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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 n...... study, that is, 57.5%. The simplified procedure proposed, although not an absolute guide to safety, is designed to screen against gross unreliability of a test program, without the need to repeat a massive clinical endpoint study for each and every program.......Based on the results of the previous European Action on Anticoagulation (EAA) multicenter study, a simplified minimum procedure is described for screening the safety and effectiveness of marketed programs for dosage of oral anticoagulant drugs (vitamin K antagonists). The aim was to demonstrate non...

  2. Nalmefene: intravenous safety and kinetics of a new opioid antagonist.

    Science.gov (United States)

    Dixon, R; Howes, J; Gentile, J; Hsu, H B; Hsiao, J; Garg, D; Weidler, D; Meyer, M; Tuttle, R

    1986-01-01

    In a placebo-controlled, double-blind study we evaluated the safety and kinetics of a new narcotic antagonist, nalmefene, after 2, 6, 12, and 24 mg intravenous doses to healthy men. At each dose level four subjects received active drug and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, the most common of which was lightheadedness. The plasma concentration-time data were best fit with a triexponential equation, and the terminal elimination phase had a harmonic mean t1/2 of 8 to 9 hours. Only about 5% of the dose was excreted in the urine as intact nalmefene, with up to 60% excreted as nalmefene glucuronide. Although intersubject differences were noted, mean or dose-normalized mean kinetic parameters such as clearance, steady-state volume of distribution, terminal t1/2, and AUC showed no consistent trends related to increasing doses, indicating that nalmefene has linear pharmacokinetics.

  3. Operational design for safety of minimum operators; Shoninka no tameno opereshon anzen sekkei

    Energy Technology Data Exchange (ETDEWEB)

    Yamamuro, N. [Nippon Zeon Co., Ltd., Tokyo (Japan)

    2000-07-05

    One of the keywords of the chemical plant in the twenty-first century is the minimum operators. It requires the plant with the more advanced reliability it maintains the safe level along the convention in little personnel. Here, it limits the target to automation and computerization design, which are a key point of minimum operators plant design, and on the design strategy of new operation safety design, it introduces the outline. (NEDO)

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

    Directory of Open Access Journals (Sweden)

    L. Riente

    2011-09-01

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

  5. 12 CFR Appendix A to Part 1720 - Policy Guidance; Minimum Safety and Soundness Requirements

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Policy Guidance; Minimum Safety and Soundness Requirements A Appendix A to Part 1720 Banks and Banking OFFICE OF FEDERAL HOUSING ENTERPRISE OVERSIGHT... Enterprise's liquidity effectively, and to identify and anticipate various market environments and...

  6. Screening for cardiovascular safety: a structure-activity approach for guiding lead selection of melanin concentrating hormone receptor 1 antagonists.

    Science.gov (United States)

    Kym, Philip R; Souers, Andrew J; Campbell, Thomas J; Lynch, John K; Judd, Andrew S; Iyengar, Rajesh; Vasudevan, Anil; Gao, Ju; Freeman, Jennifer C; Wodka, Dariusz; Mulhern, Mathew; Zhao, Gang; Wagaw, Seble H; Napier, James J; Brodjian, Sevan; Dayton, Brian D; Reilly, Regina M; Segreti, Jason A; Fryer, Ryan M; Preusser, Lee C; Reinhart, Glenn A; Hernandez, Lisa; Marsh, Kennan C; Sham, Hing L; Collins, Christine A; Polakowski, James S

    2006-04-06

    An inactin-anesthetized rat cardiovascular (CV) assay was employed in a screening mode to triage multiple classes of melanin-concentrating hormone receptor 1 (MCHr1) antagonists. Lead identification was based on a compound profile producing high drug concentration in both plasma (>40 microM) and brain (>20 microg/g) with optimization activities on multiple classes of MCHr1 antagonists were terminated. After providing evidence that the cardiovascular liabilities were not a function of MCHr1 antagonism, continued screening identified the chromone-substituted aminopiperidine amides as a class of MCHr1 antagonists that demonstrated a safe cardiovascular profile at high drug concentrations in both plasma and brain. The high incidence of adverse cardiovascular effects associated with an array of MCHr1 antagonists of significant chemical diversity, combined with the stringent safety requirements for antiobesity drugs, highlight the importance of incorporating cardiovascular safety assessment early in the lead selection process.

  7. Minimum Safety Factor for Evaluation of Critical Buckling Pressure of Zirconium Alloy Tube

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyung Kyu; Kim, Jae Yong; Yoon, Kyung Ho; Lee, Young Ho; Lee, Kang Hee; Kang, Heung Seok [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-03-15

    We consider the uncertainty in the elastic buckling formula for a thin tube. We take into account the measurement uncertainty of Young's modulus and Poisson's ratio and the tolerance of the tube thickness and diameter. Elastic buckling must be prohibited for a thin tube such as a nuclear fuel rod that must satisfy a self-stand criterion. Since the predicted critical buckling pressure overestimated that found in the experiment, the determination of the minimum safety factor is crucial. The uncertainty in each parameter (i.e., Young's modulus, Poisson's ratio, thickness, and diameter) is mutually independent, so the safety factor is evaluated as the sum of the inverse of each uncertainty. We found that the thickness variation greatly affects the uncertainty. The minimum safety factor of a thin tube of Zirconium alloy is evaluated as 1.547 for a thickness of 0.87 mm and 3.487 for a thickness of 0.254 mm.

  8. On the Minimum Safety Factor in Elastic Buckling of Fuel Rod

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyung Kyu; Kim, Jae Yong; Yoon, Kyung Ho; Lee, Young Ho; Lee, Kang Hee; Kang, Heung Seok; Song, Kun Woo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2010-10-15

    Elastic buckling of a thin tube is an instantaneous collapse phenomenon due to an external pressure. This should be prohibited for a PWR (Pressurized Water Reactor) fuel rod. There is an engineering formula of it; however, safety factor used to be applied to the calculation results since there will be uncertainty in the parameters of the formulae such as dimensional tolerances, environmental conditions and so forth. It is a designer's responsibility to determine an appropriate safety factor that is acceptably economically conservative. Mechanical properties of a material are usually adopted from a material handbook. However, they are usually different from the measured values of the material actually used. A local dimension anomaly critically affects the elastic buckling. Conventional safety factors against the elastic buckling seemed to be large (more than 3.5). However, the reason for this is rarely found. Engineering experience may be incorporated. Therefore, it is highly necessary to propose a minimum safety factor on the elastic buckling while accommodating the above mentioned uncertainties. It is so especially for the dual cooled fuel rod since it has never been used before. The primary purpose of this work is to quantify the aforementioned uncertainties of the parameters in the elastic buckling formula, especially for an outer cladding of the currently studied dual cooled fuel rod. It is extended from the previous theoretical and experimental study

  9. 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.

  10. Nalmefene: safety and kinetics after single and multiple oral doses of a new opioid antagonist.

    Science.gov (United States)

    Dixon, R; Gentile, J; Hsu, H B; Hsiao, J; Howes, J; Garg, D; Weidler, D

    1987-03-01

    The aim of these two studies was to evaluate the safety and pharmacokinetics of oral nalmefene, a new orally effective opioid antagonist. In the first study, single ascending doses of 50, 100, 200, and 300 mg of nalmefene HCl were administered in double-blind fashion to four groups of healthy men. There were six subjects in each group; four received nalmefene and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, such as lightheadedness, at the higher doses. Model-independent pharmacokinetic analysis of the plasma concentration-time data showed that nalmefene was rapidly absorbed and had an elimination half-life that ranged from seven to 15 hours (mean, 10.7 hr). There was a good linear relationship (r = .97) between administered dose and total area under the curve at each dose level. Only about 4% of the dose was excreted in the urine as unchanged nalmefene, whereas up to 60% was excreted as a beta-glucuronidase/sulfatase hydrolysable conjugate(s) of nalmefene. In the second study, six healthy men were initially administered a single 50-mg dose of drug, and plasma samples were obtained at selected time intervals for 48 hours. A dosing schedule of 20 mg q12h was then started and continued for seven days. Plasma samples were collected immediately before each dose and at selected times for up to 48 hours after the last dose. The drug was well tolerated by all subjects, and no clinically significant adverse effects were observed during the seven-day administration period.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    OpenAIRE

    2016-01-01

    Abstract 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

  13. Safety and Efficacy of Underdosing Non-vitamin K Antagonist Oral Anticoagulants in Patients Undergoing Catheter Ablation for Atrial Fibrillation

    Science.gov (United States)

    Murakami, Takashi; Hina, Kazuyoshi; Higashiya, Shunichi; Kawamura, Hiroshi; Murakami, Masaaki; Kamikawa, Shigeshi; Komatsubara, Issei; Kusachi, Shozo

    2017-01-01

    Background: Some patients with atrial fibrillation (AF) received underdoses of non-vitamin K antagonist oral anticoagulants (NOACs) in the real world. Underdosing is defined as administration of a dose lower than the manufacturer recommended dose. Objectives: To identify the efficacy and safety of underdosing NOACs as perioperative anticoagulation for atrial fibrillation ablation. Methods: We retrospectively analyzed patients who received rivaroxaban or dabigatran etexilate according to dosage: adjusted low dosage (reduced by disturbed renal function; n = 30), underdosage (n = 307), or standard dosage (n = 683). Non-vitamin K antagonist oral anticoagulants and dosing decisions were at the discretion of treating cardiologists. Results: Patients who received underdosed NOACs were older, more often female, and had lower body weight and lower renal function than those who received standard dosages. Activated clotting time at baseline in patients who received adjusted low dosage or underdosages was slightly longer than that in patients receiving standard dosages (156 ± 23, 151 ± 224, and 147 ± 24 seconds, respectively). Meaningful differences were not observed in other coagulation parameters. Adjusted low-, under-, and standard-dosing regimens did not differ in perioperative thromboembolic complications (0/30, 0.0%; 1/307, 0.3%; and 0/683, 0%, respectively) or major (0/30, 0.0%; 2/307, 0.6%; 3/683, 0.4%) and minor (1/30, 3.3%; 13/307, 4.2%; 25/683, 3.6%) bleeding episodes. When comparisons were performed for each NOAC, similar results were observed. Conclusions: With consideration of patient condition, age, sex, body weight, body mass index, and renal function, underdosing NOACs was effective and safe as a perioperative anticoagulation therapy for atrial fibrillation ablation. The therapeutic range of NOACs is potentially wider than manufacturer recommendations. PMID:28170360

  14. An investigation of the safety and pharmacokinetics of the novel TRPV1 antagonist XEN-D0501 in healthy subjects

    Science.gov (United States)

    Round, Patrick; Priestley, Anthony; Robinson, Jan

    2011-01-01

    AIMS XEN-D0501, a novel TRPV1 antagonist, is being developed to treat overactive bladder. This study investigated the safety and pharmacokinetics of repeat-dose XEN-D0501 in healthy subjects. METHODS The study was conducted in two parts. Part 1 was a double-blind, randomized, placebo-controlled, two-way crossover study in three cohorts of 12 young male subjects. Each subject received XEN-D0501 and placebo (in random order) twice daily for 13 days, with a final single dose on day 14. Doses of 1, 2.5 and 5 mg XEN-D0501 were investigated. Part 2 was an open-label, randomized, two-way crossover study in male and female subjects (45 to 65 years). Subjects received single doses of 5 mg XEN-D0501 under fasted and fed conditions in random order. Blood sampling and safety assessments were conducted throughout the study. RESULTS XEN-D0501 was rapidly absorbed (tmax generally 0.5–4 h post dose). XEN-D0501 exposure increased less than proportionally to dose over the range studied and exhibited minimal accumulation with twice daily dosing. Food had no clinically relevant effects on the pharmacokinetics of XEN-D0501. There were no severe or serious adverse events and all doses were well tolerated. A dose-related increase in body temperature was seen with XEN-D0501 which attenuated over time. Differences from placebo in mean maximum core body temperatures were 0.22°C, 0.5°C and 0.74°C following 1 mg, 2.5 mg and 5 mg twice daily XEN-D0501. The observed increase in body temperature was not considered to be of clinical concern. CONCLUSIONS XEN-D0501 appeared safe and well tolerated at doses up to 5 mg twice daily for 14 days in healthy subjects. PMID:21676011

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

    Science.gov (United States)

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

    2015-11-01

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

  16. Microbiological quality and safety of raw milk and soft cheese and detection of autochthonous lactic acid bacteria with antagonistic activity against Listeria monocytogenes, Salmonella Spp., and Staphylococcus aureus.

