law

    OpenAIRE

    Jellal, Mohamed

    2009-01-01

    In this paper, we introduce firm heterogeneity in the context of a model of non-compliance with minimum wage legislation. The introduction of heterogeneity in the ease with which firms can be monitored for non compliance allows us to show that non-compliance will persist in sectors which are relatively difficult to monitor, despite the government implementing non –stochastic monitoring. Moreover, we show that the incentive not to comply is an increasing function of the level of the minimum wa...

  18. Minimum Wage Incidence: The Case for Germany

    OpenAIRE

    Knabe, Andreas; Schöb, Ronnie

    2008-01-01

    Using data from the 2006 wave of the German Socio-Economic Panel (GSOEP), this paper analyzes how a minimum wage affects employment, wage inequality, public expenditures, and aggregate income in the low-wage sector. It is shown that a statutory minimum wage of EUR 7.50 per hour would cost 840,000 low-paid jobs and increases the fiscal burden by aboutEUR 4 billion per year, while household income rises only by EUR 1.1 billion per year. Poor households, i.e. those eligible for Unemployment Bene...

  19. A Minimum-Mass Extrasolar Nebula

    CERN Document Server

    Kuchner, M J

    2004-01-01

    By analogy with the minimum-mass solar nebula, we construct a surface-density profile using the orbits of the 26 precise-Doppler planets found in multiple planet systems: Sigma = 2200 grams per square centimeter (a/1 AU)^- beta, where a is the circumstellar radius, and beta = 2.0 plus or minus 0.5. The minimum-mass solar nebula (beta = 1.5) is consistent with this model, but the uniform-alpha accretion disk model (beta ~ 1) is not. In a nebula with beta > 2, the center of the disk is the likely cradle of planet formation.

  20. Deep solar minimum and global climate changes

    OpenAIRE

    Ahmed A. Hady

    2013-01-01

    This paper examines the deep minimum of solar cycle 23 and its potential impact on climate change. In addition, a source region of the solar winds at solar activity minimum, especially in the solar cycle 23, the deepest during the last 500 years, has been studied. Solar activities have had notable effect on palaeoclimatic changes. Contemporary solar activity are so weak and hence expected to cause global cooling. Prevalent global warming, caused by building-up of green-house gases in the trop...

  1. A Minimum-Mass Extrasolar Nebula

    OpenAIRE

    Kuchner, Marc J.

    2004-01-01

    By analogy with the minimum-mass solar nebula, we construct a surface-density profile using the orbits of the 26 precise-Doppler planets found in multiple planet systems: Sigma = 2200 grams per square centimeter (a/1 AU)^- beta, where a is the circumstellar radius, and beta = 2.0 plus or minus 0.5. The minimum-mass solar nebula is consistent with this model, but the uniform-alpha accretion disk model is not. In a nebula with beta > 2, the center of the disk is the likely cradle of planet form...

  2. Deep solar minimum and global climate changes.

    Science.gov (United States)

    Hady, Ahmed A

    2013-05-01

    This paper examines the deep minimum of solar cycle 23 and its potential impact on climate change. In addition, a source region of the solar winds at solar activity minimum, especially in the solar cycle 23, the deepest during the last 500 years, has been studied. Solar activities have had notable effect on palaeoclimatic changes. Contemporary solar activity are so weak and hence expected to cause global cooling. Prevalent global warming, caused by building-up of green-house gases in the troposphere, seems to exceed this solar effect. This paper discusses this issue. PMID:25685420

  3. Minimum wage in the Czech Republic and European Union

    OpenAIRE

    Šmíd, Marek

    2010-01-01

    The Master's thesis deals with analysis of the minimum wage in the Czech Republic and European Union. The first three chapters describe the function and development of the minimum wage, as well as the theoretical approaches of the minimum wage. Furthermore the arguments for and against the minimum wage are summarized. In the practical part the development of the minimum wage in the Czech Republic from 1991 is analyzed and the minimum wage across the EU countries is compared. The last analysis...

  4. Minimum short-circuit ratios for grid interconnection of wind farms with induction generators

    Energy Technology Data Exchange (ETDEWEB)

    Reginatto, Romeu; Rocha, Carlos [Western Parana State University (UNIOESTE), Foz do Iguacu, PR (Brazil). Center for Engineering and Exact Sciences], Emails: romeu@unioeste.br, croberto@unioeste.br

    2009-07-01

    This paper concerns the problem of determining the minimum value for the short-circuit ratio which is adequate for the interconnection of a given wind farms to a given grid point. First, a set of 3 criteria is defined in order to characterize the quality/safety of the interconnection: acceptable terminal voltage variations, a minimum active power margin, and an acceptable range for the internal voltage angle. Then, the minimum short circuit ratio requirement is determined for 6 different induction generator based wind turbines, both fixed-speed (with and without reactive power compensation) and variable-speed (with the following control policies: reactive power, power factor, and terminal voltage regulation). The minimum short-circuit ratio is determined and shown in graphical results for the 6 wind turbines considered, for X/R in the range 0-15, also analyzing the effect of more/less stringent tolerances for the interconnection criteria. It is observed that the tighter the tolerances the larger the minimum short-circuit ratio required. For the same tolerances in the interconnection criteria, a comparison of the minimum short circuit ratio required for the interconnection of both squirrel-cage and doubly-fed induction generators is presented, showing that the last requires much smaller values for the short-circuit ratio. (author)

  5. Minimum training requirement in ultrasound imaging of peripheral arterial disease

    DEFF Research Database (Denmark)

    Eiberg, J P; Hansen, M A; Grønvall Rasmussen, J B;

    2008-01-01

    To demonstrate the minimum training requirement when performing ultrasound of peripheral arterial disease.......To demonstrate the minimum training requirement when performing ultrasound of peripheral arterial disease....

  6. SAFETY INSTRUCTION AND SAFETY NOTE

    CERN Multimedia

    TIS Secretariat

    2002-01-01

    Please note that the SAFETY INSTRUCTION N0 49 (IS 49) and the SAFETY NOTE N0 28 (NS 28) entitled respectively 'AVOIDING CHEMICAL POLLUTION OF WATER' and 'CERN EXHIBITIONS - FIRE PRECAUTIONS' are available on the web at the following urls: http://edms.cern.ch/document/335814 and http://edms.cern.ch/document/335861 Paper copies can also be obtained from the TIS Divisional Secretariat, email: TIS.Secretariat@cern.ch

  7. Evaluation of the abuse potential of AM281, a new synthetic cannabinoid CB1 receptor antagonist.

    Science.gov (United States)

    Botanas, Chrislean Jun; de la Peña, June Bryan; Dela Pena, Irene Joy; Tampus, Reinholdgher; Kim, Hee Jin; Yoon, Seong Shoon; Seo, Joung-Wook; Jeong, Eun Ju; Cheong, Jae Hoon

    2015-11-01

    AM281 (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide) is a new synthetic cannabinoid CB1 receptor antagonist. Similar to other cannabinoid antagonists, AM281 has been suggested to have therapeutic indications. However, recent reports have suggested that cannabinoid CB1 receptor antagonists may share similar behavioral effects with other drugs of abuse such as cocaine and amphetamine. These reports cast doubts on the safety profile of AM281. Thus, in the present study we evaluated the abuse potential (rewarding and reinforcing effects) of AM281 through two of the most widely used animal models for assessing the abuse potential of drugs: the conditioned place preference (CPP) and self-administration (SA) tests. Experiments were performed in Sprague-Dawley rats in various dosages [CPP (0.1, 0.5 or 2.5mg/kg), SA (0.005, 0.025 or 0.1mg/kg/infusion)]. We also delved into the consequences of repeated drug exposure on the subsequent response to the drug. Thus, parallel experiments were carried out in rats pretreated with AM281 for 7 or 14 days. Our findings indicated that AM281, at any dose, did not induce CPP and SA in drug-naïve rats. Interestingly, significant CPP (0.5mg/kg of AM281), but not SA, was observed in 14 days pretreated rats. These observations suggest that AM281 per se has no or minimal rewarding and reinforcing properties, but alterations in neuronal functions and behavior due to repeated AM281 exposure may contribute in part to the abuse potential of this drug. In view of this finding, we advocate the careful use, monitoring, and dispensation of AM281.

  8. Novel class of medications, orexin receptor antagonists, in the treatment of insomnia - critical appraisal of suvorexant.

    Science.gov (United States)

    Norman, Jessica L; Anderson, Sarah L

    2016-01-01

    Insomnia, a highly prevalent disorder, can be detrimental to patients' overall health and worsen existing comorbidities. Patients may have acute episodes of insomnia related to a traumatic event, but more commonly insomnia occurs chronically. While proper sleep hygiene and behavioral therapy play important roles in the nonpharmacologic management of short-term and chronic insomnia, medications may also be required. Historically, insomnia has been treated with agents such as benzodiazepines, nonbenzodiazepine receptor agonists, and melatonin agonists. Dual orexin receptor antagonists represent a new class of medications for the treatment of insomnia, which block the binding of wakefulness-promoting neuropeptides orexin A and orexin B to their respective receptor sites. Suvorexant (Belsomra) is the first dual orexin receptor antagonist to be approved in the US and Japan and has demonstrated efficacy in decreasing time to sleep onset and increasing total sleep time. Its unique mechanism of action, data to support efficacy and safety over 12 months of use, and relative lack of withdrawal effects when discontinued may represent an alternative for patients with chronic insomnia who cannot tolerate or do not receive benefit from more traditional sleep agents. Suvorexant is effective and well tolerated, but precautions exist for certain patient populations, including females, obese patients, and those with respiratory disease. Suvorexant has only been studied vs placebo, and hence it is unknown how it directly compares with other medications approved by the US Food and Drug Administration for insomnia. Suvorexant is not likely to replace benzodiazepines or nonbenzodiazepine receptor antagonists as a first-line sleep agent but does represent a novel option for the treatment of patients with chronic insomnia. PMID:27471419

  9. System safety education focused on flight safety

    Science.gov (United States)

    Holt, E.

    1971-01-01

    The measures necessary for achieving higher levels of system safety are analyzed with an eye toward maintaining the combat capability of the Air Force. Several education courses were provided for personnel involved in safety management. Data include: (1) Flight Safety Officer Course, (2) Advanced Safety Program Management, (3) Fundamentals of System Safety, and (4) Quantitative Methods of Safety Analysis.

  10. A Minimum Relative Entropy Principle for AGI

    NARCIS (Netherlands)

    Ven, Antoine van de; Schouten, Ben

    2010-01-01

    In this paper the principle of minimum relative entropy (PMRE) is proposed as a fundamental principle and idea that can be used in the field of AGI. It is shown to have a very strong mathematical foundation, that it is even more fundamental then Bayes rule or MaxEnt alone and that it can be related

  11. Minimum Description Length Shape and Appearance Models

    DEFF Research Database (Denmark)

    Thodberg, Hans Henrik

    2003-01-01

    The Minimum Description Length (MDL) approach to shape modelling is reviewed. It solves the point correspondence problem of selecting points on shapes defined as curves so that the points correspond across a data set. An efficient numerical implementation is presented and made available as open s...

  12. Approximating the Balanced Minimum Evolution Problem

    CERN Document Server

    Fiorini, Samuel

    2011-01-01

    We prove a strong inapproximability result for the Balanced Minimum Evolution Problem. Our proof also implies that the problem remains NP-hard even when restricted to metric instances. Furthermore, we give a MST-based 2-approximation algorithm for the problem for such instances.

  13. Minimum impact house prototype for sustainable building

    NARCIS (Netherlands)

    Drexler, H.; Jauslin, D.

    2010-01-01

    The Minihouse is a prototupe for a sustainable townhouse. On a site of only 29 sqm it offers 154 sqm of urban life. The project 'Minimum Impact House' adresses two important questions: How do we provide living space in the cities without distroying the landscape? How to improve sustainably the ecolo

  14. The minimum state of dwarf novae

    International Nuclear Information System (INIS)

    Infrared photometry with the Kitt Peak National Observatory (KPNO) 50 inch (1.3 m) telescope, simultaneous photometry in u, b, v, and r with the KPNO 36 inch (91 cm) and 16 inch (41 cm) telescopes, and standard UBVr photometry and scanner measurements of the Balmer lines with the Manastash Ridge Observatory (MRO) 30 inch (76 cm) telescope were obtained for five dwarf novae (SS Cyg, Rx And, Z Cam, AH Her, and AB Dra). The observed magnitudes were converted to fluxes and the flux distribution over wavelength at minimum light was studied. Comparison of the observed distributions with that expected from free-free emission with various temperature hot spots and with different types of secondary stars yields the contribution of spot and secondary for each system. Assuming a size and distance enables the determination of the density of the spot (about 10/sup 15/ cm/sup -3/). Rough analysis of the Balmer decrement shows that the lines are optically thick at minimum.The differences among the systems are discussed in terms of the period between maxima. The systems with the shortest period (Z Cam types) have the hottest spots so that the secondary is unimportant at minimum.The flickering of Z Cam at minimum is explained in terms of a temperature change in the spot which could be caused by density clumps in the stream

  15. Statistical inference of Minimum Rank Factor Analysis

    NARCIS (Netherlands)

    Shapiro, A; Ten Berge, JMF

    2002-01-01

    For any given number of factors, Minimum Rank Factor Analysis yields optimal communalities for an observed covariance matrix in the sense that the unexplained common variance with that number of factors is minimized, subject to the constraint that both the diagonal matrix of unique variances and the

  16. 7 CFR 35.13 - Minimum quantity.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Minimum quantity. 35.13 Section 35.13 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT...

  17. 7 CFR 33.10 - Minimum requirements.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... ISSUED UNDER AUTHORITY OF THE EXPORT APPLE ACT Regulations § 33.10 Minimum requirements. No person shall... Early: Provided, That apples for export to Pacific ports of Russia shall grade at least U.S. Utility...

  18. The periodicity of Grand Solar Minimum

    Science.gov (United States)

    Velasco Herrera, Victor Manuel

    2016-07-01

    The sunspot number is the most used index to quantify the solar activity. Nevertheless, the sunspot is a syn- thetic index and not a physical index. Therefore, we should be careful to use the sunspot number to quantify the low (high) solar activity. One of the major problems of using sunspot to quantify solar activity is that its minimum value is zero. This zero value hinders the reconstruction of the solar cycle during the Maunder minimum. All solar indexes can be used as analog signals, which can be easily converted into digital signals. In con- trast, the conversion of a digital signal into an analog signal is not in general a simple task. The sunspot number during the Maunder minimum can be studied as a digital signal of the solar activity In 1894, Maunder published a discovery that has maintained the Solar Physics in an impasse. In his fa- mous work on "A Prolonged Sunspot Minimum" Maunder wrote: "The sequence of maximum and minimum has, in fact, been unfailing during the present century [..] and yet there [..], the ordinary solar cycle was once interrupted, and one long period of almost unbroken quiescence prevailed". The search of new historical Grand solar minima has been one of the most important questions in Solar Physics. However, the possibility of estimating a new Grand solar minimum is even more valuable. Since solar activity is the result of electromagnetic processes; we propose to employ the power to quantify solar activity: this is a fundamental physics concept in electrodynamics. Total Solar Irradiance is the primary energy source of the Earth's climate system and therefore its variations can contribute to natural climate change. In this work, we propose to consider the fluctuations in the power of the Total Solar Irradiance as a physical measure of the energy released by the solar dynamo, which contributes to understanding the nature of "profound solar magnetic field in calm". Using a new reconstruction of the Total Solar Irradiance we found the

  19. What causes geomagnetic activity during sunspot minimum?

    Science.gov (United States)

    Kirov, B.; Asenovski, S.; Georgieva, K.; Obridko, V. N.

    2015-12-01

    It is well known that the main drivers of geomagnetic disturbances are coronal mass ejections whose number and intensity are maximum in sunspot maximum, and high speed solar wind streams from low latitude solar coronal holes which maximize during sunspot declining phase. But even during sunspot minimum periods when there are no coronal mass ejections and no low latitude solar coronal holes, there is some "floor" below which geomagnetic activity never falls. Moreover, this floor changes from cycle to cycle. Here we analyze the factors determining geomagnetic activity during sunspot minimum. It is generally accepted that the main factor is the thickness of the heliospheric current sheet on which the portion of time depends which the Earth spends in the slow and dense heliospheric current sheet compared to the portion of time it spends in the fast solar wind from superradially expanding polar coronal holes. We find, however, that though the time with fast solar wind has been increasing in the last four sunspot minima, the geomagnetic activity in minima has been decreasing. The reason is that the parameters of the fast solar wind from solar coronal holes change from minimum to minimum, and the most important parameter for the fast solar wind's geoeffectivity—its dynamic pressure—has been decreasing since cycle 21. Additionally, we find that the parameters of the slow solar wind from the heliospheric current sheet which is an important driver of geomagnetic activity in sunspot minimum also change from cycle to cycle, and its magnetic field, velocity and dynamic pressure have been decreasing during the last four minima.

  20. [Cathepsin K antagonists: preclinical and clinical data].

    Science.gov (United States)

    Gamsjäger, Marion; Resch, Heinrich

    2015-02-01

    Cathepsin K, a cysteine protease, is an essential enzyme in degradation of collagen type I. Since cathepsin K is relatively specific to osteoclasts, it represents a promising candidate for drug development. In the past decades, efforts have been made in developing highly potent, selective and orally applicable cathepsin K inhibitors. In contrast to balicatib and relacatib, whose drug development programmes were stopped due to cutaneous side-effects related to limited drug specificity, the more specific cathepsin K inhibitors odanacatib (ODN) and ONO-5334 have entered clinical trials. Odanacatib progressively increases bone mineral density (BMD) and decreases bone resorption markers in postmenopausal women with low BMD. Its clinical efficacy and safety was confirmed by several clinical studies but indicates that odanacatib is characterized by a resolution-of-effect with increases in bone resorption and rapid decreases in BMD following treatment discontinuation. A phase III fracture prevention study in postmenopausal women with osteoporosis is currently in the final phase. PMID:25572547

  1. Non-vitamin K antagonist oral anticoagulants for the prevention of recurrent venous thromboembolism.

    Science.gov (United States)

    Bauersachs, Rupert

    2016-08-01

    Venous thromboembolism (VTE) is associated with a risk of recurrence that depends on factors specific to index event and patient. A first unprovoked VTE increases the risk of a recurrent event, particularly during the first year after anticoagulation cessation. Determining a strategy for the long-term prevention of recurrent VTE poses challenges that stem from a lack of agreement on recommended therapy duration and varying treatment burden for the patient. Oral anticoagulants, including vitamin K antagonists and non-vitamin K antagonist oral anticoagulants (NOACs), are the main treatment options for the long-term prevention of recurrent VTE. However, the risk of VTE recurrence must be balanced against the risk of bleeding in each patient. Phase III clinical trials have evaluated rivaroxaban, apixaban and dabigatran for extended treatment and prevention of VTE versus placebo, and versus warfarin in the case of dabigatran. Compared with placebo treatment, each NOAC showed superior efficacy together with an acceptable safety profile during extended treatment periods of 6-18months. Patients receiving long-term NOAC therapy will still require regular risk factor assessment, but these agents may permit longer treatment duration with an improved benefit-risk profile. PMID:27263046

  2. Operational safety

    International Nuclear Information System (INIS)

    The PNL Safety, Standards and Compliance Program contributed to the development and issuance of safety policies, standards, and criteria; for projects in the nuclear and nonnuclear areas. During 1976 the major emphasis was on developing criteria, instruments and methods to assure that radiation exposure to occupational personnel and to people in the environs of nuclear-related facilities is maintained at the lowest level technically and economically practicable. Progress in 1976 is reported on the preparation of guidelines for radiation exposure; Pu dosimetry studies; the preparation of an environmental monitoring handbook; and emergency instrumentation preparedness

  3. Minimum secure speed of fully mechanized coal face based on critical temperature of coal spontaneous combustion

    Institute of Scientific and Technical Information of China (English)

    Wei LIU; Yue-Ping QIN; Yong-Jiang HAO; Tian-Zhu GUI; Jing-Yan JIA

    2013-01-01

    The critical temperature theory of spontaneous combustion of coal and the numerical simulation method are used to explore the minimum secure speed of fully mechanized coal face to prevent the spontaneous combustion in goaf.Combined with the actual situation of workface 31005 in a coal mine,the highest temperatures in goaf at different advancing speeds were obtained by the numerical simulation of spontaneous combustion in goaf,and then a power function equation between the highest temperature and the advancing speed was achieved by regression analysis.The advancing speed corresponding to the critical temperature value was taken as the minimum safe speed of workface based on the equation.Finally,the accuracy and reliability of the speed were verified by the actual advancing process of workface 31005.The results of this research show that the new judgment method of the minimum safety speed has a higher value to be applied in the field.

  4. Automatic adjustment of the minimum wage: Linking the minimum wage to productivity

    OpenAIRE

    Oren M. Levin-Waldman

    1998-01-01

    The fact that every change in the minimum wage requires an act of Congress means that debate over the wisdom of having a minimum is repeatedly returned to the political arena. As inflation continues to erode the value of the minimum wage, each legislative delay means that a larger increase is required. The larger the increase, the more resistance to its passage, so that by the time Congress acts, the political compromise is an increase that is too little and too late to be of much help in lif...

  5. Pharmacovigilance in India, Uganda and South Africa with reference to WHO’s minimum requirements

    OpenAIRE

    Karen Maigetter; Pollock, Allyson M; Abhay Kadam; Kim Ward; Weiss, Mitchell G.

    2015-01-01

    Background Pharmacovigilance (PV) data are crucial for ensuring safety and effectiveness of medicines after drugs have been granted marketing approval. This paper describes the PV systems of India, Uganda and South Africa based on literature and Key Informant (KI) interviews and compares them with the World Health Organization’s (WHO’s) minimum PV requirements for a Functional National PV System.   Methods A documentary analysis of academic literature and policy r...

  6. The temperature minimum at tidal fronts

    Directory of Open Access Journals (Sweden)

    D. G. Bowers

    Full Text Available This paper presents a mechanism to explain the observed formation of a surface temperature minimum at tidal fronts in shelf seas. Tidal fronts mark the boundary between water which is kept vertically mixed by fast tidal currents and water which stratifies in summer. The fronts are associated with strong horizontal surface gradients of several water properties, including temperature. In the early studies of tidal fronts, a minimum in surface temperature was occasionally observed between the cool surface waters on the mixed side of the front and the warm surface waters on the stratified side. It was suggested that this was caused by upwelling of deep water at the front. In this paper we describe an alternative and simpler explanation based on the local balance of heating and stirring. The net heat flux into the sea in spring and early summer is greater on the mixed side of the front than on the stratified side. This happens because the heat loss mechanism is dependent on sea surface temperature and stratified waters, having a higher surface temperature, lose more heat. The stratified water near the front therefore has lower heat content (and lower depth-mean temperature than the mixed water. If some of the stratified water becomes mixed, for example with increased tidal stirring at spring tides, a zone of minimum surface temperature will be formed at the front. A numerical model for the study of this mechanism shows that the temperature minimum at tidal fronts can be explained by the process described above. The minimum appears most clearly at spring tides, but can still be present in a weaker form at neap tides. A further prediction of the model is an increase of the horizontal temperature gradient at spring tides, which is in agreement with observations. An unexpected outcome of the modelling is the prediction of the formation of a marked sea surface temperature minimum, not yet observed, occurring in the autumn and located at the summer

  7. SAFETY BULLETIN

    CERN Multimedia

    TIS Secretariat

    2002-01-01

    Please note that the Safety Bulletin no 4 (TIS 2002-04) entitled 'KNOW THE RISKS' is available on the web. Paper copies can also be obtained from the TIS Divisional Secretariat, e-mail: TIS.Secretariat@cern.ch TIS Secretariat

  8. 14 CFR 25.149 - Minimum control speed.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Minimum control speed. 25.149 Section 25... Minimum control speed. (a) In establishing the minimum control speeds required by this section, the method... prevent a heading change of more than 20 degrees. (e) VMCG, the minimum control speed on the ground,...

  9. 12 CFR 3.6 - Minimum capital ratios.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Minimum capital ratios. 3.6 Section 3.6 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MINIMUM CAPITAL RATIOS; ISSUANCE OF DIRECTIVES Minimum Capital Ratios § 3.6 Minimum capital ratios. (a) Risk-based capital ratio....

  10. Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients

    DEFF Research Database (Denmark)

    Kerstjens, Huib A; Bjermer, Leif; Eriksson, Leif;

    2010-01-01

    OBJECTIVE: This study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD. METHODS: This double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300mug or placebo twice daily via Turbuhaler......((R)) for 4 weeks. Safety, lung function, functional capacity and health status measures were measured. Plasma concentrations of AZD4818 were measured after the first dose and after 2 and 4 weeks' treatment. RESULTS: Sixty-five patients (47 male; median age 65.6 years) received AZD4818 (n=33) or placebo (n=32...

  11. The Apolipoprotein E Antagonistic Pleiotropy Hypothesis: Review and Recommendations

    Directory of Open Access Journals (Sweden)

    Elizabeth R. Tuminello

    2011-01-01

    Full Text Available Research on apolipoprotein E (APOE has consistently revealed a relationship between the gene's ε4 allele and risk for development of Alzheimer's disease (AD. However, research with younger populations of ε4 carriers has suggested that the APOE ε4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an evolutionary biology concept that proposes certain genes or alleles that may differentially impact fitness during different life stages. We critically review this hypothesis in light of new research of the impact of APOE on cognition and neural integrity across the lifespan. We provide recommendations for the revision of the antagonistic pleiotropy hypothesis of APOE and suggest important avenues for future research in this area.

  12. ANTAGONISTIC BACTERIA AGAINST SCHIZOPHYLLUM COMMUNE FR. IN PENINSULAR MALAYSIA

    Directory of Open Access Journals (Sweden)

    ANTARJO DIKIN

    2006-01-01

    Full Text Available Schizophyllum commune Fr., is one of the important fungi, causes brown germ and seed rot of oil palm. Biodiversity of antagonistic bacteria from oil palm plantations in Peninsular Malaysia is expected to support in development of biopesticide. Isolation with liquid assay and screening antagonistic bacteria using dual culture assay were carried out in the bioexploration. A total of 265 bacterial isolates from plant parts of oil palm screened 52 antagonistic bacterial isolates against 5. commune. Bacterial isolates were identified by using Biolog* Identification System i.e. Bacillus macroccanus, B. thermoglucosidasius, Burkholderia cepacia, B. gladioli, B. multivorans, B pyrrocinia, B. spinosa, Corynebacterium agropyri, C. misitidis, Enterobacter aerogenes, Microbacterium testaceum, Pseudomonas aeruginosa, P. citronellolis, Rhodococcus rhodochrous, Serratia ficaria, Serratia sp., S. marcescens, Staphylococcus sciuri, Sternotrophomonas maltophilia.

  13. First Irish birth following IVF therapy using antagonist protocol.

    LENUS (Irish Health Repository)

    Mocanu, E V

    2012-02-01

    BACKGROUND: During in vitro fertilization (IVF), the prevention of a premature LH surge was traditionally achieved using a gonadotrophin releasing hormone agonist (GnRH-a), and more recently, a GnRH antagonist. AIMS: We report a case of a 37 year old treated using the GnRH antagonist in a second completed cycle of IVF. METHODS: IVF was performed for primary infertility of 5-year duration due to frozen pelvis secondary to endometriosis. RESULTS: Following controlled ovarian hyperstimulation, oocyte recovery and fertilization, cleavage and transfer of two zygotes, a pregnancy established. A twin gestation was diagnosed at 7-weeks scan and pregnancy ended with the delivery of twin girls by emergency caesarean section. CONCLUSION: This is a first report of a delivery following IVF using the antagonist protocol in Ireland. Such therapy is patient friendly and its use should be introduced on a larger scale in clinical practice.

