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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......-inferiority to the manual dosage at the experienced centers in the EAA study. With the use of a cluster sampling procedure, a minimum number of centers and a minimum total of patients required to establish non-inferiority were determined. At least four centers, each recruiting 50 patients over a period of 6...... months, were shown to be required (excluding the results from the first 3 weeks of treatment). To achieve non-inferiority, the lower 95% confidence interval of the 'time in target International Normalized Ratio range' (TIR) of a marketed program must be above the TIR limit set by the manual dosage group...

  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. Developing and implementing a minimum safety program

    International Nuclear Information System (INIS)

    This presentation highlighted the six elements of a basic safety program. These are: (1) management involvement, (2) hazard identification and control, (3) rules and work procedures, (4) training, (5) communication, and (6) incident and accident reporting and investigation. Steps to implement a safety program were described. The importance of measuring and auditing the program, and the importance of recognizing achievement in safe operations were emphasized. 5 diapositives

  4. 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

  5. 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.

  6. 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...

  7. 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

  8. radiation safety culture for developing country: Basis for s minimum operational radiation protection programme

    International Nuclear Information System (INIS)

    The purpose of this document is to present a methodology for an integrated strategy aiming at establishing an adequate radiation Safety infrastructure for developing countries, non major power reactor programme. Its implementation will allow these countries, about 50% of the IAEA's Member States, to improve marginal radiation safety, specially to those recipients of technical assistance and do not meet the Minimum radiation Safety Requirements of the IAEA's Basic Safety Standards for radiation protection Progress in the implementation of safety regulations depends on the priority of the government and its understanding and conviction about the basic requirements for protection against the risks associated with exposure to ionizing radiation. There is no doubt to conclude that the reasons for the deficiency of sources control and dose limitation 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, to avoid overlap and conflict, that is: A 'Memorandum of Understanding' among Regulatory Authorities in the Country, dealing with similar type of licensing and inspection

  9. 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... with an internal combustion engine (ICE). The PSEA defines ``conventional motor vehicle'' as ``a motor... CFR Parts 571 and 585 Federal Motor Vehicle Safety Standards; Minimum Sound Requirements for...

  10. 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.

  11. 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

  12. 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)

  13. Comparative safety and tolerability of endothelin receptor antagonists in pulmonary arterial hypertension.

    Science.gov (United States)

    Aversa, Meghan; Porter, Sandra; Granton, John

    2015-05-01

    Pulmonary arterial hypertension (PAH) is a condition that leads to progressive right heart failure and death unless recognized and treated early. Endothelin, a potent endogenous vasoconstrictor, has been identified as an important mediator of PAH. Endothelin receptor antagonists (ERAs) have been associated with an improvement in exercise capacity and time to clinical worsening in patients with Group 1 PAH, and three different ERAs are currently approved for use in this population: bosentan, ambrisentan, and macitentan. While all three ERAs are generally well-tolerated, they each have important adverse effects that need to be recognized and monitored. In particular, they may cause anemia, peripheral edema, and mild cardiac, respiratory, neurologic, and gastrointestinal adverse effects to varying degrees. Although bosentan increases a patient's risk of developing liver transaminitis, ambrisentan and macitentan do not appear to confer the same risk of hepatotoxicity at this time. Important drug-drug interactions, particularly involving other drugs metabolized via the cytochrome P450 pathway, are important to recognize when prescribing ERAs. In this review, we provide a brief overview of the current state of knowledge as it relates to the adverse effect profiles, tolerability, and drug-drug interactions of this class of medication as informed by the results of randomized clinical trials, drug surveillance programs, and regulatory agencies. PMID:25792028

  14. Integration of efficacy, pharmacokinetic and safety assessment of interleukin-1 receptor antagonist in a preclinical model of arthritis.

    Science.gov (United States)

    Zuurmond, Anne-Marie; Koudijs, Angela; van El, Benno; Doornbos, Robert P; van Manen-Vernooij, Babs C T; Bastiaans, Jacqueline H M W; Penninks, André H; van Bilsen, Jolanda H M; Cnubben, Nicole H P; Degroot, Jeroen

    2011-04-01

    Pharmacokinetic properties and safety profile of a drug are likely influenced by the disease state of a patient. In this study, we investigated the influence of arthritic processes on pharmacokinetics and immunotoxicity of interleukin-1 receptor antagonist (Anakinra) in the rat adjuvant arthritis model. Anakinra dose-dependently suppressed joint inflammation and degradation as demonstrated by reduced clinical arthritis score, paw thickness, synovial infiltration and bone degradation. In addition, plasma levels of chemokines MCP-1 and GRO/KC were reduced. Pharmacokinetic behaviour of Anakinra was influenced by disease state of the rats as judged from a decrease in C(max) and an increase of the MRT as the disease progressed at a dose of 24 and 72 mg Anakinra/kg body weight. The pharmacokinetic parameters increased dose-dependently, but non-proportionally with increasing dose. Low level anti-Anakinra antibody formation was observed at prolonged exposure to the biologic. Safety parameters, including haematology, splenic lymphocyte subset analysis, ex vivo stimulation of spleen cells and histopathology of immune system organs were affected by the disease itself to such extent that no additional effects of Anakinra could be observed. In conclusion, we demonstrated that pharmacokinetic behaviour of Anakinra was influenced by the arthritis background of the rats resulting in decreased internal exposure. PMID:21300126

  15. 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

  16. 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

  17. 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

  18. 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.)

  19. 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

  20. 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

  1. Minimum safety-relevant requirements on the construction and operation of steel pipelines for hydropower installations; Sicherheitsrelevante Mindestanforderungen an Bau und Betrieb von Druckrohrleitungen aus Stahlrohren fuer Wasserkraftanlagen

    Energy Technology Data Exchange (ETDEWEB)

    Kiesselbach, Gerhard [Dr. Kiesselbach Consulting GmbH, Wien (Austria)

    2010-10-15

    Steel has been in successful use in the penstocks of hydroelectric power plants from the very beginning, and still remains one of the most reliable piping materials today. An essential precondition for sustained safe and reliable operation of such pipes in a hydroelectric or mini hydroelectric power plant is strict adherence to the minimum safety-relevant requirements for design, construction and operation, and the verification of such adherence in the acceptance inspection. In view of the potential hazard for persons and property, the mere assumption that the penstock of a hydroelectric or mini hydroelectric power plant will conform to the minimum safety-relevant specifications, without verification at the acceptance inspection, is under no circumstances justifiable in terms of sustained safe and reliable operation. Experience has demonstrated that, in practice, such assumptions are frequently made, a fact which cannot be reconciled with the general safety-relevant stipulations of the responsible authorities. (orig.)

  2. 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

  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. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study

    Science.gov (United States)

    Skjøth, Flemming; Nielsen, Peter Brønnum; Kjældgaard, Jette Nordstrøm; Lip, Gregory Y H

    2016-01-01

    Objective To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation. Design Observational nationwide cohort study. Setting Three Danish nationwide databases, August 2011 to October 2015. Participants 61 678 patients with non-valvular atrial fibrillation who were naïve to oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The study population was distributed according to treatment type: warfarin (n=35 436, 57%), dabigatran 150 mg (n=12 701, 21%), rivaroxaban 20 mg (n=7192, 12%), and apixaban 5 mg (n=6349, 10%). Main outcome measures Effectiveness outcomes defined a priori were ischaemic stroke; a composite of ischaemic stroke or systemic embolism; death; and a composite of ischaemic stroke, systemic embolism, or death. Safety outcomes were any bleeding, intracranial bleeding, and major bleeding. Results When the analysis was restricted to ischaemic stroke, NOACs were not significantly different from warfarin. During one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99). The hazard ratios for dabigatran and apixaban (2.8% and 4.9% annually, respectively) were non-significant compared with warfarin. The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%). For the combined endpoint of any bleeding, annual rates for apixaban (3.3%) and dabigatran (2.4%) were significantly lower than for warfarin (5.0%) (0.62, 0.51 to 0.74). Warfarin and rivaroxaban had comparable annual bleeding rates (5

  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. 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

  8. 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...

  9. Safety

    International Nuclear Information System (INIS)

    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.)

  10. 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...... platelet inhibition than clopidogrel in patients with stable coronary artery disease. METHODS: A total of 990 patients with NSTE-ACS, treated with aspirin and standard therapy for ACS, were randomized in a 1:1:1 double-blind fashion to receive either twice-daily AZD6140 90 mg, AZD6140 180 mg, or...... clopidogrel 300-mg loading dose plus 75 mg once daily for up to 12 weeks. RESULTS: The primary end point, the Kaplan-Meier rate of major or minor bleeding through 4 weeks, was 8.1% in the clopidogrel group, 9.8% in the AZD6140 90-mg group, and 8.0% in the AZD6140 180-mg group (p = 0.43 and p = 0...

  11. 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.

  12. A Foldable Antagonistic Actuator

    OpenAIRE

    Shintake, Jun; Rosset, Samuel; Schubert, Bryan Edward; Floreano, Dario; Shea, Herbert

    2015-01-01

    We report on an actuator based on dielectric elastomers that is capable of antagonistic actuation and passive folding. This actuator enables foldability in robots with simple structures. Unlike other antagonistic dielectric elastomer devices, our concept uses elastic hinges to allow the folding of the structure, which also provides an additional design parameter. To validate the actuator concept through a specific application test, a foldable elevon actuator with outline size of 70 mm × 130 m...

  13. 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...

  14. 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...

  15. Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up.

    Science.gov (United States)

    Gambacorti-Passerini, Carlo; Brümmendorf, Tim H; Kim, Dong-Wook; Turkina, Anna G; Masszi, Tamas; Assouline, Sarit; Durrant, Simon; Kantarjian, Hagop M; Khoury, H Jean; Zaritskey, Andrey; Shen, Zhi-Xiang; Jin, Jie; Vellenga, Edo; Pasquini, Ricardo; Mathews, Vikram; Cervantes, Francisco; Besson, Nadine; Turnbull, Kathleen; Leip, Eric; Kelly, Virginia; Cortes, Jorge E

    2014-07-01

    Bosutinib is an orally active, dual Src/Abl tyrosine kinase inhibitor for treatment of chronic myeloid leukemia (CML) following resistance/intolerance to prior therapy. Here, we report the data from the 2-year follow-up of a phase 1/2 open-label study evaluating the efficacy and safety of bosutinib as second-line therapy in 288 patients with chronic phase CML resistant (n = 200) or intolerant (n = 88) to imatinib. The cumulative response rates to bosutinib were as follows: 85% achieved/maintained complete hematologic response, 59% achieved/maintained major cytogenetic response (including 48% with complete cytogenetic response), and 35% achieved major molecular response. Responses were durable, with 2-year estimates of retaining response >70%. Two-year probabilities of progression-free survival and overall survival were 81% and 91%, respectively. The most common toxicities were primarily gastrointestinal adverse events (diarrhea [84%], nausea [45%], vomiting [37%]), which were primarily mild to moderate, typically transient, and first occurred early during treatment. Thrombocytopenia was the most common grade 3/4 hematologic laboratory abnormality (24%). Outcomes were generally similar among imatinib-resistant and imatinib-intolerant patients and did not differ with age. The longer-term results of the present analysis confirm that bosutinib is an effective and tolerable second-line therapy for patients with imatinib-resistant or imatinib-intolerant chronic phase CML. ClinicalTrials.gov Identifier: NCT00261846. PMID:24711212

  16. 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...

  17. Vasopressin receptor antagonists: Characteristics and clinical role.

    Science.gov (United States)

    Rondon-Berrios, Helbert; Berl, Tomas

    2016-03-01

    Hyponatremia, the most common electrolyte disorder in hospitalized patients is associated with increased risk of mortality even when mild and apparently asymptomatic. Likewise morbidity manifested as attention deficits, gait disturbances, falls, fractures, and osteoporosis is more prevalent in hyponatremic subjects. Hyponatremia also generates a significant financial burden. Therefore, it is important to explore approaches that effectively and safely treat hyponatremia. Currently available strategies are physiologically sound and affordable but lack evidence from clinical trials and are limited by variable efficacy, slow response, and/or poor compliance. The recent emergence of vasopressin receptor antagonists provides a class of drugs that target the primary pathophysiological mechanism, namely vasopressin mediated impairment of free water excretion. This review summarizes the historical development, pharmacology, clinical trials supporting efficacy and safety, shortcomings, as well as practical suggestions for the use of vasopressin receptor antagonists. PMID:27156765

  18. Selective orexin receptor antagonists.

    Science.gov (United States)

    Lebold, Terry P; Bonaventure, Pascal; Shireman, Brock T

    2013-09-01

    The orexin, or hypocretin, neuropeptides (orexin-A and orexin-B) are produced on neurons in the hypothalamus which project to key areas of the brain that control sleep-wake states, modulation of food intake, panic, anxiety, emotion, reward and addictive behaviors. These neuropeptides exert their effects on a pair of G-protein coupled receptors termed the orexin-1 (OX1) and orexin-2 (OX2) receptors. Emerging biology suggests the involvement of these receptors in psychiatric disorders as they are thought to play a key role in the regulation of multiple systems. This review is intended to highlight key selective OX1 or OX2 small-molecule antagonists. PMID:23891187

  19. Oxytocin antagonists for the management of preterm birth: a review.

    Science.gov (United States)

    Usta, Ihab M; Khalil, Ali; Nassar, Anwar H

    2011-06-01

    Preterm birth, the leading cause of neonatal morbidity and mortality, is estimated at incidence of 12.7% of all births, which has not decreased over the last four decades despite intensive antenatal care programs aimed at high-risk groups, the widespread use of tocolytics, and a series of other preventive and therapeutic interventions. Oxytocin antagonists, namely atosiban, represent an appealing choice that seems to be effective with apparently fewer side effects than the traditional tocolytics. This article reviews the available literature on the pharmacokinetics, mode of administration, and clinical utility of oxytocin antagonists for acute and maintenance tocolysis with special emphasis on its safety profile. PMID:21170825

  20. 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...

  1. 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....

  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. ANTIHYPERTENSIVE TREATMENT IN ELDERLY PATIENTS WITH DIHYDROPYRIDINE CALCIUM ANTAGONISTS

    OpenAIRE

    Y. A. Karpov; V. V. Buza

    2016-01-01

    The proofs of necessity of active arterial hypertension (AH) treatment in elderly patients are given. Peculiarities of pathogenesis of AH in elderly patients, connected predominantly with loss of big arteries elasticity and reasoning widely spread of isolated systolic AH in these patients, are discussed. Advantages of dihydropyridine calcium antagonists (DPCA) for AH treatment in elderly patients are proved, safety of treatment with DPCA is discussed. Data of clinical studies is analyzed. Ana...

  4. 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...

  5. BOUNDED MINIMUM INHERENT AVAILABILITY REQUIREMENTS FOR THE SYSTEM DESCRIPTION DOCUMENTS

    International Nuclear Information System (INIS)

    The purpose of this analysis is to establish bounded minimum inherent availability requirements for the Mined Geologic Disposal System (MGDS) System Description Documents (SDDs). The purpose of the bounded minimum inherent availability is to provide a lower bound on availability which will allow design to meet throughput requirements while not affecting the ability of the items to perform their intended safety function

  6. Minimum Probability Flow Learning

    CERN Document Server

    Sohl-Dickstein, Jascha; DeWeese, Michael R

    2009-01-01

    Learning in probabilistic models is often severely hampered by the general intractability of the normalization factor and its derivatives. Here we propose a new learning technique that obviates the need to compute an intractable normalization factor or sample from the equilibrium distribution of the model. This is achieved by establishing dynamics that would transform the observed data distribution into the model distribution, and then setting as the objective the minimization of the initial flow of probability away from the data distribution. Score matching, minimum velocity learning, and certain forms of contrastive divergence are shown to be special cases of this learning technique. We demonstrate the application of minimum probability flow learning to parameter estimation in Ising models, deep belief networks, multivariate Gaussian distributions and a continuous model with a highly general energy function defined as a power series. In the Ising model case, minimum probability flow learning outperforms cur...

  7. 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...

  8. 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

  9. Minimum Critical Values Study

    Energy Technology Data Exchange (ETDEWEB)

    Fox, P.B.

    2005-07-11

    This report provides minimum critical values for various 30-cm water-reflected uranium and plutonium oxide and nitrate aqueous mixtures as calculated by the SCALE CSAS1X sequence using the 238-group ENDF/B-V neutron cross-section library. The minimum values were determined through parametric searches in one-dimensional geometry. The calculations have been performed to obtain the minimum values: critical volume and mass for spheres, critical radius for cylinders, critical thickness for slabs, and minimum critical concentration (infinite geometry) for the following homogeneous mixtures: (1) UO{sub 2}-H{sub 2}O for 3, 4, 5, 20, and 100 wt % {sup 235}U; (2) UNH for 3, 4, 5, 20, and 100 wt % {sup 235}U; (3) PuO{sub 2}-H{sub 2}O for 100/0/0, 95/5/0, 90/5/5, 80/10/10, and 71/17/11/1 wt % of {sup 239}Pu/{sup 240}Pu/{sup 241}Pu(/{sup 242}Pu); and (4) PuNH for 100/0/0, 95/5/0, 90/5/5, 80/10/10, and 71/17/11/1 wt % of {sup 239}Pu/{sup 240}Pu/{sup 241}Pu(/{sup 242}Pu). All bounding surfaces were fully reflected by 30 cm of H{sub 2}O.

  10. 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.

  11. 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.

  12. 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...