    Science.gov (United States)

    Ortolani, Maria Beatriz Tassinari; Yamazi, Anderson Keizo; Moraes, Paula Mendonça; Viçosa, Gabriela Nogueira; Nero, Luís Augusto

    2010-02-01

    This study aimed to characterize the microbiological quality and safety of raw milk and soft cheese, verifying possible associations between microbial populations, and the detection of lactic acid bacteria (LAB) with antagonistic activity against foodborne pathogens. Raw milk (n = 36) and soft cheese (n = 18) samples were collected and submitted for the analysis of mesophilic aerobes, total coliforms, Escherichia coli, LAB, coagulase-positive Staphylococcus (CPS), Listeria monocytogenes, and Salmonella spp. In all, 389 LAB isolates were randomly selected and submitted for antagonistic tests against L. monocytogenes, St. aureus, Salmonella Typhimurium, and Lactobacillus sakei. The samples presented high counts of mesophilic aerobes, total coliforms, and LAB, and also high and significant correlation indices between these populations. Low levels of CPS and E. coli were observed, as well as an absence of Salmonella spp. and L. monocytogenes. A substantial portion of the analyzed samples presented LAB cultures with antagonistic activity, but not against Salmonella Typhimurium. The obtained results indicate the antimicrobial potential of the autochthonous microbiota of raw milk and soft cheese. Despite the spoilage potential, the LAB present in the studied food products can be isolated and properly characterized as antagonistic cultures, to be used in bioconservation studies for pathogen control in foods.

  17. 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)

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

    2016-01-01

    Abstract 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 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

  18. 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 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.

  19. 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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  1. A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults.

    Directory of Open Access Journals (Sweden)

    Pablo Tebas

    Full Text Available BACKGROUND: Neurokinin-1 receptor (NK1R antagonists have anti-HIV activity in monocyte-derived macrophages, decrease CCR5 expression and improve natural killer cell function ex vivo. Aprepitant is a NK1R antagonist approved by FDA as an antiemetic. METHODS: We conducted a phase IB randomized, placebo controlled, double masked study to evaluate the safety, antiviral activity, pharmacokinetics and immune-modulatory effects of aprepitant in HIV-infected adults not receiving antiretroviral therapy, with CD4+ cell count ≥350 cells/mm(3 and plasma viral load ≥2,000 copies/ml. Subjects were stratified by viral load (< vs. ≥20,000 copies/ml and randomized within each stratum to receive aprepitant at 125 mg QD(Low, or 250 mg QD(High, or placebo(PL for 14 days, and followed for 42 days. RESULTS: Thirty subjects were randomized and 27 completed treatment (9, 8, 10 subjects in 125 (Low, 250 (High, and PL groups. 63% were male; 37% white; mean (SD age 43 (9.3 years. Geometric mean baseline viral load (copies/ml for Low, High, and PL was 15,709, 33,013, and 19,450, respectively. Mean (95%CI change in log10 viral load at day 14 for Low, High, and PL was -0.02(-0.24,+0.20, -0.05(-0.21,+0.10, and +0.04(-0.08,+0.16, respectively. The number of subjects with AEs was 4(44.4%, 5(62.5%, and 1(10% for Low, High, and PL. No Grade 4 AEs occurred. CONCLUSIONS: Adverse events of aprepitant were more common in the treated groups. At the dose used in this two-week phase IB study, aprepitant showed biological activity, but no significant antiviral activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00428519.

  2. 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

  3. 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 chroma...

  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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  5. 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...

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

    NARCIS (Netherlands)

    Akkerhuis, KM; van den Brand, MJBM; van der Zwaan, C; Suryapranata, H; van der Wieken, LR; Stibbe, J; Hoffmann, J; Baardman, T; Deckers, JW

    2001-01-01

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

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  8. Safety

    CERN Multimedia

    2003-01-01

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

  9. The association of bacterial C9-based TTX-like compounds with Prorocentrum minimum opens new uncertainties about shellfish seafood safety

    Science.gov (United States)

    Rodríguez, Inés; Alfonso, Amparo; Alonso, Eva; Rubiolo, Juan A.; Roel, María; Vlamis, Aristidis; Katikou, Panagiota; Jackson, Stephen A.; Menon, Margassery Lekha; Dobson, Alan; Botana, Luis M.

    2017-01-01

    In 2012, Tetrodotoxin (TTX) was identified in mussels and linked to the presence of Prorocentrum minimum (P. minimum) in Greece. The connexion between TTX and P. minimum was further studied in this paper. First, the presence of TTX-producer bacteria, Vibrio and Pseudomonas spp, was confirmed in Greek mussels. In addition these samples showed high activity as inhibitors of sodium currents (INa). P. minimum was before associated with neurotoxic symptoms, however, the nature and structure of toxins produced by this dinoflagellate remains unknown. Three P. minimum strains, ccmp1529, ccmp2811 and ccmp2956, growing in different conditions of temperature, salinity and light were used to study the production of toxic compounds. Electrophysiological assays showed no effect of ccmp2811 strain on INa, while ccmp1529 and ccmp2956 strains were able to significantly reduce INa in the same way as TTX. In these samples two new compounds, m/z 265 and m/z 308, were identified and characterized by liquid chromatography tandem high-resolution mass spectrometry. Besides, two TTX-related bacteria, Roseobacter and Vibrio sp, were observed. These results show for the first time that P. minimum produce TTX-like compounds with a similar ion pattern and C9-base to TTX analogues and with the same effect on INa. PMID:28106083

  10. 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...

  11. 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...

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

    Science.gov (United States)

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

    2014-05-01

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

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

    Institute of Scientific and Technical Information of China (English)

    戴士鹏(综述); 徐泽升(审校)

    2015-01-01

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

  14. 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.

  15. Perampanel: A Selective AMPA Antagonist for Treating Seizures

    OpenAIRE

    Krauss, Gregory L.

    2013-01-01

    Perampanel is a selective, noncompetitive AMPA receptor antagonist that has recently been approved for treating localization-related epilepsy. This article reviews the pharmacology, clinical development, efficacy, and safety/tolerability of perampanel.

  16. Opioid Antagonist Impedes Exposure.

    Science.gov (United States)

    Merluzzi, Thomas V.; And Others

    1991-01-01

    Thirty spider-phobic adults underwent exposure to 17 phobic-related, graded performance tests. Fifteen subjects were assigned to naltrexone, an opioid antagonist, and 15 were assigned to placebo. Naltrexone had a significant effect on exposure, with naltrexone subjects taking significantly longer to complete first 10 steps of exposure and with…

  17. Minimum Length - Maximum Velocity

    CERN Document Server

    Panes, Boris

    2011-01-01

    We study a framework where the hypothesis of a minimum length in space-time is complemented with the notion of reference frame invariance. It turns out natural to interpret the action of the obtained reference frame transformations in the context of doubly special relativity. As a consequence of this formalism we find interesting connections between the minimum length properties and the modified velocity-energy relation for ultra-relativistic particles. For example we can predict the ratio between the minimum lengths in space and time using the results from OPERA about superluminal neutrinos.

  18. Tetrahydroindolizinone NK1 antagonists.

    Science.gov (United States)

    Bao, Jianming; Lu, Huagang; Morriello, Gregori J; Carlson, Emma J; Wheeldon, Alan; Chicchi, Gary G; Kurtz, Marc M; Tsao, Kwei-Lan C; Zheng, Song; Tong, Xinchun; Mills, Sander G; DeVita, Robert J

    2010-04-01

    A new class of potent NK(1) receptor antagonists with a tetrahydroindolizinone core has been identified. This series of compounds demonstrated improved functional activities as compared to previously identified 5,5-fused pyrrolidine lead structures. SAR at the 7-position of the tetrahydroindolizinone core is discussed in detail. A number of compounds displayed high NK(1) receptor occupancy at both 1 h and 24 h in a gerbil foot tapping model. Compound 40 has high NK(1) binding affinity, good selectivity for other NK receptors and promising in vivo properties. It also has clean P(450) inhibition and hPXR induction profiles.

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

    Science.gov (United States)

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

    2014-02-14

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

  20. Minimum Entropy Orientations

    CERN Document Server

    Cardinal, Jean; Joret, Gwenaël

    2008-01-01

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

  1. 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.

  2. Minimum quality standards and exports

    OpenAIRE

    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 ex ante 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 quali...

  3. 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

  4. Minimum Error Entropy Classification

    CERN Document Server

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

    2013-01-01

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

  5. Do Minimum Wages Fight Poverty?

    OpenAIRE

    David Neumark; William Wascher

    1997-01-01

    The primary goal of a national minimum wage floor is to raise the incomes of poor or near-poor families with members in the work force. However, estimates of employment effects of minimum wages tell us little about whether minimum wages are can achieve this goal; even if the disemployment effects of minimum wages are modest, minimum wage increases could result in net income losses for poor families. We present evidence on the effects of minimum wages on family incomes from matched March CPS s...

  6. Minimum fuel mode evaluation

    Science.gov (United States)

    Orme, John S.; Nobbs, Steven G.

    1995-01-01

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

  7. Biological Safety Detection of Antagonistic Bacteria Bacillus Amyloliquefaciens KL-1%生防菌解淀粉芽孢杆菌KL-1的生物安全性检测

    Institute of Scientific and Technical Information of China (English)

    吴雨龙; 贲爱玲; 江海涛; 杨齐; 高晨阳

    2016-01-01

    To detect the biological safety of Bacillus amyloliquefaciens KL-1 , acute oral toxicity-fixed dose proce-dure, chromosomal aberration, bone marrow cell micronucleus and phagocytic function of macrophage tests were carried out in mice. The results showed that there were no significant signs of toxicity and mortality in acute toxicity study in 14 days, and the oral lethal dose of Bacillus amyloliquefaciens KL-1 was more than 2000 mg/kg. The re-sults of chromosomal aberration test, bone marrow cell micronucleus test and macrophage phagocytic function test were all negative. Therefore, it is concluded that Bacillus amyloliquefaciens KL-1 has no toxic and side effects on mammals, and this provides the evidence for the safe use of this strain as a biological pesticide.%为了检测解淀粉芽孢杆菌KL-1菌株的生物安全性,以小鼠为对象,经口急性毒性试验固定剂量法、染色体畸变分析法、骨髓细胞微核分析法和巨噬细胞吞噬功能分析法评价解淀粉芽孢杆菌KL-1对哺乳动物的安全性.结果表明,14 d的观察中,急性毒性试验中各组小鼠未出现明显中毒症状和死亡情况,且解淀粉芽孢杆菌KL-1对小鼠的半数致死量( LD50)超过2000 mg/kg.染色体畸变分析、骨髓细胞微核分析和巨噬细胞吞噬功能分析结果均为阴性.由此可推断解淀粉芽孢杆菌KL-1菌株对哺乳动物安全无毒副作用,为该菌株作为生物农药的安全使用提供依据.

  8. Popularity at Minimum Cost

    CERN Document Server

    Kavitha, Telikepalli; Nimbhorkar, Prajakta

    2010-01-01

    We consider an extension of the {\\em popular matching} problem in this paper. The input to the popular matching problem is a bipartite graph G = (A U B,E), where A is a set of people, B is a set of items, and each person a belonging to A ranks a subset of items in an order of preference, with ties allowed. The popular matching problem seeks to compute a matching M* between people and items such that there is no matching M where more people are happier with M than with M*. Such a matching M* is called a popular matching. However, there are simple instances where no popular matching exists. Here we consider the following natural extension to the above problem: associated with each item b belonging to B is a non-negative price cost(b), that is, for any item b, new copies of b can be added to the input graph by paying an amount of cost(b) per copy. When G does not admit a popular matching, the problem is to "augment" G at minimum cost such that the new graph admits a popular matching. We show that this problem is...

  9. Social Security's special minimum benefit.

    Science.gov (United States)

    Olsen, K A; Hoffmeyer, D

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

  10. Synthesis of potential mescaline antagonists.

    Science.gov (United States)

    DeSantis, F; Nieforth, K A

    1976-10-01

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

  11. Excitatory amino acid receptor antagonists

    DEFF Research Database (Denmark)

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

    1997-01-01

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

  12. DEVELOPMENT OF NEW LHRH ANTAGONISTS

    Institute of Scientific and Technical Information of China (English)

    PENGDun-Ren; XIAOShao-Bo

    1989-01-01

    An ideal antagonist of LHRH is one which can act on the pitutary to inhibit LHRH-stimulatod LH / FSH secretion by competitive occupying the LHRH receptor in the pitutary gland. Its action should be very specific, fast and highly effective, the durations

  13. 75 FR 6151 - Minimum Capital

    Science.gov (United States)

    2010-02-08

    ... sound operations.\\4\\ Also, section 1362(e) provides for additional capital and reserve requirements to... provide additional authorities for FHFA regarding minimum capital requirements. Section 1362(a... section.\\6\\ \\3\\ The Bank Act's current minimum capital requirements apply to the eleven banks that...

  14. Minimum signals in classical physics

    Institute of Scientific and Technical Information of China (English)

    邓文基; 许基桓; 刘平

    2003-01-01

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

  15. Glutamate antagonists limit tumor growth

    OpenAIRE

    2001-01-01

    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...