  14. Long-term safety of pegvisomant in patients with acromegaly: Comprehensive review of 1288 subjects in ACROSTUDY

    NARCIS (Netherlands)

    A-J. van der Lely (Aart-Jan); B.M.K. Biller; T. Brue (Thierry); M. Buchfelder; E. Ghigo (Ezio); R. Gomez (Roy); J. Hey-Hadavi (Judith); F. Lundgren (Frida); N. Rajicic; C.J. Strasburger; S.M. Webb (Susan); M. Kołtowska-Häggström (Maria)

    2012-01-01

    textabstractContext: Pegvisomant is a GH receptor antagonist. The ACROSTUDY is a global safety surveillance study of long-term treatment of acromegaly with pegvisomant. Objective: The objective of the study was to monitor long-term safety and treatment outcomes. Design: ACROSTUDY is open to all pati

  15. Bistable dielectric elastomer minimum energy structures

    Science.gov (United States)

    Zhao, Jianwen; Wang, Shu; McCoul, David; Xing, Zhiguang; Huang, Bo; Liu, Liwu; Leng, Jinsong

    2016-07-01

    Dielectric elastomer minimum energy structures (DEMES) can realize large angular deformations by small voltage-induced strains, which make them an attractive candidate for use as soft actuators. If the task only needs binary action, the bistable structure will be an efficient solution and can save energy because it requires only a very short duration of voltage to switch its state. To obtain bistable DEMES, a method to realize the two stable states of traditional DEMES is provided in this paper. Based on this, a type of symmetrical bistable DEMES is proposed, and the required actuation pulse duration is shorter than 0.1 s. When a suitable mass is attached to end of the DEMES, or two layers of dielectric elastomer are affixed to both sides of the primary frame, the DEMES can realize two stable states and can be switched by a suitable pulse duration. To calculate the required minimum pulse duration, a mathematical model is provided and validated by experiment.

  16. Minimum and terminal velocities in projectile motion

    CERN Document Server

    Miranda, E N; Riba, R

    2012-01-01

    The motion of a projectile with horizontal initial velocity V0, moving under the action of the gravitational field and a drag force is studied analytically. As it is well known, the projectile reaches a terminal velocity Vterm. There is a curious result concerning the minimum speed Vmin; it turns out that the minimum velocity is lower than the terminal one if V0 > Vterm and is lower than the initial one if V0 < Vterm. These results show that the velocity is not a monotonous function. If the initial speed is not horizontal, there is an angle range where the velocity shows the same behavior mentioned previously. Out of that range, the volocity is a monotonous function. These results come out from numerical simulations.

  17. On finding minimum-diameter clique trees

    Energy Technology Data Exchange (ETDEWEB)

    Blair, J.R.S. (Tennessee Univ., Knoxville, TN (United States). Dept. of Computer Science); Peyton, B.W. (Oak Ridge National Lab., TN (United States))

    1991-08-01

    It is well-known that any chordal graph can be represented as a clique tree (acyclic hypergraph, join tree). Since some chordal graphs have many distinct clique tree representations, it is interesting to consider which one is most desirable under various circumstances. A clique tree of minimum diameter (or height) is sometimes a natural candidate when choosing clique trees to be processed in a parallel computing environment. This paper introduces a linear time algorithm for computing a minimum-diameter clique tree. The new algorithm is an analogue of the natural greedy algorithm for rooting an ordinary tree in order to minimize its height. It has potential application in the development of parallel algorithms for both knowledge-based systems and the solution of sparse linear systems of equations. 31 refs., 7 figs.

  18. DETERMINING MINIMUM HIKING TIME USING DEM

    Directory of Open Access Journals (Sweden)

    ZSOLT MAGYARI-SÁSKA

    2012-11-01

    Full Text Available Determining minimum hiking time using DEM. Minimum hiking time calculus can be used to assess the maximum area where a lost person can be. Such area delimitation can help rescue teams to efficiently organize their missions. The two well known walking time rules was used to determine, compare and correlate the obtained result in a test area. The calculated times has a high correlation coefficient which makes possible a precise conversion between Naismith and Tobler walking times. For delimiting the rescue area a graph based modeling from a raster layer was implemented using R environment. The main challenge in such a modeling is the efficient memory management as the use of Dijkstra algorithm on directional costgraph requires high memory resources.

  19. Development and characterization of high affinity leptins and leptin antagonists.

    Science.gov (United States)

    Shpilman, Michal; Niv-Spector, Leonora; Katz, Meirav; Varol, Chen; Solomon, Gili; Ayalon-Soffer, Michal; Boder, Eric; Halpern, Zamir; Elinav, Eran; Gertler, Arieh

    2011-02-11

    Leptin is a pleiotropic hormone acting both centrally and peripherally. It participates in a variety of biological processes, including energy metabolism, reproduction, and modulation of the immune response. So far, structural elements affecting leptin binding to its receptor remain unknown. We employed random mutagenesis of leptin, followed by selection of high affinity mutants by yeast surface display and discovered that replacing residue Asp-23 with a non-negatively charged amino acid leads to dramatically enhanced affinity of leptin for its soluble receptor. Rational mutagenesis of Asp-23 revealed the D23L substitution to be most effective. Coupling the Asp-23 mutation with alanine mutagenesis of three amino acids (L39A/D40A/F41A) previously reported to convert leptin into antagonist resulted in potent antagonistic activity. These novel superactive mouse and human leptin antagonists (D23L/L39A/D40A/F41A), termed SMLA and SHLA, respectively, exhibited over 60-fold increased binding to leptin receptor and 14-fold higher antagonistic activity in vitro relative to the L39A/D40A/F41A mutants. To prolong and enhance in vivo activity, SMLA and SHLA were monopegylated mainly at the N terminus. Administration of the pegylated SMLA to mice resulted in a remarkably rapid, significant, and reversible 27-fold more potent increase in body weight (as compared with pegylated mouse leptin antagonist), because of increased food consumption. Thus, recognition and mutagenesis of Asp-23 enabled construction of novel compounds that induce potent and reversible central and peripheral leptin deficiency. In addition to enhancing our understanding of leptin interactions with its receptor, these antagonists enable in vivo study of the role of leptin in metabolic and immune processes and hold potential for future therapeutic use in disease pathologies involving leptin.

  20. Development and Characterization of High Affinity Leptins and Leptin Antagonists*

    Science.gov (United States)

    Shpilman, Michal; Niv-Spector, Leonora; Katz, Meirav; Varol, Chen; Solomon, Gili; Ayalon-Soffer, Michal; Boder, Eric; Halpern, Zamir; Elinav, Eran; Gertler, Arieh

    2011-01-01

    Leptin is a pleiotropic hormone acting both centrally and peripherally. It participates in a variety of biological processes, including energy metabolism, reproduction, and modulation of the immune response. So far, structural elements affecting leptin binding to its receptor remain unknown. We employed random mutagenesis of leptin, followed by selection of high affinity mutants by yeast surface display and discovered that replacing residue Asp-23 with a non-negatively charged amino acid leads to dramatically enhanced affinity of leptin for its soluble receptor. Rational mutagenesis of Asp-23 revealed the D23L substitution to be most effective. Coupling the Asp-23 mutation with alanine mutagenesis of three amino acids (L39A/D40A/F41A) previously reported to convert leptin into antagonist resulted in potent antagonistic activity. These novel superactive mouse and human leptin antagonists (D23L/L39A/D40A/F41A), termed SMLA and SHLA, respectively, exhibited over 60-fold increased binding to leptin receptor and 14-fold higher antagonistic activity in vitro relative to the L39A/D40A/F41A mutants. To prolong and enhance in vivo activity, SMLA and SHLA were monopegylated mainly at the N terminus. Administration of the pegylated SMLA to mice resulted in a remarkably rapid, significant, and reversible 27-fold more potent increase in body weight (as compared with pegylated mouse leptin antagonist), because of increased food consumption. Thus, recognition and mutagenesis of Asp-23 enabled construction of novel compounds that induce potent and reversible central and peripheral leptin deficiency. In addition to enhancing our understanding of leptin interactions with its receptor, these antagonists enable in vivo study of the role of leptin in metabolic and immune processes and hold potential for future therapeutic use in disease pathologies involving leptin. PMID:21119198

  1. 10 April 2014: Safety Day at CERN

    CERN Multimedia

    Antonella Del Rosso

    2014-01-01

    A wide variety of chemicals is used every day in the different laboratories and workshops around CERN. Potentially toxic, corrosive, polluting or hazardous in other ways, these chemicals all have to be handled carefully, as we will be reminded by the Safety Day campaign to be held by the HSE Unit on 10 April to mark World Day for Safety and Health at Work.   The use of chemicals at CERN is regulated by "Safety Regulation SR-C, Chemical Agents", which defines the minimum health and safety protection requirements for people exposed to the potentially hazardous effects of dangerous chemicals. This regulation is complemented by other Safety guides. Regretfully, despite strict procedures and regular inspections, accidents caused by the improper use of chemicals do occur every year. "Unfortunately, each year we see a small number of accidents related to the handling of chemicals," confirms chemicals expert Jonathan Gulley, who is a member of the Prevention and Sa...

  2. Does 'insertion' work? France's minimum income"

    OpenAIRE

    Whitton, Timothy

    1993-01-01

    International audience France's Revenu Minimum d Insertion (RMI) received the approval of the French Parliament on 1st December1988, and came into effect shortly afterwardsi. In addition to a means test, the RMI is conditional upon signature of a contract (le contrat d'insertion) by which its recipients pledge themselves to take whatever action the RMI authorities recommend in order to re-insert themselves in main-stream society. Insertion is a difficult concept to translate into English. ...

  3. On the Smoothed Minimum Error Entropy Criterion

    OpenAIRE

    Badong Chen; Principe, Jose C.

    2012-01-01

    Recent studies suggest that the minimum error entropy (MEE) criterion can outperform the traditional mean square error criterion in supervised machine learning, especially in nonlinear and non-Gaussian situations. In practice, however, one has to estimate the error entropy from the samples since in general the analytical evaluation of error entropy is not possible. By the Parzen windowing approach, the estimated error entropy converges asymptotically to the entropy of the error plus an indepe...

  4. Minimum degree and density of binary sequences

    DEFF Research Database (Denmark)

    Brandt, Stephan; Müttel, J.; Rautenbach, D.;

    2010-01-01

    For d,k∈N with k ≤ 2d, let g(d,k) denote the infimum density of binary sequences (x)∈{0,1} which satisfy the minimum degree condition σ(x+) ≥ k for all i∈Z with xi=1. We reduce the problem of computing g(d,k) to a combinatorial problem related to the generalized k-girth of a graph G which is defi...

  5. Minimum Description Length Shape and Appearance Models

    DEFF Research Database (Denmark)

    Thodberg, Hans Henrik

    2003-01-01

    The Minimum Description Length (MDL) approach to shape modelling is reviewed. It solves the point correspondence problem of selecting points on shapes defined as curves so that the points correspond across a data set. An efficient numerical implementation is presented and made available as open s...... source Matlab code. The problems with the early MDL approaches are discussed. Finally the MDL approach is extended to an MDL Appearance Model, which is proposed as a means to perform unsupervised image segmentation....

  6. Time crystals from minimum time uncertainty

    Energy Technology Data Exchange (ETDEWEB)

    Faizal, Mir [University of Waterloo, Department of Physics and Astronomy, Waterloo, ON (Canada); Khalil, Mohammed M. [Alexandria University, Department of Electrical Engineering, Alexandria (Egypt); Das, Saurya [University of Lethbridge, Department of Physics and Astronomy, Lethbridge, AB (Canada)

    2016-01-15

    Motivated by the Generalized Uncertainty Principle, covariance, and a minimum measurable time, we propose a deformation of the Heisenberg algebra and show that this leads to corrections to all quantum mechanical systems. We also demonstrate that such a deformation implies a discrete spectrum for time. In other words, time behaves like a crystal. As an application of our formalism, we analyze the effect of such a deformation on the rate of spontaneous emission in a hydrogen atom. (orig.)

  7. Rocket Locations for Minimum Time Interception

    Directory of Open Access Journals (Sweden)

    T. N. Srivastava

    1971-07-01

    Full Text Available Interception of target rocket moving along a trajectory in a gravitational field by an interceptor rocket has been analysed to achieve interception in minimum time duration. Numerical values of the parameters of the intercepting trajectory and locations of the target rocket for launch and target orbits in Earth's gravitational field have been calculated for different impulsive velocity changes applied to the interceptor rocket.

  8. Minimum quality standards and international trade

    DEFF Research Database (Denmark)

    Baltzer, Kenneth Thomas

    2011-01-01

    This paper investigates the impact of a non-discriminating minimum quality standard (MQS) on trade and welfare when the market is characterized by imperfect competition and asymmetric information. A simple partial equilibrium model of an international Cournot duopoly is presented in which...... prefer different levels of regulation. As a result, international trade disputes are likely to arise even when regulation is non-discriminating....

  9. Phase III trial of casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Apornwirat, Wichit; Shaharyar, Ahmed;

    2009-01-01

    PURPOSE: The purpose of this phase III trial was to evaluate the efficacy and safety of regimens containing casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting during the first cycle in patients receiving moderately emetogenic...... proportion of patients with nausea or significant nausea in those receiving casopitant. Adverse events were balanced among study arms. CONCLUSION: All casopitant regimens studied were more effective than the control regimen. Casopitant was generally well tolerated....

  10. What causes geomagnetic activity during sunspot minimum

    CERN Document Server

    Kirov, Boian; Georgieva, Katya; Obridko, Vladimir

    2014-01-01

    The average geomagnetic activity during sunspot minimum has been continuously decreasing in the last four cycles. The geomagnetic activity is caused by both interplanetary disturbances - coronal mass ejections and high speed solar wind streams, and the background solar wind over which these disturbances ride. We show that the geomagnetic activity in cycle minimum does not depend on the number and parameters of coronal mass ejections or high speed solar wind streams, but on the background solar wind. The background solar wind has two components: slower and faster. The source of the slower component is the heliospheric current sheet, and of the faster one the polar coronal holes. It is supposed that the geomagnetic activity in cycle minimum is determined by the thickness of the heliospheric current sheet which is related to the portions of time the Earth spends in slow and in fast solar wind. We demonstrate that it is also determined by the parameters of these two components of the background solar wind which v...

  11. On the Minimum Induced Drag of Wings

    Science.gov (United States)

    Bowers, Albion H.

    2011-01-01

    Of all the types of drag, induced drag is associated with the creation and generation of lift over wings. Induced drag is directly driven by the span load that the aircraft is flying at. The tools by which to calculate and predict induced drag we use were created by Ludwig Prandtl in 1903. Within a decade after Prandtl created a tool for calculating induced drag, Prandtl and his students had optimized the problem to solve the minimum induced drag for a wing of a given span, formalized and written about in 1920. This solution is quoted in textbooks extensively today. Prandtl did not stop with this first solution, and came to a dramatically different solution in 1932. Subsequent development of this 1932 solution solves several aeronautics design difficulties simultaneously, including maximum performance, minimum structure, minimum drag loss due to control input, and solution to adverse yaw without a vertical tail. This presentation lists that solution by Prandtl, and the refinements by Horten, Jones, Kline, Viswanathan, and Whitcomb.

  12. Indexation of the Minimum Wage with Rational Expectations

    OpenAIRE

    Herschel I. Grossman

    1981-01-01

    This paper considers the possible employment effects of reforming minimum-wage policy to incorporate indexation of the nominal minimum wage .The analysis assumes that both the demand for the labor services of minimum-wage workers and the setting of the nominal minimum wage rate under existing policy depend in part on rational expectations of future average wage rates. The analysis implies that, if the indexation ratio of the nominal minimum wage to the recent-past average wage rate were large...

  13. The Wage and Employment Dynamics of Minimum Wage Workers

    OpenAIRE

    William E. Even; Macpherson, David A.

    2004-01-01

    This study uses 20 years of short panel data sets on minimum wage workers to examine the wage and employment dynamics of minimum wage workers. Compared to workers earning above the minimum wage, minimum wage workers differ substantially in several ways. First, minimum wage workers are much more likely to be new entrants and much more likely to exit the labor market. Second, changes in industry and occupation and access to job training are particularly important to improving the wages of minim...

  14. The Maunder minimum (1645-1715) was indeed a grand minimum: a reassessment of multiple datasets

    OpenAIRE

    I. G. Usoskin; Arlt, R.; Asvestari, E.; Hawkins, Ed; Käpylä, M.; Kovaltsov, G. A.; Krivova, N.; Lockwood, Mike; K. Mursula(Oulu Southern Institute and Department of Physics, University of Oulu, Finland); O'Reilly, J.; Owens, Mathew; Scott, Chris J.; Sokoloff, D. D.; Solanki, S. K.; Soon, W.

    2015-01-01

    Aims. Although the time of the Maunder minimum (1645–1715) is widely known as a period of extremely low solar activity, it is still being debated whether solar activity during that period might have been moderate or even higher than the current solar cycle (number 24). We have revisited all existing evidence and datasets, both direct and indirect, to assess the level of solar activity during the Maunder minimum. Methods. We discuss the East Asian naked-eye sunspot observations, the ...

  15. Optimizing Reactors Selection and Sequencing:Minimum Cost versus Minimum Volume

    Institute of Scientific and Technical Information of China (English)

    Rachid Chebbi

    2014-01-01

    The present investigation targets minimum cost of reactors in series for the case of one single chemical reaction, considering plug flow and stirred tank reactor(s) in the sequence of flow reactors. Using Guthrie’s cost correlations three typical cases were considered based on the profile of the reaction rate reciprocal versus conversion. Significant differences were found compared to the classical approach targeting minimum total reactor volume.

  16. Pharmacokinetic interactions with calcium channel antagonists (Part II).

    Science.gov (United States)

    Schlanz, K D; Myre, S A; Bottorff, M B

    1991-12-01

    Since calcium channel antagonists are a diverse class of drugs frequently administered in combination with other agents, the potential for clinically significant pharmacokinetic drug interactions exists. These interactions occur most frequently via altered hepatic blood flow and impaired hepatic enzyme activity. Part I of the article, which appeared in the previous issue of the Journal, dealt with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. Part II examines interactions with cyclosporin, anaesthetics, carbamazepine and cardiovascular agents. PMID:1782739

  17. Hyperglycemia of Diabetic Rats Decreased by a Glucagon Receptor Antagonist

    Science.gov (United States)

    Johnson, David G.; Ulichny Goebel, Camy; Hruby, Victor J.; Bregman, Marvin D.; Trivedi, Dev

    1982-02-01

    The glucagon analog [l-Nα-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.

  18. A randomized assessor-blind trial comparing highly purified hMG and recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer

    DEFF Research Database (Denmark)

    Devroey, Paul; Pellicer, Antonio; Nyboe Andersen, Anders;

    2012-01-01

    OBJECTIVE: To compare the efficacy and safety of highly purified menotropin (hphMG) and recombinant FSH (rFSH) for controlled ovarian stimulation in a GnRH antagonist cycle with compulsory single-blastocyst transfer. DESIGN: Randomized, open-label, assessor-blind, parallel groups, multicenter...

  19. Solar Cycle Predictions Near Sunspot Minimum

    Science.gov (United States)

    Hathaway, David H.

    1997-01-01

    Observations of solar magnetic activity and the dynamics of the solar convection zone have produced severe constraints on models of the Sun's magnetic dynamo. These constraints are so severe that, at present, we do not have numerical models that can accept the current conditions and then march forward in time to predict future activity. Given this state of solar dynamo theory we are forced to examine previous behavior to discover patterns and trends that afford us some measure of predictability. Here we examine the behavior of several indicators of solar activity near solar minimum that are well correlated with the amplitude of the following solar maximum to predict the level of solar activity over cycle 23. Sunspot numbers, areas, and positions are useful for characterizing solar cycle behavior due to the extent of the data (12 cycles or more). These data exhibit several patterns that relate future activity to past behavior. With the Odd-Even effect the odd numbered cycles have been larger than their even numbered predecessors for each of the last six cycle pairs. With the Amplitude-Period effect short period cycles have been followed by large amplitude cycles and long period cycles have been followed by small amplitude cycles for 10 of the last 13 cycles. With the Maximum-Minimum effect the sunspot number at minimum is directly correlated with the sunspot number at maximum for a given cycle. The geomagnetic indices aa and Ap are also related to solar activity by the connections between disturbances in the solar wind and variations in the Earth's magnetic field. Like the Maximum-Minimum effect for sunspots, the size of the aa and Ap indices at minimum are directly related to the amplitude of the following maximum. The number of geomagnetically disturbed days (days with Ap >= 25) over the course of a cycle is another indicator for the size of the next cycle. The aa and Ap indices can each be separated into a component in phase with the current sunspot cycle and an

  20. Efficacy and Safety of Vasopressin Receptor Antagonists for Euvolemic or Hypervolemic Hyponatremia: A Meta-Analysis.

    Science.gov (United States)

    Zhang, Xiangyun; Zhao, Mingyi; Du, Wei; Zu, Dongni; Sun, Yingwei; Xiang, Rongwu; Yang, Jingyu

    2016-04-01

    Hyponatremia, defined as a nonartifactual serum sodium level hypernatremia, urinary tract infection, renal failure, pyrexia, upper gastrointestinal bleeding, diarrhea, vomiting, peripheral edema, and dizziness between the 2 groups. Random effect meta-analyses showed that post treatment urine osmolality, supine systolic blood pressure, and diastolic blood pressure were lowered (WMDrandom = -233.07 mOsmol/kg, 95%CIs = -298.20-147.94; WMDrandom = -6.11 mmHg, 95%CIs = -9.810 to -2.41; WMDrandom = -2.59 mmHg, 95%CIs = -4.06 to -1.11, respectively), but serum osmolality was increased (WMDrandom = 9.29 mOsmol/kg, 95%CIs = 5.56-13.03). There was no significant change from baseline in serum potassium concentration between the 2 groups (WMDfixed = 0.00 mmHg, 95%CIs = -0.07-0.06).VRAs are relatively effective and safe for the treatment of hypervolemic and euvolemic hyponatremia. PMID:27082573

  1. Efficacy and Safety of Vasopressin Receptor Antagonists for Euvolemic or Hypervolemic Hyponatremia

    Science.gov (United States)

    Zhang, Xiangyun; Zhao, Mingyi; Du, Wei; Zu, Dongni; Sun, Yingwei; Xiang, Rongwu; Yang, Jingyu

    2016-01-01

    Abstract Hyponatremia, defined as a nonartifactual serum sodium level hypernatremia, urinary tract infection, renal failure, pyrexia, upper gastrointestinal bleeding, diarrhea, vomiting, peripheral edema, and dizziness between the 2 groups. Random effect meta-analyses showed that post treatment urine osmolality, supine systolic blood pressure, and diastolic blood pressure were lowered (WMDrandom = −233.07 mOsmol/kg, 95%CIs = −298.20–147.94; WMDrandom = −6.11 mmHg, 95%CIs = −9.810 to −2.41; WMDrandom = −2.59 mmHg, 95%CIs = −4.06 to −1.11, respectively), but serum osmolality was increased (WMDrandom = 9.29 mOsmol/kg, 95%CIs = 5.56–13.03). There was no significant change from baseline in serum potassium concentration between the 2 groups (WMDfixed = 0.00 mmHg, 95%CIs = −0.07–0.06). VRAs are relatively effective and safe for the treatment of hypervolemic and euvolemic hyponatremia. PMID:27082573

  2. 30 CFR 75.518-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric equipment and circuits; overload and short circuit protection; minimum requirements. 75.518-1 Section 75.518-1 Mineral Resources MINE SAFETY...-UNDERGROUND COAL MINES Electrical Equipment-General § 75.518-1 Electric equipment and circuits; overload...

  3. 30 CFR 71.402 - Minimum requirements for bathing facilities, change rooms, and sanitary flush toilet facilities.

    Science.gov (United States)

    2010-07-01

    ...) Showers shall be provided with both hot and cold water. (ii) At least one shower head shall be provided..., change rooms, and sanitary flush toilet facilities. 71.402 Section 71.402 Mineral Resources MINE SAFETY... Rooms, and Sanitary Flush Toilet Facilities at Surface Coal Mines § 71.402 Minimum requirements...

  4. Safety Note

    CERN Multimedia

    SC Secretariat

    2004-01-01

    Please note that the Safety Note no 29 (NS 29) entitled 'Fire Prevention for Insulating Core (Sandwich) Panel Structures for Inside Use Guidelines for Selection, Installation and Use' is available on the web at the following url: https://edms.cern.ch/document/475438/LAST_RELEASED Paper copies can also be obtained from the SC Unit secretariat, e-mail : sc.secretariat@cern.ch SC Secretariat

  5. Novel class of medications, orexin receptor antagonists, in the treatment of insomnia – critical appraisal of suvorexant

    Directory of Open Access Journals (Sweden)

    Norman JL

    2016-07-01

    Full Text Available Jessica L Norman, Sarah L Anderson Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA Abstract: Insomnia, a highly prevalent disorder, can be detrimental to patients’ overall health and worsen existing comorbidities. Patients may have acute episodes of insomnia related to a traumatic event, but more commonly insomnia occurs chronically. While proper sleep hygiene and behavioral therapy play important roles in the nonpharmacologic management of short-term and chronic insomnia, medications may also be required. Historically, insomnia has been treated with agents such as benzodiazepines, nonbenzodiazepine receptor agonists, and melatonin agonists. Dual orexin receptor antagonists represent a new class of medications for the treatment of insomnia, which block the binding of wakefulness-promoting neuropeptides orexin A and orexin B to their respective receptor sites. Suvorexant (Belsomra is the first dual orexin receptor antagonist to be approved in the US and Japan and has demonstrated efficacy in decreasing time to sleep onset and increasing total sleep time. Its unique mechanism of action, data to support efficacy and safety over 12 months of use, and relative lack of withdrawal effects when discontinued may represent an alternative for patients with chronic insomnia who cannot tolerate or do not receive benefit from more traditional sleep agents. Suvorexant is effective and well tolerated, but precautions exist for certain patient populations, including females, obese patients, and those with respiratory disease. Suvorexant has only been studied vs placebo, and hence it is unknown how it directly compares with other medications approved by the US Food and Drug Administration for insomnia. Suvorexant is not likely to replace benzodiazepines or nonbenzodiazepine receptor antagonists as a first-line sleep agent but does represent a novel option for the treatment of

  6. Komplikationer til langtidsbehandling med vitamin K-antagonister

    DEFF Research Database (Denmark)

    May, O; Garne, E; Mickley, H

    1990-01-01

    Long-term treatment with vitamin K antagonists (vKA) frequently involves complications. The commonest complication is haemorrhage and cases of serious haemorrhage are stated in the literature to occur with a frequency per 1,000 treatment years of 12-108, of which 2-17 are fatal. The majority...

  7. Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies.

    Science.gov (United States)

    Palmer, G C

    2001-09-01

    Because of adverse reactions, early efforts to introduce high affinity competitive or use-dependent NMDA receptor antagonists into patients suffering from stroke, head trauma or epilepsy met with failure. Later it was discovered that both low affinity use-dependent NMDA receptor antagonists and compounds with selective affinity for the NR2B receptor subunit met the criteria for safe administration into patients. Furthermore, these low affinity antagonists exhibit significant mechanistic differences from their higher affinity counterparts. Success of the latter is attested to the ability of the following low affinity compounds to be marketed: 1) Cough suppressant-dextromethorphan (available for decades); 2) Parkinson's disease--amantadine, memantine and budipine; 3) Dementia--memantine; and 4) Epilepsy--felbamate. Moreover, Phase III clinical trials are ongoing with remacemide for epilepsy and Huntington's disease and head trauma for HU-211. A host of compounds are or were under evaluation for the possible treatment of stroke, head trauma, hyperalgesia and various neurodegenerative disorders. Despite the fact that other drugs with associated NMDA receptor mechanisms have reached clinical status, this review focuses only on those competitive and use-dependent NMDA receptor antagonists that reached clinical trails. The ensuing discussions link the in vivo pharmacological investigations that led to the success/mistakes/ failures for eventual testing of promising compounds in the clinic. PMID:11554551

  8. Determinants of effective, safe and convenient vitamin K antagonist use

    NARCIS (Netherlands)

    Kooistra, Hilde Afra Margaretha

    2016-01-01

    Vitamin K antagonists (VKA) are frequently used anticoagulants. They are very effective in preventing atrial fibrillation related strokes and recurrent venous thrombosis. However, it can be difficult to achieve an optimal balance between the efficacy and side effects (bleeding), as the dose response

  9. The Effect of Antagonist Muscle Sensory Input on Force Regulation.

    Directory of Open Access Journals (Sweden)

    Tanya Onushko

    Full Text Available The purpose of this study was to understand how stretch-related sensory feedback from an antagonist muscle affects agonist muscle output at different contraction levels in healthy adults. Ten young (25.3 ± 2.4 years, healthy subjects performed constant isometric knee flexion contractions (agonist at 6 torque levels: 5%, 10%, 15%, 20%, 30%, and 40% of their maximal voluntary contraction. For half of the trials, subjects received patellar tendon taps (antagonist sensory feedback during the contraction. We compared error in targeted knee flexion torque and hamstring muscle activity, with and without patellar tendon tapping, across the 6 torque levels. At lower torque levels (5%, 10%, and 15%, subjects produced greater knee torque error following tendon tapping compared with the same torque levels without tendon tapping. In contrast, we did not find any difference in torque output at higher target levels (20%, 30%, and 40% between trials with and without tendon tapping. We also observed a load-dependent increase in the magnitude of agonist muscle activity after tendon taps, with no associated load-dependent increase in agonist and antagonist co-activation, or reflex inhibition from the antagonist tapping. The findings suggest that at relatively low muscle activity there is a deficiency in the ability to correct motor output after sensory disturbances, and cortical centers (versus sub-cortical are likely involved.