  13. Misleading Advertising and Minimum Quality Standards

    OpenAIRE

    Keisuke Hattori; Keisaku Higashida

    2011-01-01

    This paper examines the relationship between misinformation about product quality and quality standards, such as minimum quality standards and certi cation criteria, when products are vertically di erentiated in their health/safety aspects. We investigate the welfare e ect of regulating misinformation and strengthening MQSs. We nd that when the amount of misinformation on both low- and high-quality products is small, regulating misinformation on low-quality products reduces welfare, although ...

  14. Minimum quality standards and exports

    OpenAIRE

    Birg, Laura; Voßwinkel, Jan S.

    2015-01-01

    This paper studies the interaction of a minimum quality standard and exports in a vertical product differentiation model when firms sell global products. If exante quality of foreign firms is lower (higher) than the quality of exporting firms, a mild minimum quality standard in the home market hinders (supports) exports. The minimum quality standard increases quality in both markets. A welfare maximizing minimum quality standard is always lower under trade than under autarky. A Minimum qualit...

  15. 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.

  16. 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.

  17. Endothelin receptors and their antagonists.

    Science.gov (United States)

    Maguire, Janet J; Davenport, Anthony P

    2015-03-01

    All three members of the endothelin (ET) family of peptides, ET-1, ET-2, and ET-3, are expressed in the human kidney, with ET-1 being the predominant isoform. ET-1 and ET-2 bind to two G-protein-coupled receptors, ETA and ETB, whereas at physiological concentrations ET-3 has little affinity for the ET(A) receptor. The human kidney is unusual among the peripheral organs in expressing a high density of ET(B). The renal vascular endothelium only expresses the ET(B) subtype and ET-1 acts in an autocrine or paracrine manner to release vasodilators. Endothelial ETB in kidney, as well as liver and lungs, also has a critical role in scavenging ET-1 from the plasma. The third major function is ET-1 activation of ET(B) in in the nephron to reduce salt and water re-absorption. In contrast, ET(A) predominate on smooth muscle, causing vasoconstriction and mediating many of the pathophysiological actions of ET-1. The role of the two receptors has been delineated using highly selective ET(A) (BQ123, TAK-044) and ET(B) (BQ788) peptide antagonists. Nonpeptide antagonists, bosentan, macitentan, and ambrisentan, that are either mixed ET(A)/ET(B) antagonists or display ET(A) selectivity, have been approved for clinical use but to date are limited to pulmonary hypertension. Ambrisentan is in clinical trials in patients with type 2 diabetic nephropathy. This review summarizes ET-receptor antagonism in the human kidney, and considers the relative merits of selective versus nonselective antagonism in renal disease. PMID:25966344

  18. 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 ...

  19. Antianginal Actions of Beta-Adrenoceptor Antagonists

    OpenAIRE

    O'Rourke, Stephen T.

    2007-01-01

    Angina pectoris is usually the first clinical sign of underlying myocardial ischemia, which results from an imbalance between oxygen supply and oxygen demand in the heart. This report describes the pharmacology of β-adrenoceptor antagonists as it relates to the treatment of angina. The β-adrenoceptor antagonists are widely used in long-term maintenance therapy to prevent acute ischemic episodes in patients with chronic stable angina. Beta-adrenoceptor antagonists competitively inhibit the bin...

  20. Endothelin receptor antagonists in pulmonary arterial hypertension.

    Science.gov (United States)

    Dupuis, J; Hoeper, M M

    2008-02-01

    The endothelin (ET) system, especially ET-1 and the ET(A) and ET(B) receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients. PMID:18238950

  1. 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 ...

  2. 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...

  3. ANTIHYPERTENSIVE TREATMENT IN ELDERLY PATIENTS WITH DIHYDROPYRIDINE CALCIUM ANTAGONISTS

    Directory of Open Access Journals (Sweden)

    Y. A. Karpov

    2016-01-01

    Full Text Available The proofs of necessity of active arterial hypertension (AH treatment in elderly patients are given. Peculiarities of pathogenesis of AH in elderly patients, connected predominantly with loss of big arteries elasticity and reasoning widely spread of isolated systolic AH in these patients, are discussed. Advantages of dihydropyridine calcium antagonists (DPCA for AH treatment in elderly patients are proved, safety of treatment with DPCA is discussed. Data of clinical studies is analyzed. Analysis of target levels of blood pressure for antihypertensive treatment in elderly hypertensive patients is made. As a conclusion DPCA are the medicines of choice for AH treatment in elderly patients.

  4. 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…

  5. 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).

  6. 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.

  7. 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...

  8. Effects of VLA-4 antagonists in rat whole embryo culture.

    Science.gov (United States)

    Spence S; Vetter C; Hagmann WK; Van Riper G; Williams H; Mumford RA; Lanza TJ; Lin LS; Schmidt JA

    2002-01-01

    fold lower than those that affect the conceptus, depending on the tissue penetration of the compound and the route of administration. VLA-4 also exists in a range of conformations and activation states in vivo and the gene KOs and present studies do not define whether these developmental processes are dependent upon a particular activation state of VLA-4. Therefore, state-selective antagonists may have an improved embryonic safety profile. Additional studies will be required to determine potential effects of VLA-4 antagonists on embryo/fetal development in vivo.

  9. Cytokine antagonists and their potential therapeutic use

    OpenAIRE

    Debets, Reno; Savelkoul, Huub

    1994-01-01

    textabstractNew and exciting developments in the understanding of the interaction between cytokines and their receptors, and the clinical application of cytokine antagonists, were discussed at a recent meeting. Here, Reno Debets and Huub Savelkoul revisit this progress.

  10. High-affinity neuropeptide Y receptor antagonists.

    OpenAIRE

    Daniels, A J; Matthews, J. E.; Slepetis, R J; Jansen, M; Viveros, O. H.; Tadepalli, A.; Harrington, W; Heyer, D; Landavazo, A; Leban, J J

    1995-01-01

    Neuropeptide Y (NPY) is one of the most abundant peptide transmitters in the mammalian brain. In the periphery it is costored and coreleased with norepinephrine from sympathetic nerve terminals. However, the physiological functions of this peptide remain unclear because of the absence of specific high-affinity receptor antagonists. Three potent NPY receptor antagonists were synthesized and tested for their biological activity in in vitro, ex vivo, and in vivo functional assays. We describe he...

  11. 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....

  12. GABAA receptor partial agonists and antagonists

    DEFF Research Database (Denmark)

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

    2015-01-01

    A high degree of structural heterogeneity of the GABAA receptors (GABAARs) has been revealed and is reflected in multiple receptor subtypes. The subunit composition of GABAAR subtypes is believed to determine their localization relative to the synapses and adapt their functional properties to the...... antagonists have been essential in defining the tonic current but both remaining issues concerning the GABAARs involved and the therapeutic possibilities of modulating tonic inhibition underline the need for GABAAR antagonists with improved selectivity....

  13. SOUTH CAROLINA GUIDE AND MINIMUM SPECIFICATIONS FOR MOBILE CLASSROOM UNITS.

    Science.gov (United States)

    South Carolina State Education Finance Commission, Columbia. Office of Schoolhouse Planning.

    THIS GUIDE OF REQUIRED AND RECOMMENDED STANDARDS FOR MOBILE CLASSROOM UNITS IS INTENDED TO--(1) PROVIDE A GUIDE TO LOCAL SCHOOL AUTHORITIES TO ASSIST THEM IN DETERMINING THE FEASIBILITY OF MOBILE UNITS, (2) SET MINIMUM SAFETY AND UTILITY REQUIREMENTS FOR MOBILE UNITS, (3) ASSURE LOCAL SCHOOL AUTHORITIES OF A MOBILE UNIT MEETING THE ABOVE…

  14. 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 ...

  15. 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 dysfunct......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...

  16. 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.

  17. 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 ...

  18. 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...

  19. Histamine-2 Receptor Antagonists and Semen Quality.

    Science.gov (United States)

    Banihani, Saleem A

    2016-01-01

    Histamine-2 receptor antagonists are a class of drugs used to treat the acid-related gastrointestinal diseases such as ulcer and gastro-oesophageal reflux disease. Although such drugs, especially ranitidine and famotidine, are still widely used, their effects on semen quality, and hence on male infertility, is still unclear. This MiniReview systematically addresses and summarizes the effect of histamine-2 receptor antagonists (cimetidine, ranitidine, nizatidine and famotidine) on semen quality, particularly, on sperm function. Cimetidine appears to have adverse effects on semen quality. While the effects of ranitidine and nizatidine on semen quality are still controversial, famotidine does not appear to change semen quality. Therefore, additional studies will be required to clarify whether histamine-2 receptor-independent effects of these drugs play a role in semen quality as well as further clinical studies including direct comparison of the histamine-2 receptor antagonists. PMID:26176290

  20. 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.

  1. Minimum DNBR Prediction Using Artificial Intelligence

    International Nuclear Information System (INIS)

    The minimum DNBR (MDNBR) for prevention of the boiling crisis and the fuel clad melting is very important factor that should be consistently monitored in safety aspects. Artificial intelligence methods have been extensively and successfully applied to nonlinear function approximation such as the problem in question for predicting DNBR values. In this paper, support vector regression (SVR) model and fuzzy neural network (FNN) model are developed to predict the MDNBR using a number of measured signals from the reactor coolant system. Also, two models are trained using a training data set and verified against test data set, which does not include training data. The proposed MDNBR estimation algorithms were verified by using nuclear and thermal data acquired from many numerical simulations of the Yonggwang Nuclear Power Plant Unit 3 (YGN-3)

  2. 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...

  3. Rivaroxaban versus enoxaparin/vitamin K antagonist therapy in patients with venous thromboembolism and renal impairment

    OpenAIRE

    Bauersachs, Rupert M.; Lensing, Anthonie WA; Prins, Martin H.; Kubitza, Dagmar; Pap, Ákos F; Decousus, Hervé; Beyer-Westendorf, Jan; Prandoni, Paolo

    2014-01-01

    Background Patients with renal impairment receiving classical anticoagulation for venous thromboembolism (VTE) are at increased risk of bleeding and possibly pulmonary embolism. We examined the efficacy and safety of oral rivaroxaban in patients with VTE with and without renal impairment. Methods Prespecified subgroup analysis of the EINSTEIN DVT and EINSTEIN PE studies comparing fixed-dose rivaroxaban with enoxaparin/a vitamin K antagonist (VKA), performed in 8246 patients enrolled from 2007...

  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. 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...... results for a multiarm spherical helix antenna confirm the theoretical predictions. For example, a 4-arm spherical helix antenna with a magnetic-coated perfectly electrically conducting core (ka=0.254) exhibits the Q of 0.66 times the Chu lower bound, or 1.25 times the minimum Q....

  6. 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

  7. 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

  8. 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

  9. Minimum Thermal Conductivity of Superlattices

    International Nuclear Information System (INIS)

    The phonon thermal conductivity of a multilayer is calculated for transport perpendicular to the layers. There is a crossover between particle transport for thick layers to wave transport for thin layers. The calculations show that the conductivity has a minimum value for a layer thickness somewhat smaller then the mean free path of the phonons. (c) 2000 The American Physical Society

  10. 76 FR 11668 - Minimum Capital

    Science.gov (United States)

    2011-03-03

    ... amended. See 74 FR 5597 (January 30, 2009). As a result, the definition of ``minimum capital level'' as... by HERA. Final Rule: Capital Requirements for the Federal Home Loan Banks, 66 FR 8262, 8282-83... 12 U.S.C. 4612(d). The 60-day comment period closed on April 9, 2010. See Federal Register 75 FR...

  11. Minimum Wage in EU Countries

    OpenAIRE

    Emilia BUCUR

    2007-01-01

    This article discusses the possibility that EU will introduce a minimum salary, according to the financial configuration of each member state, presenting benefic effects which this system should bring, such as an improvement of economic conditions and the avoidance of economic collapse. Also, it presents the salary situation at EU level, focusing on the case of Romania.

  12. 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.

  13. 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....

  14. 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. ...

  15. 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.

  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. 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) ...

  18. GMTI radar minimum detectable velocity.

    Energy Technology Data Exchange (ETDEWEB)

    Richards, John Alfred

    2011-04-01

    Minimum detectable velocity (MDV) is a fundamental consideration for the design, implementation, and exploitation of ground moving-target indication (GMTI) radar imaging modes. All single-phase-center air-to-ground radars are characterized by an MDV, or a minimum radial velocity below which motion of a discrete nonstationary target is indistinguishable from the relative motion between the platform and the ground. Targets with radial velocities less than MDV are typically overwhelmed by endoclutter ground returns, and are thus not generally detectable. Targets with radial velocities greater than MDV typically produce distinct returns falling outside of the endoclutter ground returns, and are thus generally discernible using straightforward detection algorithms. This document provides a straightforward derivation of MDV for an air-to-ground single-phase-center GMTI radar operating in an arbitrary geometry.

  19. Jets in minimum bias physics

    International Nuclear Information System (INIS)

    Discussion was made on a phenomenological evidence to support the hypothesis that several new phenomena observed in low psub(t) physics are due to the presence of low-x QCD jets in minimum bias physics. The phenomena we examine are KNO scaling violations, growth of with multiplicity and rise of the non-single diffractive part of the total cross-section. We have discussed the importance of low-x hard parton scattering in minimum bias events and pointed out its connection to both KNO scaling violations as well as to the observed growth of with multiplicity in inclusive pion distributions. The contribution of these mini-jets to the total cross-section has been calculated and a model for the transverse energy distribution characterizing any event accompanied by jets has been presented. (author)

  20. The Minimum Expectation Selection Problem

    OpenAIRE

    Eppstein, David; Lueker, George

    2001-01-01

    We define the min-min expectation selection problem (resp. max-min expectation selection problem) to be that of selecting k out of n given discrete probability distributions, to minimize (resp. maximize) the expectation of the minimum value resulting when independent random variables are drawn from the selected distributions. We assume each distribution has finitely many atoms. Let d be the number of distinct values in the support of the distributions. We show that if d is a constant greater ...

  1. Minimum feature size preserving decompositions

    CERN Document Server

    Aloupis, Greg; Demaine, Martin L; Dujmovic, Vida; Iacono, John

    2009-01-01

    The minimum feature size of a crossing-free straight line drawing is the minimum distance between a vertex and a non-incident edge. This quantity measures the resolution needed to display a figure or the tool size needed to mill the figure. The spread is the ratio of the diameter to the minimum feature size. While many algorithms (particularly in meshing) depend on the spread of the input, none explicitly consider finding a mesh whose spread is similar to the input. When a polygon is partitioned into smaller regions, such as triangles or quadrangles, the degradation is the ratio of original to final spread (the final spread is always greater). Here we present an algorithm to quadrangulate a simple n-gon, while achieving constant degradation. Note that although all faces have a quadrangular shape, the number of edges bounding each face may be larger. This method uses Theta(n) Steiner points and produces Theta(n) quadrangles. In fact to obtain constant degradation, Omega(n) Steiner points are required by any al...

  2. Bicycloorthocarboxylate convulsants. Potent GABAA receptor antagonists

    International Nuclear Information System (INIS)

    4-t-Butyl-1-(4-bromophenyl)-bicycloorthocarboxylate antagonizes gamma-aminobutyric acid (GABA)-mediated relaxation at a functional insect nerve-muscle synapse, mimicking the action of picrotoxinin, suggesting that it causes GABA antagonism through blockade of the chloride ionophore. It is also a potent GABAA receptor antagonist, inhibiting the binding of [35S]t-butyl-bicyclophosphorothionate ([35S]TBPS) to EDTA/water-dialyzed human brain P2 membranes. Structure-activity relationships of 74 1,4-bis-substituted bicycloorthocarboxylates, mostly new compounds, reveal that for high potency as a GABAA receptor antagonist the optimal 4-substituent is a C4 to C6 branched chain alkyl or cycloalkyl group (e.g., t-butyl, s-butyl, or cyclohexyl) and the optimal 1-substituent is a phenyl moiety with one or more electron-withdrawing groups (e.g., 4-cyano, 4-bromo, 4-chloro, 3,4-dichloro, or pentafluoro). Bicycloorthocarboxylate inhibitors of [35S]TBPS binding with IC50 values of 5-10 nM exceed by several-fold the potency of any GABAA receptor antagonist previously reported. The 4-t-butyl-1-(4-azidophenyl) analog, synthesized as a candidate photoaffinity label, gives an IC50 of 315 nM. The potency of bicycloorthocarboxylates for decreasing [35S]TBPS binding generally correlates with their toxicity, i.e., compounds without inhibitory activity in this brain receptor assay are of low toxicity on intraperitoneal administration to mice, and the analogs most potent as inhibitors are generally those most toxic to mice (e.g., IC50 of 5 nM and LD50 of 0.06 mg/kg for 4-t-butyl-1-(4-cyanophenyl)-bicycloorthocarboxylate). The effects of phenyl substituents on the potency of the orthobenzoates as GABAA receptor antagonists are similar to those on toxicity

  3. 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.

  4. 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...

  5. Antagonistic neural networks underlying differentiated leadership roles

    OpenAIRE

    Boyatzis, Richard E.; Rochford, Kylie; Jack, Anthony I.

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks – the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN...