  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. Newer calcium channel antagonists and the treatment of hypertension.

    Science.gov (United States)

    Cummins, D F

    1999-07-01

    Calcium channel antagonists have become popular medications for the management of hypertension. These agents belong to the diphenylalkylamine, benzothiazepine, dihydropyridine, or tetralol chemical classes. Although the medications share a common pharmacological mechanism in reducing peripheral vascular resistance, clinical differences between the sub-classes can be linked to structural profiles. This heterogeneity is manifested by differences in vascular selectivity, effects on cardiac conduction and adverse events. The lack of differentiation between calcium channel antagonists in clinical trials has contributed to uncertainty associated with their impact on morbidity and mortality. Data from more recent studies in specific patient populations underscores the importance of investigating these antihypertensives as individual agents. A proposed therapeutic classification system suggests that newer agents should share the slow onset and long-acting antihypertensive effect of amlodipine. Additionally, a favourable trough-to-peak ratio has been recommended as an objective measurement of efficacy. The newer drugs, barnidipine and lacidipine, have a therapeutic profile similar to amlodipine, but trough-to-peak ratios are not substantially greater than the recommended minimum of 0.50. Aranidipine, cilnidipine and efonidipine have unique pharmacological properties that distinguish them from traditional dihydropyridines. Although clinical significance is unconfirmed, these newer options may be beneficial for patients with co-morbid conditions that preclude use of older antagonists.

  18. Minimum length-maximum velocity

    Science.gov (United States)

    Panes, Boris

    2012-03-01

    We study a framework where the hypothesis of a minimum length in space-time is complemented with the notion of reference frame invariance. It turns out natural to interpret the action of the obtained reference frame transformations in the context of doubly special relativity. As a consequence of this formalism we find interesting connections between the minimum length properties and the modified velocity-energy relation for ultra-relativistic particles. For example, we can predict the ratio between the minimum lengths in space and time using the results from OPERA on superluminal neutrinos.

  19. Against a Minimum Voting Age

    OpenAIRE

    Cook, Philip

    2013-01-01

    A minimum voting age is defended as the most effective and least disrespectful means of ensuring all members of an electorate are sufficiently competent to vote. Whilst it may be reasonable to require competency from voters, a minimum voting age should be rejected because its view of competence is unreasonably controversial, it is incapable of defining a clear threshold of sufficiency and an alternative test is available which treats children more respectfully. This alternative is a procedura...

  20. Muscarinic Receptor Agonists and Antagonists

    Directory of Open Access Journals (Sweden)

    David R. Kelly

    2001-02-01

    Full Text Available A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes. Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

  1. A short-term safety study of tumor necrosis factor antagonists in rheumatic diseases%肿瘤坏死因子拮抗剂治疗风湿性疾病安全性的短期临床观察

    Institute of Scientific and Technical Information of China (English)

    马丹; 张莉芸; 李小峰; 茹晋丽; 陈俊伟; 王彩虹; 张改连; 魏华

    2009-01-01

    目的 描述肿瘤坏死因子(TNF)-α拮抗剂治疗风湿性疾病发生的不良反应,评价临床应用的安全性和耐受性.方法 对2007年1月至2008年10月使用TNF-α拮抗剂的患者从临床症状、体征及实验室检查方面记录使用过程中发生的不良反应及程度和最终结局.结果 78例患者中35%(27/78)为类风湿关节炎(RA),41%(32/78)为强直性脊柱炎(AS),17%(13/78)为银屑病关节炎(PsA),6%(5/78)为未分化脊柱关节病(uSpA).59例患者使用依那西普,7例(12%)发生注射局部反应、上呼吸道感染及结核病等不良反应.19例患者使用英夫利西单抗,3例(16%)发生不良反应,1例(AS)为上呼吸道感染,1例(AS)前两次均在输注完24 h内出现伞身红色丘疹及心悸,1例(RA)输注4次后出现不明原因发热.部分不良反应可自行消失,其余经适当处理后痊愈.结论 证实依那西普和英夫利西单抗治疗风湿性疾病具有较好的安全性和耐受性,发生的不良反应是温和的,经适当处理可痊愈.%Objective To evaluate the safety and tolerance of tumor necrosis factor-or (TNF-α)antagonists in the treatment of rheumatic diseases. Methods The incidence of adverse events and their ultimate outcomes based on the clinical symptoms, signs and laboratory parameters of patients treated with etanereept or infliximab during January 2007 to October 2008 were analyzed. Results Severty eight patients were included. Most were rheumatoid arthritis (35%) and ankylosing spondylitis (41%) patients. Few of them were psoriasis arthritis (17%) patients and undifferentiated spondyloarthropathy (6%) patients. Among those patients, 59 patients were treated with etanercept, 7 patients (12%) had adverse events in which the majority were injection reactions, upper respiratory tract infection and tuberculosis. Nineteen patients were treated with infliximab, in which 3 patients (16%) had adverse events. One patient (AS) had upper respiratory tract infection. One

  2. 30 CFR 75.1107-10 - High expansion foam devices; minimum capacity.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false High expansion foam devices; minimum capacity. 75.1107-10 Section 75.1107-10 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF... foam devices; minimum capacity. (a) On unattended underground equipment the amount of water...

  3. 30 CFR 75.1107-7 - Water spray devices; capacity; water supply; minimum requirements.

    Science.gov (United States)

    2010-07-01

    ... Water spray devices; capacity; water supply; minimum requirements. (a) Where water spray devices are... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Water spray devices; capacity; water supply; minimum requirements. 75.1107-7 Section 75.1107-7 Mineral Resources MINE SAFETY AND HEALTH...

  4. Minimum Q Electrically Small Antennas

    DEFF Research Database (Denmark)

    Kim, O. S.

    2012-01-01

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

  5. Safety in paediatric imaging

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-01-01

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

  6. New antagonist agents of neuropeptide y receptors

    Directory of Open Access Journals (Sweden)

    Ignacio Aldana

    2000-12-01

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

  7. Minimum aanlandingsmaat Brasem (Abramis brama)

    NARCIS (Netherlands)

    Hal, van R.; Miller, D.C.M.

    2016-01-01

    Ter ondersteuning van een besluit aangaande een minimum aanlandingsmaat voor brasem, primair voor het IJsselmeer en Markermeer, heeft het ministerie van Economische Zaken IMARES verzocht een overzicht te geven van aanlandingsmaten voor brasem in andere landen en waar mogelijk de motivatie achter dez

  8. Minimum Thermal Conductivity of Superlattices

    Energy Technology Data Exchange (ETDEWEB)

    Simkin, M. V.; Mahan, G. D.

    2000-01-31

    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.

  9. 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...

  10. 75 FR 38423 - Minimum Levels of Financial Responsibility for Motor Carriers

    Science.gov (United States)

    2010-07-02

    ... Federal Motor Carrier Safety Administration 49 CFR Part 387 RIN 2126-AB05 Minimum Levels of Financial Responsibility for Motor Carriers AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Final... for motor carriers to allow Canada-domiciled motor carriers and freight forwarders to maintain,...

  11. 78 FR 57585 - Minimum Training Requirements for Entry-Level Commercial Motor Vehicle Operators

    Science.gov (United States)

    2013-09-19

    ... Federal Motor Carrier Safety Administration 49 CFR Parts 380, 383, and 384 RIN 2126-AB06 Minimum Training Requirements for Entry-Level Commercial Motor Vehicle Operators AGENCY: Federal Motor Carrier Safety... applying for a commercial driver's license (CDL) to operate commercial motor vehicles (CMVs) in...

  12. Role Of Biopreservation In Improving Food Safety And Storage

    OpenAIRE

    Swarnadyuti Nath; Chowdhury, S.

    2014-01-01

    Biopreservation refers to the use of antagonistic microorganisms or their metabolic products to inhibit or destroy undesired microorganisms in foods to enhance food safety and extend shelf life. In order to achieve improved food safety and to harmonize consumer demands with the necessary safety standards, traditional means of controlling microbial spoilage and safety hazards in foods are being replaced by combinations of innovative technologies that include biological antimicrobial systems su...

  13. Safety culture

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-07-01

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

  14. Quantum mechanics the theoretical minimum

    CERN Document Server

    Susskind, Leonard

    2014-01-01

    From the bestselling author of The Theoretical Minimum, an accessible introduction to the math and science of quantum mechanicsQuantum Mechanics is a (second) book for anyone who wants to learn how to think like a physicist. In this follow-up to the bestselling The Theoretical Minimum, physicist Leonard Susskind and data engineer Art Friedman offer a first course in the theory and associated mathematics of the strange world of quantum mechanics. Quantum Mechanics presents Susskind and Friedman’s crystal-clear explanations of the principles of quantum states, uncertainty and time dependence, entanglement, and particle and wave states, among other topics. An accessible but rigorous introduction to a famously difficult topic, Quantum Mechanics provides a tool kit for amateur scientists to learn physics at their own pace.

  15. Minimum thickness anterior porcelain restorations.

    Science.gov (United States)

    Radz, Gary M

    2011-04-01

    Porcelain laminate veneers (PLVs) provide the dentist and the patient with an opportunity to enhance the patient's smile in a minimally to virtually noninvasive manner. Today's PLV demonstrates excellent clinical performance and as materials and techniques have evolved, the PLV has become one of the most predictable, most esthetic, and least invasive modalities of treatment. This article explores the latest porcelain materials and their use in minimum thickness restoration.

  16. Fingerprinting with Minimum Distance Decoding

    CERN Document Server

    Lin, Shih-Chun; Gamal, Hesham El

    2007-01-01

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

  17. 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...

  18. 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&...

  19. Antagonists of the kappa opioid receptor.

    Science.gov (United States)

    Urbano, Mariangela; Guerrero, Miguel; Rosen, Hugh; Roberts, Edward

    2014-05-01

    The research community has increasingly focused on the development of OPRK antagonists as pharmacotherapies for the treatment of depression, anxiety, addictive disorders and other psychiatric conditions produced or exacerbated by stress. Short-acting OPRK antagonists have been recently developed as a potential improvement over long-acting prototypic ligands including nor-BNI and JDTic. Remarkably the short-acting LY2456302 is undergoing phase II clinical trials for the augmentation of the antidepressant therapy in treatment-resistant depression. This Letter reviews relevant chemical and pharmacological advances in the identification and development of OPRK antagonists.

  20. 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.

  1. Vehicle Optimal Velocity Curves for Minimum-Time Maneuver

    Directory of Open Access Journals (Sweden)

    Li-xia Zhang

    2014-02-01

    Full Text Available 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 time and the optimal control model were established. The optimal velocity curves for three types of paths, namely, monotonically increasing path, monotonically decreasing path, and constant radius path, were analyzed. On this basis, the optimal velocity curves were solved for two kinds of concrete paths: a path of decreasing curvature radius followed by a path of increasing curvature radius and another path of increasing curvature radius followed by a path of decreasing curvature radius. Nine cases of possible optimal velocity curves were acquired. The optimal velocity curve of the given path, that is, a parabola followed by a semicircle, was obtained. Optimal velocity curves can be used as reference for vehicle minimum-time maneuver, which is an important issue for driver safety in fast-moving vehicles.

  2. Outer Space Traffic Safety Standards

    Science.gov (United States)

    Larsen, Paul B.

    2013-09-01

    Management of traffic in outer space is a major safety problem. Traffic is increasing. Most satellites are navigable but they have to co-exist with space debris which is not navigable. We need minimum safety rules for outer space traffic. We have the possible beginnings of international safety standards in the form of national space object tracking; Global Navigation Satellite Systems (GNSS) standardization through ICAO and the International Committee on GNSS (ICG); the IADC space debris guidelines; and the proposed Code of Conduct. However, safety could be improved by standards for such activities as licensing launches of satellites into outer space; standards for accident investigation and search and rescue: operational safety zones around space objects such as the International Space Station. This paper describes legal authority for minimum safety standards. It considers safety standards established by private agreements among commercial operators. Finally it examines a number of options for an international forum to establish safety standards, including self-regulation, COPUOS, ICAO, ITU, a space code of conduct, and a new space organization.

  3. 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....

  4. Ceramic veneers with minimum preparation.

    Science.gov (United States)

    da Cunha, Leonardo Fernandes; Reis, Rachelle; Santana, Lino; Romanini, Jose Carlos; Carvalho, Ricardo Marins; Furuse, Adilson Yoshio

    2013-10-01

    The aim of this article is to describe the possibility of improving dental esthetics with low-thickness glass ceramics without major tooth preparation for patients with small to moderate anterior dental wear and little discoloration. For this purpose, a carefully defined treatment planning and a good communication between the clinician and the dental technician helped to maximize enamel preservation, and offered a good treatment option. Moreover, besides restoring esthetics, the restorative treatment also improved the function of the anterior guidance. It can be concluded that the conservative use of minimum thickness ceramic laminate veneers may provide satisfactory esthetic outcomes while preserving the dental structure.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  6. Asymmetric k-Center with Minimum Coverage

    DEFF Research Database (Denmark)

    Gørtz, Inge Li

    2008-01-01

    In this paper we give approximation algorithms and inapproximability results for various asymmetric k-center with minimum coverage problems. In the k-center with minimum coverage problem, each center is required to serve a minimum number of clients. These problems have been studied by Lim et al. [A....... Lim, B. Rodrigues, F. Wang, Z. Xu, k-center problems with minimum coverage, Theoret. Comput. Sci. 332 (1–3) (2005) 1–17] in the symmetric setting....