  10. Voltage-Gated Calcium Channel Antagonists and Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Bruce Lyeth

    2013-06-01

    Full Text Available Traumatic brain injury (TBI is a leading cause of death and disability in the United States. Despite more than 30 years of research, no pharmacological agents have been identified that improve neurological function following TBI. However, several lines of research described in this review provide support for further development of voltage gated calcium channel (VGCC antagonists as potential therapeutic agents. Following TBI, neurons and astrocytes experience a rapid and sometimes enduring increase in intracellular calcium ([Ca2+]i. These fluxes in [Ca2+]i drive not only apoptotic and necrotic cell death, but also can lead to long-term cell dysfunction in surviving cells. In a limited number of in vitro experiments, both L-type and N-type VGCC antagonists successfully reduced calcium loads as well as neuronal and astrocytic cell death following mechanical injury. In rodent models of TBI, administration of VGCC antagonists reduced cell death and improved cognitive function. It is clear that there is a critical need to find effective therapeutics and rational drug delivery strategies for the management and treatment of TBI, and we believe that further investigation of VGCC antagonists should be pursued before ruling out the possibility of successful translation to the clinic.

  11. Interleukin-1-receptor antagonist in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Larsen, Claus M; Faulenbach, Mirjam; Vaag, Allan;

    2007-01-01

    BACKGROUND: The expression of interleukin-1-receptor antagonist is reduced in pancreatic islets of patients with type 2 diabetes mellitus, and high glucose concentrations induce the production of interleukin-1beta in human pancreatic beta cells, leading to impaired insulin secretion, decreased cell...

  12. About the use of antagonistic bacteria and fungi

    OpenAIRE

    Tilcher, R.; Schmidt, C.; Lorenz, D.; Wolf, G. A.

    2002-01-01

    Microorganisms isolated from the phylloplane of vine and cereal plants inhibiting different phytopathogenic fungi were tested as biological control agents against Plasmopara viticola (downy mildew of grapevine). Based on screening in vitro against Phytophthora infestans, P. parasitica, Pythium ultimum, Botrytis cinerea 62 bacterial isolates were selected for tests with Plasmopara viticola.. Antifungal bacterial strains were assayed for antagonistic activity towards the grapevine dieback fungu...

  13. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy

    DEFF Research Database (Denmark)

    Als-Nielsen, B; Kjaergard, L L; Gluud, C

    2001-01-01

    The pathogenesis of hepatic encephalopathy is unknown. It has been suggested that liver failure leads to the accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition which may progress to coma. Several trials have assessed benzodiazepine receptor...... antagonists for hepatic encephalopathy, but the results are conflicting....

  14. Epiminocyclohepta[b]indole analogs as 5-HT6 antagonists

    DEFF Research Database (Denmark)

    Henderson, Alan J; Guzzo, Peter R; Ghosh, Animesh;

    2012-01-01

    A new series of epiminocyclohepta[b]indoles with potent 5-HT(6) antagonist activity were discovered and optimized using in vitro protocols. One compound from this series was progressed to advanced pharmacokinetic (PK) studies followed by 5-HT(6) receptor occupancy studies. The compound was found ...

  15. Possible site of action of CGRP antagonists in migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Olesen, Jes

    2011-01-01

    The calcitonin gene-related peptide (CGRP) receptor antagonists olcegepant and telcagepant are very potent drugs. Both are effective in migraine but in doses much higher than would be predicted from receptor binding and other in vitro results. This could perhaps suggest an effect of CGRP antagoni...

  16. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qun-Yi; Zhang, Meng [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Hallis, Tina M.; DeRosier, Therese A. [Cell Systems Division, Invitrogen, Madison, WI (United States); Yue, Jian-Min; Ye, Yang [State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Mais, Dale E. [The National Center for Drug Screening, Shanghai (China); MPI Research, Mattawan, MI (United States); Wang, Ming-Wei, E-mail: wangmw@mail.shcnc.ac.cn [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China)

    2010-01-15

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  17. Medium-Induced Antagonistic Behavior in Staphylococcus Aureus.

    Science.gov (United States)

    Benathen, Isaiah A.

    1992-01-01

    Antagonism is the production of substances by microorganisms that inhibit or prevent the growth of other bacteria. This paper demonstrates the antagonistic behavior of gram-positive coccus on the B. subtilis and Enterococcus faecalis gram-positive microorganisms, showing that the process of antagonism is sometimes dependent on the nutritional…

  18. Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

    NARCIS (Netherlands)

    Parry-Jones, A.R.; Napoli, M. Di; Goldstein, J.N.; Schreuder, F.H.; Tetri, S.; Tatlisumak, T.; Yan, B.; Nieuwenhuizen, K.M.; Dequatre-Ponchelle, N.; Lee-Archer, M.; Horstmann, S.; Wilson, D.; Pomero, F.; Masotti, L.; Lerpiniere, C.; Godoy, D.A.; Cohen, A.S.; Houben, R.; Al-Shahi Salman, R.; Pennati, P.; Fenoglio, L.; Werring, D.; Veltkamp, R.; Wood, E.; Dewey, H.M.; Cordonnier, C.; Klijn, C.J.M.; Meligeni, F.; Davis, S.M.; Huhtakangas, J.; Staals, J.; Rosand, J.; Meretoja, A.

    2015-01-01

    OBJECTIVE: There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different

  19. Reversal strategies for vitamin K antagonists in acute intracerebral hemorrhage

    NARCIS (Netherlands)

    Parry-Jones, Adrian R.; Di Napoli, Mario; Goldstein, Joshua N.; Schreuder, Floris H B M; Tetri, Sami; Tatlisumak, Turgut; Yan, Bernard; Van Nieuwenhuizen, Koen M.; Dequatre-Ponchelle, Nelly; Lee-Archer, Matthew; Horstmann, Solveig; Wilson, Duncan; Pomero, Fulvio; Masotti, Luca; Lerpiniere, Christine; Godoy, Daniel Agustin; Cohen, Abigail S.; Houben, Rik; Al-Shahi Salman, Rustam; Pennati, Paolo; Fenoglio, Luigi; Werring, David; Veltkamp, Roland; Wood, Edith; Dewey, Helen M.; Cordonnier, Charlotte; Klijn, Catharina J M; Meligeni, Fabrizio; Davis, Stephen M.; Huhtakangas, Juha; Staals, Julie; Rosand, Jonathan; Meretoja, Atte

    2015-01-01

    Objective There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different

  20. Precycle Estradiol in Synchronization and Scheduling of Antagonist Cycles.

    Science.gov (United States)

    Saple, Shilpa; Agrawal, Mukesh; Kawar, Simi

    2016-08-01

    Antagonist cycles have an inherent issue of lack of flexibility. As a result where batching of cycles is desired, it is not the preferred protocol in ART cycles. There is also the limitation of ovarian response in antagonist cycle due to the size heterogenesities of antral follicles at the start of stimulation. Among the different options available, use of estrogen in the luteal phase of the preceding cycle has definitely shown benefits with regard to better control of cycle as well as synchronization of follicles available for stimulation. The article gives a detailed analysis of the different options available for timing the egg collection in antagonist cycles, the advantages and drawbacks, and the method of use of estrogen. Whereas in the majority of the trials where estrogen pretreatment was used, the goal of scheduling of egg collection was definitely achieved, increased duration and dose of gonadotropin stimulation were required. There was definite advantage of higher oocyte yield in these cycles. The possibility of premature LH rise later during stimulation and subsequent poor implantation in these cycles has to be further evaluated. Nevertheless, batching of patient friendly antagonist cycles can be effectively possible by use of precycle estrogen treatment. PMID:27382226

  1. Effects of alpha 1-adrenoceptor antagonists on male sexual function

    NARCIS (Netherlands)

    M.M. van Dijk; J.J.M.C.H. de la Rosette; M.C. Michel

    2006-01-01

    alpha(1)-Adrenoceptor antagonists such as alfuzosin, doxazosin, tamsulosin and terazosin are first-line agents for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH), but are only second-line agents (doxazosin and terazosin only) for the treatment of arter

  2. Commentary: legal minimum tread depth for passenger car tires in the U.S.A.--a survey.

    Science.gov (United States)

    Blythe, William; Seguin, Debra E

    2006-06-01

    Available tire traction is a significant highway safety issue, particularly on wet roads. Tire-roadway friction on dry, clean roads is essentially independent of tread depth, and depends primarily on roadway surface texture. However, tire-wet-roadway friction, both for longitudinal braking and lateral cornering forces, depends on several variables, most importantly on water depth, speed and tire tread depth, and the roadway surface texture. The car owner-operator has control over speed and tire condition, but not on water depth or road surface texture. Minimum tire tread depth is legislated throughout most of the United States and Europe. Speed reduction for wet road conditions is not.A survey of state requirements for legal minimum tread depth for passenger vehicle tires in the United States is presented. Most states require a minimum of 2/32 of an inch (approximately 1.6 mm) of tread, but two require less, some have no requirements, and some defer to the federal criterion for commercial vehicle safety inspections. The requirement of 2/32 of an inch is consistent with the height of the tread-wear bars built in to passenger car tires sold in the United States, but the rationale for that requirement, or other existing requirements, is not clear. Recent research indicates that a minimum tread depth of 2/32 of an inch does not prevent significant loss of friction at highway speeds, even for minimally wet roadways. The research suggests that tires with less than 4/32 of an inch tread depth may lose approximately 50 percent of available friction in those circumstances, even before hydroplaning occurs. It is concluded that the present requirements for minimum passenger car tire tread depth are not based upon rational safety considerations, and that an increase in the minimum tread depth requirements would have a beneficial effect on highway safety.

  3. Myofascial force transmission via extramuscular pathways occurs between antagonistic muscles.

    Science.gov (United States)

    Huijing, Peter A; Baan, Guus C

    2008-01-01

    Most often muscles (as organs) are viewed as independent actuators. To test if this is true for antagonistic muscles, force was measured simultaneously at: (1) the proximal and distal tendons of the extensor digitorum muscle (EDL) to quantify any proximo-distal force differences, as an indicator of myofascial force transmission, (2) at the distal tendons of the whole antagonistic peroneal muscle group (PER) to test if effects of EDL length changes are present and (3) at the proximal end of the tibia to test if myofascially transmitted force is exerted there. EDL length was manipulated either at the proximal or distal tendons. This way equal EDL lengths are attained at two different positions of the muscle with respect to the tibia and antagonistic muscles. Despite its relatively small size, lengthening of the EDL changed forces exerted on the tibia and forces exerted by its antagonistic muscle group. Apart from its extramuscular myofascial connections, EDL has no connections to either the tibia or these antagonistic muscles. Proximal EDL lengthening increased distal muscular forces (active PER DeltaF approximately +1.7%), but decreased tibial forces (passive from 0.3 to 0 N; active DeltaF approximately -5%). Therefore, it is concluded that these antagonistic muscles do not act independently, because of myofascial force transmission between them. Such a decrease in tibial force indicates release of pre-strained connections. Distal EDL lengthening had opposite effects (tripling passive force exerted on tibia; active PER force DeltaF approximately -3.6%). It is concluded that the length and relative position of the EDL is a co-determinant of passive and active force exerted at tendons of nearby antagonistic muscle groups. These results necessitate a new view of the locomotor apparatus, which needs to take into account the high interdependence of muscles and muscle fibres as force generators, as well as proximo-distal force differences and serial and parallel

  4. Context quantization by minimum adaptive code length

    DEFF Research Database (Denmark)

    Forchhammer, Søren; Wu, Xiaolin

    2007-01-01

    Context quantization is a technique to deal with the issue of context dilution in high-order conditional entropy coding. We investigate the problem of context quantizer design under the criterion of minimum adaptive code length. A property of such context quantizers is derived for binary symbols....... A fast context quantizer design algorithm for conditioning binary symbols is presented and its complexity analyzed. It is conjectured that this algorithm is optimal. The context quantization is performed in what may be perceived as a probability simplex space rather than in the space of context instances....

  5. The minimum jet power and equipartition

    OpenAIRE

    Zdziarski, Andrzej A.

    2014-01-01

    We derive the minimum power of jets and their magnetic field strength based on their observed non-thermal synchrotron emission. The correct form of this method takes into account both the internal energy in the jet and the ion rest-mass energy associated with the bulk motion. The latter was neglected in a number of papers, which instead adopted the well-known energy-content minimization method. That method was developed for static sources, for which there is no bulk-motion component of the en...

  6. Iterative Regularization with Minimum-Residual Methods

    DEFF Research Database (Denmark)

    Jensen, Toke Koldborg; Hansen, Per Christian

    2007-01-01

    We study the regularization properties of iterative minimum-residual methods applied to discrete ill-posed problems. In these methods, the projection onto the underlying Krylov subspace acts as a regularizer, and the emphasis of this work is on the role played by the basis vectors of these Krylov...... subspaces. We provide a combination of theory and numerical examples, and our analysis confirms the experience that MINRES and MR-II can work as general regularization methods. We also demonstrate theoretically and experimentally that the same is not true, in general, for GMRES and RRGMRES their success...... as regularization methods is highly problem dependent....

  7. Iterative regularization with minimum-residual methods

    DEFF Research Database (Denmark)

    Jensen, Toke Koldborg; Hansen, Per Christian

    2006-01-01

    We study the regularization properties of iterative minimum-residual methods applied to discrete ill-posed problems. In these methods, the projection onto the underlying Krylov subspace acts as a regularizer, and the emphasis of this work is on the role played by the basis vectors of these Krylov...... subspaces. We provide a combination of theory and numerical examples, and our analysis confirms the experience that MINRES and MR-II can work as general regularization methods. We also demonstrate theoretically and experimentally that the same is not true, in general, for GMRES and RRGMRES - their success...... as regularization methods is highly problem dependent....

  8. Decentralized Pricing in Minimum Cost Spanning Trees

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moulin, Hervé; Østerdal, Lars Peter

    In the minimum cost spanning tree model we consider decentralized pricing rules, i.e. rules that cover at least the ecient cost while the price charged to each user only depends upon his own connection costs. We de ne a canonical pricing rule and provide two axiomatic characterizations. First......, the canonical pricing rule is the smallest among those that improve upon the Stand Alone bound, and are either superadditive or piece-wise linear in connection costs. Our second, direct characterization relies on two simple properties highlighting the special role of the source cost....

  9. Minimum QOS Parameter Set in Transport Layer

    Institute of Scientific and Technical Information of China (English)

    汪芸; 顾冠群

    1997-01-01

    QOS(Quality Of Service)parameter definitions are the basis of further QOS control.But QOS parameters defined by organizations such as ISO and ITU are incoherent and incompatible.It leads to the imefficiency of QOS controls.Based on the analysis of QOS parameters defined by ISO and ITU,this paper first promotes Minimum QOS Parameter Set in transport layer.It demonstrates that the parameters defined by ISO and ITU can be represented b parameters or a combination of parameters of the Set.The paper also expounds that the Set is open and manageable and it can be the potential unified base for QOS parameters.

  10. First minimum bias physics results at LHCb

    CERN Document Server

    Dettori, Francesco

    2010-01-01

    We report on the first measurements of the LHCb experiment, as obtained from $pp$ collisions at $\\sqrt{s}$ = 0.9 TeV and 7 TeV recorded using a minimum bias trigger. In particular measurements of the absolute $K_S^0$ production cross section at $\\sqrt{s}$ = 0.9 TeV and of the $\\overline{\\Lambda/}\\Lambda$ ratio both at $\\sqrt{s}$ = 0.9 TeV and 7 TeV are discussed and preliminary results are presented

  11. How unprecedented a solar minimum was it?

    OpenAIRE

    Russell, C. T.; L. K. Jian; Luhmann, J. G.

    2012-01-01

    The end of the last solar cycle was at least 3 years late, and to date, the new solar cycle has seen mainly weaker activity since the onset of the rising phase toward the new solar maximum. The newspapers now even report when auroras are seen in Norway. This paper is an update of our review paper written during the deepest part of the last solar minimum [1]. We update the records of solar activity and its consequent effects on the interplanetary fields and solar wind density. The arrival of s...

  12. Linking the Minimum Wage to Productivity

    OpenAIRE

    Oren M. Levin-Waldman

    1998-01-01

    One of the principal problems with the minimum wage is that adjustments to it must be voted on by Congress. Although recent congressional action solves the immediate problem of restoring value to a wage that has otherwise failed to keep pace with inflation it has not removed the issue from the political agenda. Every time Congress acts, it does so amidst debate about the legitimacy of the wage. When Congress does act, it is usually too little and too late. Therefore, it might be preferable to...

  13. Topology optimization for simplified structural fire safety

    DEFF Research Database (Denmark)

    Madsen, Søren; Lange, Nis P.; Giuliani, Luisa;

    2016-01-01

    Topology optimization is applied in an idealized structural fire safety model, where the minimum compliance problem is constrained by temperature-controlled structural degradation. The constraint ensures a certain structural stiffness after a prescribed time. As this time period is extended......, resulting optimized topologies tend to become thicker or introduce redundant members that can take over when structural parts near the origin of the fire lose their load carrying capability. Hence, the structural degradation model acts as an erosion operator on the topology and indirectly enforces a minimum...

  14. Accumulation of Deleterious Mutations Near Sexually Antagonistic Genes.

    Science.gov (United States)

    Connallon, Tim; Jordan, Crispin Y

    2016-01-01

    Mutation generates a steady supply of genetic variation that, while occasionally useful for adaptation, is more often deleterious for fitness. Recent research has emphasized that the fitness effects of mutations often differ between the sexes, leading to important evolutionary consequences for the maintenance of genetic variation and long-term population viability. Some forms of sex-specific selection-i.e., stronger purifying selection in males than females-can help purge a population's load of female-harming mutations and promote population growth. Other scenarios-e.g., sexually antagonistic selection, in which mutations that harm females are beneficial for males-inflate genetic loads and potentially dampen population viability. Evolutionary processes of sexual antagonism and purifying selection are likely to impact the evolutionary dynamics of different loci within a genome, yet theory has mostly ignored the potential for interactions between such loci to jointly shape the evolutionary genetic basis of female and male fitness variation. Here, we show that sexually antagonistic selection at a locus tends to elevate the frequencies of deleterious alleles at tightly linked loci that evolve under purifying selection. Moreover, haplotypes that segregate for different sexually antagonistic alleles accumulate different types of deleterious mutations. Haplotypes that carry female-benefit sexually antagonistic alleles preferentially accumulate mutations that are primarily male harming, whereas male-benefit haplotypes accumulate mutations that are primarily female harming. The theory predicts that sexually antagonistic selection should shape the genomic organization of genetic variation that differentially impacts female and male fitness, and contribute to sexual dimorphism in the genetic basis of fitness variation. PMID:27226163

  15. A Product Safety Primer

    Science.gov (United States)

    Brown, Mary Anne Symons

    1975-01-01

    The article offers an overview of the product safety issue and offers ideas for helping students develop product safety awareness. The role of the Consumer Product Safety Commission and safety legislation are discussed. (MW)

  16. The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia.

    Science.gov (United States)

    Dallmann, R; Weyermann, P; Anklin, C; Boroff, M; Bray-French, K; Cardel, B; Courdier-Fruh, I; Deppe, H; Dubach-Powell, J; Erb, M; Haefeli, R H; Henneböhle, M; Herzner, H; Hufschmid, M; Marks, D L; Nordhoff, S; Papp, M; Rummey, C; Santos, G; Schärer, F; Siendt, H; Soeberdt, M; Sumanovski, L T; Terinek, M; Mondadori, C; Güven, N; Feurer, A

    2011-09-01

    BACKGROUND: Under physiological conditions, the melanocortin system is a crucial part of the complex network regulating food intake and energy expenditure. In pathological states, like cachexia, these two parameters are deregulated, i.e., food intake is decreased and energy expenditure is increased-a vicious combination leading to catabolism. Agouti-related protein (AgRP), the endogenous antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food intake and to reduce energy expenditure. This qualifies MC-4R blockade as an attractive mode of action for the treatment of cachexia. Based on this rationale, a novel series of small-molecule MC-4R antagonists was designed, from which the orally active compound BL-6020/979 (formerly known as SNT207979) emerged as the first promising development candidate showing encouraging pre-clinical efficacy and safety properties which are presented here. METHODS AND RESULTS: BL-6020/979 is an orally available, selective and potent MC-4R antagonist with a drug-like profile. It increased food intake and decreased energy expenditure in healthy wild-type but not in MC-4R deficient mice. More importantly, it ameliorated cachexia-like symptoms in the murine C26 adenocarcinoma model; with an effect on body mass and body composition and on the expression of catabolic genes. Moreover, BL-6020/979 showed antidepressant-like properties in the chronic mild stress model in rats and exhibits a favorable safety profile. CONCLUSION: The properties of BL-6020/979 demonstrated in animal models and presented here make it a promising candidate suitable for further development towards a first-in-class treatment option for cachexia that potentially opens up the opportunity to treat two hallmarks of the disease, i.e., decreased food intake and increased energy expenditure, with one drug.

  17. Dopamine D3 Receptor Antagonist (GSK598809) Potentiates the Hypertensive Effects of Cocaine in Conscious, Freely-Moving Dogs.

    Science.gov (United States)

    Appel, Nathan M; Li, Shou-Hua; Holmes, Tyson H; Acri, Jane B

    2015-09-01

    The chronic and relapsing nature of addiction presents unique challenges for ensuring the safety of a potential medication. A patient may use cocaine, for example, while taking the medication or take more medication than prescribed. Thus, a potential medication must be safe and not exacerbate the effects of cocaine. Multiple published studies support antagonism of brain dopamine D3 receptor function as a potential mechanism of action for an anti-addiction medication. Dopamine D3 receptors are widely distributed outside the central nervous system, however; for example, dopamine D3 receptors in the kidneys are implicated in regulating blood pressure. The selective dopamine D3 receptor antagonist GSK598809 [1-(2-fluoro-4-trifluoromethyl-phenyl)-3-{3-[4-methyl-5-(4-methyl-oxazol-5-yl)-4H-[1,2,4]triazol-3-ylsulfanyl]-propyl}-3-aza-bicyclo[3.1.0]hexane] has been proposed as a medication to treat cocaine and other substance use disorders. The US Food and Drug Administration has established guidelines recommending safety studies to investigate potential undesirable pharmacodynamic effects of a substance in relation to exposure in the therapeutic range and above. Hence, we assessed the interaction between this selective dopamine D3 receptor antagonist and cocaine on hemodynamics and cardiac function in freely-moving, telemetered dogs before conducting a clinical trial. GSK598809 increased the hemodynamic effect of cocaine in this model. Thus, the increase in blood pressure after intravenous cocaine was greater in animals that had been pretreated with GSK598809 compared with vehicle. This finding suggests that GSK598809 in particular, and perhaps dopamine D3 receptor antagonists as a class, may produce unacceptable cardiovascular risks as medications to treat cocaine use disorder. PMID:26177654

  18. Delivering safety

    International Nuclear Information System (INIS)

    In the United Kingdom there have been significant recent changes to the management of civil nuclear liabilities. With the formation in April 2005 of the Nuclear Decommissioning Authority (NDA), ownership of the civil nuclear licensed sites in the UK, including the Magnox Reactor Stations, passed to this new organisation. The NDAs mission is to seek acceleration of the nuclear clean up programme and deliver increased value for money and, consequently, are driving their contractors to seek more innovative ways of performing work. British Nuclear Group manages the UK Magnox stations under contract to the NDA. This paper summarises the approach being taken within its Reactor Sites business to work with suppliers to enhance working arrangements at sites, improve the delivery of decommissioning programmes and deliver improvements in safety and environmental performance. The UK Magnox stations are 1. generation gas-graphite reactors, constructed in the 1950's and 1960's. Two stations are currently still operating, three are shut-down undergoing defueling and the other five are being decommissioned. Despite the distractions of industry restructuring, an uncompromising policy of demanding improved performance in conjunction with improved safety and environmental standards has been adopted. Over the past 5 years, this policy has resulted in step-changes in performance at Reactor Sites, with increased electrical output and accelerated defueling and decommissioning. The improvements in performance have been mirrored by improvements in safety (DACR of 0 at 5 sites); environmental standards (reductions in energy and water consumption, increased waste recycling) and the overall health of the workforce (20% reduction in sickness absence). These achievements have, in turn, been recognised by external bodies, resulting in several awards, including: the world's first ISRS and IERS level 10 awards (Sizewell, 2006), the NUMEX plant maintenance award (Bradwell, 2006), numerous Ro

  19. SAFETY NOTES

    CERN Multimedia

    TIS Secretariat

    2001-01-01

    Please note that the revisions of safety notes no 3 (NS 3 Rev. 2) and no 24 (NS 24 REV.) entitled respectively 'FIRE PREVENTION FOR ENCLOSED SPACES IN LARGE HALLS' and 'REMOVING UNBURIED ELV AND LVA ELECTRIC CONDUITS' are available on the web at the following urls: http://edmsoraweb.cern.ch:8001/cedar/doc.download?document_id=322811&version=1&filename=version_francaise.pdf http://edmsoraweb.cern.ch:8001/cedar/doc.download?document_id=322861&version=2&filename=version_francaise.pdf Paper copies can also be obtained from the TIS Divisional Secretariat, email tis.secretariat@cern.ch

  20. Safety training

    CERN Multimedia

    SC Unit

    2009-01-01

    Habilitation électrique A course entitled "Habilitation électrique pour personnel de laboratoire" (electrical safety qualification for laboratory personnel) will be held on 22 and 23 June. Registration by e-mail to isabelle.cusato@cern.ch. Explosion Hazards in the handling of flammable solvents and gases A course entitled "Explosion Hazards in the handling of flammable solvents and gases" given in French will be held on 18-19 June 2009. This course is obligatory for all FGSOs at CERN, and it is recommended for anyone handling flammable gas or solvents. To sign up please visit this page. For more information please contact Isabelle Cusato, tel. 73811.

  1. Insight into 144 patients with ocular vascular events during VEGF antagonist injections

    DEFF Research Database (Denmark)

    Mansour, Ahmad M; Shahin, Maha; Kofoed, Peter K;

    2012-01-01

    To record ocular vascular events following injections of vascular endothelium growth factor (VEGF) antagonists.......To record ocular vascular events following injections of vascular endothelium growth factor (VEGF) antagonists....