  6. 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)

  7. 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

  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. From the Cover: Glutamate antagonists limit tumor growth

    Science.gov (United States)

    Rzeski, Wojciech; Turski, Lechoslaw; Ikonomidou, Chrysanthy

    2001-05-01

    Neuronal progenitors and tumor cells possess propensity to proliferate and to migrate. Glutamate regulates proliferation and migration of neurons during development, but it is not known whether it influences proliferation and migration of tumor cells. We demonstrate that glutamate antagonists inhibit proliferation of human tumor cells. Colon adenocarcinoma, astrocytoma, and breast and lung carcinoma cells were most sensitive to the antiproliferative effect of the N-methyl-D-aspartate antagonist dizocilpine, whereas breast and lung carcinoma, colon adenocarcinoma, and neuroblastoma cells responded most favorably to the -amino-3-hydroxy-5-methyl-4-isoxazole-propionate antagonist GYKI52466. The antiproliferative effect of glutamate antagonists was Ca2+ dependent and resulted from decreased cell division and increased cell death. Morphological alterations induced by glutamate antagonists in tumor cells consisted of reduced membrane ruffling and pseudopodial protrusions. Furthermore, glutamate antagonists decreased motility and invasive growth of tumor cells. These findings suggest anticancer potential of glutamate antagonists.

  10. 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

  11. Clinical and preclinical characterization of the histamine H(4) receptor antagonist JNJ-39758979.

    Science.gov (United States)

    Thurmond, Robin L; Chen, Bin; Dunford, Paul J; Greenspan, Andrew J; Karlsson, Lars; La, David; Ward, Peter; Xu, Xie L

    2014-05-01

    The histamine H4 receptor (H(4)R) has been shown to have preclinical involvement in both inflammatory and pruritic responses. JNJ-39758979 [(R)-4-(3-amino-pyrrolidin-1-yl)-6-isopropyl-pyrimidin-2-ylamine] is a potent and selective H(4)R antagonist with a Ki at the human receptor of 12.5 ± 2.6 nM and greater than 80-fold selectivity over other histamine receptors. The compound also exhibited excellent selectivity versus other targets. JNJ-39758979 showed dose-dependent activity in models of asthma and dermatitis consistent with other H(4)R antagonists. Preclinical toxicity studies of up to 6 months in rats and 9 months in monkeys indicated an excellent safety profile, supporting the clinical testing of the compound. An oral formulation of JNJ-39758979 was studied in a phase 1 human volunteer study to assess safety, pharmacokinetics, and pharmacodynamics. The compound was well tolerated, with the exception of dose-dependent nausea, and no safety issues were noted in the phase 1 study. JNJ-39758979 exhibited good pharmacokinetics upon oral dosing with a plasma half-life of 124-157 hours after a single oral dose. In addition, dose-dependent inhibition of histamine-induced eosinophil shape change was detected, suggesting that the H4R was inhibited in vivo. In conclusion, JNJ-39758979 is a potent and selective H(4)R antagonist that exhibited good preclinical and phase 1 safety in healthy volunteers with evidence of a pharmacodynamics effect in humans. PMID:24549371

  12. The minimum yield in channeling

    International Nuclear Information System (INIS)

    A first estimate of the minimum yield was obtained from Lindhard's theory, with the assumption of a statistical equilibrium in the transverse phase-space of channeled particles guided by a continuum axial potential. However, computer simulations have shown that this estimate should be corrected by a fairly large factor, C (approximately equal to 2.5), called the Barrett factor. We have shown earlier that the concept of a statistical equilibrium can be applied to understand this result, with the introduction of a constraint in phase-space due to planar channeling of axially channeled particles. Here we present an extended test of these ideas on the basis of computer simulation of the trajectories of 2 MeV α particles in Si. In particular, the gradual trend towards a full statistical equilibrium is studied. We also discuss the introduction of this modification of standard channeling theory into descriptions of the multiple scattering of channeled particles (dechanneling) by a master equation and show that the calculated minimum yields are in very good agreement with the results of a full computer simulation

  13. 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)

  14. 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.

  15. 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...

  16. 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...

  17. 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. PMID:26074891

  18. Implementation of a fluorescence-based screening assay identifies histamine H3 receptor antagonists clobenpropit and iodophenpropit as subunit-selective N-methyl-D-aspartate receptor antagonists

    DEFF Research Database (Denmark)

    Hansen, Kasper Bø; Mullasseril, Praseeda; Dawit, Sara; Kurtkaya, Natalie L; Yuan, Hongjie; Vance, Katie M; Orr, Anna G; Kvist, Trine; Ogden, Kevin K; Le, Phuong; Vellano, Kimberly M; Lewis, Iestyn; Kurtkaya, Serdar; Du, Yuhong; Qui, Min; Murphy, T J; Snyder, James P; Bräuner-Osborne, Hans; Traynelis, Stephen F

    2010-01-01

    NMDA receptor function, including the histamine H3 receptor antagonists clobenpropit and iodophenpropit, as well as the vanilloid receptor transient receptor potential cation channel, subfamily V, member 1 (TRPV1) antagonist capsazepine. These compounds are noncompetitive antagonists and the histamine...

  19. 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

  20. 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

  1. Safety Education.

    Science.gov (United States)

    Daniels, James H.; And Others

    1980-01-01

    Five articles in this issue focus on safety education in agricultural laboratories. Topics discussed include teacher liability; elements of a safety instruction program; state and federal safety standards; ground fault current protection; and eye protection requirements and equipment. (SK)

  2. 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&...

  3. 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...

  4. 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.

  5. Antagonistic coevolution between quantitative and Mendelian traits.

    Science.gov (United States)

    Yamamichi, Masato; Ellner, Stephen P

    2016-03-30

    Coevolution is relentlessly creating and maintaining biodiversity and therefore has been a central topic in evolutionary biology. Previous theoretical studies have mostly considered coevolution between genetically symmetric traits (i.e. coevolution between two continuous quantitative traits or two discrete Mendelian traits). However, recent empirical evidence indicates that coevolution can occur between genetically asymmetric traits (e.g. between quantitative and Mendelian traits). We examine consequences of antagonistic coevolution mediated by a quantitative predator trait and a Mendelian prey trait, such that predation is more intense with decreased phenotypic distance between their traits (phenotype matching). This antagonistic coevolution produces a complex pattern of bifurcations with bistability (initial state dependence) in a two-dimensional model for trait coevolution. Furthermore, with eco-evolutionary dynamics (so that the trait evolution affects predator-prey population dynamics), we find that coevolution can cause rich dynamics including anti-phase cycles, in-phase cycles, chaotic dynamics and deterministic predator extinction. Predator extinction is more likely to occur when the prey trait exhibits complete dominance rather than semidominance and when the predator trait evolves very rapidly. Our study illustrates how recognizing the genetic architectures of interacting ecological traits can be essential for understanding the population and evolutionary dynamics of coevolving species. PMID:27009218

  6. 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

  7. 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.

  8. 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,...

  9. 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,...

  10. Safety culture and public acceptance

    International Nuclear Information System (INIS)

    After the Chernobyl NPP accident a public acceptance has become a key factor in nuclear power development all over the world. Therefore, nuclear safety culture should be based not only on technical principles, responsibilities, supervision, regulatory provisions, emergency preparedness, but the public awareness of minimum risk during the operation and decommissioning of NPPs, radioactive waste management, etc. (author)

  11. 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

  12. Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    M Kathryn Steiner

    2008-07-01

    Full Text Available M Kathryn Steiner1, Ioana R Preston21Pulmonary Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; 2Pulmonary Critical Care and Sleep Division, Department of Medicine, Tufts Medical Center, Boston, MA, USAAbstract: Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH. Bench to bedside scientific research has shown that endothelin-1 (ET-1 is overexpressed in several forms of pulmonary vascular disease and may play an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs improved exercise capacity, functional status, pulmonary hemodymanics, and delayed the time to clinical worsening in several randomized placebo-controlled trials. Two ERAs are currently approved by the US Food and Drug Administration: bosentan, a dual ERA for patients with class III and IV PAH, and ambrisentan, a selective ERA for patients with class II and III PAH. Sitaxsentan, another selective ERA, has been approved in Europe, Canada, and Australia. The objective of this review is to evaluate the available evidence describing the pharmacology, efficacy, safety, and tolerability, and patient-focused perspectives regarding the different types of endothelin receptor antagonists. Ongoing and forthcoming randomized trials are also highlighted including the approach of combining this class of drugs with other drugs that target different cellular pathways believed to be etiologically important in PAH.Keywords: ambrisentan, bosentan, endothelin receptor antagonists, pulmonary arterial hypertension, sitaxsentan

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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 chemo...

  19. 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

  20. Minimum-Volume Conversion Duct

    International Nuclear Information System (INIS)

    The authors consider, in connection with an MHD conversion duct with known upstream and downstream stagnation conditions, what conditions will give the minimum volume, which is thought to correspond largely to the most economic conditions. On this basis, the problem of the optimum for the duct and the optima for the other components of the power plant are separated. The authors therefore discuss the most general problem of the optimum specific power σU2B2K(1 - K) for a segmented-electrode Faraday duct in the absence of thermal losses and friction, without the usual arbitrary separation of the optimization of the factor K(1 - K) and that of the product σU2; the magnetic field is assumed to be constant. The conversion equations are written in a simple form which makes it possible to utilize the calculus of variations. A system of two differential equations is obtained characterizing the evolution of the fluid. It is shown that the Mach number and the load factor are no longer independent. The integration of the differential system is performed numerically for a perfect gas in the case of thermodynamic equilibrium, the load factor at the inlet being varied for given initial conditions. It is ascertained that the evolution is different depending on whether the inlet load factor is more or less than 0.5. If a diagram is drawn showing the mean specific power-efficiency, the scatter of points representing all the optimum ducts possible, it is found that this scatter has an envelope. Similarly, all the figurate points of the ducts with constant velocities and load factors are found in an envelope inside the first. The differential equations for the optimization of a real gas are set forth in an annex, but no numerical treatment is given. (author)

  1. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn Hylsebeck; Rasmussen, Hans; Arnt, Jørn; Glenthøj, Birte Yding

    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...

  2. 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.

  3. 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…

  4. Pros and cons of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants.

    Science.gov (United States)

    Riva, Nicoletta; Ageno, Walter

    2015-03-01

    Anticoagulant treatment can be currently instituted with two different classes of drugs: the vitamin K antagonists (VKAs) and the newer, "novel" or non-vitamin K antagonist oral anticoagulant drugs (NOACs). The NOACs have several practical advantages over VKAs, such as the rapid onset/offset of action, the lower potential for food and drug interactions, and the predictable anticoagulant response. However, the VKAs currently have a broader spectrum of indications, a standardized monitoring test, and established reversal strategies. The NOACs emerged as alternative options for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Nevertheless, there remain some populations for whom the VKAs remain the most appropriate anticoagulant drug. This article discusses the advantages and disadvantages of VKAs and NOACs. PMID:25703519

  5. 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...

  6. 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...

  7. 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...

  8. 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 ...

  9. 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...

  10. 7 CFR 35.11 - Minimum requirements.

    Science.gov (United States)

    2010-01-01

    ..., Denmark, East Germany, England, Finland, France, Greece, Hungary, Iceland, Ireland, Italy, Liechtenstein..., Switzerland, Wales, West Germany, Yugoslavia), or Greenland shall meet each applicable minimum requirement...

  11. 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

  12. 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)

  13. 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.

  14. 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.)

  15. 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

  16. 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.

  17. 30 CFR 202.352 - Minimum royalty.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Minimum royalty. 202.352 Section 202.352 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR MINERALS REVENUE MANAGEMENT ROYALTIES Geothermal Resources § 202.352 Minimum royalty. In no event shall the lessee's annual...

  18. 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)

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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)

  4. 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.

  5. 9 CFR 113.45 - Sheep safety test.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Sheep safety test. 113.45 Section 113... Procedures § 113.45 Sheep safety test. The sheep safety test provided in this section shall be conducted when.... (1) Inject each of two sheep of the minimum age for which the product is recommended with...

  6. 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.

  7. Safety Handbook.

    Science.gov (United States)

    Montgomery County Public Schools, Rockville, MD.

    Safety policies, procedures, and related information are presented in this manual to assist school personnel in a continuing program of accident prevention. Chapter 1 discusses safety education and accident prevention in general. Chapter 2 covers traffic regulations relating to school safety patrols, school bus transportation, bicycles, and…

  8. 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.

  9. 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.

  10. 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

  11. Antagonistic neural networks underlying differentiated leadership roles.

    Science.gov (United States)

    Boyatzis, Richard E; Rochford, Kylie; Jack, Anthony I

    2014-01-01

    The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950s. Recent research in neuroscience suggests that the division between task-oriented and socio-emotional-oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks - the task-positive network (TPN) and the default mode network (DMN). Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task-oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions, and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success. PMID:24624074

  12. Antagonistic Neural Networks Underlying Differentiated Leadership Roles

    Directory of Open Access Journals (Sweden)

    Richard Eleftherios Boyatzis

    2014-03-01

    Full Text Available The emergence of two distinct leadership roles, the task leader and the socio-emotional leader, has been documented in the leadership literature since the 1950’s. Recent research in neuroscience suggests that the division between task oriented and socio-emotional oriented roles derives from a fundamental feature of our neurobiology: an antagonistic relationship between two large-scale cortical networks -- the Task Positive Network (TPN and the Default Mode Network (DMN. Neural activity in TPN tends to inhibit activity in the DMN, and vice versa. The TPN is important for problem solving, focusing of attention, making decisions, and control of action. The DMN plays a central role in emotional self-awareness, social cognition, and ethical decision making. It is also strongly linked to creativity and openness to new ideas. Because activation of the TPN tends to suppress activity in the DMN, an over-emphasis on task oriented leadership may prove deleterious to social and emotional aspects of leadership. Similarly, an overemphasis on the DMN would result in difficulty focusing attention, making decisions and solving known problems. In this paper, we will review major streams of theory and research on leadership roles in the context of recent findings from neuroscience and psychology. We conclude by suggesting that emerging research challenges the assumption that role differentiation is both natural and necessary, in particular when openness to new ideas, people, emotions, and ethical concerns are important to success.

  13. 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

  14. 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

  15. 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.

  16. Safety through organizational learning

    International Nuclear Information System (INIS)

    Systems safety is a characteristic of a system enabling it to function under the required operating conditions with a minimum of losses and unforeseen damage to the system and its environment and without any systems breakdowns. The system is influenced by human factors as those factors which, in a general way, influence people in working with a technical system, i.e., people, technology, and organization. Different approaches to learning from events, and processes of event analysis in nuclear technology are presented. The theoretical basis of the 'Safety through Organizational Learning' event analysis technique is the sociotechnical event creation model, which postulates that events can be described as a chain of individual events arising from the joint action of factors contributing directly and indirectly. (orig.)

  17. 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.)

  18. 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

  19. New requirements on safety of nuclear power plants according to the IAEA safety standards

    International Nuclear Information System (INIS)

    In this presentation author presents new requirements on safety of nuclear power plants according to the IAEA safety standards. It is concluded that: - New set of IAEA Safety Standards is close to completion: around 40 standards for NPPs; - Different interpretation of IAEA Safety Standards at present: best world practices instead of previous 'minimum common denominator'; - A number of safety improvements required for NPPs; - Requirements related to BDBAs and severe accidents are the most demanding due to degradation of barriers: hardware modifications and accident management; - Large variety between countries in implementation of accident management programmes: from minimum to major hardware modifications; -Distinction between existing and new NPPs is essential from the point of view of the requirements; WWER 440 reactors have potential to reflect IAEA Safety Standards for existing NPPs; relatively low reactor power offers broader possibilities

  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. 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.

  2. 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...

  3. 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...

  4. 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.

  5. 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

  6. 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 and...

  7. TRPV1 Antagonists and Chronic Pain: Beyond Thermal Perception

    OpenAIRE

    Brandt, Michael R.; Beyer, Chad E; Stahl, Stephen M.

    2012-01-01

    In the last decade, considerable evidence as accumulated to support the development of Transient Receptor Potential Vanilloid 1 (TRPV1) antagonists for the treatment of various chronic pain conditions. Whereas there is a widely accepted rationale for the development of TRPV1 antagonists for the treatment of various inflammatory pain conditions, their development for indications of chronic pain, where conditions of tactical, mechanical and spontaneous pain predominate, is less clear. Preclinic...

  8. 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

  9. 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...

  10. Deficiency of interleukin-1 receptor antagonist responsive to anakinra.

    Science.gov (United States)

    Schnellbacher, Charlotte; Ciocca, Giovanna; Menendez, Roxanna; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela; Duarte, Ana M; Rivas-Chacon, Rafael

    2013-01-01

    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 acute-phase 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. PMID:22471702

  11. 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.......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....

  12. Minimum-cost control of complex networks

    Science.gov (United States)

    Li, Guoqi; Hu, Wuhua; Xiao, Gaoxi; Deng, Lei; Tang, Pei; Pei, Jing; Shi, Luping

    2016-01-01

    Finding the solution for driving a complex network at the minimum energy cost with a given number of controllers, known as the minimum-cost control problem, is critically important but remains largely open. We propose a projected gradient method to tackle this problem, which works efficiently in both synthetic and real-life networks. The study is then extended to the case where each controller can only be connected to a single network node to have the lowest connection complexity. We obtain the interesting insight that such connections basically avoid high-degree nodes of the network, which is in resonance with recent observations on controllability of complex networks. Our results provide the first technical path to enabling minimum-cost control of complex networks, and contribute new insights to locating the key nodes from a minimum-cost control perspective.

  13. 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

  14. Impact of the Minimum Wage on Compression.

    Science.gov (United States)

    Wolfe, Michael N.; Candland, Charles W.

    1979-01-01

    Assesses the impact of increases in the minimum wage on salary schedules, provides guidelines for creating a philosophy to deal with the impact, and outlines options and presents recommendations. (IRT)

  15. 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...

  16. How unprecedented a solar minimum was it?

    Directory of Open Access Journals (Sweden)

    C.T. Russell

    2013-05-01

    Full Text Available 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.