  7. Minimum Competency Testing and the Handicapped.

    Science.gov (United States)

    Wildemuth, Barbara M.

    This brief overview of minimum competency testing and disabled high school students discusses: the inclusion or exclusion of handicapped students in minimum competency testing programs; approaches to accommodating the individual needs of handicapped students; and legal issues. Surveys of states that have mandated minimum competency tests indicate…

  8. Minimum income protection in the Netherlands

    NARCIS (Netherlands)

    van Peijpe, T.

    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

  9. Safety Plan

    Data.gov (United States)

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

  10. Water Safety

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Water Safety KidsHealth > For Parents > Water Safety Print A ... best measure of protection. previous continue Making Kids Water Wise It's important to teach your kids proper ...

  11. 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.

  12. Hand Safety

    Science.gov (United States)

    ... Gardening Safety Turkey Carving Removing a Ring Español Artritis de la base del pulgar Dedo en gatillo ... Gardening Safety Turkey Carving Removing a Ring Español Artritis de la base del pulgar Dedo en gatillo ...

  13. 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. ...

  14. 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.

  15. 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

  16. 75 FR 9018 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2010-02-26

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

  17. 46 CFR 62.25-15 - Safety control systems.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Safety control systems. 62.25-15 Section 62.25-15... AUTOMATION General Requirements for All Automated Vital Systems § 62.25-15 Safety control systems. (a) Minimum safety trip controls required for specific types of automated vital systems are listed in Table...

  18. GnRH agonist for final oocyte maturation in GnRH antagonist co-treated IVF/ICSI treatment cycles: Systematic review and meta-analysis

    OpenAIRE

    Youssef, M.A.F.; Abdelmoty, Hatem I; Ahmed, Mohamed A.S.; Maged Elmohamady

    2015-01-01

    Final oocyte maturation in GnRH antagonist co-treated IVF/ICSI cycles can be triggered with HCG or a GnRH agonist. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of the final oocyte maturation trigger in GnRH antagonist co-treated cycles. Outcome measures were ongoing pregnancy rate (OPR) and ovarian hyperstimulation syndrome (OHSS) incidence. Searches: were conducted in MEDLINE, EMBASE, Science Direct, Cochrane Library, ...

  19. Linear Minimum variance estimation fusion

    Institute of Scientific and Technical Information of China (English)

    ZHU Yunmin; LI Xianrong; ZHAO Juan

    2004-01-01

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

  20. Dose variation during solar minimum

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-12-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  2. 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

  3. Why are mineralocorticoid receptor antagonists cardioprotective?

    NARCIS (Netherlands)

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

    2006-01-01

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

  4. 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.

  5. Minimum wages, globalization and poverty in Honduras

    OpenAIRE

    Gindling, T. H.; Terrell, Katherine

    2008-01-01

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

  6. 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.)

  7. 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...

  8. Effect of Pressure on Minimum Fluidization Velocity

    Institute of Scientific and Technical Information of China (English)

    Zhu Zhiping; Na Yongjie; Lu Qinggang

    2007-01-01

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

  9. Medication safety.

    Science.gov (United States)

    Keohane, Carol A; Bates, David W

    2008-03-01

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

  10. 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

  11. SB-258741: a 5-HT7 receptor antagonist of potential clinical interest.

    Science.gov (United States)

    Pouzet, Bruno

    2002-01-01

    Recently, a series of 5-HT7 receptor antagonists have been developed (24,29,36,68). Among them SB-258741, R-(+)-1-(toluene-3-sulfonyl)-2-[2-(4-methylpiperidin-1-yl)ethyl]-pyrrolidine, (compound "13" in 36,37) was one of the most potent and specific compounds. Due to a lack of specific ligands the pharmacology of 5-HT7 receptor antagonists is still relatively unexplored. It has been suggested, however, that 5-HT7 receptor ligands could be useful in the therapy of various disorders such as sleep disorders, schizophrenia, depression, migraine, epilepsy, pain, or memory impairment. Many of these conceivable indications are not supported by pharmacological data. It is, therefore, of particular interest to review the data generated from studies of one of these most potent and specific 5-HT7 receptor antagonists, SB-258741, with a goal of testing the validity of the proposed clinical indications. In this review, the author describes pharmacology of this compound in order to define its potential clinical use. The available safety pharmacology data are discussed in an attempt to predict potential side effects of specific 5-HT7 receptor antagonists.

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

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

    Science.gov (United States)

    Bendtzen, Klaus

    2013-04-01

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

  14. Mineralocorticoid and glucocorticoid receptor antagonists in animal models of anxiety

    NARCIS (Netherlands)

    Korte, SM; KorteBouws, GAH; Koob, GF; DeKloet, ER; Bohus, B

    1996-01-01

    The behavioral effects of intracerebroventricular (ICV) administration of a specific mineralocorticoid receptor (MR) antagonist [RU28318 (10-50 ng/2 mu l)], a glucocorticoid receptor (GR) antagonist [RU38486 (1-50 ng/2 mu l)], or both antagonists (50 ng/2 mu l), were studied in two different animal

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

    Science.gov (United States)

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

    1999-02-22

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

  16. Novel benzimidazole-based MCH R1 antagonists.

    Science.gov (United States)

    Carpenter, Andrew J; Al-Barazanji, Kamal A; Barvian, Kevin K; Bishop, Michael J; Britt, Christy S; Cooper, Joel P; Goetz, Aaron S; Grizzle, Mary K; Hertzog, Donald L; Ignar, Diane M; Morgan, Ronda O; Peckham, Gregory E; Speake, Jason D; Swain, Will R

    2006-10-01

    The identification of an MCH R1 antagonist screening hit led to the optimization of a class of benzimidazole-based MCH R1 antagonists. Structure-activity relationships and efforts to optimize pharmacokinetic properties are detailed along with the demonstration of the effectiveness of an MCH R1 antagonist in an animal model of obesity.

  17. Safety Instructions

    CERN Multimedia

    2003-01-01

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

  18. Safety Systems

    Science.gov (United States)

    Halligan, Tom

    2009-01-01

    Colleges across the country are rising to the task by implementing safety programs, response strategies, and technologies intended to create a secure environment for teachers and students. Whether it is preparing and responding to a natural disaster, health emergency, or act of violence, more schools are making campus safety a top priority. At…

  19. Laser safety in the lab

    CERN Document Server

    Barat, Ken L

    2012-01-01

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

  20. 78 FR 11793 - Minimum Internal Control Standards

    Science.gov (United States)

    2013-02-20

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

  1. 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)

  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. 30 CFR 77.807-3 - Movement of equipment; minimum distance from high-voltage lines.

    Science.gov (United States)

    2010-07-01

    ... high-voltage lines. 77.807-3 Section 77.807-3 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.807-3 Movement of equipment; minimum distance from high-voltage lines. When any part of any equipment operated on the surface of...

  4. 30 CFR 77.807-2 - Booms and masts; minimum distance from high-voltage lines.

    Science.gov (United States)

    2010-07-01

    ...-voltage lines. 77.807-2 Section 77.807-2 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... WORK AREAS OF UNDERGROUND COAL MINES Surface High-Voltage Distribution § 77.807-2 Booms and masts; minimum distance from high-voltage lines. The booms and masts of equipment operated on the surface of...

  5. [Cutaneous adverse effects of TNFalpha antagonists].

    Science.gov (United States)

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

    2012-01-01

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

  6. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    OpenAIRE

    Kleynhans, Janke

    2013-01-01

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

  7. The Justification of Antagonistic Response to Wrongdoing

    OpenAIRE

    Goldman, David Michael

    2012-01-01

    There is a strong Western tradition of opposing angry, hostile, or antagonistic reactions to wrongdoing. In the twentieth century, leaders like Mahatma Gandhi and Dr. Martin Luther King, Jr. counseled responding to wrongdoing with forgiveness and love rather than anger, hate, or vindictiveness.This ideal has taken on an exalted status in Western culture. Gandhi and King are widely regarded as moral saints. And yet sometimes antagonism seems deeply appropriate. Consider a very serious wrong: s...

  8. 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.

  9. The minimum work requirement for distillation processes

    Energy Technology Data Exchange (ETDEWEB)

    Yunus, Cerci; Yunus, A. Cengel; Byard, Wood [Nevada Univ., Las Vegas, NV (United States). Dept. of Mechanical Engineering

    2000-07-01

    A typical ideal distillation process is proposed and analyzed using the first and second-laws of thermodynamics with particular attention to the minimum work requirement for individual processes. The distillation process consists of an evaporator, a condenser, a heat exchanger, and a number of heaters and coolers. Several Carnot engines are also employed to perform heat interactions of the distillation process with the surroundings and determine the minimum work requirement for processes. The Carnot engines give the maximum possible work output or the minimum work input associated with the processes, and therefore the net result of these inputs and outputs leads to the minimum work requirement for the entire distillation process. It is shown that the minimum work relation for the distillation process is the same as the minimum work input relation found by Cerci et al [1] for an incomplete separation of incoming saline water, and depends only on the properties of the incoming saline water and the outgoing pure water and brine. Also, certain aspects of the minimum work relation found are discussed briefly. (authors)

  10. EXPERIMENTAL STUDY OF MINIMUM IGNITION TEMPERATURE

    Directory of Open Access Journals (Sweden)

    Igor WACHTER

    2015-12-01

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

  11. 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.

  12. 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.

  13. Minimum emittance in TBA and MBA lattices

    Science.gov (United States)

    Xu, Gang; Peng, Yue-Mei

    2015-03-01

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

  14. Vaccine Safety

    Science.gov (United States)

    ... Tweet Share Compartir Back to School: Vaccines for Preteens Learn about the safety of Tdap, Meningococcal, and ... file Microsoft Word file Microsoft Excel file Audio/Video file Apple Quicktime file RealPlayer file Text file ...

  15. 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 ...

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

    Directory of Open Access Journals (Sweden)

    Eneas eAguirre-Von-Wobeser

    2015-05-01

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

  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.

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

    Institute of Scientific and Technical Information of China (English)

    张建梅; 陈永红; 王晓红; 唐朝枢

    2001-01-01

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

  19. Oxygen minimum seafloor ecological (mal) functioning

    Digital Repository Service at National Institute of Oceanography (India)

    Moodley, L.; Nigam, R.; Ingole, B.S.; PrakashBabu, C.; Panchang, R.; Nanajkar, M.; Sivadas, S.; van Breugel, P.; van Ijzerloo, L.; Rutgers, R.; Heip, C.H.R.; Soetaert, K.; Middelburg, J.J.

    under certain oceanic settings such as the oxygen minimum zones (OMZ) where OM accumulates in underlying sediments. A basic question that remains is as to what extent this Corg accumulation reflects ecological ‘malfunctioning’ or a shunting of ecological...

  20. 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...

  1. Graph theory for FPGA minimum configurations

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  2. 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...

  3. 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.

  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. 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

  6. 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 local temporal pattern of GABA impact, enabling phasic or tonic inhibition. Specific GABAAR antagonists are essential tools for physiological and pharmacological elucidation of the different type of GABAAR inhibition. However, distinct selectivity among the receptor subtypes (populations) has been shown...

  7. First Aid and Safety

    Science.gov (United States)

    ... Playground Safety Preventing Children's Sports Injuries Safety Tips: Baseball Safety Tips: Basketball Safety Tips: Hockey Safety Tips: ... it a Medical Emergency? Knowing Your Child's Medical History Nosebleeds Seizures Serious Allergic Reactions (Anaphylaxis) Teaching Your ...

  8. Effect of transient receptor potential vanilloid 1 (TRPV1) receptor antagonist compounds SB705498, BCTC and AMG9810 in rat models of thermal hyperalgesia measured with an increasing-temperature water bath.