  2. The Maunder minimum (1645--1715) was indeed a Grand minimum: A reassessment of multiple datasets

    CERN Document Server

    Usoskin, Ilya G; Asvestari, Eleanna; Hawkins, Ed; Käpylä, Maarit; Kovaltsov, Gennady A; Krivova, Natalie; Lockwood, Michael; Mursula, Kalevi; O'Reilly, Jezebel; Owens, Matthew; Scott, Chris J; Sokoloff, Dmitry D; Solanki, Sami K; Soon, Willie; Vaquero, José M

    2015-01-01

    Aims: Although the time of the Maunder minimum (1645--1715) is widely known as a period of extremely low solar activity, claims are still debated that solar activity during that period might still have been moderate, even higher than the current solar cycle #24. We have revisited all the existing pieces of evidence and datasets, both direct and indirect, to assess the level of solar activity during the Maunder minimum. Methods: We discuss the East Asian naked-eye sunspot observations, the telescopic solar observations, the fraction of sunspot active days, the latitudinal extent of sunspot positions, auroral sightings at high latitudes, cosmogenic radionuclide data as well as solar eclipse observations for that period. We also consider peculiar features of the Sun (very strong hemispheric asymmetry of sunspot location, unusual differential rotation and the lack of the K-corona) that imply a special mode of solar activity during the Maunder minimum. Results: The level of solar activity during the Maunder minimu...

  3. Constrained length minimum inductance gradient coil design.

    Science.gov (United States)

    Chronik, B A; Rutt, B K

    1998-02-01

    A gradient coil design algorithm capable of controlling the position of the homogeneous region of interest (ROI) with respect to the current-carrying wires is required for many advanced imaging and spectroscopy applications. A modified minimum inductance target field method that allows the placement of a set of constraints on the final current density is presented. This constrained current minimum inductance method is derived in the context of previous target field methods. Complete details are shown and all equations required for implementation of the algorithm are given. The method has been implemented on computer and applied to the design of both a 1:1 aspect ratio (length:diameter) central ROI and a 2:1 aspect ratio edge ROI gradient coil. The 1:1 design demonstrates that a general analytic method can be used to easily obtain very short gradient coil designs for use with specialized magnet systems. The edge gradient design demonstrates that designs that allow imaging of the neck region with a head sized gradient coil can be obtained, as well as other applications requiring edge-of-cylinder regions of uniformity.

  4. The minimum jet power and equipartition

    CERN Document Server

    Zdziarski, Andrzej A

    2014-01-01

    We derive the minimum power of jets and their magnetic field strength based on their observed non-thermal synchrotron emission. The correct form of this method takes into account both the internal energy in the jet and the ion rest-mass energy associated with the bulk motion. The latter was neglected in a number of papers, which instead adopted the well-known energy-content minimization method. That method was developed for static sources, for which there is no bulk-motion component of the energy. In the case of electron power-law spectra with index >2 in ion-electron jets, the rest-mass component dominates. The minimization method for the jet power taking it into account was considered in some other work, but only based on either an assumption of a constant total synchrotron flux or a fixed range of the Lorentz factors. Instead, we base our method on an observed optically-thin synchrotron spectrum. We find the minimum jet power is independent of its radius when the rest-mass power dominates, which becomes th...

  5. Minimum Mass Solar Nebulae and Planetary Migration

    CERN Document Server

    Crida, A

    2009-01-01

    The Minimum Mass Solar Nebula (MMSN) is a protoplanetary disk that contains the minimum amount of solids necessary to build the planets of the Solar System. Assuming that the giant planets formed in the compact configuration they have at the beginning of the "Nice model", Desch (2007) built a new MMSN. He finds a decretion disk, about ten times denser than the well-known Hayashi MMSN. The disk profile is almost stationary for about ten million years. However, a planet in a protoplanetary disk migrates. In a massive, long-lived disk, this question has to be addressed. With numerical simulations, we show that the four giant planets of the Solar System could not survive in this disk. In particular, Jupiter enters the type III, runaway regime, and falls into the Sun like a stone. Known planet-planet interaction mechanisms to prevent migration, fail in this nebula, in contrast to the Hayashi MMSN. Planetary migration constrains the construction of a MMSN. We show how this should be done self-consistently.

  6. NOAC monitoring, reversal agents, and post-approval safety and effectiveness evaluation: A cardiac safety research consortium think tank.

    Science.gov (United States)

    Reiffel, James A; Weitz, Jeffrey I; Reilly, Paul; Kaminskas, Edvardas; Sarich, Troy; Sager, Philip; Seltzer, Jonathan

    2016-07-01

    Four non-vitamin K antagonist oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) have been approved in the United States for treatment of atrial fibrillation (AF) and venous thromboembolic disease. They have been as or more effective than the prior standards of care, with less fatal or intracranial bleeding, fewer drug and dietary interactions, and greater patient convenience. Nonetheless, the absence of the ability for clinicians to assess compliance or washout with a simple laboratory test (or to adjust dosing with a similar assessment) and the absence of an antidote to rapidly stop major hemorrhage or to enhance safety in the setting of emergent or urgent surgery/procedures have been limitations to greater non-vitamin K antagonist oral anticoagulant usage and better thromboembolic prevention. Accordingly, a Cardiac Research Safety Consortium "think tank" meeting was held in February 2015 to address these concerns. This manuscript reports on the discussions held and the conclusions reached at that meeting. PMID:27297852

  7. Interleukin-1 Antagonist Anakinra in Amyotrophic Lateral Sclerosis--A Pilot Study.

    Directory of Open Access Journals (Sweden)

    André Maier

    Full Text Available Preclinical studies show that blocking Interleukin-1 (IL-1 retards the progression of Amyotrophic Lateral Sclerosis (ALS. We assessed the safety of Anakinra (ANA, an IL-1 receptor antagonist, in ALS patients. In a single arm pilot study we treated 17 ALS patients with ANA (100 mg daily for one year. We selected patients with dominant or exclusive lower motor neuron degeneration (LMND presentation, as peripheral nerves may be more accessible to the drug. Our primary endpoint was safety and tolerability. Secondary endpoints included measuring disease progression with the revised ALS functional rating scale (ALSFRSr. We also quantified serum inflammatory markers. For comparison, we generated a historical cohort of 47 patients that fit the criteria for enrollment, disease characteristics and rate of progression of the study group. Only mild adverse events occurred in ALS patients treated with ANA. Notably, we observed lower levels of cytokines and the inflammatory marker fibrinogen during the first 24 weeks of treatment. Despite of this, we could not detect a significant reduction in disease progression during the same period in patients treated with ANA compared to controls as measured by the ALSFRSr. In the second part of the treatment period we observed an increase in serum inflammatory markers. Sixteen out of the 17 patients (94% developed antibodies against ANA. This study showed that blocking IL-1 is safe in patients with ALS. Further trials should test whether targeting IL-1 more efficiently can help treating this devastating disease.ClinicalTrials.gov NCT01277315.

  8. DIHYDROPYRIDINE CALCIUM ANTAGONISTS: DATA OF EVIDENCE BASED MEDICINE AND RECOM-MENDATIONS ON PRACTICAL USE

    Directory of Open Access Journals (Sweden)

    S. Y. Martsevich

    2015-12-01

    Full Text Available The classification of calcium antagonists is presented. There were considered the results of large randomized trials, which were devoted to study of influence of dihydropyridine calcium antagonists on the risk of cardiovascular complications. The place of dihydropyridine calcium antagonists in modern recommendations on treatment of arterial hypertension and ischemic heart disease is defined. The clinical importance of differences between various presentations of dihy-dropyridine calcium antagonists is stressed.

  9. Safety first

    CERN Multimedia

    2012-01-01

    Safety is a priority for CERN. That is a message I conveyed in my New Year’s address and that I reiterated at one of the first Enlarged Directorate meetings of 2012 when I outlined five key safety objectives for the year, designed and implemented according to accepted international standards.   As we move from spring to summer, it’s time to take stock of how we are doing. Objective number one for 2012, which overarches everything else, is to limit the number of incidents in the workplace. That means systematically investigating and acting on every incident that involves work stoppage, along with all the most frequent workplace accidents: falls, trips and slips. The performance indicator we set ourselves is the percentage of investigations and follow-ups completed. Year on year, these figures are rising but we can never be complacent, and must strive to reach and sustain 100% follow-up. The second objective is to improve hazard control, with a focus in 2012 on chemical ha...

  10. Plasma Processes : Minimum dissipative relaxed states in toroidal plasmas

    Indian Academy of Sciences (India)

    R Bhattacharyya; M S Janaki; B Dasgupta

    2000-11-01

    Relaxation of toroidal discharges is described by the principle of minimum energy dissipation together with the constraint of conserved global helicity. The resulting Euler-Lagrange equation is solved in toroidal coordinates for an axisymmetric torus by expressing the solutions in terms of Chandrasekhar-Kendall (C-K) eigenfunctions analytically continued in the complex domain. The C-K eigenfunctions are obtained as hypergeometric functions that are solutions of scalar Helmholtz equation in toroidal coordinates in the large aspect-ratio approximation. Equilibria are constructed by assuming the current to vanish at the edge of plasma. For the = 0; = 0 ( and are the poloidal and toroidal mode numbers respectively) relaxed states, the magnetic field, current, (safety factor) and pressure profiles are calculated for a given value of aspect-ratio of the torus and for different values of the eigenvalue 0. The new feature of the present model is that solutions allow for both tokamak as well as RFP-like behaviour with increase in the values of 0, which is related directly to volt-sec in the experiment.

  11. 36 CFR 223.61 - Establishing minimum stumpage rates.

    Science.gov (United States)

    2010-07-01

    ... offering where deposits are to be required for reforestation under the Act of June 9, 1930, as amended (46... reforestation deposits and a minimum deposit to the Treasury. Minimum rates in timber sale contracts will not be... reforestation....

  12. Tax evasion, minimum wage non-compliance and informality

    OpenAIRE

    Basu, Arnab K.; Chau, Nancy; Siddique, Zahra

    2011-01-01

    We study the impact of tax and minimum wage reforms on the incidence of informality. To gauge the incidence of informality, we use measures of the extent of tax evasion, the extent of minimum wage non-compliance, and the size of the informal workforce. Our approach allows us to examine (i) the distinction between determinants of firm-level reported wage distribution and actual wage distribution, (ii) the complementarity of tax and minimum wage enforcement, (iii) the impact that a minimum wage...

  13. The Minimum Wage: Labor Market Consequences in the Czech Republic

    OpenAIRE

    Kamila Fialová; Martina Mysíková

    2009-01-01

    This paper aims to quantify the impact of the minimum wage on labor market performance in the Czech Republic. Using regional data for 1995–2004, it estimates the effect of the minimum wage adjusted for the regional wage differential on regional unemployment. Consequently, using detailed individual data from 2004/2005, the authors analyze the annual hikes in the minimum wage, which allow them to estimate employment probabilities for workers with a wage level at, or close to, the new minimum wa...

  14. The parameters of a national minimum hourly wage

    OpenAIRE

    Askenazy, Philippe

    2014-01-01

    Both academic and political debates over the minimum wage generally focus on the minimum wage rate. However, the minimum wage is a complex institution composed of a wide variety of parameters. In this note, I show that nominal rates provide a very crude picture of minimal compensation and of actual employer cost by the comparison of the French, British and US Federal national minimum hourly wages. The extent of their coverage, enforcement procedures, and how the "wage" is defined differ widel...

  15. The Effects of Minimum Wages Throughout the Wage Distribution

    OpenAIRE

    David Neumark; Mark Schweitzer; William Wascher

    2000-01-01

    This paper provides evidence on a wide set of margins along which labor markets can adjust in response to increases in the minimum wage, including wages, hours, employment, and ultimately labor income, representing the central margins of adjustment that impact the economic well-being of workers potentially affected by minimum wage increases. The evidence indicates that workers initially earning near the minimum wage are adversely affected by minimum wage increases, while, not surprisingly, hi...

  16. Flare and CME Properties and Rates at Sunspot Minimum

    OpenAIRE

    Hudson, Hugh S.; Li, Yan

    2010-01-01

    The corona at solar minimum generally differs greatly from that during active times. We discuss the current Cycle 23/24 minimum from the point of view of the occurrence of flares and CMEs (Coronal Mass Ejections). By comparison with the previous minimum, the flare/CME ratio diminished by almost an order of magnitude. This suggests that the environmental effect in flare/CME association differed in the sense that the Cycle 23/24 minimum corona was relatively easy to disrupt.

  17. Oral mineralocorticoid antagonists for recalcitrant central serous chorioretinopathy

    Directory of Open Access Journals (Sweden)

    Chin EK

    2015-08-01

    Full Text Available Eric K Chin, David RP Almeida, C Nathaniel Roybal, Philip I Niles, Karen M Gehrs, Elliott H Sohn, H Culver Boldt, Stephen R Russell, James C FolkDepartment of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USAPurpose: To evaluate the effect and tolerance of oral mineralocorticoid antagonists, eplerenone and/or spironolactone, in recalcitrant central serous chorioretinopathy.Methods: Retrospective consecutive observational case series. Primary outcome measures included central macular thickness (CMT, µm, macular volume (MV, mm3, Snellen visual acuity, and prior treatment failures. Secondary outcomes included duration of treatment, treatment dosage, and systemic side effects.Results: A total of 120 patients with central serous chorioretinopathy were reviewed, of which 29 patients were treated with one or more mineralocorticoid antagonists. The average age of patients was 58.4 years. Sixteen patients (69.6% were recalcitrant to other interventions prior to treatment with oral mineralocorticoid antagonists, with an average washout period of 15.3 months. The average duration of mineralocorticoid antagonist treatment was 3.9±2.3 months. Twelve patients (52.2% showed decreased CMT and MV, six patients (26.1% had increase in both, and five patients (21.7% had negligible changes. The mean decrease in CMT of all patients was 42.4 µm (range, -136 to 255 µm: 100.7 µm among treatment-naïve patients, and 16.9 µm among recalcitrant patients. The mean decrease in MV of all patients was 0.20 mm3 (range, -2.33 to 2.90 mm3: 0.6 mm3 among treatment-naïve patients, and 0.0 mm3 among recalcitrant patients. Median visual acuity at the start of therapy was 20/30 (range, 20/20–20/250, and at final follow-up it was 20/40 (range, 20/20–20/125. Nine patients (39.1% experienced systemic side effects, of which three patients (13.0% were unable to continue therapy.Conclusion: Mineralocorticoid antagonist treatment had a positive treatment

  18. Antagonistic activity of dairy lactobacilli against gram-foodborne pathogens - doi: 10.4025/actascitechnol.v36i1.18776

    Directory of Open Access Journals (Sweden)

    Marco Geria

    2014-01-01

    Full Text Available Thirty-five strains of lactic acid bacteria were isolated from artisanal raw milk cheese, presumptively identified and tested against one dairy Escherichia coli strain. Six lactobacilli, exhibiting antagonistic activity, were identified at the species level and their action was evaluated against four strains of Gram-foodborne pathogens (Escherichia coli O26, Escherichia coli O157:H7, Salmonella spp. 1023, and Salmonella Typhimurium and the control strain Escherichia coli ATCC 45922. The antagonistic activity was determined by spot method and the inhibition zones were measured by Autodesk AutoCAD 2007. Three strains, all Lactobacillus paracasei, were active against all the pathogens; the other strains, all Lactobacillus plantarum, showed antagonistic activity against some pathogens. This study highlights the intense and different antagonistic activity induced by lactobacilli against various foodborne pathogens thus demonstrating that using selected lactic acid bacteria strains as adjunct cultures could be an effective strategy to prevent the development of foodborne pathogens in artisanal raw milk cheeses, and thus improving their safety.

  19. 14 CFR 23.1513 - Minimum control speed.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Minimum control speed. 23.1513 Section 23.1513 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... Information § 23.1513 Minimum control speed. The minimum control speed V MC, determined under § 23.149,...

  20. 14 CFR 25.1513 - Minimum control speed.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Minimum control speed. 25.1513 Section 25.1513 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... Limitations § 25.1513 Minimum control speed. The minimum control speed V MC determined under § 25.149 must...

  1. 14 CFR 29.49 - Performance at minimum operating speed.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Performance at minimum operating speed. 29... minimum operating speed. (a) For each Category A helicopter, the hovering performance must be determined... than helicopters, the steady rate of climb at the minimum operating speed must be determined over...

  2. 14 CFR 27.49 - Performance at minimum operating speed.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Performance at minimum operating speed. 27... minimum operating speed. (a) For helicopters— (1) The hovering ceiling must be determined over the ranges... climb at the minimum operating speed must be determined over the ranges of weight, altitude,...

  3. 12 CFR 263.82 - Establishment of minimum capital levels.

    Science.gov (United States)

    2010-01-01

    ... Maintain Adequate Capital § 263.82 Establishment of minimum capital levels. The Board has established minimum capital levels for state member banks and bank holding companies in its Capital Adequacy... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Establishment of minimum capital levels....

  4. 7 CFR 953.43 - Minimum standards of quality.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Minimum standards of quality. 953.43 Section 953.43... SOUTHEASTERN STATES Order Regulating Handling Regulations § 953.43 Minimum standards of quality. (a) Recommendation. Whenever the committee deems it advisable to establish and maintain minimum standards of...

  5. Observational Constraint to the Minimum Flux Corona Model

    OpenAIRE

    NAKATA, Michinori

    1985-01-01

    The minimum flux corona model proposed by Hearn was compared with the observational data. The temperature derived from Hearn's model is lower than that derived from X-ray observation for latetype main-sequence stars. In the solar coronal hole, Hearn's minimum condition is not realized. The minimum flux corona model seems to be adequate only to the solar quiet region.

  6. 29 CFR 505.3 - Prevailing minimum compensation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Prevailing minimum compensation. 505.3 Section 505.3 Labor... HUMANITIES § 505.3 Prevailing minimum compensation. (a)(1) In the absence of an alternative determination...)(2) of this section, the prevailing minimum compensation required to be paid under the Act to...

  7. 27 CFR 40.256 - Minimum manufacturing and activity requirements.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Minimum manufacturing and... Provisions Relating to Operations § 40.256 Minimum manufacturing and activity requirements. The minimum manufacturing and activity requirement prescribed in § 40.61(b) of this part is a continuing condition of...

  8. AHR-16303B, a novel antagonist of 5-HT2 receptors and voltage-sensitive calcium channels

    International Nuclear Information System (INIS)

    In vivo and in vitro methods were used to characterize AHR-16303B, a novel compound with antagonistic action at 5-HT2 receptors and voltage-sensitive calcium channels. The 5-HT2 receptor-antagonistic properties of AHR-16303B were demonstrated by inhibition of (a) [3H]ketanserin binding to rat cerebral cortical membranes (IC50 = 165 nM); (b) 5-hydroxytryptamine (5-HT)-induced foot edema in rats (minimum effective dose, (MED) = 0.32 mg/kg orally, p.o.); (c) 5-HT-induced vasopressor responses in spontaneously hypertensive rats (SHR) (ID50 = 0.18 mg/kg intravenously (i.v.), 1.8 mg/kg p.o.), (d) 5-HT-induced antidiuresis in rats (MED = 1 mg/kg p.o.), and (e) platelet aggregation induced by 5-HT + ADP (IC50 = 1.5 mM). The calcium antagonist properties of AHR-16303B were demonstrated by inhibition of (a) [3H]nimodipine binding to voltage-sensitive calcium channels on rabbit skeletal muscle membranes (IC50 = 15 nM), (b) KCl-stimulated calcium flux into cultured PC12 cells (IC50 = 81 nM), and (c) CaCl2-induced contractions of rabbit thoracic aortic strips (pA2 = 8.84). AHR-16303B had little or no effect on binding of radioligands to dopamine2 (DA2) alpha 1, alpha 2, H1, 5-HT1 alpha, beta 2, muscarinic M1, or sigma opioid receptors; had no effect on 5-HT3 receptor-mediated vagal bradycardia; and had only minor negative inotropic, chronotropic, and dromotropic effects on isolated guinea pig atria. In conscious SHR, 30 mg/kg p.o. AHR-16303B completely prevented the vasopressor responses to i.v. 5-HT, and decreased blood pressure (BP) by 24% 3 h after dosing

  9. Safety for Users

    CERN Document Server

    HR Department

    2008-01-01

    CERN welcomes more than 8000 Users every year. The PH Department as host to these scientific associates requires the highest safety standards. The PH Safety Office has published a Safety Flyer for Users. Important safety topics and procedures are presented. Although the Flyer is intended primarily to provide safety information for Users, the PH Safety Office invites all those on the CERN sites to keep a copy of the flyer as it gives guidance in matters of safety and explains what to do in the event of an emergency. Link: http://ph-dep.web.cern.ch/ph-dep/Safety/SafetyOffice.html PH-Safety Office PH Department

  10. Safety for Users

    CERN Document Server

    HR Department

    2008-01-01

    CERN welcomes more than 8000 Users every year. The PH Department as host to these scientific associates requires the highest safety standards. The PH Safety Office has published a safety flyer for Users. Important safety topics and procedures are presented. Although the flyer is intended primarily to provide safety information for Users, the PH Safety Office invites all those on the CERN sites to keep a copy of the flyer as it gives guidance in matters of safety and explains what to do in the event of an emergency. The flyer is available at: http://ph-dep.web.cern.ch/ph-dep/Safety/SafetyOffice.html PH-Safety Office PH Department

  11. Interpretability, validity, and the minimum important difference.

    Science.gov (United States)

    McClimans, Leah

    2011-12-01

    Patient-reported outcomes are increasingly used as dependent variables in studies regarding the effectiveness of clinical interventions. But patient-reported outcome measures (PROMs) do not provide intuitively meaningful data. For instance, it is not clear what a five point increase or decrease on a particular scale signifies. Establishing 'interpretability' involves making changes in outcomes meaningful. Attempts to interpret PROMs have led to the development of methods for identifying a minimum important difference (MID). In this paper, however, I draw on Charles Taylor's distinction between weak and strong evaluations to suggest that identifying a MID, specifically, a MID that uses a patient-reported reference group, may not provide an adequate interpretation of these measures. Moreover, I argue that the difficulty with interpreting these measures is tied to a larger problem concerning their validity. If researchers wish to interpret PROMs, they may first need to know more about the constructs they attempt to measure, namely, quality of life. PMID:21792659

  12. Galactic Archaeology and Minimum Spanning Trees

    CERN Document Server

    Macfarlane, B A; Flynn, C M L

    2015-01-01

    Chemical tagging of stellar debris from disrupted open clusters and associations underpins the science cases for next-generation multi-object spectroscopic surveys. As part of the Galactic Archaeology project TraCD (Tracking Cluster Debris), a preliminary attempt at reconstructing the birth clouds of now phase-mixed thin disk debris is undertaken using a parametric minimum spanning tree (MST) approach. Empirically-motivated chemical abundance pattern uncertainties (for a 10-dimensional chemistry-space) are applied to NBODY6-realised stellar associations dissolved into a background sea of field stars, all evolving in a Milky Way potential. We demonstrate that significant population reconstruction degeneracies appear when the abundance uncertainties approach 0.1 dex and the parameterised MST approach is employed; more sophisticated methodologies will be required to ameliorate these degeneracies.

  13. Aligning Sequences by Minimum Description Length

    Directory of Open Access Journals (Sweden)

    John S. Conery

    2008-01-01

    Full Text Available This paper presents a new information theoretic framework for aligning sequences in bioinformatics. A transmitter compresses a set of sequences by constructing a regular expression that describes the regions of similarity in the sequences. To retrieve the original set of sequences, a receiver generates all strings that match the expression. An alignment algorithm uses minimum description length to encode and explore alternative expressions; the expression with the shortest encoding provides the best overall alignment. When two substrings contain letters that are similar according to a substitution matrix, a code length function based on conditional probabilities defined by the matrix will encode the substrings with fewer bits. In one experiment, alignments produced with this new method were found to be comparable to alignments from CLUSTALW. A second experiment measured the accuracy of the new method on pairwise alignments of sequences from the BAliBASE alignment benchmark.

  14. The chemical logic of a minimum protocell

    Science.gov (United States)

    Morowitz, Harold J.; Heinz, Bettina; Deamer, David W.

    1988-09-01

    Traditional schemes for the origin of cellular life on earth generally suppose that the chance assembly of polymer synthesis systems was the initial event, followed by incorporation into a membrane-enclosed volume to form the earliest cells. Here we discuss an alternative system consisting of replicating membrane vesicles, which we define as minimum protocells. These consist of vesicular bilayer membranes that self-assemble from relatively rare organic amphiphiles present in the prebiotic environment. If some of the amphiphiles are primitive pigment molecules asymmetrically oriented in the bilayer, light energy can be captured in the form of electrochemical ion gradients. This energy could then be used to convert relatively common precursor molecules into membrane amphiphiles, thereby providing an initial photosynthetic growth process, as well as an appropriate microenvironment for incorporation and evolution of polymer synthesis systems.

  15. Radiation belt dynamics during solar minimum

    Energy Technology Data Exchange (ETDEWEB)

    Gussenhoven, M.S.; Mullen, E.G. (Geophysics Lab., Air Force Systems Command, Hanscom AFB, MA (US)); Holeman, E. (Physics Dept., Boston College, Chestnut Hill, MA (US))

    1989-12-01

    Two types of temporal variation in the radiation belts are studied using low altitude data taken onboard the DMSP F7 satellite: those associated with the solar cycle and those associated with large magnetic storm effects. Over a three-year period from 1984 to 1987 and encompassing solar minimum, the protons in the heart of the inner belt increased at a rate of approximately 6% per year. Over the same period, outer zone electron enhancements declined both in number and peak intensity. During the large magnetic storm of February 1986, following the period of peak ring current intensity, a second proton belt with energies up to 50 MeV was found at magnetic latitudes between 45{degrees} and 55{degrees}. The belt lasted for more than 100 days. The slot region between the inner and outer electron belts collapsed by the merging of the two populations and did not reform for 40 days.

  16. Duality of Maximum Entropy and Minimum Divergence

    Directory of Open Access Journals (Sweden)

    Shinto Eguchi

    2014-06-01

    Full Text Available We discuss a special class of generalized divergence measures by the use of generator functions. Any divergence measure in the class is separated into the difference between cross and diagonal entropy. The diagonal entropy measure in the class associates with a model of maximum entropy distributions; the divergence measure leads to statistical estimation via minimization, for arbitrarily giving a statistical model. The dualistic relationship between the maximum entropy model and the minimum divergence estimation is explored in the framework of information geometry. The model of maximum entropy distributions is characterized to be totally geodesic with respect to the linear connection associated with the divergence. A natural extension for the classical theory for the maximum likelihood method under the maximum entropy model in terms of the Boltzmann-Gibbs-Shannon entropy is given. We discuss the duality in detail for Tsallis entropy as a typical example.

  17. Perspectives of CB1 Antagonist in Treatment of Obesity: Experience of RIO-Asia

    Directory of Open Access Journals (Sweden)

    Changyu Pan

    2011-01-01

    Full Text Available Rimonabant, a selective cannabinoid-1 (CB1 receptor antagonist, has been shown to reduce weight and enhance improvements in cardiometabolic risk parameters in Western populations. This study assessed these effects of rimonabant in Asian population. A total of 643 patients (BMI 25 kg/m2 or greater without diabetes from China, Republic of Korea, and Taiwan were prescribed a hypocaloric diet (600 kcal/day deficit and randomized to rimonabant 20 mg (n=318 or placebo (n=325 for 9months. The primary efficacy variable was weight change from baseline after 9 months of treatment. Results showed that rimonabant group lost more weight than placebo, (LSM ± SEM of −4.7 ± 0.3 kg vs. −1.7 ± 0.3 kg, P<.0001. The 5% and 10% responders were 2 or 3 folds more in the rimonabant group (53.0% vs. 20.0% and 21.5% vs. 5.7%, resp. (P<.0001. Rimonabant also significantly increased HDL-cholesterol, decreased triglycerides and waist circumference,by 7.1%, 10.6%, and 2.8 cm, respectively (P<.0001. This study confirmed the comparable efficacy and safety profile of rimonabant in Asian population to Caucasians. Owing to the recent suspension of all the CB1 antagonists off the pharmaceutical market for weight reduction in Europe and USA, a perspective in drug discovery for intervening peripheral CB1 receptor in the management of obesity is discussed.