  17. How unprecedented a solar minimum was it?

    Science.gov (United States)

    Russell, C.T.; Jian, L.K.; 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 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. PMID:25685425

  18. 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...

  19. Minimum length effects in black hole physics

    CERN Document Server

    Casadio, Roberto; Nicolini, Piero

    2014-01-01

    We review the main consequences of the possible existence of a minimum measurable length, of the order of the Planck scale, on quantum effects occurring in black hole physics. In particular, we focus on the ensuing minimum mass for black holes and how modified dispersion relations affect the Hawking decay, both in four space-time dimensions and in models with extra spatial dimensions. In the latter case, we briefly discuss possible phenomenological signatures.

  20. 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...

  1. 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...

  2. 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.

  3. 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.)

  4. Reactive Safety

    OpenAIRE

    Rüdiger Ehlers; Bernd Finkbeiner

    2011-01-01

    The distinction between safety and liveness properties is a fundamental classification with immediate implications on the feasibility and complexity of various monitoring, model checking, and synthesis problems. In this paper, we revisit the notion of safety for reactive systems, i.e., for systems whose behavior is characterized by the interplay of uncontrolled environment inputs and controlled system outputs. We show that reactive safety is a strictly larger class of properties than standard...

  5. 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

  6. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years

    DEFF Research Database (Denmark)

    Knorr, B; Franchi, L M; Bisgaard, H;

    2001-01-01

    BACKGROUND: The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled....... To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool...... children. OBJECTIVE: Our primary objective was to determine the safety profile of montelukast, an oral leukotriene receptor antagonist, in preschool children with persistent asthma. Secondarily, the effect of montelukast on exploratory measures of asthma control was also studied. DESIGN AND STATISTICAL...

  7. 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

    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......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......-bleeding patients. We investigated various outcomes and predefined subgroups and performed sensitivity analysis. We examined risks of bias and applied trial sequential analyses (TSA) to examine the level of evidence, and we prepared a 'Risk of bias' table to test the quality of the evidence. SEARCH METHODS: We...

  8. 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......-inferiority criterion. There were 62 deaths with idraparinux and 61 with vitamin K anatagonists (3.2 vs 2.9 per 100 patient-years; p=0.49). INTERPRETATION: In patients with atrial fibrillation at risk for thromboembolism, long-term treatment with idraparinux was no worse than vitamin K antagonists in terms of efficacy...

  9. 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 ...

  10. 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

  11. 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)

  12. Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension.

    Science.gov (United States)

    Steiner, M Kathryn; Preston, Ioana R

    2008-01-01

    Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has shown that endothelin-1 (ET-1) is overexpressed in several forms of pulmonary vascular disease and may play an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) improved exercise capacity, functional status, pulmonary hemodynamics, and delayed the time to clinical worsening in several randomized placebo-controlled trials. Two ERAs are currently approved by the US Food and Drug Administration: bosentan, a dual ERA for patients with class III and IV PAH, and ambrisentan, a selective ERA for patients with class II and III PAH. Sitaxsentan, another selective ERA, has been approved in Europe, Canada, and Australia. The objective of this review is to evaluate the available evidence describing the pharmacology, efficacy, safety, and tolerability, and patient-focused perspectives regarding the different types of endothelin receptor antagonists. Ongoing and forthcoming randomized trials are also highlighted including the approach of combining this class of drugs with other drugs that target different cellular pathways believed to be etiologically important in PAH. PMID:19183742

  13. 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

  14. [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

  15. Biocontrol of Some Tomato Disease Using Some Antagonistic Microorganisms

    Directory of Open Access Journals (Sweden)

    Ilham M. El–Rafai

    2003-01-01

    Full Text Available Four biocontrol�agents, namely : Trichoderma harzianum, T. hamatum, Bacillus subtilis and Pseudomonas fluorescens, have been tested for their potential antagonism for controlling fusarium wilt, verticillium wilt and early blight diseases of tomato. In vitro studies showed that culture filtrates of all antagonistic organisms significantly decrease the spore germination and germ tube-length of the tested pathogens, F. oxysporum f. sp. lycopersici, Verticillium dahliae and Alternaria solani. The linear growth and sporulation of the concerned pathogens were also inhibited the degree of inhibition was varied according to the tested antagonistic filtrate. In vivo studies, three treatments were applied; inoculation of the soil with antagonist period to sowing, soaking tomato seeds in the filtrate of the tested antagonist before sowing and coating of tomato seeds with spores of the antagonist before planting. Soil inoculation and seed coating with T. hamatum spores completely controlled the concerned diseases and improved the yield. However, P. fluorescens seed coating controlled the early blight disease and improved the tomato growth as well. Concerning the chemical assessment, T. hamatum soil inoculation and seed coating treatments gave the highest increase for chlorophyll a, b and cartenoids. Also the same treatments showed the highest increase of phenolic compounds (free and conjugated and the lowest percentage for sugars content of tomato leaves infected with the concerned pathogens.

  16. Minimum specific runoff; 1 : 2 000 000

    International Nuclear Information System (INIS)

    On this map the minimum specific runoff (map scale 1 : 2 000 000) on the territory of the Slovak Republic are shown. On these Isolines express the minimum specific runoffs (dm s-1 km-2) calculated from 364 daily discharges, i.e. 99.7 % of daily discharges for the period of 1931 - 1980. This mean daily discharge was reached or exceeded on 99.7 % of days of period. The minimum specific discharges derive from the hydrological orders for the period of 1931 - 1980. Processing was based on 140 hydrological orders of catchment with an area under 100 km2 and approximately 40 catchment with an area under 250 km2. (authors)

  17. Risk control and the minimum significant risk

    International Nuclear Information System (INIS)

    Risk management implies that the risk manager can, by his actions, exercise at least a modicum of control over the risk in question. In the terminology of control theory, a management action is a control signal imposed as feedback on the system to bring about a desired change in the state of the system. In the terminology of risk management, an action is taken to bring a predicted risk to lower values. Even if it is assumed that the management action taken is 100% effective and that the projected risk reduction is infinitely well known, there is a lower limit to the desired effects that can be achieved. It is based on the fact that all risks, such as the incidence of cancer, exhibit a degree of variability due to a number of extraneous factors such as age at exposure, sex, location, and some lifestyle parameters such as smoking or the consumption of alcohol. If the control signal is much smaller than the variability of the risk, the signal is lost in the noise and control is lost. This defines a minimum controllable risk based on the variability of the risk over the population considered. This quantity is the counterpart of the minimum significant risk which is defined by the uncertainties of the risk model. Both the minimum controllable risk and the minimum significant risk are evaluated for radiation carcinogenesis and are shown to be of the same order of magnitude. For a realistic management action, the assumptions of perfectly effective action and perfect model prediction made above have to be dropped, resulting in an effective minimum controllable risk which is determined by both risk limits. Any action below that effective limit is futile, but it is also unethical due to the ethical requirement of doing more good than harm. Finally, some implications of the effective minimum controllable risk on the use of the ALARA principle and on the evaluation of remedial action goals are presented

  18. Design of concrete structures important to safety of nuclear facilities

    International Nuclear Information System (INIS)

    Civil engineering structures in nuclear installations form an important feature having implications to safety performance of these installations. The objective and minimum requirements for the design of civil engineering buildings/structures to be fulfilled to provide adequate assurance for safety of nuclear installations in India (such as pressurised heavy water reactor and related systems) are specified in the Safety standard for civil engineering structures important to safety of nuclear facilities. This standard is written by AERB to specify guidelines for implementation of the above civil engineering safety standard in the design of concrete structures important to safety

  19. 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.)

  20. Safety culture

    International Nuclear Information System (INIS)

    The concept of Safety Culture was defined after Chernobyl's nuclear accident in 1986. It has not been exempt from discussion interpretations, adding riders, etc..., over the last 24 years because it has to do with human behavior and performance in the organizations. Safety Culture is not an easy task to define, assess and monitor. The proof of it is that today we still discussing and writing about it. How has been the evolution of Safety Culture at the Juzbado Factory since 1985 to today?. What is the strategy that we will be following in the future. (Author)

  1. 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...

  2. 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...

  3. 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...

  4. 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

  5. Minimum and terminal velocities in projectile motion

    OpenAIRE

    Miranda, E. N.; Nikolskaya, S.; 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 i...

  6. Blind system identification using minimum noise subspace

    OpenAIRE

    Hua, Yingbo; Abed-Meraim, Karim; Wax, Mati

    1997-01-01

    Developing fast and robust methods for identifying multiple FIR channels driven by an unknown common source is important for wireless communications, speech reverberation cancellation, and other applications. In this correspondence, we present a new method that exploits a minimum noisesubspace (MNS). The MNS is computed from a set of channel output pairs that form a “tree”. The “tree” exploits, with minimum redundancy, the diversity among all channels. The MNS method is much more efficient in...

  7. 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.

  8. 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...

  9. 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...

  10. 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...

  11. 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)

  12. 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....

  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. 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.

  15. Food Safety

    Science.gov (United States)

    ... are four basic steps to food safety at home: Clean - always wash your fruits and vegetables, hands, counters, and cooking utensils. Separate - keep raw foods to themselves. Germs can spread from one food ...

  16. 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 ...

  17. Safety culture

    International Nuclear Information System (INIS)

    The response to a previous publication by the International Nuclear Safety Advisory Group (INSAG) indicated a broad international interest in expanding the concept of safety culture in such a way that its effectiveness in particular cases may be judged. This has two major components: the framework determined by organizational policy and by managerial action, and the response of individuals in working within and benefiting by the framework. (Z.S.) 1 fig

  18. Increased earthquake safety through optimised mounting concept

    International Nuclear Information System (INIS)

    Since Fukushima, there has been intensive work on earthquake safety in all nuclear power plants. A large part of these efforts aim at the earthquake safety of safety-relevant pipeline systems. The problem with earthquake safety here is not the pipeline system itself but rather its mountings and connections to components. This is precisely the topic that the KAE dealt with in years of research and development work. It has developed an algorithm that determines the optimal mounting concept with a few iteration steps depending on arbitrary combinations of loading conditions whilst maintaining compliance with relevant regulations for any pipeline systems. With this tool at hand, we are now in a position to plan and realise remedial measures accurately with minimum time and hardware expenditure, and so distinctly improve the earthquake safety of safety-relevant systems. (orig.)

  19. Safety first!

    CERN Multimedia

    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 ...

  20. Microbial oceanography of anoxic oxygen minimum zones

    DEFF Research Database (Denmark)

    Ulloa, Osvaldo; Canfield, Donald E; DeLong, Edward F;

    2012-01-01

    Vast expanses of oxygen-deficient and nitrite-rich water define the major oxygen minimum zones (OMZs) of the global ocean. They support diverse microbial communities that influence the nitrogen economy of the oceans, contributing to major losses of fixed nitrogen as dinitrogen (N(2)) and nitrous ...

  1. Job protection renders minimum wages less harmful

    OpenAIRE

    Schöb, Ronnie; Thum, Marcel

    2011-01-01

    Individual labour productivities are often unobservable for firms when hiring new workers. Job protection may prevent firms ex post from using information about labour productivities. We show that a binding minimum wage introduced in the presence of job protection will lead to lower unemployment levels than predicted by the standard labour market model with heterogeneous labour and full information.

  2. Broadband Minimum Variance Beamforming for Ultrasound Imaging

    DEFF Research Database (Denmark)

    Holfort, Iben Kraglund; Gran, Fredrik; Jensen, Jørgen Arendt

    2009-01-01

    A minimum variance (MV) approach for near-field beamforming of broadband data is proposed. The approach is implemented in the frequency domain, and it provides a set of adapted, complex apodization weights for each frequency subband. The performance of the proposed MV beamformer is tested on...

  3. 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... recently on September 21, 2012. 77 FR 58708. III. Development of the Proposed Rule On September 21, 2012... National Indian Gaming Commission 25 CFR Part 543 RIN 3141-AA27 Minimum Internal Control Standards...

  4. 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... surveillance standards to Part 543 on February 20, 2013 (78 FR 11793). The Commission received numerous... technology and has substantively amended them numerous times, most recently on September 21, 2012. 77...

  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... (67 FR 43390), August 12, 2005 (70 FR 47108), and October 10, 2008 (73 FR 60498). In addition to... process NIGC should utilize to make revisions. 75 FR 70680. On April 4, 2011, after consulting with...

  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..., 2002 (67 FR 43390), August 12, 2005 (70 FR 47108), and October 10, 2008 (73 FR 60498). In addition to... regulations, and the process NIGC should utilize to make revisions. 75 FR 70680 (Nov. 18, 2010). On April...

  7. 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

  8. Computing Minimum Diameter Color-Spanning Sets

    Science.gov (United States)

    Fleischer, Rudolf; Xu, Xiaoming

    We study the minimum diameter color-spanning set problem which has recently drawn some attention in the database community. We show that the problem can be solved in polynomial time for L 1 and L ∞ metrics, while it is NP-hard for all other L p metrics even in two dimensions. However, we can efficiently compute a constant factor approximation.

  9. 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.

  10. 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...

  11. 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...

  12. Discovery of small molecule antagonists of TRPV1.

    Science.gov (United States)

    Rami, Harshad K; Thompson, Mervyn; Wyman, Paul; Jerman, Jeffrey C; Egerton, Julie; Brough, Stephen; Stevens, Alexander J; Randall, Andrew D; Smart, Darren; Gunthorpe, Martin J; Davis, John B

    2004-07-16

    Small molecule antagonists of the vanilloid receptor 1 (TRPV1, also known as VR1) are disclosed. Ureas such as 5 (SB-452533) were used to explore the structure activity relationship with several potent analogues identified. Pharmacological studies using electrophysiological and FLIPR Ca(2+) based assays showed compound 5 was an antagonist versus capsaicin, noxious heat and acid mediated activation of TRPV1. Study of a quaternary salt of 5 supports a mode of action in which compounds from this series cause inhibition via an extracellularly accessible binding site on the TRPV1 receptor. PMID:15203132

  13. 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

  14. 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

  15. Planetary tides during the Maunder sunspot minimum

    International Nuclear Information System (INIS)

    Sun-centered planetary conjunctions and tidal potentials are here constructed for the AD1645 to 1715 period of sunspot absence, referred to as the 'Maunder Minimum'. These are found to be effectively indistinguishable from patterns of conjunctions and power spectra of tidal potential in the present era of a well established 11 year sunspot cycle. This places a new and difficult restraint on any tidal theory of sunspot formation. Problems arise in any direct gravitational theory due to the apparently insufficient forces and tidal heights involved. Proponents of the tidal hypothesis usually revert to trigger mechanisms, which are difficult to criticise or test by observation. Any tidal theory rests on the evidence of continued sunspot periodicity and the substantiation of a prolonged period of solar anomaly in the historical past. The 'Maunder Minimum' was the most drastic change in the behaviour of solar activity in the last 300 years; sunspots virtually disappeared for a 70 year period and the 11 year cycle was probably absent. During that time, however, the nine planets were all in their orbits, and planetary conjunctions and tidal potentials were indistinguishable from those of the present era, in which the 11 year cycle is well established. This provides good evidence against the tidal theory. The pattern of planetary tidal forces during the Maunder Minimum was reconstructed to investigate the possibility that the multiple planet forces somehow fortuitously cancelled at the time, that is that the positions of the slower moving planets in the 17th and early 18th centuries were such that conjunctions and tidal potentials were at the time reduced in number and force. There was no striking dissimilarity between the time of the Maunder Minimum and any period investigated. The failure of planetary conjunction patterns to reflect the drastic drop in sunspots during the Maunder Minimum casts doubt on the tidal theory of solar activity, but a more quantitative test

  16. 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.

  17. Antagonistic Activities of Bacillus spp. Strains Isolated from Tidal Flat Sediment Towards Anthracnose Pathogens Colletotrichum acutatum and C. gloeosporioides in South Korea

    OpenAIRE

    Han, Joon-Hee; Shim, Hongsik; Shin, Jong-Hwan; Kim, Kyoung Su

    2015-01-01

    Anthracnose is a fungal disease caused by Colletotrichum species that is detrimental to numerous plant species. Anthracnose control with fungicides has both human health and environmental safety implications. Despite increasing public concerns, fungicide use will continue in the absence of viable alternatives. There have been relatively less efforts to search antagonistic bacteria from mudflats harboring microbial diversity. A total of 420 bacterial strains were isolated from mudflats near th...

  18. 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

  19. 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.

  20. 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.

  1. 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...

  2. 77 FR 54836 - Federal Motor Vehicle Safety Standards

    Science.gov (United States)

    2012-09-06

    ... National Highway Traffic Safety Administration 49 CFR Part 571 Federal Motor Vehicle Safety Standards CFR... motorcycles. * * * * * Table II--Minimum Static Breaking Energy Tire characteristic Motorcycle All 12 rim diameter Light truck and 17.5 Tires other than Light Truck, Motorcycle, 12 rim diameter code or...

  3. Designing Financial Safety Nets to Fit Country Circumstances

    OpenAIRE

    Kane, Edward J.

    2000-01-01

    The author explains how differences in the informational and contracting environments of countries affect the optimal design of their financial safety nets and their optimal strategies for managing financial crises. He explains how to design and operate safety nets at minimum cost to taxpayers and well-managed banks in countries whose informational and contracting technologies differ. His basic ...

  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... Percentage Rate for Random Drug Testing. SUMMARY: PHMSA has determined that the minimum random drug...

  5. 77 FR 2606 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2012-01-18

    ... percent for calendar year 2012. 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... Percentage Rate for Random Drug Testing. SUMMARY: PHMSA has determined that the minimum random drug...