    Science.gov (United States)

    Tékus, Valéria; Bölcskei, Kata; Kis-Varga, Agnes; Dézsi, László; Szentirmay, Eva; Visegrády, András; Horváth, Csilla; Szolcsányi, János; Petho, Gábor

    2010-09-01

    The transient receptor potential vanilloid 1 (TRPV1) receptor is activated by noxious heat, various endogenous mediators and exogenous irritants. The aim of the present study was to compare three TRPV1 receptor antagonists (SB705498, BCTC and AMG9810) in rat models of heat hyperalgesia. The behavioural noxious heat threshold, defined as the lowest temperature evoking nocifensive reaction, was measured with an increasing-temperature water bath. The effects of TRPV1 receptor antagonists were assessed in thermal hyperalgesia induced by the TRPV1 agonist resiniferatoxin (RTX), mild heat injury (51 degrees C, 20s) or plantar incision in rats. The control heat threshold was 43.2+/-0.4 degrees C. RTX induced an 8-10 degrees C decrease in heat threshold which was dose-dependently inhibited by oral pre-treatment with any of the TRPV1 receptor antagonists with a minimum effective dose of 1mg/kg. The mild heat injury-evoked 7-8 degrees C heat threshold drop was significantly reversed by all three antagonists injected i.p. as post-treatment. The minimum effective doses were as follows: SB705498 10, BCTC 3 and AMG9810 1mg/kg. Plantar incision-induced heat threshold drop (7-8 degrees C) was dose-dependently diminished by an oral post-treatment with any of the antagonists with minimum effective doses of 10, 3 and 3mg/kg, respectively. Assessment of RTX hyperalgesia by measurement of the paw withdrawal latency with a plantar test apparatus yielded 30 mg/kg minimum effective dose for each antagonist. In conclusion, measurement of the noxious heat threshold with the increasing-temperature water bath is suitable to sensitively detect the effects of TRPV1 receptor antagonists in thermal hyperalgesia models.

  9. Antioxidant effects of calcium antagonists in rat brain homogenates.

    Science.gov (United States)

    Yao, K; Ina, Y; Nagashima, K; Ohmori, K; Ohno, T

    2000-06-01

    We studied the antioxidant activities of calcium antagonists against autoxidation in rat brain homogenates. The homogenates were incubated for 30 min at 37 degrees C with or without a calcium antagonist and subsequently assayed for lipid peroxide content. Percent inhibition of the lipid peroxidation was used as an index of the antioxidant effect. Dihydropyridine calcium antagonists exhibited concentration-dependent (3-300 micromol/l) inhibitory effects against lipid peroxidation. The relative order of antioxidant potency and associated IC50 values (micromol/l) of the calcium antagonists for inhibition of the lipid peroxidation were as follows: nifedipine (51.5)>barnidipine (58.6)>benidipine (71.2)>nicardipine (129.3)>amlodipine (135.5)>nilvadipine (167.3)>nitrendipine (252.1)> diltiazem (>300)=verapamil (>300). These results suggest that some dihydropyridine calcium antagonists show antioxidant properties. The antioxidant effects of the calcium antagonists may contribute to their pharmacological actions.

  10. Sexually antagonistic selection in human male homosexuality.

    Directory of Open Access Journals (Sweden)

    Andrea Camperio Ciani

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

  11. Sexually antagonistic selection in human male homosexuality.

    Science.gov (United States)

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

    2008-06-18

    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.

  12. Activins and activin antagonists in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  13. ETA-receptor antagonists or allosteric modulators?

    DEFF Research Database (Denmark)

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

    2011-01-01

    The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects. In resista......The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects....... In resistance arteries, the long-lasting contractile effects can only be partly and reversibly relaxed by low-molecular-weight ET(A) antagonists (ERAs). However, the neuropeptide calcitonin-gene-related peptide selectively terminates binding of ET1 to ET(A). We propose that ET1 binds polyvalently to ET(A......) and that ERAs and the physiological antagonist allosterically reduce ET(A) functions. Combining the two-state model and the two-domain model of GPCR function and considering receptor activation beyond agonist binding might lead to better anti-endothelinergic drugs. Future studies could lead to compounds...

  14. Zebrafish phenotypic screen identifies novel Notch antagonists.

    Science.gov (United States)

    Velaithan, Vithya; Okuda, Kazuhide Shaun; Ng, Mei Fong; Samat, Norazwana; Leong, Sze Wei; Faudzi, Siti Munirah Mohd; Abas, Faridah; Shaari, Khozirah; Cheong, Sok Ching; Tan, Pei Jean; Patel, Vyomesh

    2017-04-01

    Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors. Subsequent secondary screens using HEK293T cells overexpressing truncated Notch1 (HEK293TΔE) identified 2 compounds, EDD3 and 3H4MB, to be potential Notch antagonists. Both compounds reduced protein expression of NOTCH1, Notch intracellular domain (NICD) and hairy and enhancer of split-1 (HES1) in HEK293TΔE and downregulated Notch target genes. Importantly, EDD3 treatment of human oral cancer cell lines demonstrated reduction of Notch target proteins and genes. EDD3 also inhibited proliferation and induced G0/G1 cell cycle arrest of ORL-150 cells through inducing p27(KIP1). Our data demonstrates the utility of the zebrafish phenotypic screen and identifying EDD3 as a promising Notch antagonist for further development as a novel therapeutic agent.

  15. Evaluation of H2 receptor antagonists in chronic idiopathic urticaria

    Directory of Open Access Journals (Sweden)

    Minocha Y

    1995-01-01

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

  16. Nowcasting daily minimum air and grass temperature

    Science.gov (United States)

    Savage, M. J.

    2016-02-01

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

  17. SAFETY BULLETIN

    CERN Multimedia

    TIS Secretariat

    2002-01-01

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

  18. Safety Resources.

    Science.gov (United States)

    Hoot, James L.; Bartkowiak, Elaine T.

    1994-01-01

    Lists 72 organizations and programs that deal with child safety, grouped by the following categories: (1) general; (2) general violence; (3) gun violence; (4) media violence; (5) drugs and alcohol; (6) child abuse and at-risk children; (7) parenting programs; (8) community service programs; (9) leadership programs; (10) peer counseling; (11)…

  19. A minimum achievable PV electrical generating cost

    Energy Technology Data Exchange (ETDEWEB)

    Sabisky, E.S. [11 Carnation Place, Lawrenceville, NJ 08648 (United States)

    1996-03-22

    The role and share of photovoltaic (PV) generated electricity in our nation`s future energy arsenal is primarily dependent on its future production cost. This paper provides a framework for obtaining a minimum achievable electrical generating cost (a lower bound) for fixed, flat-plate photovoltaic systems. A cost of 2.8 $cent/kWh (1990$) was derived for a plant located in Southwestern USA sunshine using a cost of money of 8%. In addition, a value of 22 $cent/Wp (1990$) was estimated as a minimum module manufacturing cost/price

  20. 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.

  1. Weight-Constrained Minimum Spanning Tree Problem

    OpenAIRE

    Henn, Sebastian Tobias

    2007-01-01

    In an undirected graph G we associate costs and weights to each edge. The weight-constrained minimum spanning tree problem is to find a spanning tree of total edge weight at most a given value W and minimum total costs under this restriction. In this thesis a literature overview on this NP-hard problem, theoretical properties concerning the convex hull and the Lagrangian relaxation are given. We present also some in- and exclusion-test for this problem. We apply a ranking algorithm and the me...

  2. 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.

  3. 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.

  4. Antagonists of IAP proteins as cancer therapeutics.

    Science.gov (United States)

    Dynek, Jasmin N; Vucic, Domagoj

    2013-05-28

    Inhibitor of apoptosis (IAP) proteins play pivotal roles in cellular survival by blocking apoptosis, modulating signal transduction, and affecting cellular proliferation. Through their interactions with inducers and effectors of apoptosis IAP proteins can effectively suppress apoptosis triggered by diverse stimuli including death receptor signaling, irradiation, chemotherapeutic agents, or growth factor withdrawal. Evasion of apoptosis, in part due to the action of IAP proteins, enhances resistance of cancer cells to treatment with chemotherapeutic agents and contributes to tumor progression. Additionally, IAP genes are known to be subject to amplification, mutation, and chromosomal translocation in human malignancies and autoimmune diseases. In this review we will discuss the role of IAP proteins in cancer and the development of antagonists targeting IAP proteins for cancer treatment.

  5. 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.

  6. 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...

  7. 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

  8. 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.

  9. Time Crystals from Minimum Time Uncertainty

    CERN Document Server

    Faizal, Mir; Das, Saurya

    2016-01-01

    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.

  10. Context quantization by minimum adaptive code length

    DEFF Research Database (Denmark)

    Forchhammer, Søren; Wu, Xiaolin

    2007-01-01

    Context quantization is a technique to deal with the issue of context dilution in high-order conditional entropy coding. We investigate the problem of context quantizer design under the criterion of minimum adaptive code length. A property of such context quantizers is derived for binary symbols...

  11. Minimum impact house prototype for sustainable building

    NARCIS (Netherlands)

    Drexler, H.; Jauslin, D.

    2010-01-01

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

  12. What's Happening in Minimum Competency Testing.

    Science.gov (United States)

    Frahm, Robert; Covington, Jimmie

    An examination of the current status of minimum competency testing is presented in a series of short essays, which discuss case studies of individual school systems and state approaches. Sections are also included on the viewpoints of critics and supporters, teachers and teacher organizations, principals and students, and the federal government.…

  13. The Minimum Distance of Graph Codes

    DEFF Research Database (Denmark)

    Høholdt, Tom; Justesen, Jørn

    2011-01-01

    We study codes constructed from graphs where the code symbols are associated with the edges and the symbols connected to a given vertex are restricted to be codewords in a component code. In particular we treat such codes from bipartite expander graphs coming from Euclidean planes and other geome...... geometries. We give results on the minimum distances of the codes....

  14. 44 CFR 62.6 - Minimum commissions.

    Science.gov (United States)

    2010-10-01

    ... ADJUSTMENT OF CLAIMS Issuance of Policies § 62.6 Minimum commissions. (a) The earned commission which shall be paid to any property or casualty insurance agent or broker duly licensed by a state insurance regulatory authority, with respect to each policy or renewal the agent duly procures on behalf of the...

  15. Minimum Bias and Underlying Event at CMS

    CERN Document Server

    Fano, Livio

    2006-01-01

    The prospects of measuring minimum bias collisions (MB) and studying the underlying event (UE) at CMS are discussed. Two methods are described. The first is based on the measurement of charged tracks in the transverse region with respect to a charge-particle jet. The second technique relies on the selection of muon-pair events from Drell-Yan process.

  16. A Minimum Relative Entropy Principle for AGI

    NARCIS (Netherlands)

    Ven, Antoine van de; Schouten, Ben

    2010-01-01

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

  17. Statistical inference of Minimum Rank Factor Analysis

    NARCIS (Netherlands)

    Shapiro, A; Ten Berge, JMF

    2002-01-01

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

  18. Completeness properties of the minimum uncertainty states

    Science.gov (United States)

    Trifonov, D. A.

    1993-01-01

    The completeness properties of the Schrodinger minimum uncertainty states (SMUS) and of some of their subsets are considered. The invariant measures and the resolution unity measures for the set of SMUS are constructed and the representation of squeezing and correlating operators and SMUS as superpositions of Glauber coherent states on the real line is elucidated.

  19. Minimum intervention dentistry: periodontics and implant dentistry.

    Science.gov (United States)

    Darby, I B; Ngo, L

    2013-06-01

    This article will look at the role of minimum intervention dentistry in the management of periodontal disease. It will discuss the role of appropriate assessment, treatment and risk factors/indicators. In addition, the role of the patient and early intervention in the continuing care of dental implants will be discussed as well as the management of peri-implant disease.

  20. Minimum output entropy of Gaussian channels

    CERN Document Server

    Lloyd, S; Maccone, L; Pirandola, S; Garcia-Patron, R

    2009-01-01

    We show that the minimum output entropy for all single-mode Gaussian channels is additive and is attained for Gaussian inputs. This allows the derivation of the channel capacity for a number of Gaussian channels, including that of the channel with linear loss, thermal noise, and linear amplification.

  1. 7 CFR 35.13 - Minimum quantity.

    Science.gov (United States)

    2010-01-01

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

  2. 7 CFR 33.10 - Minimum requirements.

    Science.gov (United States)

    2010-01-01

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

  3. 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

  4. Safety Note

    CERN Multimedia

    SC Secretariat

    2004-01-01

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

  5. PARTIAL AGONISTS, FULL AGONISTS, ANTAGONISTS - DILEMMAS OF DEFINITION

    NARCIS (Netherlands)

    HOYER, D; BODDEKE, HWGM

    1993-01-01

    The absence of selective antagonists makes receptor characterization difficult, and largely dependent on the use of agonists. However, there has been considerable debate as to whether certain drugs acting at G protein-coupled receptors are better described as agonists, partial agonists or antagonist

  6. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology

    NARCIS (Netherlands)

    Al-Inany, Hesham G.; Youssef, Mohamed A.; Ayeleke, Reuben Olugbenga; Brown, Julie; Lam, Wai Sun; Broekmans, Frank J.