  18. Mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction (HFpEF).

    Science.gov (United States)

    Capuano, Annalisa; Scavone, Cristina; Vitale, Cristiana; Sportiello, Liberata; Rossi, Francesco; Rosano, Giuseppe M C; Coats, Andrew J Stewart

    2015-12-01

    The role of spironolactone and eplerenone in patients with Heart Failure with preserved Ejection Fraction (HFpEF) is not well defined. Since a growing medical literature has suggested that mineralocorticoid receptor antagonists may be beneficial for patients with HFpEF, this review gives an in-depth update on the role of spironolactone and eplerenone and their implications for therapy in the setting of HFpEF. Eleven clinical studies, including seven randomized trials, were reviewed. Two randomized controlled trials evaluated the effect of eplerenone on different end-points, including 6 minute walk distance (6 MWD), cardiovascular mortality, non-fatal reinfarction, hospitalization for unstable angina and congestive heart failure. Eplerenone did not affect either 6 MWD or event-free survival rates in the overall study population in these two reports. The effects of spironolactone on similar composite endpoints were evaluated in 7 studies in patients with HFpEF. Compared to placebo, hospitalization for heart failure was significantly lower in the spironolactone group and spironolactone was also shown to improve diastolic function and induced beneficial remodeling through a reduction in myocardial fibrosis. The safety profile of spironolactone and eplerenone has been assessed in two recent studies. Data showed that eplerenone and spironolactone are both associated with the occurrence of gynecomastia, mastodynia, and abnormal vaginal bleeding and in addition, they can increase natriuresis and cause renal retention of potassium; furthermore, eplerenone may cause hyperkalemia and promote the onset of metabolic acidosis or hyponatremia. In conclusion although the mineralocorticoid receptor antagonists eplerenone and spironolactone improve clinical outcomes in patients with HFrEF, additional data will be necessary to better define their risk-benefit profile, especially for eplerenone, in the treatment of HFpEF.

  19. Construction safety

    CERN Document Server

    Li, Rita Yi Man

    2013-01-01

    A close-to-ideal blend of suburb and city, speedy construction of towers of Babylon, the sparkling proportion of glass and steel buildings’ facade at night showcase the wisdom of humans. They also witness the footsteps, sweats and tears of architects and engineers. Unfortunately, these signatures of human civilizations are swathed in towering figures of construction accidents. Fretting about these on sites, different countries adopt different measures on sites. This book firstly sketches the construction accidents on sites, followed by a review on safety measures in some of the developing countries such as Bermuda, Egypt, Kuwait and China; as well as developed countries, for example, the United States, France and Singapore. It also highlights the enormous compensation costs with the courts’ experiences in the United Kingdom and Hong Kong.

  20. A unified model-free controller for switching minimum phase, non-minimum phase and time-delay systems

    CERN Document Server

    Michel, Loïc

    2012-01-01

    This preliminary work presents a simple derivation of the standard model-free control in order to control switching minimum phase, non-minimum phase and time-delay systems. The robustness of the proposed method is studied in simulation.

  1. Global safety

    Directory of Open Access Journals (Sweden)

    Dorien J. DeTombe

    2010-08-01

    Full Text Available Global Safety is a container concept referring to various threats such as HIV/Aids, floods and terrorism; threats with different causes and different effects. These dangers threaten people, the global economy and the slity of states. Policy making for this kind of threats often lack an overview of the real causes and the interventions are based on a too shallow analysis of the problem, mono-disciplinary and focus mostly only on the effects. It would be more appropriate to develop policy related to these issues by utilizing the approaches, methods and tools that have been developed for complex societal problems. Handling these complex societal problems should be done multidisciplinary instead of mono-disciplinary. In order to give politicians the opportunity to handle complex problems multidisciplinary, multidisciplinary research institutes should be created. These multidisciplinary research institutes would provide politicians with better approaches to handle this type of problem. In these institutes the knowledge necessary for the change of these problems can be created through the use of the Compram methodology which has been developed specifically for handling complex societal problems. In a six step approach, experts, actors and policymakers discuss the content of the problem and the possible changes. The framework method uses interviewing, the Group Decision Room, simulation models and scenario's in a cooperative way. The methodology emphasizes the exchange of knowledge and understanding by communication among and between the experts, actors and politicians meanwhile keeping emotion in mind. The Compram methodology will be further explained in relation to global safety in regard to terrorism, economy, health care and agriculture.

  2. Control of Wilt and Blight Diseases of Cumin through Antagonistic Fungi under in Vitro and Field Conditions

    Directory of Open Access Journals (Sweden)

    P. DEEPAK

    2008-08-01

    Full Text Available The experiment was carried out to assess their possible use as bio-agents for several antagonistic fungi on growth of two cumin fungal pathogens under in vitro and field conditions. Under in vitro conditions maximum inhibition (82.86% of radial growth of Fusarium oxysporum f. sp. cumini was observed with the treatment of Trichoderma harzianum strain I, whereas maximum inhibition (85.45% of the mycelial growth of Alternaria burnsii was observed in the presence of Trichoderma harzianum strain II. The antagonists who showed maximum inhibition of the pathogen in laboratory conditions were applied in field conditions as soil treatment/seed treatment or as foliar spray. The incidence of wilt disease was found to be lowest (PDI 27.40% when soil was treated with Trichoderma harzianium strain I at the rate of 24g / 6m2 (weight of fungus with sorghum seeds. Minimum blight disease incidence was observed when T. harzianum strain II was applied to the soil at the rate of 24g / 6m2 (36.15% or when 10% spore suspension of T. harzianum strain II was applied as seed treatment at the time of sowing and as spray at the time of flowering (PDI 35.10%. Thus treatments of Trichoderma harzianum strain I for wilt and Trichoderma harzianum strain II for blight diseases of cumin under both the conditions @ 24g / 6m2 or 40kg / ha seems promising for sustainable management of crop diseases.

  3. Biological effects of growth hormone and its antagonist.

    Science.gov (United States)

    Okada, S; Kopchick, J J

    2001-03-01

    Serum levels of growth hormone (GH) can vary. Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly and has been implicated in diabetic eye and kidney damage. Additionally the GH/IGF-1 system has been postulated as a risk factor for several types of cancers. Thus both elevated and suppressed circulating levels of GH can have pronounced physiological effects. More than a decade ago the first drug of a new class, a GH antagonist, was discovered. This molecule is now being tested for its ability to combat the effects of high circulating levels of GH. Here, we discuss some of the detrimental actions of GH, and how a GH antagonist can be used to combat these effects. PMID:11286784

  4. Antagonistic otolith-visual units in cat vestibular nuclei

    Science.gov (United States)

    Daunton, Nancy G.; Christensen, Carol A.

    1992-01-01

    The nature of neural coding of visual (Vis) and vestibular (Vst) information on translational motion in the region of the vestibular nuclei was investigated using extracellular single-unit recordings in alert adult cats. Responses were recorded and averaged over 60 cycles of stimulation in the vertical and horizontal planes, which included the Vst (movement of the animal in the dark), Vis (movement within lighted visual surround), and combined Vis and Vst (movement of the animal within the lighted stationary visual surround). Data are reported on responses to stimulations along the axis showing maximal sensitivity. A small number of units were identified that showed an antagonistic relationship between their Vis and Vst responses (since they were maximally excited by Vis and by Vst stimulations in the same direction). Results suggest that antagonistic units may belong to an infrequently encountered, but functionally distinct, class of neurons.

  5. Potential Clinical Implications of the Urotensin II Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Emilie Kane

    2011-07-01

    Full Text Available Urotensin-II (UII, which binds to its receptor UT, plays an important role in the heart, kidneys, pancreas, adrenal gland and CNS. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in heart disease, metabolic syndrome and kidney failure. The increase in UII release and UT expression suggest that UII system may be implicated in the pathology and pathogenesis of these diseases by causing an increase in ACAT-1 activity leading to SMC proliferation and foam cell infiltration, insulin resistance (DMII, as well as inflammation, high blood pressure and plaque formation. Recently, UT antagonists such as SB-611812, palosuran, and most recently a piperazino-isoindolinone based antagonist have been developed in the hope of better understanding the UII system and treating its associated diseases.

  6. Histamine-2 receptor antagonists as immunomodulators: new therapeutic views?

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1996-01-01

    Considerable evidence has emerged to suggest that histamine participates in the regulation of the inflammatory response, immune reaction, coagulation cascade, and cardiovascular function. Furthermore, histamine may play a major role in the growth of normal and malignant tissue as a regulator...... of proliferation and angiogenesis. Specific histamine receptors have been identified on the surface of bone marrow cells, immune competent cells, endothelial cells, fibroblasts, and also on malignant cells. This has prompted research in regulation by specific histamine receptor agonists and antagonists. Results...... from such studies are currently accumulating and suggest that the histamine-2 receptor antagonists have potential beneficial effects in the treatment of certain malignant, autoimmune and skin diseases, either alone or in combination with other drugs. The beneficial effect of histamine-2 receptor...

  7. The Effects Of The Minimum Wage On Wages And Employment In Brazil - A Menu Of Minimum Wage Variables

    OpenAIRE

    Lemos, S.

    2004-01-01

    The international literature on minimum wage strongly lacks empirical evidence from developing countries. In Brazil, not only are increases in the minimum wage large and frequent - unlike the typically small increases focused upon in most of the existing literature - but also the minimum wage plays a central and complex role. In addition to its social role the minimum wage has been used as anti-inflationary policy, confirming its importance to the Brazilian Economy. This paper ana...

  8. 5-HT3 antagonist for cognition improvement in schizophrenia: a double blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Neyousha Mohammadi

    2010-01-01

    Full Text Available   Abstract   Introduction: Patients with schizophrenia characteristically exhibit cognitive deficits. The level of cognitive impairment is found to predict the functional outcome of the illness more strongly than the severity of positive or negative symptoms. The purpose of this study was to assess the efficacy of ondansetron, a 5-HT3 receptor antagonist as an adjuvant agent in the treatment of chronic schizophrenia in particular for cognitive impairments.   Methods: This investigation was a 12-week, double blind study of parallel groups of patients with stable chronic schizophrenia. Thirty patients were recruited from inpatient and outpatient departments. All participants met Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR criteria for schizophrenia. To be eligible, patients were required to have been treated with a stable dose of risperidone as their primary antipsychotic treatment for a minimum period of 8 weeks. The subjects were randomized to receive ondansetron (8 mg/day or the placebo in addition to risperidone. Cognition was measured by a cognitive battery. Patients were assessed at baseline and after 8, and 12 weeks after the medication started.   Results: Administration of ondansetron significantly improved visual memory based on improvement on visual reproduction, visual paired associate and figural memory sub tests of Wechsler Memory Scale Revised.  Discussion: The present study indicates ondansetron as potential adjunctive treatment strategy for chronic schizophrenia particularly for cognitive impairments.

  9. EVALUATION OF PHOSPHATE SOLUBILIZING MICROORGANISMS (PSMs FROM RHIZOSPHERE SOIL OF DIFFERENT CROP PLANTS AND ITS ANTAGONISTIC ACTIVITY

    Directory of Open Access Journals (Sweden)

    Samikan Krishnakumar

    2014-04-01

    Full Text Available Indigenous rhizosphere soil samples were collected during study period (October 2011 – March 2012 of different crop plant from Thiruvannamalai District, Tamilnadu, India for the enumeration of Phosphate solubilizing microorganisms (PSMs. Efficient phosphate solubilizing bacteria, fungi and heterotrophic bacteria were enumerated. Maximum heterotrophic bacterial populations (19.4 X105, phosphate solubilizing bacteria (4.7 X 105 were recorded in the month of February and phosphate solubilizing fungi (3.9 X 102 were documented in the month of December in rhizosphere soil of ground nut. Minimum bacterial populations (14.3 X 105 were observed in rhizosphere soil of chilli in the month of March. Lowest phosphate solubilizing bacteria (1.2 X105 and phosphate solubilzing fungi (1.2 X 102 were observed in rhizosphere soil of paddy during the month of October. Phosphate solubilizing bacteria Pseudomonassp. - BS1, Bacillus sp. – BS2, Micrococcus sp. – BS3 and fungi Aspergillus sp. – FS1, Penicillium sp. – FS2.and Trichoderma sp. – FS3 were identified. Pseudomonas sp. - BS1. exhibited maximum solubilizing efficiency (SE and solubilizing index (SI of 300.0 and 4.0 respectively. In fungi Aspergillus sp. – FS1 showed a maximum solubilizing efficiency (SE and solubilizing index(SI of 283.3 and 3.8 respectively. Antagonistic activity of P-solubilizing Pseudomonassp. - BS1 was deliberated against selected fungal plant pathogens. Among pathogens studied Aspergillus sp. showed a maximum inhibition activity (16 mm and minimum activity (12 mm was observed against Fusarium sp. Moreover inhibition efficiency (IE and inhibition index (II of Pseudomonas sp. - BS1. also calculated base on the antagonistic activity. Aspergillus sp. exhibited highest inhibition efficiency and inhibition index of 166.6 and 3.6 respectively.

  10. Construction, purification, and characterization of a chimeric TH1 antagonist

    Directory of Open Access Journals (Sweden)

    Javier-González Luís

    2006-05-01

    Full Text Available Abstract Background TH1 immune response antagonism is a desirable approach to mitigate some autoimmune and inflammatory reactions during the course of several diseases where IL-2 and IFN-γ are two central players. Therefore, the neutralization of both cytokines could provide beneficial effects in patients suffering from autoimmune or inflammatory illnesses. Results A chimeric antagonist that can antagonize the action of TH1 immunity mediators, IFN-γ and IL-2, was designed, engineered, expressed in E. coli, purified and evaluated for its in vitro biological activities. The TH1 antagonist molecule consists of the extracellular region for the human IFNγ receptor chain 1 fused by a four-aminoacid linker peptide to human 60 N-terminal aminoacid residues of IL-2. The corresponding gene fragments were isolated by RT-PCR and cloned in the pTPV-1 vector. E. coli (W3110 strain was transformed with this vector. The chimeric protein was expressed at high level as inclusion bodies. The protein was partially purified by pelleting and washing. It was then solubilized with strong denaturant and finally refolded by gel filtration. In vitro biological activity of chimera was demonstrated by inhibition of IFN-γ-dependent HLA-DR expression in Colo 205 cells, inhibition of IFN-γ antiproliferative effect on HEp-2 cells, and by a bidirectional effect in assays for IL-2 T-cell dependent proliferation: agonism in the absence versus inhibition in the presence of IL-2. Conclusion TH1 antagonist is a chimeric protein that inhibits the in vitro biological activities of human IFN-γ, and is a partial agonist/antagonist of human IL-2. With these attributes, the chimera has the potential to offer a new opportunity for the treatment of autoimmune and inflammatory diseases.

  11. Alternation of Agonists and Antagonists During Turtle Hindlimb Motor Rhythms

    OpenAIRE

    Stein, Paul S.G.

    2010-01-01

    In a variety of vertebrates, including turtle, many classical and contemporary studies of spinal cord neuronal networks generating rhythmic motor behaviors emphasize a Reciprocal Model with alternation of agonists and antagonists, alternation of excitatory and inhibitory postsynaptic potentials, and reciprocal inhibition. Some studies of spinal cord neuronal networks, including those in turtle during scratch motor rhythms, describe a Balanced Model with concurrent excitatory and inhibitory po...

  12. Ondansetron, a 5-HT3 antagonist, improves cerebellar tremor.

    OpenAIRE

    Rice, G P; Lesaux, J; Vandervoort, P.; Macewan, L; Ebers, G C

    1997-01-01

    It has been previously shown that ondansetron, a 5-HT3 antagonist, can ameliorate vertigo in patients with acute brainstem disorders. A coincidental benefit was the improvement of cerebellar tremor in some patients with both vertigo and tremor. To further evaluate this effect, a placebo controlled, double blind, crossover study was conducted of a single dose of intravenous ondansetron in 20 patients with cerebellar tremor caused by multiple sclerosis, cerebellar degeneration, or drug toxicity...

  13. attracting antagonists: does floral nectar increase leaf herbivory?

    OpenAIRE

    Adler, L.S.; Bronstein, J. L.

    2004-01-01

    Traits that are attractive to mutualists may also attract antagonists, resulting in conflicting selection pressures. Here we develop the idea that increased floral nectar production can, in some cases, increase herbivory. In these situations, selection for increased nectar production to attract pollinators may be constrained by a linked cost of herbivore attraction. In support of this hypothesis, we report that experimentally supplementing nectar rewards in Datura stramonium led to increased ...

  14. Biological control of Fusarium graminearum on wheat by antagonistic bacteria

    OpenAIRE

    Javad Nourozian; Hassan Reza Etebarian; Gholam Khodakaramian

    2006-01-01

    Bacillus subtilis strains 53 and 71, Pseudomonas fluorescens biov1 strain 32 and Streptomyces sp. Strain 3 were evaluated as potential biological agents for control of fusarium head blight (FHB) caused by Fusarium graminearum. Mycelial growth of the pathogen was reduced by cell free and volatile metabolites of bacterial antagonists by 37%-97%. Streptomyces sp. Strain 3 reduced disease severity of FHB 21 d after inoculation. The yield of wheat from plants treated with Streptomyces sp. strain 3...

  15. Wage discrimination and partial compliance with the minimum wage law

    OpenAIRE

    Yang-Ming Chang; Bhavneet Walia

    2007-01-01

    This paper presents a simple model to characterize the discriminatory behavior of a non-complying firm in a minimum-wage economy. In the analysis, the violating firm pays one “favored†group of workers the statutory minimum and the other “non-favored†group of workers a sub-minimum. We find conditions under which law enforcement is ineffective in improving the between-group wage differentials. We show that an increase in the minimum wage raises the sub-minimum wage and employment of wor...

  16. Histamine H1 antagonists and clinical characteristics of febrile seizures

    Directory of Open Access Journals (Sweden)

    Zolaly MA

    2012-03-01

    Full Text Available Mohammed A ZolalyDepartment of Pediatrics, College of Medicine, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi ArabiaBackground: The purpose of this study was to determine whether seizure susceptibility due to antihistamines is provoked in patients with febrile seizures.Methods: The current descriptive study was carried out from April 2009 to February 2011 in 250 infants and children who visited the Madinah Maternity and Children's Hospital as a result of febrile convulsions. They were divided into two groups according to administration of antihistamines at the onset of fever.Results: Detailed clinical manifestations were compared between patients with and without administration of antihistamines. The time from fever detection to seizure onset was significantly shorter in the antihistamine group than that in the nonantihistamine group, and the duration of seizures was significantly longer in the antihistamine group than in the nonantihistamine group. No significant difference was found in time from fever detection to seizure onset or seizure duration between patients who received a first-generation antihistamine and those who received a second-generation antihistamine.Conclusion: Due to their central nervous system effects, H1 antagonists should not be administered to patients with febrile seizures and epilepsy. Caution should be exercised regarding the use of histamine H1 antagonists in young infants, because these drugs could potentially disturb the anticonvulsive central histaminergic system.Keywords: antihistamine, nonantihistamine, histamine H1 antagonist, febrile seizures

  17. Approaches to the rational design of selective melanocortin receptor antagonists

    Science.gov (United States)

    Hruby, Victor J; Cai, Minying; Nyberg, Joel; Muthu, Dhanasekaran

    2015-01-01

    Introduction When establishing the physiological roles of specific receptors in normal and disease states, it is critical to have selective antagonist ligands for each receptor in a receptor system with several subtypes. The melanocortin receptors have five subtypes referred to as the melanocortin 1 receptor, melanocortin 2 receptor, melanocortin 3 receptor, melanocortin 4 receptor and melanocortin 5 receptor, and they are of critical importance for many aspects of human health and disease. Areas covered This article reviews the current efforts to design selective antagonistic ligands for the five human melanocortin receptors summarizing the currently published orthosteric and allosteric antagonists for each of these receptors. Expert opinion Though there has been progress, there are still few drugs available that address the many significant biological activities and diseases that are associated with these receptors, which is possibly due to the lack of receptor selectivity that these designed ligands are currently showing. The authors believe that further studies into the antagonists’ 3D conformational and topographical properties in addition to future mutagenesis studies will provide greater insight into these ligands which could play a role in the treatment of various diseases in the future. PMID:22646078

  18. Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury.

    Directory of Open Access Journals (Sweden)

    Sachiko Yamada

    Full Text Available Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7 in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1, a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.

  19. μ Opioid receptor: novel antagonists and structural modeling

    Science.gov (United States)

    Kaserer, Teresa; Lantero, Aquilino; Schmidhammer, Helmut; Spetea, Mariana; Schuster, Daniela

    2016-02-01

    The μ opioid receptor (MOR) is a prominent member of the G protein-coupled receptor family and the molecular target of morphine and other opioid drugs. Despite the long tradition of MOR-targeting drugs, still little is known about the ligand-receptor interactions and structure-function relationships underlying the distinct biological effects upon receptor activation or inhibition. With the resolved crystal structure of the β-funaltrexamine-MOR complex, we aimed at the discovery of novel agonists and antagonists using virtual screening tools, i.e. docking, pharmacophore- and shape-based modeling. We suggest important molecular interactions, which active molecules share and distinguish agonists and antagonists. These results allowed for the generation of theoretically validated in silico workflows that were employed for prospective virtual screening. Out of 18 virtual hits evaluated in in vitro pharmacological assays, three displayed antagonist activity and the most active compound significantly inhibited morphine-induced antinociception. The new identified chemotypes hold promise for further development into neurochemical tools for studying the MOR or as potential therapeutic lead candidates.

  20. IAP antagonists sensitize murine osteosarcoma cells to killing by TNFα

    Science.gov (United States)

    Shekhar, Tanmay M.; Miles, Mark A.; Gupte, Ankita; Taylor, Scott; Tascone, Brianna; Walkley, Carl R.; Hawkins, Christine J.

    2016-01-01

    Outcomes for patients diagnosed with the bone cancer osteosarcoma have not improved significantly in the last four decades. Only around 60% of patients and about a quarter of those with metastatic disease survive for more than five years. Although DNA-damaging chemotherapy drugs can be effective, they can provoke serious or fatal adverse effects including cardiotoxicity and therapy-related cancers. Better and safer treatments are therefore needed. We investigated the anti-osteosarcoma activity of IAP antagonists (also known as Smac mimetics) using cells from primary and metastatic osteosarcomas that arose spontaneously in mice engineered to lack p53 and Rb expression in osteoblast-derived cells. The IAP antagonists SM-164, GDC-0152 and LCL161, which efficiently target XIAP and cIAPs, sensitized cells from most osteosarcomas to killing by low levels of TNFα but not TRAIL. RIPK1 expression levels and activity correlated with sensitivity. RIPK3 levels varied considerably between tumors and RIPK3 was not required for IAP antagonism to sensitize osteosarcoma cells to TNFα. IAP antagonists, including SM-164, lacked mutagenic activity. These data suggest that drugs targeting XIAP and cIAP1/2 may be effective for osteosarcoma patients whose tumors express abundant RIPK1 and contain high levels of TNFα, and would be unlikely to provoke therapy-induced cancers in osteosarcoma survivors. PMID:27129149

  1. Automatic safety rod for reactors. [LMFBR

    Science.gov (United States)

    Germer, J.H.

    1982-03-23

    An automatic safety rod for a nuclear reactor containing neutron absorbing material and designed to be inserted into a reactor core after a loss-of-flow. Actuation is based upon either a sudden decrease in core pressure drop or the pressure drop decreases below a predetermined minimum value. The automatic control rod includes a pressure regulating device whereby a controlled decrease in operating pressure due to reduced coolant flow does not cause the rod to drop into the core.

  2. Minimum Energy Requirements in Complex Distillation Arrangements

    Energy Technology Data Exchange (ETDEWEB)

    Halvorsen, Ivar J.

    2001-07-01

    Distillation is the most widely used industrial separation technology and distillation units are responsible for a significant part of the total heat consumption in the world's process industry. In this work we focus on directly (fully thermally) coupled column arrangements for separation of multicomponent mixtures. These systems are also denoted Petlyuk arrangements, where a particular implementation is the dividing wall column. Energy savings in the range of 20-40% have been reported with ternary feed mixtures. In addition to energy savings, such integrated units have also a potential for reduced capital cost, making them extra attractive. However, the industrial use has been limited, and difficulties in design and control have been reported as the main reasons. Minimum energy results have only been available for ternary feed mixtures and sharp product splits. This motivates further research in this area, and this thesis will hopefully give some contributions to better understanding of complex column systems. In the first part we derive the general analytic solution for minimum energy consumption in directly coupled columns for a multicomponent feed and any number of products. To our knowledge, this is a new contribution in the field. The basic assumptions are constant relative volatility, constant pressure and constant molar flows and the derivation is based on Underwood's classical methods. An important conclusion is that the minimum energy consumption in a complex directly integrated multi-product arrangement is the same as for the most difficult split between any pair of the specified products when we consider the performance of a conventional two-product column. We also present the Vmin-diagram, which is a simple graphical tool for visualisation of minimum energy related to feed distribution. The Vmin-diagram provides a simple mean to assess the detailed flow requirements for all parts of a complex directly coupled arrangement. The main purpose in

  3. Fire safety

    Energy Technology Data Exchange (ETDEWEB)

    Keski-Rahkonen, O.; Bjoerkman, J.; Hostikka, S.; Mangs, J. [VTT Building Technology, Espoo (Finland); Huhtanen, R. [VTT Energy, Espoo (Finland); Palmen, H.; Salminen, A.; Turtola, A. [VTT Automation, Espoo (Finland)

    1998-07-01

    According to experience and probabilistic risk assessments, fires present a significant hazard in a nuclear power plant. Fires may be initial events for accidents or affect safety systems planned to prevent accidents and to mitigate their consequences. The project consists of theoretical work, experiments and simulations aiming to increase the fire safety at nuclear power plants. The project has four target areas: (1) to produce validated models for numerical simulation programmes, (2) to produce new information on the behavior of equipment in case of fire, (3) to study applicability of new active fire protecting systems in nuclear power plants, and (4) to obtain quantitative knowledge of ignitions induced by important electric devices in nuclear power plants. These topics have been solved mainly experimentally, but modelling at different level is used to interpret experimental data, and to allow easy generalisation and engineering use of the obtained data. Numerical fire simulation has concentrated in comparison of CFD modelling of room fires, and fire spreading on cables on experimental data. So far the success has been good to fair. A simple analytical and numerical model has been developed for fire effluents spreading beyond the room of origin in mechanically strongly ventilated compartments. For behaviour of equipment in fire several full scale and scaled down calorimetric experiments were carried out on electronic cabinets, as well as on horizontal and vertical cable trays. These were carried out to supply material for CFD numerical simulation code validation. Several analytical models were developed and validated against obtained experimental results to allow quick calculations for PSA estimates as well as inter- and extrapolations to slightly different objects. Response times of different commercial fire detectors were determined for different types of smoke, especially emanating from smoldering and flaming cables to facilitate selection of proper detector

  4. Linking Safety Analysis to Safety Requirements

    DEFF Research Database (Denmark)

    Hansen, Kirsten Mark

    the same system model and that this model is formalized in a real-time, interval logic, based on a conventional dynamic systems model with a state over time. The three safety analysis techniques are interpreted in this model and it is shown how to derive safety requirements for components of a system.......Software for safety critical systems must deal with the hazards identified by safety analysistechniques: Fault trees, event trees,and cause consequence diagrams can be interpreted as safety requirements and used in the design activity. We propose that the safety analysis and the system design use...

  5. CERN's new safety policy

    CERN Multimedia

    2014-01-01

    The documents below, published on 29 September 2014 on the HSE website, together replace the document SAPOCO 42 as well as Safety Codes A1, A5, A9, A10, which are no longer in force. As from the publication date of these documents any reference made to the document SAPOCO 42 or to Safety Codes A1, A5, A9 and A10 in contractual documents or CERN rules and regulations shall be deemed to constitute a reference to the corresponding provisions of the documents listed below.   "The CERN Safety Policy" "Safety Regulation SR-SO - Responsibilities and organisational structure in matters of Safety at CERN" "General Safety Instruction GSI-SO-1 - Departmental Safety Officer (DSO)" "General Safety Instruction GSI-SO-2 - Territorial Safety Officer (TSO)" "General Safety Instruction GSI-SO-3 - Safety Linkperson (SLP)" "General Safety Instruction GSI-SO-4 - Large Experiment Group Leader In Matters of Safety (LEXGLI...