  6. 75 FR 76078 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2010-12-07

    ... percent for calendar year 2011. 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... percentage rate for random drug testing. SUMMARY: PHMSA has determined that the minimum random drug...

  7. 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...

  8. 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

  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) <1 °C for the 2-h ahead nowcasts. Model 2 (also exponential), for which a constant model coefficient ( b = 2.2) was used, was usually slightly less accurate but still with RMSEs <1 °C. Use of model 3 (square root) yielded increased RMSEs for the 2-h ahead comparisons between nowcasted and measured daily minima air temperature, increasing to 1.4 °C for some sites. For all sites for all models, the comparisons for the 4-h ahead air temperature nowcasts generally yielded increased RMSEs, <2.1 °C. Comparisons for all model nowcasts of the daily grass

  10. 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....

  11. 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,...

  12. 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.

  13. 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

  14. Synthesis and evaluation of 18F-labeled PPARγ antagonists

    International Nuclear Information System (INIS)

    Introduction: Peroxisome proliferator-activated receptor gamma (PPARγ) transcriptionally modulates fat metabolism and also plays a role in pathological conditions such as cancer, neurodegenerative disease and inflammation. PPARγ imaging agents are potential tools for investigating these diseases. Methods: Four analogs of GW9662, a PPARγ antagonist, with different fluorine-containing substituents at the para-position of the aniline ring were synthesized and evaluated using two different receptor binding assays for measuring PPARγ affinity. Micro-positron emission tomography (PET) imaging studies were performed in a transgenic mouse model having a heart-specific overexpression of PPARγ. Results: All four analogs were found to have binding affinities that were comparable to or better than the reference antagonist, GW9662, using a scintillation proximity assay (SPA). However, only the chloro-based analogs (compounds 3 and 4) had activity in a whole-cell assay measuring activation of the PPARγ/retinoid X receptor complex. The microPET imaging studies in an MHC-PPARγ transgenic mouse model showed high uptake and PPARγ-specific binding for the irreversible antagonist [18F]3, whereas the corresponding reversible methoxy analog ([18F]5) displayed only nonspecific uptake in heart. Conclusions: The results of this preliminary study show that the irreversible antagonist [18F]3 may represent a novel strategy for imaging PPARγ in vivo with PET.

  15. 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.

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

    International Nuclear Information System (INIS)

    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 (Ki = 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. 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

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

    DEFF Research Database (Denmark)

    Henderson, Alan J; Guzzo, Peter R; Ghosh, Animesh; Kaur, Jagjit; Koo, Jia-Man; Nacro, Kassoum; Panduga, Shailaja; Pathak, Rashmi; Shimpukade, Bharat; Tan, Valentina; Xiang, Kai; Wierschke, Jonathan D; Isherwood, Matthew L

    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 to...

  20. 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...

  1. 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…

  2. 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

  3. 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...

  4. How Hybrid Organizations Turn Antagonistic Assets into Complementarities

    DEFF Research Database (Denmark)

    Hockerts, Kai

    2015-01-01

    explicit social missions through business-inspired earned-income strategies, with the express goal of creating market disequilibria. This article demonstrates the challenges hybrids face and outlines how to overcome them by identifying hidden complementarities and creating new ones, by eliminating the need...... for complementarities, and by creating demands for antagonistic assets, or by using partnerships....

  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. 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

  7. Spoke Model for Calculating Reliability Index and Safety Factor of Slopes

    OpenAIRE

    Ping Wang; Dongyan Liu; Haibin Huang; Dongsheng Liu

    2013-01-01

    Considering the disadvantages of the slice method commonly employed in reliability analysis of slopes, a novel method (Spoke model) was proposed for reliability analysis and safety factor calculation of slopes in this work based on geometrical relationship among slices. The safety factor and the coefficients of limit state function of slopes could be achieved with the Gaussian integral method. The minimum safety factor and the minimum reliability index, as well as their corresponding coordina...

  8. 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

  9. Safety organization

    International Nuclear Information System (INIS)

    After a rapid definition of a nuclear basis installation, the national organization of nuclear safety in France is presented, as also the main organizations concerned and their functions. This report shows how the licensing procedure leading to the construction and exploitation of such installations is applied in the case of nuclear laboratories of research and development: examinations of nuclear safety problems are carried out at different levels: - centralized to define the frame out of which the installation has not to operate, - decentralized to follow in a more detailed manner its evolution

  10. Nuclear safety

    International Nuclear Information System (INIS)

    GAO reviewed DOE's efforts to restart three nuclear reactors at its Savannah River site in South Carolina. Restarting the reactors, which have not been in operating since 1986, is a top priority at DOE because the reactors are the nation's only production source of tritium, a radioactive gas used in nuclear weapons. This report describes factors that might delay restarting the reactors and what the operating contractor is doing to bring about a better attitude toward safety among its personnel and the Savannah River site. This report also contains information on safety attitude problems at other DOE facilities and with DOE employees

  11. Minimum wakefield achievable by waveguide damped cavity

    International Nuclear Information System (INIS)

    The authors use an equivalent circuit to model a waveguide damped cavity. Both exponentially damped and persistent (decay t-3/2) components of the wakefield are derived from this model. The result shows that for a cavity with resonant frequency a fixed interval above waveguide cutoff, the persistent wakefield amplitude is inversely proportional to the external Q value of the damped mode. The competition of the two terms results in an optimal Q value, which gives a minimum wakefield as a function of the distance behind the source particle. The minimum wakefield increases when the resonant frequency approaches the waveguide cutoff. The results agree very well with computer simulation on a real cavity-waveguide system

  12. 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.

  13. Approximating Minimum Manhattan Networks in Higher Dimensions

    CERN Document Server

    Das, Aparna; Kaufmann, Michael; Kobourov, Stephen; Spoerhase, Joachim; Wolff, Alexander

    2011-01-01

    We consider the minimum Manhattan network problem, which is defined as follows. Given a set of points called \\emph{terminals} in $\\mathbb{R}^d$, find a minimum-length network such that each pair of terminals is connected by a set of axis-parallel line segments whose total length is equal to the pair's Manhattan (that is, $L_1$-) distance. The problem is NP-hard in 2D and there is no PTAS for 3D (unless ${\\cal P}={\\cal NP}$). Approximation algorithms are known for 2D, but not for 3D. We present, for any fixed dimension $d$ and any $\\epsilon>0$, an $O(n^\\epsilon)$-approximation. For 3D, we also give a $4(k-1)$-approximation for the case that the terminals are contained in the union of $k \\ge 2$ parallel planes.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Mineralocorticoid receptor antagonists: emerging roles in cardiovascular medicine

    Directory of Open Access Journals (Sweden)

    Funder JW

    2013-10-01

    Full Text Available John W FunderPrince Henry's Institute, Clayton, Victoria, AustraliaAbstract: Spironolactone was first developed over 50 years ago as a potent mineralocorticoid receptor (MR antagonist with undesirable side effects; it was followed a decade ago by eplerenone, which is less potent but much more MR-specific. From a marginal role as a potassium-sparing diuretic, spironolactone was shown to be an extraordinarily effective adjunctive agent in the treatment of progressive heart failure, as was eplerenone in subsequent heart failure trials. Neither acts as an aldosterone antagonist in the heart as the cardiac MR are occupied by cortisol, which becomes an aldosterone mimic in conditions of tissue damage. The accepted term “MR antagonist”, (as opposed to “aldosterone antagonist” or, worse, “aldosterone blocker”, should be retained, despite the demonstration that they act not to deny agonist access but as inverse agonists. The prevalence of primary aldosteronism is now recognized as accounting for about 10% of hypertension, with recent evidence suggesting that this figure may be considerably higher: in over two thirds of cases of primary aldosteronism therapy including MR antagonists is standard of care. MR antagonists are safe and vasoprotective in uncomplicated essential hypertension, even in diabetics, and at low doses they also specifically lower blood pressure in patients with so-called resistant hypertension. Nowhere are more than 1% of patients with primary aldosteronism ever diagnosed and specifically treated. Given the higher risk profile in patients with primary aldosteronism than that of age, sex, and blood pressure matched essential hypertension, on public health grounds alone the guidelines for first-line treatment of all hypertension should mandate inclusion of a low-dose MR antagonist.Keywords: spironolactone, eplerenone, primary aldosteronism, public health, inverse agonists

  20. 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....

  1. 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...

  2. 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...

  3. 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. ...

  4. Minimum effective scale in export promotion

    OpenAIRE

    Richards, Timothy J.; Patterson, Paul M.

    2002-01-01

    Nonprice promotion has long been used by small firms or organizations to increase agricultural exports. Some believe that export promotion in these cases is often unsuccessful as the promoter is unable to achieve the “critical mass” of awareness that is required for success. The objective of this article is to develop a theoretical explanation for the likely existence of minimum expenditure thresholds and to estimate their size using an econometric model of the optimal supply of advertising. ...

  5. Time crystals from minimum time uncertainty

    International Nuclear Information System (INIS)

    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.)

  6. ORDER-STATISTICS MINIMUM ERROR RATE DETECTOR

    OpenAIRE

    Boudjellal, Abdelwaheb; Abed-Meraim, Karim; Belouchrani, Adel; Ravier, Philippe

    2014-01-01

    A new methodology for random signal detection, in presenceof closely spaced interfering signals, is introduced, namelythe Order-Statistics Minimum Error Rate (OS-MER) detector.The latter is based on the minimization of the error probabilityinstead of minimizing only the miss probability for a ConstantFalse Alarm Rate (CFAR). Results show that the OS-MER detectoris well adapted to this specific problem and overcomes, inparticular, the CFAR-based one.

  7. Minimum K_2,3-saturated Graphs

    CERN Document Server

    Chen, Ya-Chen

    2010-01-01

    A graph is K_{2,3}-saturated if it has no subgraph isomorphic to K_{2,3}, but does contain a K_{2,3} after the addition of any new edge. We prove that the minimum number of edges in a K_{2,3}-saturated graph on n >= 5 vertices is sat(n, K_{2,3}) = 2n - 3.

  8. 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.

  9. 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.)

  10. 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...

  11. 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...

  12. 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.

  13. 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...

  14. 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.

  15. 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 ...

  16. 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....

  17. Safety Benchmarking of Industrial Construction Projects Based on Zero Accidents Techniques

    OpenAIRE

    Rogers, Jennifer Kathleen

    2012-01-01

    Safety is a continually significant issue in the construction industry. The Occupation Safety and Health Administration as well as individual construction companies are constantly working on verifying that their selected safety plans have a positive effect on reduction of workplace injuries. Worker safety is a large concern for both the workers and employers in construction and the government also attempts to impose effective regulations concerning minimum safety requirements. There are ...

  18. 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

  19. 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.

  20. 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

  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. A proposal for improving safety in construction projects by strengthening coordinators’ competencies in health and safety issues

    OpenAIRE

    Ros Serrano, Antonio; Ortiz Marcos, Isabel; Palomo Sanchez, Jose Gabriel; Uruburu Colsa, Angel

    2013-01-01

    The figure of the coordinator in health and safety issues in the construction sector first appeared in our legislation through the incorporation of the European Directives (in our case Royal Decree 1627/97 on the minimum health and safety regulations in construction works), and is viewed differently in different countries of the European Union regarding the way they are hired and their role in the construction industry. Coordinating health and safety issues is also a management process th...

  3. 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

  4. 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.

  5. 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

  6. 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...

  7. 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.

  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. 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...

  10. Minimum Quench Energies of LHC Strands

    CERN Document Server

    Bauer, P; Wolf, R

    1998-01-01

    Within the framework of the LHC Project a program has been initiated at CERN to establish the influence of various strand parameters (coating, Cu/Sc ratio, RRR, billet design, cooling) on the Minimum Quench Energy (MQE) of LHC prototype strands operating in superfluid helium at 1.9K in peak-fields of 9T. The experimental technique is based on a graphite-paste tip heater described in [1]. The analysis of the measurements was facilitated by a theoretical model based on the numerical solution of the one-dimensional heat balance equation.

  11. 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...

  12. Maintenance of civil engineering structures important to safety of Nuclear Power Plants

    International Nuclear Information System (INIS)

    Civil engineering structures in nuclear installations form an important feature having implications to safety performance of these installations. This safety standard is written to specify the objectives and minimum requirements for the design of civil engineering buildings/structures that are to be fulfilled to provide adequate assurance for safety of nuclear installations in India

  13. Safety aspects

    International Nuclear Information System (INIS)

    It is assumed that in an accelerator-driven system (ADS) the same type of accidents can be envisaged as in critical reactors. After briefly describing the basic safety features of ADS, the first investigations of the behaviour of an accelerator driven fast oxide reactor during an unprotected loss-of-flow accident and the investigation of reactivity accidents in a large sodium-cooled ADS are presented

  14. Technical safety

    International Nuclear Information System (INIS)

    Technical risks are compared to the publically consciously or unconsciously accepted risks. This kind of risk analysis has the aim to achieve an optimum safety with a justifiable effort. The realization of this target requires the solving of technical, economic and sociopolitical problems. In order to minimize the risk, one can reduce the probability of occurence as well as the extent of damage. Risk situations for the population due to natural occurences such as earthquakes, strike of lightning, frost, high water etc. can be relatively well quantified. These are therefore suitable a a basis for comparison. This basis risk is increased by individual traffic and by human force effects such as terror and war. On the other hand, life in the neighbourhood of a nuclear power plant does not measurably contribute to increasing individual risk. In principle, by increased expenditure one can reduce technical risks. Due to the lack of means, one must then save correspondingly somewhere else. The safety risks there can then possibly increase overproportionally or at least the wide-spread desire for a higher standard of living cannot be fulfilled. Nevertheless, absolute safety can never be reached. The insurance business is responsible for covering the financial damage. Fault trees are used in technology to analyse the weak points. This is explained taking the example of a propylene low-temperature tank. If one keeps below the base risk it must be possible to build technical plants, even nuclear power plants, in densely populated areas. Technical safety analyses, however, only embrace one side of it, rigid building and material control and extensive elimination of human error ar just as important. (orig.)

  15. 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

  16. Nuclear safety

    International Nuclear Information System (INIS)

    The Program on Nuclear Safety comprehends Radioprotection, Radioactive Waste Management and Nuclear Material Control. These activities are developed at the Nuclear Safety Directory. The Radioactive Waste Management Department (GRR) was formally created in 1983, to promote research and development, teaching and service activities in the field of radioactive waste. Its mission is to develop and employ technologies to manage safely the radioactive wastes generated at IPEN and at its customer’s facilities all over the country, in order to protect the health and the environment of today's and future generations. The Radioprotection Service (GRP) aims primarily to establish requirements for the protection of people, as workers, contractors, students, members of the general public and the environment from harmful effects of ionizing radiation. Furthermore, it also aims to establish the primary criteria for the safety of radiation sources at IPEN and planning and preparing for response to nuclear and radiological emergencies. The procedures about the management and the control of exposures to ionizing radiation are in compliance with national standards and international recommendations. Research related to the main activities is also performed. The Nuclear Material Control has been performed by the Safeguard Service team, which manages the accountability and the control of nuclear material at IPEN facilities and provides information related to these activities to ABACC and IAEA. (author)

  17. Lead optimization studies of cinnamic amide EP2 antagonists.

    Science.gov (United States)

    Ganesh, Thota; Jiang, Jianxiong; Yang, Myung-Soon; Dingledine, Ray

    2014-05-22

    Prostanoid receptor EP2 can play a proinflammatory role, exacerbating disease pathology in a variety of central nervous system and peripheral diseases. A highly selective EP2 antagonist could be useful as a drug to mitigate the inflammatory consequences of EP2 activation. We recently identified a cinnamic amide class of EP2 antagonists. The lead compound in this class (5d) displays anti-inflammatory and neuroprotective actions. However, this compound exhibited moderate selectivity to EP2 over the DP1 prostanoid receptor (∼10-fold) and low aqueous solubility. We now report compounds that display up to 180-fold selectivity against DP1 and up to 9-fold higher aqueous solubility than our previous lead. The newly developed compounds also display higher selectivity against EP4 and IP receptors and a comparable plasma pharmacokinetics. Thus, these compounds are useful for proof of concept studies in a variety of models where EP2 activation is playing a deleterious role. PMID:24773616

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    proliferation, and apoptosis. METHODS: In this double-blind, parallel-group trial involving 70 patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg of anakinra (a recombinant human interleukin-1-receptor antagonist) subcutaneously once daily for 13 weeks and 36 patients to receive......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...... (P=0.03); C-peptide secretion was enhanced (P=0.05), and there were reductions in the ratio of proinsulin to insulin (P=0.005) and in levels of interleukin-6 (P<0.001) and C-reactive protein (P=0.002). Insulin resistance, insulin-regulated gene expression in skeletal muscle, serum adipokine levels...

  19. 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.

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

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1996-01-01

    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......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...

  1. 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.

  2. Endothelin receptor antagonists as disease modifiers in systemic sclerosis.

    Science.gov (United States)

    Shetty, Nagalakshmi; Derk, Chris T

    2011-02-01

    Systemic sclerosis (SSc) is a multisystem connective tissue disease of unknown etiology that is characterized by inflammation, vascular dysfunction and fibrosis of the skin and visceral organs. SSc is clinically diverse both in terms of the burden of skin and organ involvement and the rate of progression of the disease. Recent studies indicate that the endothelin system, especially ET-1 and the ETA and ETB receptors may play a key role in the pathogenesis of SSc. A new class of drugs, endothelin receptor antagonists has been introduced for treatment of patients with pulmonary arterial hypertension (PAH). Bosentan, a dual endothelin receptor antagonist as well as Sitaxsentan and Ambrisentan, selective blockers of the ETA receptor have proven effective in SSc-PAH. This effect may be mediated through both a vasodilatory and antifibrotic effect, thus making these agents attractive as potential disease modifying agents for SSc. PMID:21184655

  3. 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.