    2016-01-01

    Background: Gonadotrophin-releasing hormone (GnRH) antagonists can be used to prevent a luteinizing hormone (LH) surge during controlled ovarian hyperstimulation (COH) without the hypo-oestrogenic side-effects, flare-up, or long down-regulation period associated with agonists. The antagonists direct

  7. 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…

  8. Optimisation of GnRH antagonist use in ART

    NARCIS (Netherlands)

    Hamdine, O.

    2014-01-01

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

  9. Survival of TNF antagonists in spondylarthritis is better than in rheumatoid arthritis. Data from the Spanish registry BIOBADASER.

    Science.gov (United States)

    Carmona, Loreto; Gómez-Reino, Juan J

    2006-01-01

    The aim of the present work is to compare drug survival and safety of infliximab, etanercept, and adalimumab (tumor necrosis factor [TNF] antagonists) in spondylarthritis (SpA) with those of rheumatoid arthritis (RA). To this purpose, we analysed the data in BIOBADASER (2000-2005), a drug registry launched in 2000 for long-term follow-up of the safety of these biologics in rheumatic diseases. The rates of drug discontinuation and adverse events (AEs) in SpA (n = 1,524) were estimated and compared with those of RA (n = 4,006). Cox regression analyses were used to adjust for independent factors. Total exposure to TNF antagonists for SpA was 2,430 patient-years and 7,865 for RA. Drug survival in SpA was significantly greater than in RA at 1, 2, and 3 years. The hazard ratio (HR) for discontinuation in SpA compared with RA was 0.66 (95% confidence interval [CI], 0.57-0.76) after adjustment for age, gender, and use of infliximab. The difference remained after controlling for the individual medication and its place in the sequence of treatment. There were fewer SpA patients with AEs (17%) than RA patients (26%; p < 0.001). The HR for AEs in SpA was 0.80 (95% CI, 0.70-0.91) compared with RA after adjustment for age, disease duration, and use of infliximab. In conclusion, due in part to a better safety profile, survival of TNF antagonists in SpA is better than in RA. TNF antagonists are at present a safe and effective therapeutic option for long-term treatment of patients with SpA failing to respond to traditional drugs. Because chronic therapy is necessary, continual review of this issue is necessary.

  10. 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.

  11. 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.

  12. A Product Safety Primer

    Science.gov (United States)

    Brown, Mary Anne Symons

    1975-01-01

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

  13. Reasons for Supporting the Minimum Wage: Asking Signatories of the "Raise the Minimum Wage" Statement

    OpenAIRE

    2007-01-01

    In October 2006, the Economic Policy Institute released a “Raise the Minimum Wage†statement signed by more than 650 individuals. Using an open-ended, non-anonymous questionnaire, we asked the signatories to explain their thinking on the issue. The questionnaire asked about the specific mechanisms at work, possible downsides, and whether the minimum wage violates liberty. Ninety-five participated. This article reports the responses. It also summarizes findings from minimum-wage surveys sin...

  14. 49 CFR 538.5 - Minimum driving range.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 6 2010-10-01 2010-10-01 false Minimum driving range. 538.5 Section 538.5... Minimum driving range. (a) The minimum driving range that a passenger automobile must have in order to be... electricity. (b) The minimum driving range that a passenger automobile using electricity as an...

  15. 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,...

  16. 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....

  17. SAFETY NOTES

    CERN Document Server

    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. 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.

  19. 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.

  20. Minimum Energy Demand Locomotion on Space Station

    Directory of Open Access Journals (Sweden)

    Wing Kwong Chung

    2013-01-01

    Full Text Available The energy of a space station is a precious resource, and the minimization of energy consumption of a space manipulator is crucial to maintain its normal functionalities. This paper first presents novel gaits for space manipulators by equipping a new gripping mechanism. With the use of wheels locomotion, lower energy demand gaits can be achieved. With the use of the proposed gaits, we further develop a global path planning algorithm for space manipulators which can plan a moving path on a space station with a minimum total energy demand. Different from existing approaches, we emphasize both the use of the proposed low energy demand gaits and the gaits composition during the path planning process. To evaluate the performance of the proposed gaits and path planning algorithm, numerous simulations are performed. Results show that the energy demand of both the proposed gaits and the resultant moving path is also minimum.

  1. 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.

  2. 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.

  3. Time crystals from minimum time uncertainty

    Science.gov (United States)

    Faizal, Mir; Khalil, Mohammed M.; Das, Saurya

    2016-01-01

    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.

  4. 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.)

  5. Minimum Description Length Shape and Appearance Models

    DEFF Research Database (Denmark)

    Thodberg, Hans Henrik

    2003-01-01

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

  6. 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....

  7. 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...

  8. Proposed production test for reducing minimum downtime

    Energy Technology Data Exchange (ETDEWEB)

    Jaklevick, J.F.

    1961-11-29

    The object of the production test described in this report is to evaluate the operational aspects of a proposed method for reducing minimum downtime. The excess xenon poisoning, which occurs during the first 32--38 hours after the shutdown of a reactor from present equilibrium levels, will be partially overridden by a central enriched zone whose added reactivity contribution would be compensated during normal operation by means of poison splines.

  9. 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

  10. Recombinant human interleukin-1 receptor antagonist in severe traumatic brain injury: a phase II randomized control trial.

    Science.gov (United States)

    Helmy, Adel; Guilfoyle, Mathew R; Carpenter, Keri L H; Pickard, John D; Menon, David K; Hutchinson, Peter J

    2014-05-01

    Traumatic brain injury (TBI) is the commonest cause of death and disability in those aged under 40 years. Interleukin-1 receptor antagonist (IL1ra) is an endogenous competitive antagonist at the interleukin-1 type-1 receptor (IL-1R). Antagonism at the IL-1R confers neuroprotection in several rodent models of neuronal injury (i.e., trauma, stroke and excitotoxicity). We describe a single center, phase II, open label, randomized-control study of recombinant human IL1ra (rhIL1ra, anakinra) in severe TBI, at a dose of 100 mg subcutaneously once a day for 5 days in 20 patients randomized 1:1. We provide safety data (primary outcome) in this pathology, utilize cerebral microdialysis to directly determine brain extracellular concentrations of IL1ra and 41 cytokines and chemokines, and use principal component analysis (PCA) to explore the resultant cerebral cytokine profile. Interleukin-1 receptor antagonist was safe, penetrated into plasma and the brain extracellular fluid. The PCA showed a separation in cytokine profiles after IL1ra administration. A candidate cytokine from this analysis, macrophage-derived chemoattractant, was significantly lower in the rhIL1ra-treated group. Our results provide promising data for rhIL1ra as a therapeutic candidate by showing safety, brain penetration and a modification of the neuroinflammatory response to TBI by a putative neuroprotective agent in humans for the first time.

  11. On the Minimum Induced Drag of Wings

    Science.gov (United States)

    Bowers, Albion H.

    2011-01-01

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

  12. The minimum entropy principle and task performance.

    Science.gov (United States)

    Guastello, Stephen J; Gorin, Hillary; Huschen, Samuel; Peters, Natalie E; Fabisch, Megan; Poston, Kirsten; Weinberger, Kelsey

    2013-07-01

    According to the minimum entropy principle, efficient cognitive performance is produced with a neurocognitive strategy that involves a minimum of degrees of freedom. Although high performance is often regarded as consistent performance as well, some variability in performance still remains which allows the person to adapt to changing goal conditions or fatigue. The present study investigated the connection between performance, entropy in performance, and four task-switching strategies. Fifty-one undergraduates performed 7 different computer-based cognitive tasks producing sets of 49 responses under instructional conditions requiring task quotas or no quotas. The temporal patterns of performance were analyzed using orbital decomposition to extract pattern types and lengths, which were then compared with regard to Shannon entropy, topological entropy, and overall performance. Task switching strategies from a previous study were available for the same participants as well. Results indicated that both topological entropy and Shannon entropy were negatively correlated with performance. Some task-switching strategies produced lower entropy in performance than others. Stepwise regression showed that the top three predictors of performance were Shannon entropy and arithmetic and spatial abilities. Additional implications for the prediction of work performance with cognitive ability measurements and the applicability of the minimum entropy principle to multidimensional performance criteria and team work are discussed.

  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. Fine Tuning of a Type 1 Interferon Antagonist.

    Directory of Open Access Journals (Sweden)

    Victoria Urin

    Full Text Available Type I interferons are multi-potent cytokines that serve as first line of defense against viruses and other pathogens, posses immunomudolatory functions and elicit a growth inhibitory response. In recent years it has been shown that interferons are also detrimental, for example in lupus, AIDS, tuberculosis and cognitive decline, highlighted the need to develop interferon antagonists. We have previously developed the antagonist IFN-1ant, with much reduced binding to the IFNAR1 receptor and enhanced binding to IFNAR2. Here, we further tune the IFN-1ant by producing three additional antagonists based on IFN-1ant but with altered activity profiles. We show that in all three cases the antiproliferative activity of interferons is blocked and the induction of gene transcription of immunomudolatory and antiproliferative associated genes are substantially decreased. Conversely, each of the new antagonists elicits a different degree of antiviral response, STAT phosphorylation and related gene induction. Two of the new antagonists promote decreased activity in relation to the original IFN-1ant, while one of them promotes increased activity. As we do not know the exact causes of the detrimental effects of IFNs, the four antagonists that were produced and analyzed provide the opportunity to investigate the extent of antagonistic and agonistic activity optimal for a given condition.

  15. Nalmefene: radioimmunoassay for a new opioid antagonist.

    Science.gov (United States)

    Dixon, R; Hsiao, J; Taaffe, W; Hahn, E; Tuttle, R

    1984-11-01

    A specific radioimmunoassay (RIA) has been developed for the quantitation of a new opioid antagonist, nalmefene, in human plasma. The method employs a rabbit antiserum to an albumin conjugate of naltrexone-6-(O-carboxymethyl)oxime and [3H]naltrexone as the radioligand. Assay specificity was achieved by extraction of nalmefene from plasma at pH 9 into ether prior to RIA. The procedure has a limit of sensitivity of 0.2 ng/mL of nalmefene using a 0.5-mL sample of plasma for analysis. The intra- and interassay coefficients of variation did not exceed 5.6 and 11%, respectively. The specificity of the RIA was established by demonstrating excellent agreement (r = 0.99) with a less sensitive and more time consuming HPLC procedure in the analysis of clinical plasma samples. The use of the RIA for the pharmacokinetic evaluation of nalmefene is illustrated with plasma concentration profiles of the drug in humans following intravenous and oral administration.

  16. 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.

  17. 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.

  18. 30 CFR 75.518-1 - Electric equipment and circuits; overload and short circuit protection; minimum requirements.

    Science.gov (United States)

    2010-07-01

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

  19. 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...

  20. Topology optimization for simplified structural fire safety

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  1. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists.

    Science.gov (United States)

    Khanfar, Mohammad A; Affini, Anna; Lutsenko, Kiril; Nikolic, Katarina; Butini, Stefania; Stark, Holger

    2016-01-01

    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.

  2. 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.

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

    Science.gov (United States)

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

    2014-02-01

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

  4. New potential uroselective NO-donor alpha1-antagonists.

    Science.gov (United States)

    Boschi, Donatella; Tron, Gian Cesare; Di Stilo, Antonella; Fruttero, Roberta; Gasco, Alberto; Poggesi, Elena; Motta, Gianni; Leonardi, Amedeo

    2003-08-14

    A recent uroselective alpha(1)-adrenoceptor antagonist, REC15/2739, has been joined with nitrooxy and furoxan NO-donor moieties to give new NO-donor alpha(1)-antagonists. All the compounds studied proved to be potent and selective ligands of human cloned alpha(1a)-receptor subtype. Derivatives 6 and 7 were able to relax the prostatic portion of rat vas deferens contracted by (-)-noradrenaline because of both their alpha(1A)-antagonist and their NO-donor properties.

  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. Safety for Users

    CERN Document Server

    HR Department

    2008-01-01

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

  7. Safety for Users

    CERN Document Server

    HR Department

    2008-01-01

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

  8. Safety performance evaluation using proactive indicators in a selected industry

    Directory of Open Access Journals (Sweden)

    Abolfazl Barkhordari

    2015-03-01

    Full Text Available Background & Objectives: Quality and effectiveness of safety systems are critical factors in achieving their goals. This study was aimed to represent a method for performance evaluation of safety systems by proactive indicators using different updated models in the field of safety which will be tested in a selected industry. Methods: This study is a cross-sectional study. Proactive indicators used in this study were: Unsafe acts rate, Safety Climate, Accident Proneness, and Near-miss incident rate. The number of in 1473 safety climate questionnaires and 543 Accident Proneness questionnaires was completed. Results: The minimum and maximum safety climate score were 56.88 and 58.2, respectively, and the minimum and maximum scores of Accident Proneness were 98.2 and 140.7, respectively. The maximum number of Near-miss incident rate were 408 and the minimum of that was 196. The maximum number of unsafe acts rate was 43.8 percent and the minimum of that was 27.2 percent. In nine dimensions of Safety climate the eighth dimension (personal perception of risk with the score of 4.07 has the lowest score and the fourth (laws and safety regulations dimension with 8.05 has the highest score. According to expert opinions, the most important indicator in the assessment of safety performance was unsafe acts rate, while near-miss incident rate was the least important one. Conclusion: The results of this survey reveal that using proactive (Prospective indicators could be an appropriate method in organizations safety performance evaluation.