  6. Safety and tolerability of montelukast in placebo-controlled pediatric studies and their open-label extensions

    DEFF Research Database (Denmark)

    Bisgaard, H.; Skoner, D.; Boza, M.L.;

    2009-01-01

    Montelukast is a potent leukotriene-receptor antagonist administered once daily that provides clinical benefit in the treatment of asthma and allergic rhinitis in children and adults. Because of its wide use as a pediatric controller, there is a need for a further review of the safety and tolerab......Montelukast is a potent leukotriene-receptor antagonist administered once daily that provides clinical benefit in the treatment of asthma and allergic rhinitis in children and adults. Because of its wide use as a pediatric controller, there is a need for a further review of the safety...... and tolerability of montelukast in children....

  7. The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus.

    Science.gov (United States)

    Guzman-Perez, Angel; Pfefferkorn, Jeffrey A; Lee, Esther C Y; Stevens, Benjamin D; Aspnes, Gary E; Bian, Jianwei; Didiuk, Mary T; Filipski, Kevin J; Moore, Dianna; Perreault, Christian; Sammons, Matthew F; Tu, Meihua; Brown, Janice; Atkinson, Karen; Litchfield, John; Tan, Beijing; Samas, Brian; Zavadoski, William J; Salatto, Christopher T; Treadway, Judith

    2013-05-15

    A novel and potent small molecule glucagon receptor antagonist for the treatment of diabetes mellitus is reported. This candidate, (S)-3-[4-(1-{3,5-dimethyl-4-[4-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}butyl)benzamido]propanoic acid, has lower molecular weight and lipophilicity than historical glucagon receptor antagonists, resulting in excellent selectivity in broad-panel screening, lower cytotoxicity, and excellent overall in vivo safety in early pre-clinical testing. Additionally, it displays low in vivo clearance and excellent oral bioavailability in both rats and dogs. In a rat glucagon challenge model, it was shown to reduce the glucagon-elicited glucose excursion in a dose-dependent manner and at a concentration consistent with its rat in vitro potency. Its properties make it an excellent candidate for further investigation.

  8. Implications of the recent low solar minimum for the solar wind during the Maunder minimum

    OpenAIRE

    M. Lockwood; Owens, Matt J.

    2014-01-01

    The behavior of the Sun and near-Earth space during grand solar minima is not understood; however, the recent long and low minimum of the decadal-scale solar cycle gives some important clues, with implications for understanding the solar dynamo and predicting space weather conditions. The speed of the near-Earth solar wind and the strength of the interplanetary magnetic field (IMF) embedded within it can be reliably reconstructed for before the advent of spacecraft monitoring using observatio...

  9. Minimum degree condition forcing complete graph immersion

    CERN Document Server

    DeVos, Matt; Fox, Jacob; McDonald, Jessica; Mohar, Bojan; Scheide, Diego

    2011-01-01

    An immersion of a graph $H$ into a graph $G$ is a one-to-one mapping $f:V(H) \\to V(G)$ and a collection of edge-disjoint paths in $G$, one for each edge of $H$, such that the path $P_{uv}$ corresponding to edge $uv$ has endpoints $f(u)$ and $f(v)$. The immersion is strong if the paths $P_{uv}$ are internally disjoint from $f(V(H))$. It is proved that for every positive integer $t$, every simple graph of minimum degree at least $200t$ contains a strong immersion of the complete graph $K_t$. For dense graphs one can say even more. If the graph has order $n$ and has $2cn^2$ edges, then there is a strong immersion of the complete graph on at least $c^2 n$ vertices in $G$ in which each path $P_{uv}$ is of length 2. As an application of these results, we resolve a problem raised by Paul Seymour by proving that the line graph of every simple graph with average degree $d$ has a clique minor of order at least $cd^{3/2}$, where $c>0$ is an absolute constant. For small values of $t$, $1\\le t\\le 7$, every simple graph of...

  10. Matroidal Degree-Bounded Minimum Spanning Trees

    CERN Document Server

    Zenklusen, Rico

    2011-01-01

    We consider the minimum spanning tree (MST) problem under the restriction that for every vertex v, the edges of the tree that are adjacent to v satisfy a given family of constraints. A famous example thereof is the classical degree-constrained MST problem, where for every vertex v, a simple upper bound on the degree is imposed. Iterative rounding/relaxation algorithms became the tool of choice for degree-bounded network design problems. A cornerstone for this development was the work of Singh and Lau, who showed for the degree-bounded MST problem how to find a spanning tree violating each degree bound by at most one unit and with cost at most the cost of an optimal solution that respects the degree bounds. However, current iterative rounding approaches face several limits when dealing with more general degree constraints. In particular, when several constraints are imposed on the edges adjacent to a vertex v, as for example when a partition of the edges adjacent to v is given and only a fixed number of elemen...

  11. Minimum Bias Measurements at the LHC

    CERN Document Server

    Kar, Deepak; The ATLAS collaboration

    2016-01-01

    Inclusive charged particle measurements at hadron colliders probe the low-energy nonperturbative region of QCD. Pseudorapidity distributions of charged-particles produced in pp collisions at 13 TeV have been measured by the CMS experiment. The ATLAS collaboration has measured the inclusive charged particle multiplicity and its dependence on transverse momentum and pseudorapidity in special data sets with low LHC beam current, recorded at a center-of-mass energy of 13 TeV. The measurements present the first detailed studies in inclusive phase spaces with a minimum transverse momentum of 100 MeV and 500 MeV. The distribution of electromagnetic and hadronic energy in the very forward phase-space has been measured with the CASTOR calorimeters located at a pseudorapidity of -5.2 to -6.6 in the very forward region of CMS. The energy distributions are very powerful benchmarks to study the performance of MPI in hadronic interactions models at 13 TeV collision energy. All measurements are compared with predictions of ...

  12. Convective Dynamo Simulation with a Grand Minimum

    Science.gov (United States)

    Augustson, Kyle C.; Brun, A. S.; Miesch, Mark; Toomre, Juri

    2015-01-01

    The global-scale dynamo action achieved in a simulation of a Sun-like star rotating at thrice the solar rate is assessed. The 3-D MHD Anelastic Spherical Harmonic (ASH) code, augmented with a viscosity minimization scheme, is employed to capture convection and dynamo processes in this G-type star. The simulation is carried out in a spherical shell that encompasses 3.8 density scale heights of the solar convection zone. It is found that dynamo action with a high degree of time variation occurs, with many periodic polarity reversals occurring roughly every 6.2 years. The magnetic energy also rises and falls with a regular period. The magnetic energy cycles arise from a Lorentz-force feedback on the differential rotation, whereas the processes leading to polarity reversals are more complex, appearing to arise from the interaction of convection with the mean toroidal fields. Moreover, an equatorial migration of toroidal field is found, which is linked to the changing differential rotation, and potentially to a nonlinear dynamo wave. This simulation also enters a grand minimum lasting roughly 20 years, after which the dynamo recovers its regular polarity cycles.

  13. Double Circulant Minimum Storage Regenerating Codes

    CERN Document Server

    Braso, Bernat Gaston

    2010-01-01

    Storage optimization in distributed environments is a major concern when talking about reliability in this kind of schemes. Although replication is the most used option, erasure coding is a more optimized one. However, erasure coding uses a lot of bandwidth to replace one node. In a dynamic scheme, where nodes enter and leave the system frequently, bandwidth use could be an important drawback. Regenerating Codes introduced by \\textit{Dimakis et al.} minimize the code repair problem by applying Network Coding to the distributed storage scheme. However finding the coefficients for the linear combinations used to replace a node is not easy, specially for the systematic case, and must be calculated for each new node fail. For the special case when the dimension $k$ and the redundancy $n-k$ of the system are the same, and the number of nodes participating in the regeneration phase is $d=k+1$, we purpose a new optimal family of Minimum Storage Regenerating codes where coefficients are precalculated and node regener...

  14. Topside measurements at Jicamarca during solar minimum

    Directory of Open Access Journals (Sweden)

    D. L. Hysell

    2009-01-01

    Full Text Available Long-pulse topside radar data acquired at Jicamarca and processed using full-profile analysis are compared to data processed using more conventional, range-gated approaches and with analytic and computational models. The salient features of the topside observations include a dramatic increase in the Te/Ti temperature ratio above the F peak at dawn and a local minimum in the topside plasma temperature in the afternoon. The hydrogen ion fraction was found to exhibit hyperbolic tangent-shaped profiles that become shallow (gradually changing above the O+-H+ transition height during the day. The profile shapes are generally consistent with diffusive equilibrium, although shallowing to the point of changes in inflection can only be accounted for by taking the effects of E×B drifts and meridional winds into account. The SAMI2 model demonstrates this as well as the substantial effect that drifts and winds can have on topside temperatures. Significant quiet-time variability in the topside composition and temperatures may be due to variability in the mechanical forcing. Correlations between topside measurements and magnetometer data at Jicamarca support this hypothesis.

  15. Organization and Nuclear Safety: Safety culture

    International Nuclear Information System (INIS)

    This book presents the experience in nuclear safety and its influence in the exploitation on nuclear power plants. The safety organization and quality management before and after Chernobylsk and three mile island accidents

  16. 78 FR 2797 - Federal Motor Vehicle Safety Standards; Minimum Sound Requirements for Hybrid and Electric Vehicles

    Science.gov (United States)

    2013-01-14

    ...\\ 73 FR 31187; May 30, 2008. \\6\\ The presentations are in document 0012 and the transcript is in... vehicles \\18\\ (HVs). The covered types of vehicles include light vehicles (passenger cars, vans, sport... generated by the vehicle's power train or any other vehicle component, there is nothing in the PSEA to...

  17. IMPLICATIONS OF THE RECENT LOW SOLAR MINIMUM FOR THE SOLAR WIND DURING THE MAUNDER MINIMUM

    Energy Technology Data Exchange (ETDEWEB)

    Lockwood, M.; Owens, M. J., E-mail: m.lockwood@reading.ac.uk [Department of Meteorology, University of Reading, Earley Gate, RG6 6BB (United Kingdom)

    2014-01-20

    The behavior of the Sun and near-Earth space during grand solar minima is not understood; however, the recent long and low minimum of the decadal-scale solar cycle gives some important clues, with implications for understanding the solar dynamo and predicting space weather conditions. The speed of the near-Earth solar wind and the strength of the interplanetary magnetic field (IMF) embedded within it can be reliably reconstructed for before the advent of spacecraft monitoring using observations of geomagnetic activity that extend back to the mid-19th century. We show that during the solar cycle minima around 1879 and 1901 the average solar wind speed was exceptionally low, implying the Earth remained within the streamer belt of slow solar wind flow for extended periods. This is consistent with a broader streamer belt, which was also a feature of the recent low minimum (2009), and yields a prediction that the low near-Earth IMF during the Maunder minimum (1640-1700), as derived from models and deduced from cosmogenic isotopes, was accompanied by a persistent and relatively constant solar wind of speed roughly half the average for the modern era.

  18. Predictions of in vivo prolactin levels from in vitro k I values of d 2 receptor antagonists using an agonist-antagonist interaction model

    NARCIS (Netherlands)

    Petersson, K.J.; Vermeulen, A.M.J.; Friberg, L.E.

    2013-01-01

    Prolactin elevation is a side effect of all currently available D2 receptor antagonists used in the treatment of schizophrenia. Prolactin elevation is the result of a direct antagonistic D2 effect blocking the tonic inhibition of prolactin release by dopamine. The aims of this work were to assess th

  19. Food safety.

    Science.gov (United States)

    Borchers, Andrea; Teuber, Suzanne S; Keen, Carl L; Gershwin, M Eric

    2010-10-01

    Food can never be entirely safe. Food safety is threatened by numerous pathogens that cause a variety of foodborne diseases, algal toxins that cause mostly acute disease, and fungal toxins that may be acutely toxic but may also have chronic sequelae, such as teratogenic, immunotoxic, nephrotoxic, and estrogenic effects. Perhaps more worrisome, the industrial activities of the last century and more have resulted in massive increases in our exposure to toxic metals such as lead, cadmium, mercury, and arsenic, which now are present in the entire food chain and exhibit various toxicities. Industrial processes also released chemicals that, although banned a long time ago, persist in the environment and contaminate our food. These include organochlorine compounds, such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (dichlorodiphenyl dichloroethene) (DDT), other pesticides, dioxins, and dioxin-like compounds. DDT and its breakdown product dichlorophenyl dichloroethylene affect the developing male and female reproductive organs. In addition, there is increasing evidence that they exhibit neurodevelopmental toxicities in human infants and children. They share this characteristic with the dioxins and dioxin-like compounds. Other food contaminants can arise from the treatment of animals with veterinary drugs or the spraying of food crops, which may leave residues. Among the pesticides applied to food crops, the organophosphates have been the focus of much regulatory attention because there is growing evidence that they, too, affect the developing brain. Numerous chemical contaminants are formed during the processing and cooking of foods. Many of them are known or suspected carcinogens. Other food contaminants leach from the packaging or storage containers. Examples that have garnered increasing attention in recent years are phthalates, which have been shown to induce malformations in the male reproductive system in laboratory animals, and bisphenol A, which negatively

  20. Food safety.

    Science.gov (United States)

    Borchers, Andrea; Teuber, Suzanne S; Keen, Carl L; Gershwin, M Eric

    2010-10-01

    Food can never be entirely safe. Food safety is threatened by numerous pathogens that cause a variety of foodborne diseases, algal toxins that cause mostly acute disease, and fungal toxins that may be acutely toxic but may also have chronic sequelae, such as teratogenic, immunotoxic, nephrotoxic, and estrogenic effects. Perhaps more worrisome, the industrial activities of the last century and more have resulted in massive increases in our exposure to toxic metals such as lead, cadmium, mercury, and arsenic, which now are present in the entire food chain and exhibit various toxicities. Industrial processes also released chemicals that, although banned a long time ago, persist in the environment and contaminate our food. These include organochlorine compounds, such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (dichlorodiphenyl dichloroethene) (DDT), other pesticides, dioxins, and dioxin-like compounds. DDT and its breakdown product dichlorophenyl dichloroethylene affect the developing male and female reproductive organs. In addition, there is increasing evidence that they exhibit neurodevelopmental toxicities in human infants and children. They share this characteristic with the dioxins and dioxin-like compounds. Other food contaminants can arise from the treatment of animals with veterinary drugs or the spraying of food crops, which may leave residues. Among the pesticides applied to food crops, the organophosphates have been the focus of much regulatory attention because there is growing evidence that they, too, affect the developing brain. Numerous chemical contaminants are formed during the processing and cooking of foods. Many of them are known or suspected carcinogens. Other food contaminants leach from the packaging or storage containers. Examples that have garnered increasing attention in recent years are phthalates, which have been shown to induce malformations in the male reproductive system in laboratory animals, and bisphenol A, which negatively

  1. Pressure Safety Program Implementation at ORNL

    Energy Technology Data Exchange (ETDEWEB)

    Lower, Mark [ORNL; Etheridge, Tom [ORNL; Oland, C. Barry [XCEL Engineering, Inc.

    2013-01-01

    The Oak Ridge National Laboratory (ORNL) is a US Department of Energy (DOE) facility that is managed by UT-Battelle, LLC. In February 2006, DOE promulgated worker safety and health regulations to govern contractor activities at DOE sites. These regulations, which are provided in 10 CFR 851, Worker Safety and Health Program, establish requirements for worker safety and health program that reduce or prevent occupational injuries, illnesses, and accidental losses by providing DOE contractors and their workers with safe and healthful workplaces at DOE sites. The regulations state that contractors must achieve compliance no later than May 25, 2007. According to 10 CFR 851, Subpart C, Specific Program Requirements, contractors must have a structured approach to their worker safety and health programs that at a minimum includes provisions for pressure safety. In implementing the structured approach for pressure safety, contractors must establish safety policies and procedures to ensure that pressure systems are designed, fabricated, tested, inspected, maintained, repaired, and operated by trained, qualified personnel in accordance with applicable sound engineering principles. In addition, contractors must ensure that all pressure vessels, boilers, air receivers, and supporting piping systems conform to (1) applicable American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code (2004) Sections I through XII, including applicable code cases; (2) applicable ASME B31 piping codes; and (3) the strictest applicable state and local codes. When national consensus codes are not applicable because of pressure range, vessel geometry, use of special materials, etc., contractors must implement measures to provide equivalent protection and ensure a level of safety greater than or equal to the level of protection afforded by the ASME or applicable state or local codes. This report documents the work performed to address legacy pressure vessel deficiencies and comply

  2. Bromine Safety

    Energy Technology Data Exchange (ETDEWEB)

    Meyers, B

    2001-04-09

    The production and handling in 1999 of about 200 million kilograms of bromine plus substantial derivatives thereof by Great Lakes Chemical Corp. and Albemarle Corporation in their southern Arkansas refineries gave OSHA Occupational Injury/Illness Rates (OIIR) in the range of 0.74 to 1.60 reportable OIIRs per 200,000 man hours. OIIRs for similar industries and a wide selection of other U.S. industries range from 1.6 to 23.9 in the most recent OSHA report. Occupational fatalities for the two companies in 1999 were zero compared to a range in the U.S.of zero for all computer manufacturing to 0.0445 percent for all of agriculture, forestry and fishing in the most recent OSHA report. These results show that bromine and its compounds can be considered as safe chemicals as a result of the bromine safety standards and practices at the two companies. The use of hydrobromic acid as an electrical energy storage medium in reversible PEM fuel cells is discussed. A study in 1979 of 20 megawatt halogen working fluid power plants by Oronzio de Nora Group found such energy to cost 2 to 2.5 times the prevailing base rate at that time. New conditions may reduce this relative cost. The energy storage aspect allows energy delivery at maximum demand times where the energy commands premium rates. The study also found marginal cost and performance advantages for hydrobromic acid over hydrochloric acid working fluid. Separate studies in the late 70s by General Electric also showed marginal performance advantages for hydrobromic acid.

  3. A major safety overhaul

    CERN Document Server

    2003-01-01

    A redefined policy, a revamped safety course, an environmental project... the TIS (Technical Inspection and Safety) Division has begun a major safety overhaul. Its new head, Wolfgang Weingarten, explains to the Bulletin why and how this is happening.

  4. Control, Operator Support and Safety System of PVC-reactors

    Directory of Open Access Journals (Sweden)

    Jens I. Ytreeide

    1997-01-01

    Full Text Available In modern petrochemical plants the corporate and societal demands to plant safety and minimum environmental effects are high. These demands rise high performance requirements to the technical systems, specially the process control and safety systems including an effective operator support system with fault detection capability. The systems must have high reliability also against erroneous operations which may cause shutdown situations or quality deviations.

  5. New Safety rules

    CERN Multimedia

    Safety Commission

    2008-01-01

    The revision of CERN Safety rules is in progress and the following new Safety rules have been issued on 15-04-2008: Safety Procedure SP-R1 Establishing, Updating and Publishing CERN Safety rules: http://cern.ch/safety-rules/SP-R1.htm; Safety Regulation SR-S Smoking at CERN: http://cern.ch/safety-rules/SR-S.htm; Safety Regulation SR-M Mechanical Equipment: http://cern.ch/safety-rules/SR-M.htm; General Safety Instruction GSI-M1 Standard Lifting Equipment: http://cern.ch/safety-rules/GSI-M1.htm; General Safety Instruction GSI-M2 Standard Pressure Equipment: http://cern.ch/safety-rules/GSI-M2.htm; General Safety Instruction GSI-M3 Special Mechanical Equipment: http://cern.ch/safety-rules/GSI-M3.htm. These documents apply to all persons under the Director General’s authority. All Safety rules are available at the web page: http://www.cern.ch/safety-rules The Safety Commission

  6. Animal Drug Safety FAQs

    Science.gov (United States)

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Animal & Veterinary Home Animal & Veterinary Safety & Health Frequently Asked Questions Animal Drug Safety Frequently Asked Questions Share Tweet Linkedin ...

  7. Nuclear criticality safety guide

    Energy Technology Data Exchange (ETDEWEB)

    Pruvost, N.L.; Paxton, H.C. [eds.

    1996-09-01

    This technical reference document cites information related to nuclear criticality safety principles, experience, and practice. The document also provides general guidance for criticality safety personnel and regulators.

  8. Farm Health and Safety

    Science.gov (United States)

    ... jobs in the United States. Farms have many health and safety hazards, including Chemicals and pesticides Machinery, ... equipment can also reduce accidents. Occupational Safety and Health Administration

  9. HANARO Safety Performance Indicators

    International Nuclear Information System (INIS)

    HANARO is a 30 MW open-tank-in-pool type multi-purpose research reactor. Safety improvement activities have been implemented and the importance of safety management in nuclear activities for reactor application and utilization has also been emphasized. Safety performance indicators (SPIs) are used to assess the safety management status, in combination with other factors such as safety culture, human performance and operation status. The SPI system can provide a proactive approach to complement other safety assessment activities. HANARO has tried to develop a programme for the establishment of safety performance indicators. In this paper the application experience of safety performance indicators in HANARO is described. (author)

  10. Nuclear criticality safety guide

    International Nuclear Information System (INIS)

    This technical reference document cites information related to nuclear criticality safety principles, experience, and practice. The document also provides general guidance for criticality safety personnel and regulators

  11. Novel class of medications, orexin receptor antagonists, in the treatment of insomnia – critical appraisal of suvorexant

    Science.gov (United States)

    Norman, Jessica L; Anderson, Sarah L

    2016-01-01

    Insomnia, a highly prevalent disorder, can be detrimental to patients’ overall health and worsen existing comorbidities. Patients may have acute episodes of insomnia related to a traumatic event, but more commonly insomnia occurs chronically. While proper sleep hygiene and behavioral therapy play important roles in the nonpharmacologic management of short-term and chronic insomnia, medications may also be required. Historically, insomnia has been treated with agents such as benzodiazepines, nonbenzodiazepine receptor agonists, and melatonin agonists. Dual orexin receptor antagonists represent a new class of medications for the treatment of insomnia, which block the binding of wakefulness-promoting neuropeptides orexin A and orexin B to their respective receptor sites. Suvorexant (Belsomra) is the first dual orexin receptor antagonist to be approved in the US and Japan and has demonstrated efficacy in decreasing time to sleep onset and increasing total sleep time. Its unique mechanism of action, data to support efficacy and safety over 12 months of use, and relative lack of withdrawal effects when discontinued may represent an alternative for patients with chronic insomnia who cannot tolerate or do not receive benefit from more traditional sleep agents. Suvorexant is effective and well tolerated, but precautions exist for certain patient populations, including females, obese patients, and those with respiratory disease. Suvorexant has only been studied vs placebo, and hence it is unknown how it directly compares with other medications approved by the US Food and Drug Administration for insomnia. Suvorexant is not likely to replace benzodiazepines or nonbenzodiazepine receptor antagonists as a first-line sleep agent but does represent a novel option for the treatment of patients with chronic insomnia. PMID:27471419

  12. Redefining the limit dates for the Maunder Minimum

    CERN Document Server

    Vaquero, J M

    2014-01-01

    The Maunder Minimum corresponds to a prolonged minimum of solar activity a phenomenon that is of particular interest to many branches of natural and social sciences commonly considered to extend from 1645 until 1715. However, our knowledge of past solar activity has improved significantly in recent years and, thus, more precise dates for the onset and termination of this particularly episode of our Sun can be established. Based on the simultaneous analysis of distinct proxies we propose a redefinition of the Maunder Minimum period with the core "Deep Maunder Minimum" spanning from 1645 to 1700 (that corresponds to the Grand Minimum state) and a wider "Extended Maunder Minimum" for the longer period 1618-1723 that includes the transition periods.

  13. Patient safety: Safety culture and patient safety ethics

    DEFF Research Database (Denmark)

    Madsen, Marlene Dyrløv

    2006-01-01

    challenging issues of systemic, organisational, cultural and ethical relevance, which this dissertation seeks to address through the application of different disciplinary approaches. The main focus of researchis safety culture; through empirical and theoretical studies to comprehend the phenomenon, address......Patient safety - the prevention of medical error and adverse events - and the initiative of developing safety cultures to assure patients from harm have become one of the central concerns in quality improvement in healthcare both nationally andinternationally. This subject raises numerous...... the problems, and suggest possible solutions for improving patient safety through the promotion of safety culture and ethics. I seek to illuminate theissues of patient safety from several perspectives; the organizational healthcare system, in particular the healthcare workers perspectives and experiences...

  14. Minimum Distance Lasso for robust high-dimensional regression

    OpenAIRE

    Lozano, Aurélie C.; Meinshausen, Nicolai; Yang, Eunho

    2016-01-01

    We propose a minimum distance estimation method for robust regression in sparse high-dimensional settings. Likelihood-based estimators lack resilience against outliers and model misspecification, a critical issue when dealing with high-dimensional noisy data. Our method, Minimum Distance Lasso (MD-Lasso), combines minimum distance functionals customarily used in nonparametric estimation for robustness, with $\\ell_{1}$-regularization. MD-Lasso is governed by a scaling parameter capping the inf...

  15. Minimum Distance Estimation for Robust High-Dimensional Regression

    OpenAIRE

    Lozano, Aurélie C.; Meinshausen, Nicolai

    2013-01-01

    We propose a minimum distance estimation method for robust regression in sparse high-dimensional settings. The traditional likelihood-based estimators lack resilience against outliers, a critical issue when dealing with high-dimensional noisy data. Our method, Minimum Distance Lasso (MD-Lasso), combines minimum distance functionals, customarily used in nonparametric estimation for their robustness, with l1-regularization for high-dimensional regression. The geometry of MD-Lasso is key to its ...

  16. An Improved CO2-Crude Oil Minimum Miscibility Pressure Correlation

    OpenAIRE

    Hao Zhang; Dali Hou; Kai Li

    2015-01-01

    Minimum miscibility pressure (MMP), which plays an important role in miscible flooding, is a key parameter in determining whether crude oil and gas are completely miscible. On the basis of 210 groups of CO2-crude oil system minimum miscibility pressure data, an improved CO2-crude oil system minimum miscibility pressure correlation was built by modified conjugate gradient method and global optimizing method. The new correlation is a uniform empirical correlation to calculate the MMP for both t...

  17. Minimum Entangling Power is Close to Its Maximum

    OpenAIRE

    Chen, Jianxin; Ji, Zhengfeng; Kribs, David W.; Zeng, Bei

    2012-01-01

    Given a quantum gate $U$ acting on a bipartite quantum system, its maximum (average, minimum) entangling power is the maximum (average, minimum) entanglement generation with respect to certain entanglement measure when the inputs are restricted to be product states. In this paper, we mainly focus on the 'weakest' one, i.e., the minimum entangling power, among all these entangling powers. We show that, by choosing von Neumann entropy of reduced density operator or Schmidt rank as entanglement ...

  18. Underreporting of earnings and the minimum wage spike

    OpenAIRE

    Tonin, Mirco

    2013-01-01

    This paper contributes to the policy debate on minimum wage by highlighting its role in enforcing compliance with fiscal rules in economies where underreporting of earnings is wide-spread. First, I propose a simple model exploring the interaction between the minimum wage and underreporting of earnings. Then, I provide supportive evidence by documenting a positive correlation within European labour markets between the proportion of full-time employees with earnings on the minimum wage and the ...

  19. Do Minimum Wage Price Effects Hurt the Poor More?

    OpenAIRE

    Lemos, Sara

    2004-01-01

    Minimum wage legislation is potentially a powerful policy tool to help alleviate poverty in developing countries. This is especially the case when the detrimental employment effects are small. However, of critical importance is whether, and to what extent, minimum wage increases will generate price effects that might adversely affect the poor. This might occur, firstly, if the poor consume a lot of goods produced in sectors dominated by minimum wage workforces. Secondly, this may occur if min...