  4. Montelukast: More than a Cysteinyl Leukotriene Receptor Antagonist?

    OpenAIRE

    Tintinger, Gregory R.; Charles Feldman; Theron, Annette J.; Ronald Anderson

    2010-01-01

    The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the therapy of exercise- and aspirin-induced asthma. It is also used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2)-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently un...

  5. Surfen, a small molecule antagonist of heparan sulfate

    OpenAIRE

    Schuksz, Manuela; Fuster, Mark M.; Brown, Jillian R.; Crawford, Brett E.; Ditto, David P.; Lawrence, Roger; Glass, Charles A; Wang, Lianchun; Tor, Yitzhak; Esko, Jeffrey D

    2008-01-01

    In a search for small molecule antagonists of heparan sulfate, we examined the activity of bis-2-methyl-4-amino-quinolyl-6-carbamide, also known as surfen. Fluorescence-based titrations indicated that surfen bound to glycosaminoglycans, and the extent of binding increased according to charge density in the order heparin > dermatan sulfate > heparan sulfate > chondroitin sulfate. All charged groups in heparin (N-sulfates, O-sulfates, and carboxyl groups) contributed to binding, consistent with...

  6. 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.

  7. 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...

  8. NMDA antagonist properties of the putative antiaddictive drug, ibogaine.

    Science.gov (United States)

    Popik, P; Layer, R T; Fossom, L H; Benveniste, M; Geter-Douglass, B; Witkin, J M; Skolnick, P

    1995-11-01

    Both anecdotal reports in humans and preclinical studies indicate that ibogaine interrupts addiction to a variety of abused substances including alcohol, opiates, nicotine and stimulants. Based on the similarity of these therapeutic claims to recent preclinical studies demonstrating that N-methyl-D-aspartate (NMDA) antagonists attenuate addiction-related phenomena, we examined the NMDA antagonist properties of ibogaine. Pharmacologically relevant concentrations of ibogaine produce a voltage-dependent block of NMDA receptors in hippocampal cultures (Ki, 2.3 microM at -60 mV). Consistent with this observation, ibogaine competitively inhibits [3H]1-[1-(2-thienyl)-cyclohexyl]piperidine binding to rat forebrain homogenates (Ki, 1.5 microM) and blocks glutamate-induced cell death in neuronal cultures (IC50, 4.5 microM). Moreover, at doses previously reported to interfere with drug-seeking behaviors, ibogaine substitutes as a discriminative stimulus (ED50, 64.9 mg/kg) in mice trained to discriminate the prototypic voltage-dependent NMDA antagonist, dizocilpine (0.17 mg/kg), from saline. Consistent with previous reports, ibogaine reduced naloxone-precipitated jumping in morphine-dependent mice (ED50, 72 mg/kg). Although pretreatment with glycine did not affect naloxone-precipitated jumping in morphine-dependent mice, it abolished the ability of ibogaine to block naloxone-precipitated jumping. Taken together, these findings link the NMDA antagonist actions of ibogaine to a putative "antiaddictive" property of this alkaloid, its ability to reduce the expression of morphine dependence. PMID:7473163

  9. Optimization of amide-based EP3 receptor antagonists.

    Science.gov (United States)

    Lee, Esther C Y; Futatsugi, Kentaro; Arcari, Joel T; Bahnck, Kevin; Coffey, Steven B; Derksen, David R; Kalgutkar, Amit S; Loria, Paula M; Sharma, Raman

    2016-06-01

    Prostaglandin E receptor subtype 3 (EP3) antagonism may treat a variety of symptoms from inflammation to cardiovascular and metabolic diseases. Previously, most EP3 antagonists were large acidic ligands that mimic the substrate, prostaglandin E2 (PGE2). This manuscript describes the optimization of a neutral small molecule amide series with improved lipophilic efficiency (LipE) also known as lipophilic ligand efficiency (LLE) ((a) Nat. Rev. Drug Disc.2007, 6, 881; (b) Annu. Rep. Med. Chem.2010, 45, 380). PMID:27107947

  10. 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...

  11. 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 ...

  12. 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...

  13. 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.

  14. Catharanthine alkaloids are noncompetitive antagonists of muscle-type nicotinic acetylcholine receptors.

    Science.gov (United States)

    Arias, Hugo R; Feuerbach, Dominik; Targowska-Duda, Katarzyna M; Jozwiak, Krzysztof

    2010-09-01

    We compared the interaction of several catharanthine alkaloids including, ibogaine, vincristine, and vinblastine, with that for the noncompetitive antagonist phencyclidine (PCP) at muscle nicotinic acetylcholine receptors (AChRs) in different conformational states. The results established that catharanthine alkaloids: (a) inhibit, in a noncompetitive manner, (+/-)-epibatidine-induced Ca(2+) influx in TE671-halpha1beta1gammadelta cells with similar potencies (IC(50)=17-25microM), (b) inhibit [(3)H]TCP binding to the desensitized Torpedo AChR with higher affinity compared to the resting AChR, and (c) enhance [(3)H]cytisine binding to resting but activatable Torpedo AChRs, suggesting desensitizing properties. Interestingly, PCP inhibits [(3)H]ibogaine binding to the AChR in a steric fashion. This is corroborated by additional docking experiments indicating that the amino groups of neutral ibogaine form hydrogen bonds with the serine ring (position 6'), a location shared with PCP. Since protonated ibogaine forms a salt bridge with one of the acidic residues at the outer ring (position 20'), this ligand could be first attracted to the entrance of the channel by electrostatic interactions. Our data indicate that the catharanthine moiety is a minimum structural requirement for AChR inhibition including, ion channel blocking and desensitization, and that ibogaine and PCP bind to overlapping sites in the desensitized AChR ion channel. PMID:20493225

  15. 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.

  16. 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.

  17. Affinity and selectivity of beta-adrenoceptor antagonists in vitro

    International Nuclear Information System (INIS)

    The potency order of the catecholamines (-)-isoprenaline (Iso), (-)-noradrenaline (NA), and (-)-adrenaline (Adr) in competition for radiolabelled sites is used for their pharmacological classification. It is shown that the radioligand 3H-CGP 12177 exclusively labels beta 1-adrenoceptors in rat salivary gland membranes (Iso greater than NA greater than Adr), and beta 2-adrenoceptors in rat reticulocytes (Iso greater than Adr greater than or equal to NA). These models are then used to derive the subtype-selectivity of the classical beta-adrenoceptor antagonists (+/-)-propranolol (prop; twofold beta 2-selective) and (+/-)-atenolol (aten; 35-fold beta 1-selective), as well as of the newer antagonists (+/-)-betaxolol and (+/-)-bisoprolol (betax and biso; 35-fold and 75-fold beta 1-selective, respectively). The ligand with the highest selectivity is ICI 118,551 (ICI), with a 300-fold beta 2-subtype selectivity. For comparison with antagonistic effects in humans at given plasma concentrations, the equilibrium dissociation constants of the ligands are measured in the presence of native human plasma and yield values for the relative selectively labelled subtype in the mean (Ki-values in nmol/l): prop: 20, aten: 250, biso: 24, betax: 23, and ICI: 2.5

  18. 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

  19. 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...

  20. 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...

  1. Optimal Succinctness for Range Minimum Queries

    CERN Document Server

    Fischer, Johannes

    2008-01-01

    For an array A of n objects from a totally ordered universe, a range minimum query (RMQ) asks for the position of the minimum element in the sub-array A[i,j]. We focus on the setting where the array $A$ is static and known in advance, and can hence be preprocessed into a scheme in order to answer future queries faster. We make the further assumption that the input array A cannot be used at query time. Under this assumption, a natural lower bound of 2n bits for RMQ-schemes exists. We give the first truly succinct preprocessing scheme for O(1)-RMQs. Its final space consumption is 2n+o(n) bits, thus being asymptotically optimal. We also give a simple linear-time construction algorithm for this scheme that needs only n+o(n) bits of space in addition to the 2n+o(n) bits needed for the final data structure, thereby lowering the peak space consumption of previous schemes from O(n\\log n) to O(n) bits. We also improve on LCA-computation in BPS- and DFUDS-encoded trees.

  2. The minimum dissipation state for tokamaks

    International Nuclear Information System (INIS)

    The principle of minimum dissipation rate subject to helicity and energy balance is applied to tokamaks with an arbitrary aspect ratio. We solved the resulting Euler-Lagrange equations analytically and numerically. It is found that for low and general aspect ratio tokamaks, there exists different typical minimum dissipation state, corresponding to the typical experimental current profile respectively. It is also found that there exist different types of relaxed states in different regions of the parameter space for a selected device. Three forms of current profile are presented under different experimental conditions for a low aspect ratio tokamak like NSTX. The first peaks in the edge region of the high field side similar as the typical experimental form. The second peaks in the central region on the equatorial plane. The third may have a hole or reverse in the central part. E0/ηB0 is the key parameter in determining the final relaxed state; both the second and the third states could be obtained violently by increasing it to be above a critical value. (author)

  3. Ocular hypotensive efficacy and safety of once daily carteolol alginate

    OpenAIRE

    Demailly, P.; Allaire, C.; Trinquand, C.

    2001-01-01

    BACKGROUND/AIM—Carteolol is a β adrenoceptor antagonist used topically to reduce intraocular pressure, typically twice daily. In an effort to provide a once daily dosing regimen, carteolol was formulated with 1% alginic acid. The objective of this study was to evaluate the efficacy and safety of carteolol alginate solution in comparison with standard carteolol solution.
METHODS—This was a double masked, parallel group, multicentre study. Patients with ocular hypertension or open angle glaucom...

  4. 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....

  5. 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.

  6. The SMORES capability for minimum critical mass determination

    International Nuclear Information System (INIS)

    The purpose of the present work is to illustrate the capability of SMORES - a new sequence incorporated in SCALE-5, for automated minimum critical mass (MCM) determination. The illustration is done by identifying the MCM of spherical systems of 233U, 235U or 239Pu moderated and reflected with either D2O or a combination of polyethylene and Be. The latter provide the lowest critical mass of, respectively, 151.7 g, 202.2 g and 119.0 g. These masses are close to a factor of 2 lower than the MCM of the corresponding fissile material with D2O and close to a factor of 4 for the MCM in H2O. The fissile material concentration exhibit a spike near the core outer boundary, at the interface between the polyethylene and Be. The SMORES sequence of SCALE 5 could be useful for determining margins of subcriticality and for other applications encountered by the criticality safety community. (author)

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. Vehicle Optimal Velocity Curves for Minimum-Time Maneuver

    OpenAIRE

    Li-xia Zhang; Fu-quan Pan; Xiao-yuan Chen; Feng-yuan Wang; Jun Lu; Qi-ming Tong

    2014-01-01

    A problem in vehicle minimum-time maneuver is the assumption that a vehicle passes through a given path in a minimal amount of time without deviating from the boundary of the given path. Vehicle handling inverse dynamics provides a new perspective to solve such problem. Based on inverse dynamics, this paper transformed the problem of optimal vehicle velocity for minimum-time maneuver into that of optimal control with the objective function of minimum time. The path for minimum vehicle travel ...

  12. 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.

  13. Older Consumers Safety Test

    Science.gov (United States)

    ... Pool Safely Home / Safety Education / Safety Guides / Home Older Consumers Safety Test This is a quiz on consumer ... mind when you think of Safety for the Older Consumer? Smoke Alarms? Hand Rails? Good Health? These are ...

  14. 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

  15. Global safety

    OpenAIRE

    DeTombe, Dorien J.

    2010-01-01

    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 relat...

  16. 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.

  17. 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

  18. 14 CFR 23.1523 - Minimum flight crew.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Minimum flight crew. 23.1523 Section 23... Information § 23.1523 Minimum flight crew. The minimum flight crew must be established so that it is... path control, (2) Collision avoidance, (3) Navigation, (4) Communications, (5) Operation and...

  19. 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...

  20. 47 CFR 73.807 - Minimum distance separation between stations.

    Science.gov (United States)

    2010-10-01

    ... SERVICES RADIO BROADCAST SERVICES Low Power FM Broadcast Stations (LPFM) § 73.807 Minimum distance... 47 Telecommunication 4 2010-10-01 2010-10-01 false Minimum distance separation between stations... and the right-hand column lists (for informational purposes only) the minimum distance necessary...

  1. 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...

  2. 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,...

  3. 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...

  4. 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,...

  5. 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...

  6. 29 CFR 541.604 - Minimum guarantee plus extras.

    Science.gov (United States)

    2010-07-01

    ... SALES EMPLOYEES Salary Requirements § 541.604 Minimum guarantee plus extras. (a) An employer may provide... includes a guarantee of at least the minimum weekly required amount paid on a salary basis regardless of... 29 Labor 3 2010-07-01 2010-07-01 false Minimum guarantee plus extras. 541.604 Section...

  7. 50 CFR 648.72 - Minimum surf clam size.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Minimum surf clam size. 648.72 Section 648.72 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC... Atlantic Surf Clam and Ocean Quahog Fisheries § 648.72 Minimum surf clam size. (a) Minimum length....

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

    Science.gov (United States)

    2012-12-31

    ... solely of specified ingredients that EPA judged to pose minimum risk to humans and the environment (61 FR... use of specific common chemical names in lists of ingredients on minimum risk pesticide product labels... maintain the availability of minimum risk pesticide products while providing more consistent...

  9. 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.

  10. 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

  11. Helicopter rotor blade design for minimum vibration

    Science.gov (United States)

    Taylor, R. B.

    1984-01-01

    The importance of blade design parameters in rotor vibratory response and the design of a minimum vibration blade based upon this understanding are examined. Various design approaches are examined for a 4 bladed articulated rotor operating at a high speed flight condition. Blade modal shaping, frequency placement, structural and aerodynamic coupling, and intermodal cancellation are investigated to systematically identify and evaluate blade design parameters that influence blade airloads, blade modal response, hub loads, and fuselage vibration. The relative contributions of the various components of blade force excitation and response to the vibratory hub loads transmitted to the fuselage are determined in order to isolate primary candidates for vibration alleviation. A blade design is achieved which reduces the predicted fuselage vibration from the baseline blade by approximately one half. Blade designs are developed that offer significant reductions in vibration (and fatigue stresses) without resorting to special vibration alleviation devices, radical blade geometries, or weight penalties.

  12. Minimum Dissipation Principle in Nonlinear Transport

    Directory of Open Access Journals (Sweden)

    Giorgio Sonnino

    2015-10-01

    Full Text Available We extend Onsager’s minimum dissipation principle to stationary states that are only subject to local equilibrium constraints, even when the transport coefficients depend on the thermodynamic forces. Crucial to this generalization is a decomposition of the thermodynamic forces into those that are held fixed by the boundary conditions and the subspace that is orthogonal with respect to the metric defined by the transport coefficients. We are then able to apply Onsager and Machlup’s proof to the second set of forces. As an example, we consider two-dimensional nonlinear diffusion coupled to two reservoirs at different temperatures. Our extension differs from that of Bertini et al. in that we assume microscopic irreversibility, and we allow a nonlinear dependence of the fluxes on the forces.

  13. Attosecond pulse shaping around a Cooper minimum

    CERN Document Server

    Schoun, S B; Wheeler, J; Roedig, C; Agostini, P; DiMauro, L F; Schafer, K J; Gaarde, M B

    2013-01-01

    High harmonic generation (HHG) is used to measure the spectral phase of the recombination dipole matrix element (RDM) in argon over a broad frequency range that includes the 3p Cooper minimum (CM). The measured RDM phase agrees well with predictions based on the scattering phases and amplitudes of the interfering s- and d-channel contributions to the complementary photoionization process. The reconstructed attosecond bursts that underlie the HHG process show that the derivative of the RDM spectral phase, the group delay, does not have a straight-forward interpretation as an emission time, in contrast to the usual attochirp group delay. Instead, the rapid RDM phase variation caused by the CM reshapes the attosecond bursts.

  14. 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.

  15. 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.

  16. On a Minimum Problem in Smectic Elastomers

    International Nuclear Information System (INIS)

    Smectic elastomers are layered materials exhibiting a solid-like elastic response along the layer normal and a rubbery one in the plane. Balance equations for smectic elastomers are derived from the general theory of continua with constrained microstructure. In this work we investigate a very simple minimum problem based on multi-well potentials where the microstructure is taken into account. The set of polymeric strains minimizing the elastic energy contains a one-parameter family of simple strain associated with a micro-variation of the degree of freedom. We develop the energy functional through two terms, the first one nematic and the second one considering the tilting phenomenon; after, by developing in the rubber elasticity framework, we minimize over the tilt rotation angle and extract the engineering stress

  17. 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...

  18. 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...

  19. Clinical Safety, Pharmacokinetics, and Efficacy of Ambrisentan Therapy in Children With Pulmonary Arterial Hypertension

    OpenAIRE

    Takatsuki, Shinichi; Rosenzweig, Erika B; Zuckerman, Warren; Brady, Daniela; Calderbank, Michelle; Ivy, D. Dunbar

    2012-01-01

    Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, the clinical safety and pharmacokinetics of ambrisentan has not been well studied. Our aim was to investigate the clinical safety, pharmacokinetics, tolerability, and efficacy of endothelin receptor antagonist therapy with ambrisentan in children with pulmonary arterial hypertension (PAH). This retrospective cohort study provides clinical data from pediatric patients with PAH receiving ambrisentan ...