  9. 24 CFR 3280.703 - Minimum standards.

    Science.gov (United States)

    2010-04-01

    ... Pipe, Standard Sizes—ASTM B42-93. Miscellaneous Factory-Made Air Ducts and Connectors, Ninth Edition—UL 181, 1996 with 1998 revisions. Standard for Safety Closure Systems for use with Rigid Air Ducts and... Flexible Air Ducts and Air Connectors, First Edition—UL 181B, 1995, with 1998 revisions. Tube Fittings...

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

    Science.gov (United States)

    Blythe, William; Seguin, Debra E

    2006-06-01

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

  11. Safety first

    Energy Technology Data Exchange (ETDEWEB)

    Harvie, W.

    1997-06-01

    Expansion of international business opportunities for Canadian producers and service companies brings with it a dimension almost never considered on home base - security. It was pointed out that once abroad, safety and defence of people and equipment can become significant problems in many parts of the world. The nature of the security risks involved, and how best to deal with them, were discussed. The use of consultants, mostly foreign ones to date, and the kind of assistance they can provide, everything from written reports on the local situation to counter surveillance training, and bodyguard services, have been described. Examples of recent involvements with guerilla groups demanding `revolutionary war taxes`, kidnapping executives for ransom, due diligence investigations of potential partners, and the like, have been provided to illustrate the unique character of the problem, and the constant need for being alert, educated to risks, and being prepared to react to risk situations.

  12. 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.

  13. The pharmacological properties of lipophilic calcium antagonists.

    Science.gov (United States)

    van Zwieten, P A

    1998-01-01

    Several types of calcium antagonists (CA) (verapamil, diltiazem, nifedipine and related drugs) may be used as antihypertensives. In practice, the dihydropyridines (nifedipine and related drugs) are the CA used most frequently as antihypertensives. Apart from the lowering of blood pressure CA may lead to other, theoretically beneficial, effects: regression of left ventricular and vascular hypertrophy, renal protection, weak natriuretic, weak antiplatelet, anti-ischaemic and antiatherogenic activity. Several new dihydropyridine CA have been introduced in recent years. The advantages of the newer compounds, such as amlodipine, felodipine, isradipine, lacidipine and lercanidipine, may include: vasoselectivity, hence little or no cardiodepressant activity; an improved kinetic profile, resulting in a slow onset and long duration of action, fewer side-effects such as reflex tachycardia and headache, owing to the slow onset of the antihypertensive action. For a few newer CA a predominant effect on specialized circulatory beds (renal, coronary and cerebral) has been claimed. The new CA, which are clearly lipophilic, deserve special attention. Owing to the lipophilic character of such compounds considerable concentration occurs in lipid-containing membrane depots. The CA thus concentrated are slowly released from these depots and, subsequently, reach their targets, the L-type calcium channels. This phenomenon explains both the slow onset and the long duration of action of these CA. Owing to the slow onset of action reflex tachycardia is virtually absent. The long duration of action allows satisfactory control of blood pressure in hypertensives by means of a single daily dose. A few lipophilic dihydropyridine CA are vasoselective. This property implies that at therapeutic, vasodilatory dosages no cardiodepressant activity occurs. Lercanidipine is a recently introduced example of a lipophilic and vasoselective dihydropyridine CA. It is an effective vasodilator

  14. A SELECTIVE ANTAGONIST OF MINERALOCORTICOID RECEPTOR EPLERENONE IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    B. B. Gegenava

    2015-09-01

    Full Text Available The role of aldosterone in pathophysiological processes is considered. The effects of the selective antagonist of mineralocorticoid receptor eplerenone are analyzed. The advantages of eplerenone compared with spironolactone are discussed.

  15. Structure-based drug design identifies novel LPA3 antagonists.

    Science.gov (United States)

    Fells, James I; Tsukahara, Ryoko; Liu, Jianxiong; Tigyi, Gabor; Parrill, Abby L

    2009-11-01

    Compound 5 ([5-(3-nitrophenoxy)-1,3-dioxo-1,3-dihydro-2-isoindol-2-yl]acetic acid) was identified as a weak selective LPA(3) antagonist (IC(50)=4504 nM) in a virtual screening effort to optimize a dual LPA(2 and 3) antagonist. Structure-based drug design techniques were used to prioritize similarity search matches of compound 5. This strategy rapidly identified 10 novel antagonists. The two most efficacious compounds identified inhibit activation of the LPA(3) receptor by 200 nM LPA with IC(50) values of 752 nM and 2992 nM. These compounds additionally define changes to our previously reported pharmacophore that will improve its ability to identify more potent and selective LPA(3) receptor antagonists. The results of the combined computational and experimental screening are reported.

  16. 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...

  17. Complications of TNF-α antagonists and iron homeostasis

    Science.gov (United States)

    TNF-α is a central regulator of inflammation and its blockade downregulates other proinflammatory cytokines, chemokines, and growth factors. Subsequently, TNF-α antagonists are currently used in treatment regimens directed toward several inflammatory diseases. Despite a beneficia...

  18. Aerobrake assembly with minimum Space Station accommodation

    Science.gov (United States)

    Katzberg, Steven J.; Butler, David H.; Doggett, William R.; Russell, James W.; Hurban, Theresa

    1991-01-01

    The minimum Space Station Freedom accommodations required for initial assembly, repair, and refurbishment of the Lunar aerobrake were investigated. Baseline Space Station Freedom support services were assumed, as well as reasonable earth-to-orbit possibilities. A set of three aerobrake configurations representative of the major themes in aerobraking were developed. Structural assembly concepts, along with on-orbit assembly and refurbishment scenarios were created. The scenarios were exercised to identify required Space Station Freedom accommodations. Finally, important areas for follow-on study were also identified.

  19. 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....

  20. Quantization of conductance minimum and index theorem

    Science.gov (United States)

    Ikegaya, Satoshi; Suzuki, Shu-Ichiro; Tanaka, Yukio; Asano, Yasuhiro

    2016-08-01

    We discuss the minimum value of the zero-bias differential conductance Gmin in a junction consisting of a normal metal and a nodal superconductor preserving time-reversal symmetry. Using the quasiclassical Green function method, we show that Gmin is quantized at (4 e2/h ) NZES in the limit of strong impurity scatterings in the normal metal at the zero temperature. The integer NZES represents the number of perfect transmission channels through the junction. An analysis of the chiral symmetry of the Hamiltonian indicates that NZES corresponds to the Atiyah-Singer index in mathematics.

  1. First minimum bias physics results at LHCb

    CERN Document Server

    Dettori, Francesco

    2010-01-01

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

  2. Iterative Regularization with Minimum-Residual Methods

    DEFF Research Database (Denmark)

    Jensen, Toke Koldborg; Hansen, Per Christian

    2007-01-01

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

  3. Iterative regularization with minimum-residual methods

    DEFF Research Database (Denmark)

    Jensen, Toke Koldborg; Hansen, Per Christian

    2006-01-01

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

  4. 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.

  5. 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...... antagonists as adjuvant single drugs to reduce trauma-, blood transfusion- and sepsis-induced immunosuppression has led to research in combined treatment regimens in major surgery, particularly, of patients operated on for malignant diseases....

  6. Structure-activity relationships of benzothiazole GPR35 antagonists.

    Science.gov (United States)

    Abdalhameed, Manahil M; Zhao, Pingwei; Hurst, Dow P; Reggio, Patricia H; Abood, Mary E; Croatt, Mitchell P

    2017-02-01

    The first structure-activity relationships for a benzothiazole scaffold acting as an antagonist at GPR35 is presented. Analogues were designed based on a lead compound that was previously determined to have selective activity as a GPR35 antagonist. The synthetic route was modular in nature to independently explore the role of the middle and both ends of the scaffold. The activities of the analogues illustrate the importance of all three segments of the compound.

  7. 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.

  8. Multiple Targeting Approaches on Histamine H3 Receptor Antagonists

    OpenAIRE

    Mohammad eKhanfar; Anna eAffini; Kiril eLutsenko; Katarina eNikolic; Stefania eButini; Holger eStark

    2016-01-01

    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...

  9. 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....

  10. 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...

  11. Linking Safety Analysis to Safety Requirements

    DEFF Research Database (Denmark)

    Hansen, Kirsten Mark

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

  12. Fire safety

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-07-01

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

  13. 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...

  14. Minimum Cost Homomorphisms to Reflexive Digraphs

    CERN Document Server

    Gupta, Arvind; Karimi, Mehdi; Rafiey, Arash

    2007-01-01

    For digraphs $G$ and $H$, a homomorphism of $G$ to $H$ is a mapping $f:\\ V(G)\\dom V(H)$ such that $uv\\in A(G)$ implies $f(u)f(v)\\in A(H)$. If moreover each vertex $u \\in V(G)$ is associated with costs $c_i(u), i \\in V(H)$, then the cost of a homomorphism $f$ is $\\sum_{u\\in V(G)}c_{f(u)}(u)$. For each fixed digraph $H$, the {\\em minimum cost homomorphism problem} for $H$, denoted MinHOM($H$), is the following problem. Given an input digraph $G$, together with costs $c_i(u)$, $u\\in V(G)$, $i\\in V(H)$, and an integer $k$, decide if $G$ admits a homomorphism to $H$ of cost not exceeding $k$. We focus on the minimum cost homomorphism problem for {\\em reflexive} digraphs $H$ (every vertex of $H$ has a loop). It is known that the problem MinHOM($H$) is polynomial time solvable if the digraph $H$ has a {\\em Min-Max ordering}, i.e., if its vertices can be linearly ordered by $<$ so that $i

  15. Constrained length minimum inductance gradient coil design.

    Science.gov (United States)

    Chronik, B A; Rutt, B K

    1998-02-01

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

  16. 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.

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

    Science.gov (United States)

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

    2015-11-01

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

  18. 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.

  19. Minimum dV for Targeted Spacecraft Disposal

    Science.gov (United States)

    Bacon, John

    2017-01-01

    The density scale height of the Earth's atmosphere undergoes significant reduction in the final phases of a natural decay. It can be shown that for most realistic ballistic numbers, it is possible to exploit this effect to amplify available spacecraft dV by using it at the penultimate perigee to penetrate into higher drag regions at final apogee. The drag at this lower pass can more effectively propel a spacecraft towards the final target region than applying the same dV direct Hohmann transfer at that final apogee. This study analyzes the potential use of this effect-- in combination with small phasing burns--to calculate the absolute minimum delta-V that would be required to reliably guide a spacecraft to any specified safe unoccupied ocean region as a function of ballistic number, orbit inclination, and initial eccentricity. This calculation is made for controllable spacecraft in several orbit inclinations and eccentricities with arbitrary initial LAN and ArgP one week before final entry, under three-sigma atmospheric perturbations. The study analyzes the dV required under varying levels of final controllable altitude at which dV may be imparted, and various definitions of the length and location of a "safe" disposal area. The goal of such research is to improve public safety by creating assured safe disposal strategies for low-dV and/or low-thrust spacecraft that under more traditional strategies would need to be abandoned to a fully random decay.

  20. 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.

  1. 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...

  2. Minimum Energy Requirements in Complex Distillation Arrangements

    Energy Technology Data Exchange (ETDEWEB)

    Halvorsen, Ivar J.

    2001-07-01

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

  3. Patient safety: Safety culture and patient safety ethics

    DEFF Research Database (Denmark)

    Madsen, Marlene Dyrløv

    2006-01-01

    and interviews with staff and management in four hospital departments. The appendix contains the Patient Safety Culture Questionnaire tool that I have developed, tested and revised for use in theDanish hospital setting based on the research projects on safety culture described in papers 3, 4 and 5. Paper 6......Patient safety - the prevention of medical error and adverse events - and the initiative of developing safety cultures to assure patients from harm have become one of the central concerns in quality improvement in healthcare both nationally andinternationally. This subject raises numerous...... the problems, and suggest possible solutions for improving patient safety through the promotion of safety culture and ethics. I seek to illuminate theissues of patient safety from several perspectives; the organizational healthcare system, in particular the healthcare workers perspectives and experiences...

  4. Automatic safety rod for reactors. [LMFBR

    Science.gov (United States)

    Germer, J.H.