  20. How Do Minimum Wage Policies Affect Workers in Emerging Markets?

    OpenAIRE

    Albert Park

    2015-01-01

    Prof. Albert Park, Director of HKUST IEMS, Chair Professor at HKUST's Division of Social Science, and Professor at HKUST's Department of Economics, reviews the efficacy of minimum wage policies across BRICS countries, i.e. Brazil, Russia, India, China, and South Africa, highlighting their success or lackthereof as related to critical factors such as labor market coverage, policy enforcement, minimum wage level as compared to mean wages, and others. Prof. Park notes that while minimum wage pol...

  1. A note on the torsional oscillation at solar minimum

    OpenAIRE

    Howe, R.; Christensen-Dalsgaard, J.; Hill, F.; Komm, R.; Schou, J.; Thompson, M. J.

    2009-01-01

    We examine the evolution of the zonal flow pattern in the upper solar convection zone during the current extended solar minimum, and compare it with that during the previous minimum. The results suggest that a configuration matching that at the previous minimum was reached during 2008, but that the flow band corresponding to the new cycle has been moving more slowly towards the equator than was observed in the previous cycle, resulting in a gradual increase in the apparent length of the cycle...

  2. Minimum Wages and Teen Employment: A Spatial Panel Approach

    OpenAIRE

    Kalenkoski, Charlene M.; Lacombe, Donald J.

    2011-01-01

    The authors employ spatial econometrics techniques and Annual Averages data from the U.S. Bureau of Labor Statistics for 1990-2004 to examine how changes in the minimum wage affect teen employment. Spatial econometrics techniques account for the fact that employment is correlated across states. Such correlation may exist if a change in the minimum wage in a state affects employment not only in its own state but also in other, neighboring states. The authors show that state minimum wages negat...

  3. Experimental Study Of Minimum Ignition Temperature Of Spent Coffee Grounds

    OpenAIRE

    Igor Wachter; Karol Balog; Hana Kobetičová; Aleš Ház

    2016-01-01

    The aim of this scientific paper is an analysis of the minimum ignition temperature of dust layer and the minimum ignition temperatures of dust clouds. It could be used to identify the threats in industrial production and civil engineering, on which a layer of combustible dust could occure. Research was performed on spent coffee grounds. Tests were performed according to EN 50281-2-1:2002 Methods for determining the minimum ignition temperatures of dust (Method A). Objective of method A is to...

  4. 47 CFR 101.143 - Minimum path length requirements.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Minimum path length requirements. 101.143... SERVICES FIXED MICROWAVE SERVICES Technical Standards § 101.143 Minimum path length requirements. (a) The...) Minimum path length (km) Below 1,850 N/A 1,850 to 7,125 17 10,550 to 13,250 5 Above 17,700 N/A (b)...

  5. Sexually antagonistic "zygotic drive" of the sex chromosomes.

    Directory of Open Access Journals (Sweden)

    William R Rice

    2008-12-01

    Full Text Available Genomic conflict is perplexing because it causes the fitness of a species to decline rather than improve. Many diverse forms of genomic conflict have been identified, but this extant tally may be incomplete. Here, we show that the unusual characteristics of the sex chromosomes can, in principle, lead to a previously unappreciated form of sexual genomic conflict. The phenomenon occurs because there is selection in the heterogametic sex for sex-linked mutations that harm the sex of offspring that does not carry them, whenever there is competition among siblings. This harmful phenotype can be expressed as an antagonistic green-beard effect that is mediated by epigenetic parental effects, parental investment, and/or interactions among siblings. We call this form of genomic conflict sexually antagonistic "zygotic drive", because it is functionally equivalent to meiotic drive, except that it operates during the zygotic and postzygotic stages of the life cycle rather than the meiotic and gametic stages. A combination of mathematical modeling and a survey of empirical studies is used to show that sexually antagonistic zygotic drive is feasible, likely to be widespread in nature, and that it can promote a genetic "arms race" between the homo- and heteromorphic sex chromosomes. This new category of genomic conflict has the potential to strongly influence other fundamental evolutionary processes, such as speciation and the degeneration of the Y and W sex chromosomes. It also fosters a new genetic hypothesis for the evolution of enigmatic fitness-reducing traits like the high frequency of spontaneous abortion, sterility, and homosexuality observed in humans.

  6. Extra-helical binding site of a glucagon receptor antagonist.

    Science.gov (United States)

    Jazayeri, Ali; Doré, Andrew S; Lamb, Daniel; Krishnamurthy, Harini; Southall, Stacey M; Baig, Asma H; Bortolato, Andrea; Koglin, Markus; Robertson, Nathan J; Errey, James C; Andrews, Stephen P; Teobald, Iryna; Brown, Alastair J H; Cooke, Robert M; Weir, Malcolm; Marshall, Fiona H

    2016-05-12

    Glucagon is a 29-amino-acid peptide released from the α-cells of the islet of Langerhans, which has a key role in glucose homeostasis. Glucagon action is transduced by the class B G-protein-coupled glucagon receptor (GCGR), which is located on liver, kidney, intestinal smooth muscle, brain, adipose tissue, heart and pancreas cells, and this receptor has been considered an important drug target in the treatment of diabetes. Administration of recently identified small-molecule GCGR antagonists in patients with type 2 diabetes results in a substantial reduction of fasting and postprandial glucose concentrations. Although an X-ray structure of the transmembrane domain of the GCGR has previously been solved, the ligand (NNC0640) was not resolved. Here we report the 2.5 Å structure of human GCGR in complex with the antagonist MK-0893 (ref. 4), which is found to bind to an allosteric site outside the seven transmembrane (7TM) helical bundle in a position between TM6 and TM7 extending into the lipid bilayer. Mutagenesis of key residues identified in the X-ray structure confirms their role in the binding of MK-0893 to the receptor. The unexpected position of the binding site for MK-0893, which is structurally similar to other GCGR antagonists, suggests that glucagon activation of the receptor is prevented by restriction of the outward helical movement of TM6 required for G-protein coupling. Structural knowledge of class B receptors is limited, with only one other ligand-binding site defined--for the corticotropin-releasing hormone receptor 1 (CRF1R)--which was located deep within the 7TM bundle. We describe a completely novel allosteric binding site for class B receptors, providing an opportunity for structure-based drug design for this receptor class and furthering our understanding of the mechanisms of activation of these receptors. PMID:27111510

  7. The opiate antagonist, naltrexone, in the treatment of trichotillomania

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Schreiber, Liana R N;

    2014-01-01

    Trichotillomania (TTM) is characterized by repetitive hair pulling resulting in hair loss. Data on the pharmacological treatment of TTM are limited. This study examined the opioid antagonist, naltrexone, in adults with TTM who had urges to pull their hair. Fifty-one individuals with TTM were...... randomized to naltrexone or placebo in an 8-week, double-blind trial. Subjects were assessed with measures of TTM severity and selected cognitive tasks. Naltrexone failed to demonstrate significantly greater reductions in hair pulling compared to placebo. Cognitive flexibility, however, significantly...

  8. Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation.

    Science.gov (United States)

    Plitt, Anna; Ruff, Christian T; Giugliano, Robert P

    2016-10-01

    For more than 50 years, vitamin K antagonists (VKAs) have been the standard of care for treatment of atrial fibrillation (AF). However, the numerous limitations of VKAs have led to the development of non-VKA oral anticoagulants (NOACs). There are 4 NOACs currently approved for prevention of thromboembolism in patients with nonvalvular AF. This article provides an overview of AF, summarizes basic properties of NOACs, and reviews the landmark trials. Current data on use of NOACs in special populations and specific clinical scenarios are also presented. Lastly, recommendations from experts on controversial topics of bleeding management and reversal are described. PMID:27637305

  9. Synthesis of carbon-11 labelled calcium channel antagonists

    International Nuclear Information System (INIS)

    A useful synthetic approach to carbon-11 labelled 1,4-dihydropyridines is described. Carbon-11 labelled calcium channel antagonists 11C-Nifedipine, 11C-Nisoldipine, 11C-nitrendipine and 11C-CF3-Nifedipine were synthesized by a modified Hantzsch method using protected carboxy functions. Deprotection of the carboxylic acids by alkaline hydrolysis followed by conversion into the corresponding potassium salts and subsequent methylation with 11CH3I produced the labelled compounds in very good chemical and radiochemical yields (94%). (author)

  10. The role of oxytocin antagonists in repeated implantation failure

    OpenAIRE

    Decleer, W.; Osmanagaoglu, K.; Devroey, P.

    2012-01-01

    A prospective cohort study has been performed to find out if the administration of an oxytocin antagonist (Atosiban) at the occasion of embryo transfer has an effect on the pregnancy rate in patients with repeated failure of implantation. A total of 52 women with repeated failure of implantation after IVF/ICSI were included in this study. The ongoing pregnancy rate (OPR) in the total group of patients was 12 out of 52 (23.1%). Based on embryo quality all cases were categorized in two groups. ...

  11. Expression of Interleukin 1 Receptor Antagonist in Human Cornea

    OpenAIRE

    Heur, Martin; Shyam S. Chaurasia; Wilson, Steven E.

    2008-01-01

    The purpose of this study was to confirm the expression of interleukin-1 receptor antagonist (IL-1 Ra) in the human cornea. Four samples of human ex vivo corneal epithelium were obtained from patients undergoing photorefractive keratectomy. RT-PCR was performed using mRNA isolated from the corneal epithelium and oligo-dT primers. PCR was performed on the cDNA products using primers specific for human IL-1Ra. The PCR products were subcloned and sequenced. Human cornea sections were prepared fr...

  12. Decision trees with minimum average depth for sorting eight elements

    KAUST Repository

    AbouEisha, Hassan

    2015-11-19

    We prove that the minimum average depth of a decision tree for sorting 8 pairwise different elements is equal to 620160/8!. We show also that each decision tree for sorting 8 elements, which has minimum average depth (the number of such trees is approximately equal to 8.548×10^326365), has also minimum depth. Both problems were considered by Knuth (1998). To obtain these results, we use tools based on extensions of dynamic programming which allow us to make sequential optimization of decision trees relative to depth and average depth, and to count the number of decision trees with minimum average depth.

  13. Did the national minimum wage affect UK prices?

    OpenAIRE

    Wadsworth, Jonathan

    2009-01-01

    One potential channel through which the effects of the minimum wage could be directed is that firms who employ minimum wage workers could pass on any resulting higher labour costs in the form of higher prices. This study looks at the effects of the introduction and subsequent uprating of the minimum wage on the prices of UK goods and services, comparing the prices of goods produced by industries in which UK minimum wage workers make up a substantial share of total costs with the prices of goo...

  14. The impact of minimum wage on female employment in Japan

    OpenAIRE

    Kawaguchi, Daiji; Yamada, Ken

    2004-01-01

    The statutory minimum wage in Japan is revised every year and increases by almost the same amount across prefectures, regardless of the disparity in the wage distribution across prefectures. Due to this feature of minimum wagesetting, the minimum wage cuts into the wage distribution deeply in rural Japan. We examine the impact of the minimum wage on employment, focus-ing on middle-aged women, who are known to be typical, low-wage workers in Japan. The results, based on a panel estimation, sug...

  15. The Impact of the Minimum Wage on Match Stability

    OpenAIRE

    Centeno, Mario; Duarte, Claudia; Novo, Alvaro A.

    2014-01-01

    We explore increases in the nominal minimum wage in a difference-in-differences setting to estimate match survival wage elasticity. The elasticity is negative and larger than one for matches directly affected by minimum wage increases, those with paying below the new minimum wage. The impact of the minimum wage is stronger for young workers and the manufacturing sector, groups with a large and increasing share of low-wage workers. Given the low-wage mobility in the Portuguese labor market and...

  16. Apoptosis and the FLIP and NF-kappa B proteins as pharmacodynamic criteria for biosimilar TNF-alpha antagonists

    Directory of Open Access Journals (Sweden)

    Urbano PCM

    2014-07-01

    Full Text Available Paulo César Martins Urbano,1 Vanete Thomaz Soccol,1 Valderilio Feijó Azevedo2 1Biotechnology and Bioprocess Engineering Program, Federal University of Parana, Curitiba, Parana, Brazil; 2Hospital de Clínicas, Federal University of Parana, Curitiba, Parana, Brazil Abstract: Various criteria are necessary to assess the efficacy and safety of biological medications in order to grant companies the right to register these medications with the appropriate bodies that regulate their sale. The imminent expiration of the patents on reference biological products which block the cytokine TNF-α (tumor necrosis factor-α raises the possibility of bringing so-called biosimilars to the market (similar to the biologicals of reference products. This occurrence is inevitable, but criteria to adequately evaluate these medications are now needed. Even among controversy, there is a demand from publications correlating the pro-apoptotic mechanism of the original TNF-α antagonists (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol in the treatment of rheumatoid arthritis and other diseases. In this article, the authors discuss the possibility of utilizing the pro-apoptotic effect correlated with the regulation of the anti-apoptotic proteins FLIP and NF-κB as new criteria for analyzing the pharmacodynamics of possible biosimilar TNF-α antagonists which should be submitted to regulatory agencies for evaluation. Keywords: anti-TNF drugs, rheumatoid arthritis, apoptosis, NF-κB, FLIP

  17. Safety Assurance in NextGen

    Science.gov (United States)

    HarrisonFleming, Cody; Spencer, Melissa; Leveson, Nancy; Wilkinson, Chris

    2012-01-01

    The generation of minimum operational, safety, performance, and interoperability requirements is an important aspect of safely integrating new NextGen components into the Communication Navigation Surveillance and Air Traffic Management (CNS/ATM) system. These requirements are used as part of the implementation and approval processes. In addition, they provide guidance to determine the levels of design assurance and performance that are needed for each element of the new NextGen procedures, including aircraft, operator, and Air Navigation and Service Provider. Using the enhanced Airborne Traffic Situational Awareness for InTrail Procedure (ATSA-ITP) as an example, this report describes some limitations of the current process used for generating safety requirements and levels of required design assurance. An alternative process is described, as well as the argument for why the alternative can generate more comprehensive requirements and greater safety assurance than the current approach.

  18. NMDA receptor antagonists in the treatment of patients with vascular cognitive imprairments

    Directory of Open Access Journals (Sweden)

    I.S. Preobrazhenskaya

    2014-01-01

    Full Text Available The paper discusses the possibilities of using the NMDA receptor antagonist memantine in patients with vascular cognitive impairments (CIs. The author gives the data available in the literature and the results of her investigations into the efficiency and safety of treatment in patients with vascular dementia and moderate vascular CIs. The paper presents the results of a Russian multicenter trial of the efficacy and safety of akatinol memantine in patients with CIs, which enrolled 240 patients (mean age 69.5±5.5 years with moderate CIs or mild dementia (the total Mini-Mental State Examination (MMSE scores were 22–28. A study group included 148 patients who took akatinol memantine during a follow-up; a comparison group consisted of 92 patients who did not. Therapeutic effectiveness was evaluated using the quantitative neuropsychological scales and from changes in the somatic and neurological status and in the magnitude of emotional disorders at the inclusion in the study (before treatment initiation and at 1.5, 3, and 6 months of therapy. During akatinol memantine therapy, there were significant reductions in the degree of CIs (lower total MMSE scores; p<0.00000, abnormalities in programming, generalization, and control over performed actions (a change in the total frontal lobe dysfunction battery scores;p<0.00000, and memory disorders, a significant increase in speech fluency (p<0.00000 and attention level (p< 0.00000, and a decrease in the degree of visuospatial deficits (p<0.00000. The effect of the therapy showed itself at its 3 months and continued to rise later on. The performed trial has indicated that akatinol memantine is an effective symptomatic drug to treat both moderate CIs and mild dementia.

  19. Leukotriene receptor antagonists--risks and benefits for use in paediatric asthma.

    Science.gov (United States)

    Spahr, Jonathan E; Krawiec, Marzena E

    2004-05-01

    Leukotrienes (LTs) are important mediators of the pathophysiology of asthma, specifically, bronchoconstriction, airway inflammation and oedema and mucus hypersecretion. The LT receptor antagonists (LTRAs) inhibit these potent effects by selectively blocking the cysteinyl LT 1 receptor. These are the first novel therapies for asthma since the introduction of inhaled corticosteroids (ICS) in 1972. Unlike generalised inhibition of airway inflammation by ICS, the LTRAs target inhibition of specific mediators. In general, paediatric data concerning these agents remain quite limited. However, they have demonstrated efficacy against allergen- and exercise-induced bronchospasm in both adults and children. Recently, their potential role for the treatment of viral-induced wheeze in young children has been explored. In multiple, placebo-controlled trials, the LTRAs have demonstrated efficacy for the treatment of mild persistent asthma, additive benefit in the management of symptomatic moderate asthmatics on maintenance ICS and evidence of significant steroid-sparing. Findings from these clinical trials and real-world experience support the use of the LTRAs as controller agents for persistent asthma. Based on their excellent safety profiles, tolerance and ease of administration (including once daily dosing with montelukast), this drug class may offer several important features for use as controller therapy, particularly in asthmatic children as young as 1 year of age, however, this must continue to be reviewed as new paediatric data become available. PMID:15155146

  20. Biocontrol of Fusarium graminearum Growth and Deoxynivalenol Production in Wheat Kernels with Bacterial Antagonists

    Directory of Open Access Journals (Sweden)

    Cuijuan Shi

    2014-01-01

    Full Text Available Fusarium graminearum is the main causal pathogen affecting small-grain cereals, and it produces deoxynivalenol, a kind of mycotoxin, which displays a wide range of toxic effects in human and animals. Bacterial strains isolated from peanut shells were investigated for their activities against F. graminearum by dual-culture plate and tip-culture assays. Among them, twenty strains exhibited potent inhibition to the growth of F. graminearum, and the inhibition rates ranged from 41.41% to 54.55% in dual-culture plate assay and 92.70% to 100% in tip-culture assay. Furthermore, eighteen strains reduced the production of deoxynivalenol by 16.69% to 90.30% in the wheat kernels assay. Finally, the strains with the strongest inhibitory activity were identified by morphological, physiological, biochemical methods and also 16S rDNA and gyrA gene analysis as Bacillus amyloliquefaciens. The current study highlights the potential application of antagonistic microorganisms and their metabolites in the prevention of fungal growth and mycotoxin production in wheat kernels. As a biological strategy, it might avoid safety problems and nutrition loss which always caused by physical and chemical strategies.

  1. The minimum wage, employment, and the AS-IF methodology: A forecasting approach to evaluating the minimum wage

    OpenAIRE

    Paul Wolfson; Dale Belman

    2001-01-01

    Out-of-sample employment forecasts for 33 U.S. industries which are likely to be sensitive to the federal minimum wage are, more often than not, more accurate when information about the minimum wage is not taken into account. This is true even in instances where this information improves wage forecasts. When employment forecasts conditional on the minimum wage are better, the improvement is typically small. These results are invariant to the number of workers previously making less than the n...

  2. Do Low-Income Families Benefit from Minimum Wage Increases? Evidence from State-Level Minimum Wage Laws

    OpenAIRE

    Mark D. Partridge; Partridge, Jamie S.

    1999-01-01

    Several recent studies contend that falling real minimum wage rates are an important factor behind rising wage inequality and increasing poverty rates. Other studies find the more conventional result that they have very little influence on poverty and inequality, but these studies are generally based on simulated labor market responses. This study examines the influence of minimum wage rates on poverty rates and family income inequality using state-level minimum wages. The methodology has the...

  3. Constantly evolving safety assessment protocols for GM foods.

    Science.gov (United States)

    Sesikeran, B; Vasanthi, Siruguri

    2008-01-01

    he introduction of GM foods has led to the evolution of a food safety assessment paradigm that establishes safety of the GM food relative to its conventional counterpart. The GM foods currently approved and marketed in several countries have undergone extensive safety testing under a structured safety assessment framework evolved by international organizations like FAO, WHO, Codex and OECD. The major elements of safety assessment include molecular characterization of inserted genes and stability of the trait, toxicity and allergenicity potential of the expressed substances, compositional analysis, potential for gene transfer to gut microflora and unintentional effects of the genetic modification. As more number and type of food crops are being brought under the genetic modification regime, the adequacy of existing safety assessment protocols for establishing safety of these foods has been questioned. Such crops comprise GM crops with higher agronomic vigour, nutritional or health benefit/ by modification of plant metabolic pathways and those expressing bioactive substances and pharmaceuticals. The safety assessment challenges of these foods are the potential of the methods to detect unintentional effects with higher sensitivity and rigor. Development of databases on food compositions, toxicants and allergens is currently seen as an important aid to development of safety protocols. With the changing global trends in genetic modification technology future challenge would be to develop GM crops with minimum amount of inserted foreign DNA so as to reduce the burden of complex safety assessments while ensuring safety and utility of the technology.

  4. Where the minimum wage bites hard: the introduction of the UK national minimum wage to a low wage sector

    OpenAIRE

    Machin, Stephen; Manning, Alan; Rahman, Lupin

    2002-01-01

    Between 1993 and April 1999 there was no minimum wage in the United Kingdom (except in agriculture). In this paper we study the effects of the introduction of a National Minimum Wage (NMW) in April 1999 on one heavily affected sector, the residential care homes industry. This sector contains a large number of low paid workers and as such can be viewed as being very vulnerable to minimum wage legislation. We look at the impact on both wages and employment. Our results suggest that the minimum ...

  5. The neuromedin B receptor antagonist, BIM-23127, is a potent antagonist at human and rat urotensin-II receptors

    OpenAIRE

    Herold, Christopher L; Behm, David J.; Buckley, Peter T.; Foley, James J; William E Wixted; Sarau, Henry M; Douglas, Stephen A

    2003-01-01

    The functional activity of the peptidic neuromedin B receptor antagonist BIM-23127 was investigated at recombinant and native urotensin-II receptors (UT receptors). Human urotensin-II (hU-II) promoted intracellular calcium mobilization in HEK293 cells expressing the human UT (hUT) or rat UT (rUT) receptors with pEC50 values of 9.80±0.34 (n=6) and 9.06±0.32 (n=4), respectively. While BIM-23127 alone had no effect on calcium responses in either cell line, it was a potent and competitive antagon...

  6. The kappa opioid receptor antagonist JDTic attenuates alcohol seeking and withdrawal anxiety

    OpenAIRE

    Schank, Jesse R.; Goldstein, Andrea L.; Rowe, Kelly E.; King, Courtney E.; Marusich, Julie A.; Wiley, Jenny L; Carroll, F. Ivy; Thorsell, Annika; Heilig, Markus

    2012-01-01

    The role of kappa-opioid receptors (KOR) in regulation of alcohol-related behaviors is not completely understood. For example, alcohol consumption has been reported to increase following treatment with KOR antagonists in rats, but was decreased in mice with genetic deletion of KOR. Recent studies have further suggested that KOR antagonists may selectively decrease alcohol self-administration in rats following a history of dependence. We assessed the effects of the KOR antagonist JDTic on alco...

  7. Safety in construction?

    NARCIS (Netherlands)

    Swuste, P.H.J.J.

    2013-01-01

    The available literature on Construction Safety is not very optimistic about the chances of evidence-based safety in the construction industry exerting a positive influence. Many articles indicate that the structures and processes that are designed to ensure safety in the industry are poor. Safety m

  8. Fusion safety status report

    International Nuclear Information System (INIS)

    This report includes information on a) tritium handling and safety; b) activation product generation and release; c) lithium safety; d) superconducting magnet safety; e) operational safety and shielding; f) environmental impact; g) recycling, decommissioning and waste management; and h) accident analysis. Recommendations for high priority research and development are presented, as well as the current status in each area

  9. Scaffold Optimisation of Tetravalent Antagonists of the Mannose Binding Lectin.

    Science.gov (United States)

    Goti, Giulio; Palmioli, Alessandro; Stravalaci, Matteo; Sattin, Sara; De Simoni, Maria-Grazia; Gobbi, Marco; Bernardi, Anna

    2016-03-01

    Antagonists of mannose binding lectin (MBL) have shown a protective role against brain reperfusion damage after acute ischemic stroke. Here we describe the design and streamlined synthesis of glycomimetic MBL antagonists based on a new tetravalent dendron scaffold. The dendron was developed by optimisation of a known polyester structure previously demonstrated to be very efficient for ligand presentation to MBL. Replacement of a labile succinyl ester bond with a more robust amide functionality, use of a longer and more hydrophilic linker, fast modular synthesis and orthogonal functionalisation at the focal point are the main features of the new scaffold. The glycoconjugate constructs become stable to silica gel chromatography and to water solutions at physiological pH, while preserving water solubility and activity in an SPR assay against the murine MBL-C isoform. Higher-order constructs were easily assembled, as demonstrated by the synthesis of a 16-valent dendrimer, which leads to two orders of magnitude increase in activity over the tetravalent version against MBL-C. PMID:26696414

  10. Human homosexuality: a paradigmatic arena for sexually antagonistic selection?

    Science.gov (United States)

    Camperio Ciani, Andrea; Battaglia, Umberto; Zanzotto, Giovanni

    2015-01-29

    Sexual conflict likely plays a crucial role in the origin and maintenance of homosexuality in our species. Although environmental factors are known to affect human homosexual (HS) preference, sibling concordances and population patterns related to HS indicate that genetic components are also influencing this trait in humans. We argue that multilocus, partially X-linked genetic factors undergoing sexually antagonistic selection that promote maternal female fecundity at the cost of occasional male offspring homosexuality are the best candidates capable of explaining the frequency, familial clustering, and pedigree asymmetries observed in HS male proband families. This establishes male HS as a paradigmatic example of sexual conflict in human biology. HS in females, on the other hand, is currently a more elusive phenomenon from both the empirical and theoretical standpoints because of its fluidity and marked environmental influence. Genetic and epigenetic mechanisms, the latter involving sexually antagonistic components, have been hypothesized for the propagation and maintenance of female HS in the population. However, further data are needed to truly clarify the evolutionary dynamics of this trait.

  11. Implications of hedgehog signaling antagonists for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Jingwu Xie

    2008-01-01

    The hedgehog(Hh)pathway,initially discovered inDrosophila by two Nobel laureates,Dr.Eric Wieschaus and Dr.Christiane Nusslein-Volhard,is a major regulator for cell differentiation,tissue polarity and cell proliferation.Studies from many laboratories,including ours,reveal activation of this pathway in most basal cell carcinomas and in approximately 30% of extracutaneous human cancers,including medulloblastomas,gastrointestinal,lung,breast and prostate cancers.Thus,it is believed that targeted inhibition of Hh signaling may be effective in treating and preventing many types of human cancers.Even more exciting is the discovery and synthesis of specific signaling antagonists for the Hh pathway,which have significant clinical implications in novel cancer therapeutics.This review discusses the major advances in the current understanding of Hh signaling activation in different types of human cancers,the molecular basis of Hh signaling activation,the major antagonists for Hh signaling inhibition and their potential clinical application in human cancer therapy.

  12. Suppression of Aldosterone Synthesis and Secretion by Channel Antagonists

    Directory of Open Access Journals (Sweden)

    Keiichi Ikeda

    2012-01-01

    Full Text Available Aldosterone, a specific mineralocorticoid receptor (MR agonist and a key player in the development of hypertension, is synthesized as a final product of renin-angiotensin-aldosterone system. Hypertension can be generally treated by negating the effects of angiotensin II through the use of angiotensin-converting enzyme inhibitors (ACE-Is or angiotensin II type 1 receptor antagonists (ARBs. However, the efficacy of angiotensin II blockade by such drugs is sometimes diminished by the so-called “aldosterone breakthrough” effect, by which ACE-Is or ARBs (renin-angiotensin system (RAS inhibitors gradually lose their effectiveness against hypertension due to the overproduction of aldosterone, known as primary aldosteronism. Although MR antagonists are used to antagonize the effects of aldosterone, these drugs may, however, give rise to life-threatening adverse actions, such as hyperkalemia, particularly when used in conjunction with RAS inhibitors. Recently, several groups have reported that some dihydropyridine Ca2+ channel blockers (CCBs have inhibitory actions on aldosterone production in in vitro and in the clinical setting. Therefore, the use of such dihydropyridine CCBs to treat aldosterone-related hypertension may prove beneficial to circumvent such therapeutic problems. In this paper, we discuss the mechanism of action of CCBs on aldosterone production and clinical perspectives for CCB use to inhibit MR activity in hypertensive patients.