  20. 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...

  1. Measurement of the minimum film boiling temperature using a hot patch technique

    International Nuclear Information System (INIS)

    The minimum film boiling temperature (TMFB) is of vital importance in nuclear safety analysis since it plays a major role in judging whether the heat transfer is in the film boiling regime or not. Some system codes use this temperature as a decision parameter for film boiling. For example, in TRACE code, the minimum film boiling temperature is set to the maximum of that given by the Groeneveld Stewart correlation and a value of 725 K to improve the predictive capability for reflood simulations based on data from FLECHT SEASET and THTF reflood tests. However, to our experience, the minimum film boiling temperature predicted by the existing correlations is usually lower than 725 K. Literature survey reveals that in general the existing correlations were developed for high pressures and high flow rates. On the other hand, the pressure and flow rates are relatively low under the reflood circumstance during a large break loss of coolant accident. Hence, as a matter of fact, the existing correlations are out of the applicability to predict the thermal hydraulics in reflood. Lack of experimental data for low pressures and low flow rates stimulated this study. In the present study, the minimum film boiling temperatures were measured using a hot patch technique in order to assess the conventional correlations

  2. Safety balance: Analysis of safety systems

    International Nuclear Information System (INIS)

    Safety analysis, and particularly analysis of exploitation of NPPs is constantly affected by EDF and by the safety authorities and their methodologies. Periodic safety reports ensure that important issues are not missed on daily basis, that incidents are identified and that relevant actions are undertaken. French safety analysis method consists of three principal steps. First type of safety balance is analyzed at the normal start-up phase for each unit including the final safety report. This enables analysis of behaviour of units ten years after their licensing. Second type is periodic operational safety analysis performed during a few years. Finally, the third step consists of safety analysis of the oldest units with the aim to improve the safety standards. The three steps of safety analysis are described in this presentation in detail with the aim to present the objectives and principles. Examples of most recent exercises are included in order to illustrate the importance of such analyses

  3. Novel, isoform-selective, cholecystokinin A receptor antagonist inhibits colon and pancreatic cancers in preclinical models through novel mechanism of action.

    Science.gov (United States)

    Ponnusamy, Suriyan; Lattmann, Eric; Lattmann, Pornthip; Thiyagarajan, Thirumagal; Padinjarethalakal, Balaram N; Narayanan, Ramesh

    2016-04-01

    Colon and pancreatic cancers contribute to 90,000 deaths each year in the USA. These cancers lack targeted therapeutics due to heterogeneity of the disease and multiple causative factors. One important factor that contributes to increased colon and pancreatic cancer risk is gastrin. Gastrin mediates its actions through two G-protein coupled receptors (GPCRs): cholecystokinin receptor A (CCK-A) and CCK-B/gastrin receptor. Previous studies have indicated that colon cancer predominantly expresses CCK-A and responds to CCK-A isoform antagonists. However, many CCK-A antagonists have failed in the clinic due to poor pharmacokinetic properties or lack of efficacy. In the present study, we synthesized a library of CCK-A isoform-selective antagonists and tested them in various colon and pancreatic cancer preclinical models. The lead CCK-A isoform, selective antagonist PNB-028, bound to CCK-A at 12 nM with a 60-fold selectivity towards CCK-A over CCK-B. Furthermore, it inhibited the proliferation of CCK-A-expressing colon and pancreatic cancer cells without affecting the proliferation of non-cancerous cells. PNB-028 was also extremely effective in inhibiting the growth of MAC-16 and LoVo colon cancer and MIA PaCa pancreatic cancer xenografts in immune-compromised mice. Genome‑wide microarray and kinase-array studies indicate that PNB-028 inhibited oncogenic kinases and angiogenic factors to inhibit the growth of colon cancer xenografts. Safety pharmacology and toxicology studies have indicated that PNB-028 is extremely safe and has a wide safety margin. These studies suggest that targeting CCK-A selectively renders promise to treat colon and pancreatic cancers and that PNB-028 could become the next-generation treatment option. PMID:26820391

  4. Safety for Users

    CERN Multimedia

    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

  5. Safety for Users

    CERN Multimedia

    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

  6. 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

  7. 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.

  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. 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.

  10. Central actions of a novel and selective dopamine antagonist

    International Nuclear Information System (INIS)

    Receptors for the neurotransmitter dopamine traditionally have been divided into two subgroups: the D1 class, which is linked to the stimulation of adenylate cyclase-activity, and the D2 class which is not. There is much evidence suggesting that it is the D2 class which is not. There is much evidence suggesting that it is the D2 dopamine receptor that mediates the physiological and behavioral actions of dopamine in the intact animal. However, the benzazepine SCH23390 is a dopamine antagonist which has potent behavioral actions while displaying apparent neurochemical selectivity for the D1 class of dopamine receptors. The purpose of this dissertation was to (1) confirm and characterize this selectivity, and (2) test certain hypothesis related to possible modes of action of SCH233390. The inhibition of adenylate cyclase by SCH23390 occurred via an action at the dopamine receptor only. A radiolabeled analog of SCH23390 displayed the receptor binding properties of a specific high-affinity ligand, and regional receptor densities were highly correlated with dopamine levels. The subcellular distribution of [3H]-SCH23390 binding did not correspond completely with that of dopamine-stimulated adenylate cyclase. The neurochemical potency of SCH23390 as a D1 receptor antagonist was preserved following parental administration. A variety of dopamine agonists and antagonists displayed a high correlation between their abilities to compete for [3H]-SCH23390 binding in vitro and to act at an adenylate cyclase-linked receptor. Finally, the relative affinities of dopamine and SCH23390 for both D1 receptors and [3H]-SCH23390 binding sites were comparable. It is concluded that the behavioral effects of SCH23390 are mediated by actions at D1 dopamine receptors only, and that the physiological importance of this class of receptors should be reevaluated

  11. 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.

  12. 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. ...

  13. 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...

  14. 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)

  15. Interaction of palmitoyl carnitine with calcium antagonists in myocytes.

    OpenAIRE

    Patmore, L; Duncan, G. P.; Spedding, M.

    1989-01-01

    1. Beating of aggregates of embryonic chick myocytes, in primary culture, was quantified by use of a motion-detector and video-recorder technique. Interactions of palmitoyl carnitine, a putative endogenous ligand at Ca2+ channels, with calcium antagonists were investigated. 2. Bay K 8644 (1-100 nM) and palmitoyl carnitine (0.2-30 microM) increased edge movement of the aggregates; beats fused so that there was an increase in baseline 'tone'. The concentrations required to produce a 50% increas...

  16. 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 of...... deaths associated with haemorrhage are due to intracranial haemorrhage. Notifications of complications of vKA treatment in Denmark are considerably fewer than might be anticipated from the literature. The stability of anticoagulation treatment decreases with the number of drugs administered...

  17. The Rotavirus Interferon Antagonist NSP1: Many Targets, Many Questions.

    Science.gov (United States)

    Arnold, Michelle M

    2016-06-01

    Rotavirus is a leading cause of death due to diarrhea among young children across the globe. Despite the limited coding capacity that is characteristic of RNA viruses, rotavirus dedicates substantial resources to avoiding the host innate immune response. Among these strategies is use of the interferon antagonist protein NSP1, which targets cellular proteins required for interferon production to be degraded by the proteasome. Although numerous cellular targets have been described, there remain many questions about the mechanism of NSP1 activity and its role in promoting replication in specific host species. PMID:27009959

  18. 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...

  19. Dam safety operating guidelines

    International Nuclear Information System (INIS)

    As part of Ontario Hydro's dam structure assessment program, the hydraulic design review of several river systems has revealed that many existing dam sites, under current operating procedures, would not have sufficient discharge capacity to pass the Inflow Design Flood (IDF) without compromising the integrity of the associated structures. Typical mitigative measures usually considered in dealing with these dam sites include structural alterations, emergency action plans and/or special operating procedures designed for extreme floods. A pilot study was carried out for the Madawaska River system in eastern Ontario, which has seven Ontario Hydro dam sites in series, to develop and evaluate the effectiveness of the Dam Safety Operating Guidelines (DSOG). The DSOG consist of two components: the flood routing schedules and the minimum discharge schedules, the former of which would apply in the case of severe spring flood conditions when the maximum observed snowpack water content and the forecast rainfall depth exceed threshold values. The flood routing schedules would identify to the operator the optimal timing and/or extent of utilizing the discharge facilities at each dam site to minimize the potential for dam failures cased by overtopping anywhere in the system. It was found that the DSOG reduced the number of structures overtopped during probable maximum flood from thirteen to four, while the number of structures that could fail would be reduced from seven to two. 8 refs., 4 figs., 3 tabs

  20. Antagonist of prostaglandin E2 receptor 4 induces metabolic alterations in liver of mice.

    Science.gov (United States)

    Li, Ning; Zhang, Limin; An, Yanpeng; Zhang, Lulu; Song, Yipeng; Wang, Yulan; Tang, Huiru

    2015-03-01

    Prostaglandin E2 receptor 4 (EP4) is one of the receptors for prostaglandin E2 and plays important roles in various biological functions. EP4 antagonists have been used as anti-inflammatory drugs. To investigate the effects of an EP4 antagonist (L-161982) on the endogenous metabolism in a holistic manner, we employed a mouse model, and obtained metabolic and transcriptomic profiles of multiple biological matrixes, including serum, liver, and urine of mice with and without EP4 antagonist (L-161982) exposure. We found that this EP4 antagonist caused significant changes in fatty acid metabolism, choline metabolism, and nucleotide metabolism. EP4 antagonist exposure also induced oxidative stress to mice. Our research is the first of its kind to report information on the alteration of metabolism associated with an EP4 antagonist. This information could further our understanding of current and new biological functions of EP4. PMID:25669961

  1. 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...

  2. 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.

  3. 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...

  4. Minimum bias at 40 TeV

    International Nuclear Information System (INIS)

    The total rate of inelastic interactions at 40 TeV will be of the order of 100 mb. At the nominal luminosity of 1033 cm-2 sec-1, this implies an interaction rate of 108 Hz, or 1.6 interactions per bunch crossing, with the nominal bunch spacing of 16ns. At higher luminosities, the average number of overlapping events will increase accordingly. The structure of these so-called minimum-bias (MB) events has important consequences on the performance of the apparatus, on the feasibility of important measurements and on the features of important new physics signals. Today's common lore on MB events indicates the existence of two components, one soft and one semi-hard. The soft component obeys KNO scaling as far as multiplicities go, and predicts an exponential spectrum for the PT distributions. The semi-hard component originates from partonic processes with a Q2 scale large enough to justify the use of parton models, but small enough to give rates of the order of the mb. The present report collects some important inclusive distributions for MB events obtained by assuming the two extreme cases in which MB is either totally dominated by a soft component, or totally dominated by the semi-hard component. Reality will probably sit in-between, and therefore a reasonable range of expectation can be obtained by superimposing the distributions for the soft component with those for the semi-hard one with the proper relative weights. (N.K.)

  5. Minimum Certificate Dispersal with Tree Structures

    CERN Document Server

    Izumi, Taisuke; Ono, Hirotaka; Wada, Koichi

    2011-01-01

    Given an n-vertex graph G=(V,E) and a set R \\subseteq {{x,y} | x,y \\in V} of requests, we consider to assign a set of edges to each vertex in G so that for every request {u, v} in R the union of the edge sets assigned to u and v contains a path from u to v. The Minimum Certificate Dispersal Problem (MCD) is defined as one to find an assignment that minimizes the sum of the cardinality of the edge set assigned to each vertex. This problem has been shown to be LOGAPX-complete for the most general setting, and APX-hard and 2-approximable in polynomial time for dense request sets, where R forms a clique. In this paper, we investigate the complexity of MCD with sparse (tree) structures. We first show that MCD is APX-hard when R is a tree, even a star. We then explore the problem from the viewpoint of the maximum degree \\Delta of the tree: MCD for tree request set with constant \\Delta is solvable in polynomial time, while that with \\Delta=\\Omega(n) is 2.56-approximable in polynomial time but hard to approximate wit...

  6. 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...

  7. 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.

  8. Glassy slags for minimum additive waste stabilization

    International Nuclear Information System (INIS)

    Glassy slag waste forms are being developed to complement glass waste forms in implementing Minimum Additive Waste Stabilization (MAWS) for supporting DOE's environmental restoration efforts. The glassy slag waste form is composed of various crystalline and metal oxide phases embedded in a silicate glass phase. The MAWS approach was adopted by blending multiple waste streams to achieve up to 100% waste loadings. The crystalline phases, such as spinels, are very durable and contain hazardous and radioactive elements in their lattice structures. These crystalline phases may account for up to 80% of the total volume of slags having over 80% metal loading. The structural bond strength model was used to quantify the correlation between glassy slag composition and chemical durability so that optimized slag compositions were obtained with limited crucible melting and testing. Slag compositions developed through crucible melts were also successfully generated in a pilot-scale Retech plasma centrifugal furnace at Ukiah, California. Utilization of glassy slag waste forms allows the MAWS approach to be applied to a much wider range of waste streams than glass waste forms. The initial work at ANL has indicated that glassy slags are good final waste forms because of (1) their high chemical durability; (2) their ability to incorporate large amounts of metal oxides; (3) their ability to incorporate waste streams having low contents of flux components; (4) their less stringent requirements on processing parameters, compared to glass waste forms; and (5) their low requirements for purchased additives, which means greater waste volume reduction and treatment cost savings

  9. 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

  10. Pyridyl-2,5-diketopiperazines as potent, selective, and orally bioavailable oxytocin antagonists: synthesis, pharmacokinetics, and in vivo potency.

    Science.gov (United States)

    Borthwick, Alan D; Liddle, John; Davies, Dave E; Exall, Anne M; Hamlett, Christopher; Hickey, Deirdre M; Mason, Andrew M; Smith, Ian E D; Nerozzi, Fabrizio; Peace, Simon; Pollard, Derek; Sollis, Steve L; Allen, Michael J; Woollard, Patrick M; Pullen, Mark A; Westfall, Timothy D; Stanislaus, Dinesh J

    2012-01-26

    A six-stage stereoselective synthesis of indanyl-7-(3'-pyridyl)-(3R,6R,7R)-2,5-diketopiperazines oxytocin antagonists from indene is described. SAR studies involving mono- and disubstitution in the 3'-pyridyl ring and variation of the 3-isobutyl group gave potent compounds (pK(i) > 9.0) with good aqueous solubility. Evaluation of the pharmacokinetic profile in the rat, dog, and cynomolgus monkey of those derivatives with low cynomolgus monkey and human intrinsic clearance gave 2',6'-dimethyl-3'-pyridyl R-sec-butyl morpholine amide Epelsiban (69), a highly potent oxytocin antagonist (pK(i) = 9.9) with >31000-fold selectivity over all three human vasopressin receptors hV1aR, hV2R, and hV1bR, with no significant P450 inhibition. Epelsiban has low levels of intrinsic clearance against the microsomes of four species, good bioavailability (55%) and comparable potency to atosiban in the rat, but is 100-fold more potent than the latter in vitro and was negative in the genotoxicity screens with a satisfactory oral safety profile in female rats. PMID:22239250

  11. 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.

  12. Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia

    OpenAIRE

    Garami, Andras; Shimansky, Yury P.; Pakai, Eszter; Oliveira, Daniela L.; Gavva, Narender R.; Romanovsky, Andrej A

    2010-01-01

    Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic...

  13. 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...

  14. A Selective TSH Receptor Antagonist Inhibits Stimulation of Thyroid Function in Female Mice

    OpenAIRE

    Neumann, Susanne; Nir, Eshel A; Eliseeva, Elena; Huang, Wenwei; Marugan, Juan; Xiao, Jingbo; Dulcey, Andrés E.; Gershengorn, Marvin C.

    2013-01-01

    Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of...

  15. Fire safety

    International Nuclear Information System (INIS)

    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

  16. 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

  17. 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.

  18. 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...

  19. Linking Safety Analysis to Safety Requirements

    DEFF Research Database (Denmark)

    Hansen, Kirsten Mark

    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...... 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....

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

    Science.gov (United States)

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

    2015-04-01

    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. PMID:25635045

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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...

  8. Patient safety: Safety culture and patient safety ethics

    DEFF Research Database (Denmark)

    Madsen, Marlene Dyrløv

    2006-01-01

    ,demonstrating significant, consistent and sometimes large differences in terms of safety culture factors across the units participating in the survey. Paper 5 is the results of a study of the relation between safety culture, occupational health andpatient safety using a safety culture questionnaire survey......, and those of patients who experience the physical effect of poor patient safety. The dissertationconsists of nine papers and an appendix. Paper 1 describes the results of doctors and nurses attitudes towards reporting and the handling of adverse events. Paper 2 is a study and “review” of the international...

  9. 12 CFR Appendix A to Part 1720 - Policy Guidance; Minimum Safety and Soundness Requirements

    Science.gov (United States)

    2010-01-01

    ... credit quality. II. Balance sheet growth and management. III. Market risk. IV. Information technology. V. Internal controls. VI. Audits. VII. Information reporting and documentation. VIII. Board and management... growth; (3) market risks; (4) information technology; (5) internal controls; (6) audits; (7)...

  10. 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

  11. Status of safety improvements

    International Nuclear Information System (INIS)

    A review of safety improvements of the Armenian NPP, i.e. two WWER-440 units is presented. The implemented activities concerning engineering safety; radiation safety; operation safety; personnel training and qualification; operating experience are described in detail. A list of serious problems dealing with safety upgrading of NPP is given

  12. Contractor safety

    International Nuclear Information System (INIS)

    The recent trend in the United States and Shell Oil Company EandP has been to increase use of contractors to do specialized work. Many companies now use contractors almost exclusively for operations such as drilling, well workovers, construction, and many specialty and routine maintenance tasks. Today, approximately 75% of Shell Oil Company's actual operating work force in EandP is contract. Clearly, HSandE considerations must become an increasingly important part of the contractor selection process. This paper reports on the Shell Oil Company's evolution from a bidder selection process to a program of Matching Owner and Contractor. Well has begun to expand efforts to make better assessments of contractor's HSandE capabilities and values in pre-bid considerations. Focus is on pre-bid evaluations to select contractors that have strong HSandE commitments and values. Contractor safety performance in this industry must be brought up to the same standards as operating companies. In Shell Oil EandP is only willing to contractors who can and are willing to do that

  13. Safety evaluation by living probabilistic safety assessment and safety indicators

    International Nuclear Information System (INIS)

    A continuous monitoring and follow-up of the risks involved in the operation of a nuclear power plant is an important part of the operational safety management. In living probabilistic safety assessment (PSA), the plant specific PSA is applied in daily safety work to support solving of short-term problems, and maintaining as well as enhancing safety in the long term. A quicker and more problem oriented feedback of operating experience can be achieved by well defined safety indicators, highlighting important trends and possible recurrence of operational problems at the plant. Living PSA and safety indicators should be used in combination to effectively support decision making on safety related issues. The Nordic NKS/SIK-1 project also showed how a more systematic and clear basis for such decisions can be formulated by the method of decision analysis. (au) 18 refs

  14. The Cultivation of Antagonistic Bacteria in Irradiated Sludge for Biological Control of Soft Rot Erwinias : Screening of Antagonistic Bacteria for biological Control of Soft Rot Erwinias

    International Nuclear Information System (INIS)

    Pure cultures of 57 bacterial isolates for antagonistic activity screening were isolated from three areas of soft rot infested vegetable soil and 58 isolates were obtained from commercial seed compost and seed compost product of Division of Soil and Water Conservation, Department of Land Development. A total of 115 bacterial isolates were evaluated for antagonizing activity against Erwinia carotovora subsp. atroceptica in vitro. Out of them, 18 isolates were antagonists by showing zone of inhibition ranging from 1 to 17 mm by diameter. Most of antagonistic bacteria were identified as Bacillus spp. whereas only one isolate was Pseudomonas vesicularis

  15. Attentional bias toward safety predicts safety behaviors.

    Science.gov (United States)

    Xu, Yaoshan; Li, Yongjuan; Wang, Guangxi; Yuan, Xiao; Ding, Weidong; Shen, Zhongxiang

    2014-10-01

    Safety studies have primarily focused on how explicit processes and measures affect safety behavior and subsequent accidents and injuries. Recently, safety researchers have paid greater attention to the role of implicit processes. Our research focuses on the role of attentional bias toward safety (ABS) in workplace safety. ABS is a basic, early-stage cognitive process involving the automatic and selective allocation of attentional resources toward safety cues, which reflect the implicit motivational state of employees regarding safety goal. In this study, we used two reaction time-based paradigms to measure the ABS of employees in three studies: two modified Stroop tasks (Studies 1 and 2) and a visual dot-probe task (Study 3). Results revealed that employees with better safety behavior showed significant ABS (Study 2), and greater ABS than employees with poorer safety behavior (Studies 1 and 2). Moreover, ABS was positively associated with the perceived safety climate and safety motivation of employees, both of which mediate the effect of ABS on safety behavior (Study 3). These results contributed to a deeper understanding of how early-stage automatic perceptual processing affects safety behavior. The practical implications of these results were also discussed. PMID:24922613

  16. 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...

  17. 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

  18. 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...

  19. 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 ...

  20. 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)...

  1. 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...

  2. 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 ...

  3. Secondary electric power generation with minimum engine bleed

    Science.gov (United States)

    Tagge, G. E.

    1983-01-01

    Secondary electric power generation with minimum engine bleed is discussed. Present and future jet engine systems are compared. The role of auxiliary power units is evaluated. Details of secondary electric power generation systems with and without auxiliary power units are given. Advanced bleed systems are compared with minimum bleed systems. A cost model of ownership is given. The difference in the cost of ownership between a minimum bleed system and an advanced bleed system is given.

  4. Do minimum wages really increase youth drinking and drunk driving?

    OpenAIRE

    SABIA, JOSEPH J.; Pitts, M. Melinda; Argys, Laura

    2014-01-01

    Adams, Blackburn, and Cotti (ABC) found that increases in minimum wages were positively related to drunk driving-related traffic fatalities for those ages 16 to 20. The hypothesized mechanism for this relationship - increased alcohol consumption caused by minimum wage - induced income gains - remains empirically unexplored. Using data from two national behavioral surveys and an identification strategy identical to ABC, we find little evidence that an increase in the minimum wage leads to incr...

  5. 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 ...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. Momentary maximizing in concurrent schedules with a minimum interchangeover interval

    OpenAIRE

    Todorov, João Claudio; de Souza, Deisy G; Bori, Carolina M.

    1993-01-01

    Eight pigeons were trained on concurrent variable-interval variable-interval schedules with a minimum interchangeover time programmed as a consequence of changeovers. In Experiment 1 the reinforcement schedules remained constant while the minimum interchangeover time varied from 0 to 200 s. Relative response rates and relative time deviated from relative reinforcement rates toward indifference with long minimum interchangeover times. In Experiment 2 different reinforcement ratios were schedul...

  11. 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...

  12. 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

  13. Providing for decommissioning funds: minimum conditions for adequate funding and comparative analysis

    International Nuclear Information System (INIS)

    The present contribution analyses the minimum criteria that need to be applied for adequate financial arrangements for decommissioning, as well as the possible financing mechanisms and the recommended investment policy for decommissioning funds. Furthermore, practical examples of decommissioning mechanisms in the United States of America, France, the United Kingdom, Germany, Sweden, Spain and Belgium will be studied. A question frequently asked about nuclear energy is how to deal with its impact on the environment. The issue of decommissioning of nuclear power plants, and in particular the funding of such decommissioning, is part of this discussion. The IAEA fundamental safety principles and safety requirements already make clear that radioactive waste must be managed in such a way as to avoid imposing an undue burden on future generations. The government shall make provision for the safe decommissioning of facilities, the safe management and disposal of radioactive waste arising from facilities and activities, and the safe management of spent fuel. (author)

  14. 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

  15. 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

  16. 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.

  17. About Converting a Set into a Minimum-Phase Sequence

    Directory of Open Access Journals (Sweden)

    Jaakko Astola

    2009-01-01

    Full Text Available In this paper we discuss whether a given finite set ofcomplex numbers can be ordered such that the derived sequenceis minimum-phase. Knowing that every sequence can be extendedto a minimum-phase sequence, we conclude that a setcan always be converted to a minimum-phase sequence using anadditional sample. We characterize several types of sets that canbe ordered in minimum-phase sequences with no additionalsample. These sets do not span the sets of all real or complexsequences of finite length.

  18. 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...

  19. 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...

  20. 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...

  1. 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.

  2. Design, fabrication and erection of steel structures important to safety of nuclear facilities

    International Nuclear Information System (INIS)

    Civil engineering structures in nuclear installations form an important feature having implications to safety performance of these installations. The objective and minimum requirements for the design of civil engineering buildings/structures to be fulfilled to provide adequate assurance for safety of nuclear installations in India (such as pressurised heavy water reactor and related systems) are specified in the Safety Standard for Civil Engineering Structures Important to Safety of Nuclear Facilities. This standard is written by AERB to specify guidelines for implementation of the above civil engineering safety standard in the design, fabrication and erection of steel structures important to safety

  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. Functionalized Congeners of P2Y1 Receptor Antagonists:

    Energy Technology Data Exchange (ETDEWEB)

    de Castro, Sonia [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Maruoka, Hiroshi [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Hong, Kunlun [ORNL; Kilbey, II, S Michael [ORNL; Costanzi, Stefano [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Hechler, Béatrice [University of Strasbourg; Gachet, Christian [EFS-Alsace, Strasbourg, France; Harden, T. Kendall [University of North Carolina School of Medicine; Jacobson, Kenneth A. [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health

    2010-01-01

    The P2Y{sub 1} receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP. Preference for the North (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the P2Y{sub 1} receptor was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute. A series of covalently linkable N{sup 6}-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphates containing extended 2-alkynyl chains was designed, and binding affinity at the human (h) P2Y{sub 1} receptor determined. The chain of these functionalized congeners contained hydrophilic moieties, a reactive substituent, or biotin, linked via an amide. Variation of the chain length and position of an intermediate amide group revealed high affinity of carboxylic congener 8 (K{sub i} 23 nM) and extended amine congener 15 (K{sub i} 132 nM), both having a 2-(1-pentynoyl) group. A biotin conjugate 18 containing an extended {epsilon}-aminocaproyl spacer chain exhibited higher affinity than a shorter biotinylated analogue. Alternatively, click coupling of terminal alkynes of homologous 2-dialkynyl nucleotide derivatives to alkyl azido groups produced triazole derivatives that bound to the P2Y{sub 1} receptor following deprotection of the bisphosphate groups. The preservation of receptor affinity of the functionalized congeners was consistent with new P2Y{sub 1} receptor modeling and ligand docking. Attempted P2Y{sub 1} antagonist conjugation to PAMAM dendrimer carriers by amide formation or palladium-catalyzed reaction between an alkyne on the dendrimer and a 2-iodopurine-derivatized nucleotide was unsuccessful. A dialkynyl intermediate containing the chain length favored in receptor binding was conjugated to an azide-derivatized dendrimer, and the conjugate inhibited ADP-promoted human platelet aggregation. This is the first example of attaching a strategically functionalized P2Y receptor

  5. Antagonistic Activities of Bacillus spp. Strains Isolated from Tidal Flat Sediment Towards Anthracnose Pathogens Colletotrichum acutatum and C. gloeosporioides in South Korea

    Directory of Open Access Journals (Sweden)

    Joon-Hee Han

    2015-06-01

    Full Text Available Anthracnose is a fungal disease caused by Colletotrichum species that is detrimental to numerous plant species. Anthracnose control with fungicides has both human health and environmental safety implications. Despite increasing public concerns, fungicide use will continue in the absence of viable alternatives. There have been relatively less efforts to search antagonistic bacteria from mudflats harboring microbial diversity. A total of 420 bacterial strains were isolated from mudflats near the western sea of South Korea. Five bacterial strains, LB01, LB14, HM03, HM17, and LB15, were characterized as having antifungal properties in the presence of C. acutatum and C. gloeosporioides. The three Bacillus atrophaeus strains, LB14, HM03, and HM17, produced large quantities of chitinase and protease enzymes, whereas the B. amyloliquefaciens strain LB01 produced protease and cellulase enzymes. Two important antagonistic traits, siderophore production and solubilization of insoluble phosphate, were observed in the three B. atrophaeus strains. Analyses of disease suppression revealed that LB14 was most effective for suppressing the incidence of anthracnose symptoms on pepper fruits. LB14 produced antagonistic compounds and suppressed conidial germination of C. acutatum and C. gloeosporioides. The results from the present study will provide a basis for developing a reliable alternative to fungicides for anthracnose control.

  6. Antagonistic Activities of Bacillus spp. Strains Isolated from Tidal Flat Sediment Towards Anthracnose Pathogens Colletotrichum acutatum and C. gloeosporioides in South Korea.

    Science.gov (United States)

    Han, Joon-Hee; Shim, Hongsik; Shin, Jong-Hwan; Kim, Kyoung Su

    2015-06-01

    Anthracnose is a fungal disease caused by Colletotrichum species that is detrimental to numerous plant species. Anthracnose control with fungicides has both human health and environmental safety implications. Despite increasing public concerns, fungicide use will continue in the absence of viable alternatives. There have been relatively less efforts to search antagonistic bacteria from mudflats harboring microbial diversity. A total of 420 bacterial strains were isolated from mudflats near the western sea of South Korea. Five bacterial strains, LB01, LB14, HM03, HM17, and LB15, were characterized as having antifungal properties in the presence of C. acutatum and C. gloeosporioides. The three Bacillus atrophaeus strains, LB14, HM03, and HM17, produced large quantities of chitinase and protease enzymes, whereas the B. amyloliquefaciens strain LB01 produced protease and cellulase enzymes. Two important antagonistic traits, siderophore production and solubilization of insoluble phosphate, were observed in the three B. atrophaeus strains. Analyses of disease suppression revealed that LB14 was most effective for suppressing the incidence of anthracnose symptoms on pepper fruits. LB14 produced antagonistic compounds and suppressed conidial germination of C. acutatum and C. gloeosporioides. The results from the present study will provide a basis for developing a reliable alternative to fungicides for anthracnose control. PMID:26060435

  7. 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 ...

  8. 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)

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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...

  14. 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...

  15. 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 ...

  16. Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children

    DEFF Research Database (Denmark)

    Bisgaard, H; Nielsen, K G

    2000-01-01

    We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5...... repeatability of the bronchoprotection was examined by repeating the placebo-controlled study in six of the 13 children. sRaw increased by an average of 46% (95% confidence interval [CI]: 30 to 63%) after placebo treatment and 17% (95% CI: 3 to 31%) after montelukast (p < 0.01). Eight of the children were...... receiving regular treatment with budesonide delivered by an inhaler with a spacer in a mean daily dose of 350 microg, but the bronchoprotection provided by montelukast was independent of concurrent steroid treatment. There was no convincing evidence of failure to respond, and the protective effect of...

  17. Identification of Bexarotene as a PPARγ Antagonist with HDX

    Directory of Open Access Journals (Sweden)

    David P. Marciano

    2015-01-01

    Full Text Available The retinoid x receptors (RXRs are the pharmacological target of Bexarotene, an antineoplastic agent indicated for the treatment of cutaneous T cell lymphoma (CTCL. The RXRs form heterodimers with several nuclear receptors (NRs, including peroxisome proliferator-activated receptor gamma (PPARγ, to regulate target gene expression through cooperative recruitment of transcriptional machinery. Here we have applied hydrogen/deuterium exchange (HDX mass spectrometry to characterize the effects of Bexarotene on the conformational plasticity of the intact RXRα:PPARγ heterodimer. Interestingly, addition of Bexarotene to PPARγ in the absence of RXRα induced protection from solvent exchange, suggesting direct receptor binding. This observation was confirmed using a competitive binding assay. Furthermore, Bexarotene functioned as a PPARγ antagonist able to alter rosiglitazone induced transactivation in a cell based promoter:reporter transactivation assay. Together these results highlight the complex polypharmacology of lipophilic NR targeted small molecules and the utility of HDX for identifying and characterizing these interactions.

  18. Physico-chemical pathways in radioprotective action of calmodulin antagonists

    International Nuclear Information System (INIS)

    Ghost membranes prepared from erythrocytes of Swiss albino mice were irradiated with gamma rays at a dose rate of 0.9 Gy/s. The fluidity of membrane decreased with radiation dose and in the presence of calmodulin antagonists (CA) like chlorpromazine (CPZ), promethazine (PMZ), and trimeprazone (TMZ) it increased. Radiation induced release of Ca2+ from membranes. This release was inhibited by CA mainly by CPZ and PMZ. Being Ca2+ dependent, the changes in the activity of acetylcholine estrase (AchE) following irradiation was also studied. Radiation decreased the activity of AchE in dose dependent manner. Presence of CPZ and PMZ diminished the radiation induced inhibition of AchE but not in the presence of TMZ at the lower concentration tested. It is suggested that apart from scavenging of free radicals, CA perhaps exert their euxoic radioprotective effect through Ca2+ dependent processes. (author)

  19. Biological control of soybean damping-off by antagonistic rhizobacteria.

    Science.gov (United States)

    Sharifi Tehrani, A; Zebarjad, A; Hedjaroud, Gh A; Mohammadi, M

    2002-01-01

    Experiments were carried out with 133 bacterial isolates that were collected from soybean rhizosphere. These strains were used to investigate their biocontrol traits in vitro and their ability to suppress the soybean damping-off in vivo (soil and seed treatments). Three highly effective isolates were selected from these antagonists for subsequent studies. According to the biochemical, physiological and morphological tests, these isolates (B-2, B-12 and B-80) were identified as Bacillus spp. In soil treatment, the isolate B-3 with 70.8%, B-12 with 66.7%, B-80 with 54.2% had the highest effect on reducing the soybean damping-off. In seed treatment, the isolates B-43 with 62.5%, B-12 with 58.4 and B-80 with 45.8%, had the greatest effect on reducing the disease. These isolates produced volatile metabolites that inhibited mycelial growth of Phytophthora sojae. PMID:12701446

  20. Calcium-antagonists and islet function. Pt. 5

    International Nuclear Information System (INIS)

    R33711, a new drug with presumed potent calcium-antagonistic property, was found to suppress the insulinotropic action of glucose und gliclazide but not that of theophylline. A 0.2 μM concentration of R33711 was sufficient to abolish glucose-induced insulin release. At this concentration, R33711 inhibited the net uptake of 45Ca2+ by isolated islets, whether in the absence or presence of either glucose or sulfonylurea. In the isolated islets, R33711 failed to affect the glucose-stimulated production of lactate, the rate of 45Ca2+ efflux, the inhibitory action of glucose upon such an efflux and its increase in response to theophylline. These data are compatible with the view that R33711 inhibits entry of Ca2+ into the B-cell and that integrity of such an inward cationic movement usually plays a permissive role in the maintenance of the Ca2+-dependent insulin secretory process. (orig.)