  13. Growth hormone receptor antagonists: discovery and potential uses.

    Science.gov (United States)

    Kopchick, J J; Okada, S

    2001-06-01

    Serum levels of growth hormone (GH) in the human body vary and can influence the levels of insulin-like growth factor I (IGF-1). Low levels of GH can result in a dwarf phenotype and have been positively correlated with an increased life expectancy. High levels of GH can lead to gigantism or a clinical syndrome termed acromegaly, and also have been implicated in diabetic eye and kidney damage. Additionally, it has been postulated that the GH-IGF-I system can be involved in several types of cancers. Overall, both elevated and suppressed circulating levels of GH can have pronounced physiological effects. More than a decade ago a new class of drug, a GH antagonist, was discovered. It is now being tested for its ability to combat the effects of high circulating levels of GH. In this review, we will discuss some of the detrimental actions of GH and how a GH antagonist may be used to combat these effects. PMID:11527080

  14. Evodiamine as a novel antagonist of aryl hydrocarbon receptor

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Hui [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Department of Laboratory Medicine, The Affiliated Tenth People' s Hospital, Tongji University, Shanghai 200072 (China); Tu, Yongjiu; Zhang, Chun; Fan, Xia; Wang, Xi [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China); Wang, Zhanli [College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014 (China); Liang, Huaping, E-mail: huaping_liang@yahoo.com.cn [State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042 (China)

    2010-11-05

    Research highlights: {yields} Evodiamine interacted with the AhR. {yields} Evodiamine inhibited the specific binding of [{sup 3}H]-TCDD to the AhR. {yields} Evodiamine acts as an antagonist of the AhR. -- Abstract: Evodiamine, the major bioactive alkaloid isolated from Wu-Chu-Yu, has been shown to interact with a wide variety of proteins and modify their expression and activities. In this study, we investigated the interaction between evodiamine and the aryl hydrocarbon receptor (AhR). Molecular modeling results revealed that evodiamine directly interacted with the AhR. Cytosolic receptor binding assay also provided the evidence that evodiamine could interact with the AhR with the K{sub i} value of 28.4 {+-} 4.9 nM. In addition, we observed that evodiamine suppressed the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced nuclear translocation of the AhR and the expression of CYP1A1 dose-dependently. These results suggested that evodiamine was able to bind to the AhR as ligand and exhibit antagonistic effects.

  15. Novel potent selective phenylglycine antagonists of metabotropic glutamate receptors.

    Science.gov (United States)

    Bedingfield, J S; Jane, D E; Kemp, M C; Toms, N J; Roberts, P J

    1996-08-01

    The metabotropic glutamate (mGlu) receptor antagonist properties of novel phenylglycine analogues were investigated in adult rat cortical slices (mGlu receptors negatively coupled to adenylyl cyclase), neonatal rat cortical slices and in cultured rat cerebellar granule cells (mGlu receptors coupled to phosphoinositide hydrolysis). (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG), (RS)-alpha-methyl-4-sulphonophenylglycine (MSPG), (RS)-alpha-methyl-4-tetrazolylphenylglycine (MTPG), (RS)-alpha-methyl-3-carboxymethyl-4-hydroxyphenylglycine (M3CM4HPG) and (RS)-alpha-methyl-4-hydroxy-3-phosphonomethylphenylglycine (M4H3PMPG) were demonstrated to have potent and selective effects against 10 microM L-2-amino-4-phosphonobutyrate (L-AP4)- and 0.3 microM (2S,1'S,2'S)-2-(2-carboxycyclopropyl)glycine (L-CCG-1)-mediated inhibition of forskolin-stimulated cAMP accumulation in the adult rat cortex. In contrast, these compounds demonstrated either weak or no antagonism at mGlu receptors coupled to phosphoinositide hydrolysis in either neonatal rat cortex or in cultured cerebellar granule cells. These compounds thus appear to be useful discriminatory pharmacological tools for mGlu receptors and form the basis for the further development of novel antagonists. PMID:8864696

  16. Rogue sperm indicate sexually antagonistic coevolution in nematodes.

    Directory of Open Access Journals (Sweden)

    Ronald E Ellis

    2014-07-01

    Full Text Available Intense reproductive competition often continues long after animals finish mating. In many species, sperm from one male compete with those from others to find and fertilize oocytes. Since this competition occurs inside the female reproductive tract, she often influences the outcome through physical or chemical factors, leading to cryptic female choice. Finally, traits that help males compete with each other are sometimes harmful to females, and female countermeasures may thwart the interests of males, which can lead to an arms race between the sexes known as sexually antagonistic coevolution. New studies from Caenorhabditis nematodes suggest that males compete with each other by producing sperm that migrate aggressively and that these sperm may be more likely to win access to oocytes. However, one byproduct of this competition appears to be an increased probability that these sperm will go astray, invading the ovary, prematurely activating oocytes, and sometimes crossing basement membranes and leaving the gonad altogether. These harmful effects are sometimes observed in crosses between animals of the same species but are most easily detected in interspecies crosses, leading to dramatically lowered fitness, presumably because the competitiveness of the sperm and the associated female countermeasures are not precisely matched. This mismatch is most obvious in crosses involving individuals from androdioecious species (which have both hermaphrodites and males, as predicted by the lower levels of sperm competition these species experience. These results suggest a striking example of sexually antagonistic coevolution and dramatically expand the value of nematodes as a laboratory system for studying postcopulatory interactions.

  17. Discovery of tetrahydroisoquinoline-based CXCR4 antagonists.

    Science.gov (United States)

    Truax, Valarie M; Zhao, Huanyu; Katzman, Brooke M; Prosser, Anthony R; Alcaraz, Ana A; Saindane, Manohar T; Howard, Randy B; Culver, Deborah; Arrendale, Richard F; Gruddanti, Prahbakar R; Evers, Taylor J; Natchus, Michael G; Snyder, James P; Liotta, Dennis C; Wilson, Lawrence J

    2013-11-14

    A de novo hit-to-lead effort involving the redesign of benzimidazole-containing antagonists of the CXCR4 receptor resulted in the discovery of a novel series of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogues. In general, this series of compounds show good potencies (3-650 nM) in assays involving CXCR4 function, including both inhibition of attachment of X4 HIV-1IIIB virus in MAGI-CCR5/CXCR4 cells and inhibition of calcium release in Chem-1 cells. Series profiling permitted the identification of TIQ-(R)-stereoisomer 15 as a potent and selective CXCR4 antagonist lead candidate with a promising in vitro profile. The drug-like properties of 15 were determined in ADME in vitro studies, revealing low metabolic liability potential. Further in vivo evaluations included pharmacokinetic experiments in rats and mice, where 15 was shown to have oral bioavailability (F = 63%) and resulted in the mobilization of white blood cells (WBCs) in a dose-dependent manner. PMID:24936240

  18. Neuroprotection, excitotoxicicity and nmda antagonists Neuroproteção, excitotoxicidade e antagonistas do NMDA

    Directory of Open Access Journals (Sweden)

    RUBENS JOSÉ GAGLIARDI

    2000-06-01

    Full Text Available PURPOSE: To analyze the main aspects of neuroprotection and excitotoxicity. DISCUSSION: This is a significant theory on the pathophysiology of cerebral ischemia; it is based on the release of excitatory aminoacid (EAA, mainly glutamate. The sequence starts with a decrease of the blood flow and ends in neuronal death. The main stages of this reaction are herein presented and discussed. An in depth study of the effects of the excessive intracellular calcium is undertaken. Neuroprotectors (NP are a group of drugs that reduce the excitotoxicity, opposing the excessive release of EAA and its intracellular effects. Neuroprotectors represent a rational approach to stroke treatment and offer a number of potential advantages. They prevent or limit ischemia-induced damage. CONCLUSION: There are many experimental and clinical NP trials. A minimum of 800 trials are currently under study worldwide. The most important NP subgroups are: N-methyl D-aspartate (NMDA antagonists, gamma-amino butyric acid (GABA agonists, amino-hydroxy-methyl-isoxalone propionic acid (AMPA antagonists, reducers of intracellular Ca++ inhibitors of nitric oxide modulation pathway free radicals scavengers, sodium channel antagonists, glutamate release inhibitor, growth factors, hypothermia and potassium channel activators.PROPÓSITO: Analisar importantes aspectos da neuroproteção e da excitotoxicidade. DISCUSSÃO: Excitotoxicidade é teoria que explica os mecanismos básicos da fisiopatologia da isquemia cerebral; é baseada na liberação excessiva de amino-ácidos excitatórios (AAE, principalmente o glutamato. A sequência se inicia com o decréscimo do fluxo sanguíneo cerebral e termina com a morte neuronal. Os principais aspectos desta cadeia de reações são apresentados e discutidos. Os efeitos do excesso de cálcio intracelular são analisados. Neuroprotetores (NP são um grupo de drogas que reduzem a excitotoxicidade combatendo a excessiva liberação de AAE e os seus

  19. Effect of piboserod, a 5-HT4 serotonin receptor antagonist, on left ventricular function in patients with symptomatic heart failure

    DEFF Research Database (Denmark)

    Olsen, Inge C; Kjekshus, John K; Torp-Pedersen, Christian;

    2009-01-01

    AIMS: Myocardial 5-HT(4) serotonin (5-HT) receptors are increased and activated in heart failure (HF). Blockade of 5-HT(4) receptors reduced left ventricular (LV) remodelling in HF rats. We evaluated the effect of piboserod, a potent, selective, 5-HT(4) serotonin receptor antagonist, on LV function...... weeks up titration. The primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI). Secondary endpoints were LV volumes, N-terminal pro-brain natriuretic peptide, norepinephrine, quality of life, and 6 min walk test. Piboserod significantly increased LVEF by 1.7% vs. placebo (CI 0...... of life, or exercise tolerance. Patients on piboserod reported more adverse events, but numbers were too small to identify specific safety issues. CONCLUSION: Although patients with chronic HF had a small but significant improvement in LVEF when treated with piboserod for 24 weeks, the result...

  20. 76 FR 47262 - Brookwood-Sago Mine Safety Grants

    Science.gov (United States)

    2011-08-04

    ..., secondary purposes, adult learning principles and usability in the mine training environment. Develop... have, at a minimum, mine safety experience, training experience, or experience working with the mining... whether the evaluation should include a process-related outcome or an impact-related outcome or both....

  1. Plutonium Finishing Plant (PFP) Safety Class and Safety Significant Commercial Grade Items (CGI) Critical Characteristic

    International Nuclear Information System (INIS)

    This document specifies the critical characteristics for Commercial Grade Items (CGI) procured for use in the Plutonium Finishing Plant as required by HNF-PRO-268 and HNF-PRO-1819. These are the minimum specifications that the equipment must meet in order to properly perform its safety function. There may be several manufacturers or models that meet the critical characteristics of any one item

  2. Safety at CERN

    CERN Document Server

    2009-01-01

    Safety is an integral part of our working lives, and should be in our minds whatever job we do at CERN. Ultimately, safety is the responsibility of the Director General – your safety is my concern. That’s why I have this week appointed a new Safety Policy Committee (SAPOCO) that reflects the new Organizational structure of CERN. CERN’s Staff Rules and Regulations clearly lay out in chapter 3 the scope of safety at CERN as well as my responsibilities and yours in safety matters. At CERN, safety is considered in the broadest sense, encompassing occupational Health and Safety, environmental protection, and the safety of equipment and installations. It is my responsibility to put appropriate measures in place to ensure that these conditions are met. And it is the responsibility of us all to ensure that we are fully conversant with safety provisions applicable in our areas of work and that we comply with them. The appointment of a n...

  3. Determining the minimum ripening time of artisanal Minas cheese, a traditional Brazilian cheese

    Directory of Open Access Journals (Sweden)

    José M. Martins

    2015-03-01

    Full Text Available Physical, physicochemical, and microbiological changes were monitored in 256 samples of artisanal Minas cheese from eight producers from Serro region (Minas Gerais, Brazil for 64 days of ripening to determine the minimum ripening time for the cheese to reach the safe microbiological limits established by Brazilian legislation. The cheeses were produced between dry season (April–September and rainy season (October–March; 128 cheeses were ripened at room temperature (25 ± 4 °C, and 128 were ripened under refrigeration (8 ± 1 °C, as a control. No Listeria monocytogenes was found, but one cheese under refrigeration had Salmonella at first 15 days of ripening. However, after 22 days, the pathogen was not detected. Seventeen days was the minimum ripening time at room temperature to reduce at safe limits of total coliforms > 1000 cfu.g−1, Escherichia coli and Staphylococcus aureus (> 100 cfu.g−1 in both periods of manufacture. Otherwise under refrigeration, as expected, the minimum ripening time was longer, 33 days in the dry season and 63 days in the rainy season. To sum up, we suggest that the ripening of artisanal Minas cheese be done at room temperature, since this condition shortens the time needed to reach the microbiological quality that falls within the safety parameters required by Brazilian law, and at the same time maintain the appearance and flavor characteristics of this traditional cheese.

  4. 14 CFR 91.155 - Basic VFR weather minimums.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Basic VFR weather minimums. 91.155 Section...) AIR TRAFFIC AND GENERAL OPERATING RULES GENERAL OPERATING AND FLIGHT RULES Flight Rules Visual Flight Rules § 91.155 Basic VFR weather minimums. (a) Except as provided in paragraph (b) of this section...

  5. 77 FR 43196 - Minimum Internal Control Standards and Technical Standards

    Science.gov (United States)

    2012-07-24

    ... COMMISSION 25 CFR Parts 543 and 547 Minimum Internal Control Standards and Technical Standards AGENCY... . SUPPLEMENTARY INFORMATION: Part 543 addresses minimum internal control standards (MICS) for Class II gaming... their comments. DATES: The comment period for the proposed rules published June 1, 2012, at 77 FR...

  6. 14 CFR 23.149 - Minimum control speed.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Minimum control speed. 23.149 Section 23... Maneuverability § 23.149 Minimum control speed. (a) VMC is the calibrated airspeed at which, when the critical... still inoperative, and thereafter maintain straight flight at the same speed with an angle of bank...

  7. Construction of some perfect integral lattices with minimum 4

    OpenAIRE

    Bacher, Roland

    2014-01-01

    Final version, to appear in Journal de Théorie des Nombres de Bordeaux We construct several families of perfect sublattices with minimum $4$ of $\\mathbb Z^d$. In particular, the number of $d-$dimensional perfect integral lattices with minimum $4$ grows faster than $d^k$ for every exponent $k$.

  8. 77 FR 76979 - Pesticides; Revisions to Minimum Risk Exemption

    Science.gov (United States)

    2012-12-31

    ... (NAICS code 325620), and soap and detergents (NAICS code 325611). Manufacturers who may also be... this proposal is to clarify the conditions of exemption for minimum risk pesticides by making clearer... solely of specified ingredients that EPA judged to pose minimum risk to humans and the environment (61...

  9. Theoretical minimum energies to produce steel for selected conditions

    Energy Technology Data Exchange (ETDEWEB)

    Fruehan, R. J. [Carnegie Mellon Univ., Pittsburgh, PA (United States); Fortini, O. [Carnegie Mellon Univ., Pittsburgh, PA (United States); Paxton, H. W. [Carnegie Mellon Univ., Pittsburgh, PA (United States); Brindle, R. [Carnegie Mellon Univ., Pittsburgh, PA (United States)

    2000-03-01

    An ITP study has determined the theoretical minimum energy requirements for producing steel from ore, scrap, and direct reduced iron. Dr. Richard Fruehan's report, Theoretical Minimum Energies to Produce Steel for Selected Conditions, provides insight into the potential energy savings (and associated reductions in carbon dioxide emissions) for ironmaking, steelmaking, and rolling processes (PDF 459 KB).

  10. 12 CFR 615.5205 - Minimum permanent capital standards.

    Science.gov (United States)

    2010-01-01

    ... AFFAIRS, LOAN POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Capital Adequacy § 615.5205 Minimum permanent capital standards. Each institution shall at all times maintain permanent capital at a level of at... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Minimum permanent capital standards....

  11. 41 CFR 50-201.1101 - Minimum wages.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Minimum wages. 50-201.1101 Section 50-201.1101 Public Contracts and Property Management Other Provisions Relating to Public.... Determinations of prevailing minimum wages or changes therein will be published in the Federal Register by...

  12. Multiple Objective Minimum Cost Flow Problems: A Review

    DEFF Research Database (Denmark)

    Hamacher, H.W.; Pedersen, Christian Roed; Ruzika, S.

    2005-01-01

    In this paper, theory and algorithms for solving the multiple objective minimum cost flow problem are reviewed. For both the continuous and integer case exact and approximation algorithms are presented. In addition, a section on compromise solutions summarizes corresponding results. The reference...... list consists of all papers known to the authors which deal with the multiple objective minimum cost flow problem....

  13. 14 CFR 91.177 - Minimum altitudes for IFR operations.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Minimum altitudes for IFR operations. 91.177 Section 91.177 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... Instrument Flight Rules § 91.177 Minimum altitudes for IFR operations. (a) Operation of aircraft at...

  14. 7 CFR 1610.5 - Minimum Bank loan.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Minimum Bank loan. 1610.5 Section 1610.5 Agriculture Regulations of the Department of Agriculture (Continued) RURAL TELEPHONE BANK, DEPARTMENT OF AGRICULTURE LOAN POLICIES § 1610.5 Minimum Bank loan. A Bank loan will not be made unless the applicant qualifies for a...

  15. 12 CFR 931.3 - Minimum investment in capital stock.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Minimum investment in capital stock. 931.3 Section 931.3 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK RISK MANAGEMENT AND CAPITAL STANDARDS FEDERAL HOME LOAN BANK CAPITAL STOCK § 931.3 Minimum investment in capital stock. (a)...

  16. 14 CFR 93.307 - Minimum flight altitudes.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Minimum flight altitudes. 93.307 Section 93...) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES Special Flight Rules in the Vicinity of Grand Canyon National Park, AZ § 93.307 Minimum flight altitudes. Except in an emergency, or...

  17. 48 CFR 52.214-16 - Minimum Bid Acceptance Period.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Minimum Bid Acceptance... (CONTINUED) CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 52.214-16 Minimum Bid Acceptance Period. As prescribed in 14.201-6(j), insert the following provision...

  18. State Minimum Core Curricula: Arkansas Institutions of Higher Education.

    Science.gov (United States)

    Arkansas State Dept. of Higher Education, Little Rock.

    State minimum core curricula for two-year and four-year colleges and universities have been approved by the Arkansas Board of Higher Education. Within the framework of the State Minimum Core, each state institution is required to propose 35 semester/credit hours from its institutional general education core to be recognized for purposes of the…

  19. 5 CFR 844.303 - Minimum disability annuity.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Minimum disability annuity. 844.303... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES' RETIREMENT SYSTEM-DISABILITY RETIREMENT Computation of Disability Annuity § 844.303 Minimum disability annuity. Notwithstanding any other provision of this part, an...

  20. 42 CFR 84.174 - Respirator containers; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Respirator containers; minimum requirements. 84.174... Air-Purifying Particulate Respirators § 84.174 Respirator containers; minimum requirements. (a) Except..., durable container bearing markings which show the applicant's name, the type of respirator it...

  1. 42 CFR 84.74 - Apparatus containers; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Apparatus containers; minimum requirements. 84.74...-Contained Breathing Apparatus § 84.74 Apparatus containers; minimum requirements. (a) Apparatus may be equipped with a substantial, durable container bearing markings which show the applicant's name, the...

  2. 42 CFR 84.197 - Respirator containers; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Respirator containers; minimum requirements. 84.197... Cartridge Respirators § 84.197 Respirator containers; minimum requirements. Respirators shall be equipped with a substantial, durable container bearing markings which show the applicant's name, the type...

  3. 42 CFR 84.134 - Respirator containers; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Respirator containers; minimum requirements. 84.134... Respirators § 84.134 Respirator containers; minimum requirements. Supplied-air respirators shall be equipped with a substantial, durable container bearing markings which show the applicant's name, the type...

  4. 49 CFR 236.562 - Minimum rail current required.

    Science.gov (United States)

    2010-10-01

    ..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Rules and Instructions; Locomotives § 236.562 Minimum rail current required. The minimum rail current required to restore the locomotive equipment...

  5. 6 CFR 27.204 - Minimum concentration by security issue.

    Science.gov (United States)

    2010-01-01

    ... the incorporation by reference of this standard in accordance with 5 U.S.C. 552(a) and 1 CFR part 51... 6 Domestic Security 1 2010-01-01 2010-01-01 false Minimum concentration by security issue. 27.204... FACILITY ANTI-TERRORISM STANDARDS Chemical Facility Security Program § 27.204 Minimum concentration...

  6. Minimum Competencies in Undergraduate Motor Development. Guidance Document

    Science.gov (United States)

    National Association for Sport and Physical Education, 2004

    2004-01-01

    The minimum competency guidelines in Motor Development described herein at the undergraduate level may be gained in one or more motor development course(s) or through other courses provided in an undergraduate curriculum. The minimum guidelines include: (1) Formulation of a developmental perspective; (2) Knowledge of changes in motor behavior…

  7. The impact of minimum wages on youth employment in Portugal

    NARCIS (Netherlands)

    S.C. Pereira

    2003-01-01

    textabstractFrom January 1, 1987, the legal minimum wage for workers aged 18 and 19 in Portugal was uprated to the full adult rate, generating a 49.3% increase between 1986 and 1987 in the legal minimum wage for this age group. This shock is used as a ?natural experiment? to evaluate the impact of t

  8. 5 CFR 9901.407 - Minimum period of performance.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Minimum period of performance. 9901.407 Section 9901.407 Administrative Personnel DEPARTMENT OF DEFENSE HUMAN RESOURCES MANAGEMENT AND LABOR... the minimum period of performance during the applicable appraisal period will not be rated and...

  9. 27 CFR 40.526 - Minimum manufacturing and activity requirements.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Minimum manufacturing and activity requirements. 40.526 Section 40.526 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... Manufacturers of Processed Tobacco § 40.526 Minimum manufacturing and activity requirements. A permit...

  10. The Minimum Wage, Restaurant Prices, and Labor Market Structure

    Science.gov (United States)

    Aaronson, Daniel; French, Eric; MacDonald, James

    2008-01-01

    Using store-level and aggregated Consumer Price Index data, we show that restaurant prices rise in response to minimum wage increases under several sources of identifying variation. We introduce a general model of employment determination that implies minimum wage hikes cause prices to rise in competitive labor markets but potentially fall in…

  11. 20 CFR 404.260 - Special minimum primary insurance amounts.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Special minimum primary insurance amounts. 404.260 Section 404.260 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Computing Primary Insurance Amounts Special Minimum...

  12. 76 FR 30243 - Minimum Security Devices and Procedures

    Science.gov (United States)

    2011-05-24

    ... Office of Thrift Supervision Minimum Security Devices and Procedures AGENCY: Office of Thrift Supervision... related index on the OTS Internet Site at http://www.ots.treas.gov . In addition, interested persons may... following information collection. Title of Proposal: Minimum Security Devices and Procedures. OMB...

  13. 76 FR 15368 - Minimum Security Devices and Procedures

    Science.gov (United States)

    2011-03-21

    ... Office of Thrift Supervision Minimum Security Devices and Procedures AGENCY: Office of Thrift Supervision... related index on the OTS Internet Site at http: www.ots.treas.gov. In addition, interested persons may... collection. Title of Proposal: Minimum Security Devices and Procedures. OMB Number: 1550-0062. Form Number:...

  14. 17 CFR 31.9 - Minimum financial requirements.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Minimum financial requirements. 31.9 Section 31.9 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION LEVERAGE TRANSACTIONS § 31.9 Minimum financial requirements. (a) Each leverage transaction merchant must at all...

  15. 47 CFR 22.951 - Minimum coverage requirement.

    Science.gov (United States)

    2010-10-01

    ... MOBILE SERVICES Cellular Radiotelephone Service § 22.951 Minimum coverage requirement. Applications for... toward the minimum coverage requirement. Applications for authority to operate a new cellular system in... reefs only), except for unserved areas in the Gulf of Mexico MSA....

  16. Progress in the discovery of selective, high affinity A(2B) adenosine receptor antagonists as clinical candidates.

    Science.gov (United States)

    Kalla, Rao V; Zablocki, Jeff

    2009-03-01

    The selective, high affinity A(2B) adenosine receptor (AdoR) antagonists that were synthesized by several research groups should aid in determining the role of the A(2B) AdoR in inflammatory diseases like asthma or rheumatoid arthritis (RA) and angiogenic diseases like diabetic retinopathy or cancer. CV Therapeutics scientists discovered the selective, high affinity A(2B) AdoR antagonist 10, a 8-(4-pyrazolyl)-xanthine derivative [CVT-6883, K(i)(hA(2B)) = 22 nM; K(i)(hA(1)) = 1,940 nM; K(i)(hA(2A)) = 3,280; and K(i)(hA(3)) = 1,070 nM] that has favorable pharmacokinetic (PK) properties (t (1/2) = 4 h and F > 35% rat). Compound 10 demonstrated functional antagonism at the A(2B) AdoR (K(B) = 6 nM) and efficacy in a mouse model of asthma. In two phase 1 clinical trials, CVT-6883 was found to be safe, well tolerated, and suitable for once daily dosing. A second compound 20, 8-(5-pyrazolyl)-xanthine, has been nominated for development from Baraldi's group in conjunction with King Pharmaceuticals that has favorable A(2B) AdoR affinity and selectivity [K(i)(hA(2B)) = 5.5 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 1,000; and K(i)(hA(3)) > 1,000 nM], and it has been demonstrated to be a functional antagonist. A third compound 32, a 2-aminopyrimidine, from the Almirall group has high A(2B) AdoR affinity and selectivity [K(i)(hA(2B)) = 17 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 2,500; and K(i)(hA(3)) > 1,000 nM], and 32 has been moved into preclinical safety testing. Since three highly selective, high affinity A(2B) AdoR antagonists have been nominated for development with 10 (CVT-6883) being the furthest along in the development process, the role of the A(2B) AdoR in various disease states will soon be established. PMID:18568423

  17. Demand for public safety

    OpenAIRE

    Pradhan, Menno; Ravallion, Martin

    1999-01-01

    In public safety of less concern to poor people? What about people in poor areas? How is demand for public safety affected by income inequality? Is there a self-correcting mechanism whereby higher crime increases demand for public safety? The authors study subjective assessments of public safety using a comprehensive socioeconomic survey of living standards in Brazil. They find public safety to be a normal good at the household level. Marginal income effects are higher for the poor, so inequa...

  18. China's Work Safety Report

    Institute of Scientific and Technical Information of China (English)

    Liang Jiakun

    2005-01-01

    @@ General Situation of China's Work Safety in 2004 In 2004, the national work safety situation remained stable as a whole and gained momentum to improve. The totality of accidents held the line and began to drop. The safety conditions in industrial,mining, and commercial/trading enterprises improved. Progress was made in ensuring work safety in the relevant industries and fields. The safety situation in most provinces (autonomous regions, municipalities directly under the Central Government) kept stable.

  19. Nuclear safety in perspective

    OpenAIRE

    Andersson, K.; Sjöberg, B.M.D.; Lauridsen, Kurt; Wahlström, B.

    2003-01-01

    The aim of the NKS/SOS-1 project has been to enhance common understanding about requirements for nuclear safety by finding improved means of communicat-ing on the subject in society. The project, which has been built around a number of seminars, wassupported by limited research in three sub-projects: Risk assessment Safety analysis Strategies for safety management The report describes an industry in change due to societal factors. The concepts of risk and safety, safety management and systems...

  20. Training safely, Training safety

    OpenAIRE

    Jianjun Wu; An, M.; Jin, Y.; H. Geng

    2014-01-01

    It is the basic requirement of maritime safety education to guarantee the safety of teaching operation while training the crew's occupation safety capability. Marine Training Center of Shanghai Maritime University has undertaken the practical teaching of "marine survival" for many years and come up with the whole safety procedures of training. Based on the requirements of SOLAS convention and regulations of STCW over crew training, this paper introduces the safety allocation, utilization and ...