    1982-03-23

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

  5. Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention

    DEFF Research Database (Denmark)

    Ho, Tony W; Connor, Kathryn M; Zhang, Ying

    2014-01-01

    OBJECTIVE: To evaluate whether the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant might be effective for migraine prevention. METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial (ClinicalTrials.gov NCT00797667), patients experiencing 3-14 migra......OBJECTIVE: To evaluate whether the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant might be effective for migraine prevention. METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial (ClinicalTrials.gov NCT00797667), patients experiencing 3......-14 migraine days during a 4-week baseline were randomized to telcagepant 140 mg, telcagepant 280 mg, or placebo twice daily for 12 weeks. Efficacy was assessed by mean monthly headache days and migraine/probable migraine days (headache plus ≥ 1 associated symptom). RESULTS: The trial was terminated following...... a recommendation from the Safety Monitoring Board due to hepatotoxicity concerns. At termination, the planned 660 patients had been randomized, 656 had been treated with ≥ 1 dose of study medication, and 14 had completed the trial. The mean treatment duration was 48-50 days. Thirteen patients, all...

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

    Science.gov (United States)

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

    2016-07-01

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

  7. A major safety overhaul

    CERN Multimedia

    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.

  8. New H2-receptor antagonist--roxatidine acetate--in treatment of duodenal ulcer.

    Science.gov (United States)

    Amarapurkar, D N; Parikh, S S; Desai, H G

    1993-08-01

    A double blind randomised trial, comparing a new H2-receptor antagonist, Roxatidine acetate, with Cimetidine was carried out in 47 patients of uncomplicated, endoscopically proven duodenal ulcer. Twenty seven patients were treated with Roxatidine 75 mg twice daily and 20 patients were treated with Cimetidine 200 mg 3 times a day and 400 mg at bed time for 4 weeks. At the end of 4 weeks, total pain relief was obtained in 74% and 70% patients receiving Roxatidine and Cimetidine respectively. Complete endoscopic healing at the end of 4 weeks was observed in 92.3% patients receiving Roxatidine and 85% patients receiving Cimetidine. These differences were statistically not significant. No significant side effects were observed in either group. We conclude that Roxatidine acetate is comparable to cimetidine in relieving pain and endoscopic healing of duodenal ulcer and has an excellent safety profile.

  9. 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.

  10. 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

  11. 41 CFR 50-201.1101 - Minimum wages.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Minimum wages. 50-201.1101 Section 50-201.1101 Public Contracts and Property Management Other Provisions Relating to Public Contracts PUBLIC CONTRACTS, DEPARTMENT OF LABOR 201-GENERAL REGULATIONS § 50-201.1101 Minimum wages. Determinations of prevailing minimum wages...

  12. 29 CFR 505.3 - Prevailing minimum compensation.

    Science.gov (United States)

    2010-07-01

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

  13. 12 CFR 263.82 - Establishment of minimum capital levels.

    Science.gov (United States)

    2010-01-01

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

  14. 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,...

  15. 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...

  16. 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...

  17. 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,...

  18. 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...

  19. 12 CFR 931.3 - Minimum investment in capital stock.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Minimum investment in capital stock. 931.3... CAPITAL STANDARDS FEDERAL HOME LOAN BANK CAPITAL STOCK § 931.3 Minimum investment in capital stock. (a) A Bank shall require each member to maintain a minimum investment in the capital stock of the Bank,...

  20. 24 CFR 891.145 - Owner deposit (Minimum Capital Investment).

    Science.gov (United States)

    2010-04-01

    ... General Program Requirements § 891.145 Owner deposit (Minimum Capital Investment). As a Minimum Capital... Investment shall be one-half of one percent (0.5%) of the HUD-approved capital advance, not to exceed $25,000. ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Owner deposit (Minimum...

  1. 30 CFR 56.19021 - Minimum rope strength.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Minimum rope strength. 56.19021 Section 56... Wire Ropes § 56.19021 Minimum rope strength. At installation, the nominal strength (manufacturer's published catalog strength) of wire ropes used for hoisting shall meet the minimum rope strength...

  2. 30 CFR 77.1431 - Minimum rope strength.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Minimum rope strength. 77.1431 Section 77.1431... Hoisting Wire Ropes § 77.1431 Minimum rope strength. At installation, the nominal strength (manufacturer's published catalog strength) of wire ropes used for hoisting shall meet the minimum rope strength...

  3. 30 CFR 57.19021 - Minimum rope strength.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Minimum rope strength. 57.19021 Section 57... Hoisting Wire Ropes § 57.19021 Minimum rope strength. At installation, the nominal strength (manufacturer's published catalog strength) of wire ropes used for hoisting shall meet the minimum rope strength...

  4. 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...

  5. The generalized minimum spanning tree polytope and related polytopes

    NARCIS (Netherlands)

    Pop, P.C.

    2001-01-01

    The Generalized Minimum Spanning Tree problem denoted by GMST is a variant of the classical Minimum Spanning Tree problem in which nodes are partitioned into clusters and the problem calls for a minimum cost tree spanning at least one node from each cluster. A different version of the problem, calle

  6. 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.

  7. 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.

  8. 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...... environmental genomics and geochemical studies show the presence of other relevant processes, particularly those associated with the sulfur and carbon cycles. AMZs correspond to an intermediate state between two "end points" represented by fully oxic systems and fully sulfidic systems. Modern and ancient AMZs...... and sulfidic basins are chemically and functionally related. Global change is affecting the magnitude of biogeochemical fluxes and ocean chemical inventories, leading to shifts in AMZ chemistry and biology that are likely to continue well into the future....

  9. Duality of Maximum Entropy and Minimum Divergence

    Directory of Open Access Journals (Sweden)

    Shinto Eguchi

    2014-06-01

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

  10. Increasing the weight of minimum spanning trees

    Energy Technology Data Exchange (ETDEWEB)

    Frederickson, G.N.; Solis-Oba, R. [Purdue Univ., West Lafayette, IN (United States)

    1996-12-31

    Given an undirected connected graph G and a cost function for increasing edge weights, the problem of determining the maximum increase in the weight of the minimum spanning trees of G subject to a budget constraint is investigated. Two versions of the problem are considered. In the first, each edge has a cost function that is linear in the weight increase. An algorithm is presented that solves this problem in strongly polynomial time. In the second version, the edge weights are fixed but an edge can be removed from G at a unit cost. This version is shown to be NP-hard. An {Omega}(1/ log k)-approximation algorithm is presented for it, where k is the number of edges to be removed.

  11. Radiation belt dynamics during solar minimum

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-12-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  13. 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.

  14. 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

  15. 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

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

    CERN Document Server

    Michel, Loïc

    2012-01-01

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

  17. A pharmacophore model for dopamine D4 receptor antagonists

    Science.gov (United States)

    Boström, Jonas; Gundertofte, Klaus; Liljefors, Tommy

    2000-11-01

    A pharmacophore model for dopamine D4 antagonists has been developed on the basis of a previously reported dopamine D2 model. By using exhaustive conformational analyses (MM3* force field and the GB/SA hydration model) and least-squares molecular superimposition studies, a set of eighteen structurally diverse high affinity D4 antagonists have successfully been accommodated in the D4 pharmacophore model. Enantioselectivities may be rationalized by conformational energies required for the enantiomers to adopt their proposed bioactive conformations. The pharmacophore models for antagonists at the D4 and D2 receptor subtypes have been compared in order to get insight into molecular properties of importance for D2/D4 receptor selectivity. It is concluded that the bioactive conformations of antagonists at the two receptor subtypes are essentially identical. Receptor essential volumes previously identified for the D2 receptor are shown to be present also in the D4 receptor. In addition, a novel receptor essential volume in the D4 receptor, not present in the D2 receptor, has been identified. This feature may be exploited for the design of D4 selective antagonists. However, it is concluded that the major determinant for D2/D4 selectivity is the nature of the interactions between the receptor and aromatic ring systems. The effects of the electronic properties of these ring systems on the affinities for the two receptor subtypes differ substantially.

  18. Conception of high safety reactor MAVR, technical and economical fuel cycle characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Kotov, V.M.; Cherepnin, Yu.S.

    1993-12-31

    Operation safety of reactor MAVR under nominal and emergency situations is based on creation of conditions for the minimum time of fuel operation in the core at the minimum quantity of the fissionable material. The variants of core elements construction, of the reactor control systems, and the possible scheme of fuel cycles of the reactor MAVR are considered.

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

    Directory of Open Access Journals (Sweden)

    Jens I. Ytreeide

    1997-01-01

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

  20. Minimum-energy wavelet frame on the interval

    Institute of Scientific and Technical Information of China (English)

    GAO XiePing; CAO ChunHong

    2008-01-01

    The construction and properties of interval minimum-energy wavelet frame are systematically studied in this paper.They are as follows:1) give the definition of interval minimum-energy wavelet frame;2) give the necessary and sufficient conditions for the minimum-energy frames for L2[0,1];3) present the construction algorithm for minimum-energy wavelet frame associated with refinable functions on the interval with any support γ;4) give the decomposition and reconstruction formulas of the minimum-energy frame on the interval [0,1].

  1. 78 FR 2797 - Federal Motor Vehicle Safety Standards; Minimum Sound Requirements for Hybrid and Electric Vehicles

    Science.gov (United States)

    2013-01-14

    ... Engine Vehicles to Hybrid and Electric Vehicles B. Need for Independent Mobility of People Who Are... and mobility, automotive industry perspective, SAE work and status, potential solutions, and noise... might be perceived as annoying. In early 2011, NHTSA initiated additional research and data...

  2. Safety of American Heart Association-recommended minimum exercise for desmosomal mutation carriers

    NARCIS (Netherlands)

    Sawant, Abhishek C; Te Riele, Anneline S J M; Tichnell, Crystal; Murray, Brittney; Bhonsale, Aditya; Tandri, Harikrishna; Judge, Daniel P; Calkins, Hugh; James, Cynthia A

    2016-01-01

    BACKGROUND: Endurance exercise is associated with adverse outcomes in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Exercise recommendations for family members remain undetermined. OBJECTIVE: The purposes of this study were to determine if (1) endurance exercise (

  3. School violence: effective response protocols for maximum safety and minimum liability.

    Science.gov (United States)

    Miller, Laurence

    2007-01-01

    Despite the recent preoccupation with terrorism, most Americans are still killed by our own citizens, and school violence continues to be a significant source of mortality and trauma. This article describes the basic facts, features, and dynamics of school violence and presents a prevention, response, and recovery protocol adapted from the related field of workplace violence. This model may be used by educators, law enforcement professionals, and mental health clinicians in their collaborative efforts to make our academic institutions safer and healthier places to learn.

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

    Directory of Open Access Journals (Sweden)

    Elizabeth R. Tuminello

    2011-01-01

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

  5. Discovery of the improved antagonistic prolactin variants by library screening.

    Science.gov (United States)

    Liu, Yun; Gong, Wei; Breinholt, Jens; Nørskov-Lauritsen, Leif; Zhang, Jinchao; Ma, Qinhong; Chen, Jianhe; Panina, Svetlana; Guo, Wei; Li, Tengkun; Zhang, Jingyuan; Kong, Meng; Liu, Zibing; Mao, Jingjing; Christensen, Leif; Hu, Sean; Wang, Lingyun

    2011-11-01

    Prolactin (PRL), a potent growth stimulator of the mammary epithelium, has been suggested to be a factor contributing to the development and progression of breast and prostate cancer. Several PRL receptor (PRLR) antagonists have been identified in the past decades, but their in vivo growth inhibitory potency was restricted by low receptor affinity, rendering them pharmacologically unattractive for clinical treatment. Thus, higher receptor affinity is essential for the development of improved PRLR antagonistic variants with improved in vivo potency. In this study, we generated Site 1 focused protein libraries of human G129R-PRL mutants and screened for those with increased affinity to the human PRLR. By combining the mutations with enhanced affinities for PRLR, we identified a novel G129R-PRL variant with mutations at Site 1 that render nearly 50-fold increase in the antagonistic potency in vitro.

  6. 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.

  7. Neuroprotective Effects of Glutamate Antagonists and Extracellular Acidity

    Science.gov (United States)

    Kaku, David A.; Giffard, Rona G.; Choi, Dennis W.

    1993-06-01

    Glutamate antagonists protect neurons from hypoxic injury both in vivo and in vitro, but in vitro studies have not been done under the acidic conditions typical of hypoxia-ischemia in vivo. Consistent with glutamate receptor antagonism, extracellular acidity reduced neuronal death in murine cortical cultures that were deprived of oxygen and glucose. Under these acid conditions, N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isox-azolepropionate-kainate antagonists further reduced neuronal death, such that some neurons tolerated prolonged oxygen and glucose deprivation almost as well as did astrocytes. Neuroprotection induced by this combination exceeded that induced by glutamate antagonists alone, suggesting that extracellular acidity has beneficial effects beyond the attenuation of ionotropic glutamate receptor activation.

  8. 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.

  9. Safety Assurance in NextGen

    Science.gov (United States)

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

    2012-01-01

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

  10. Safety: Preventive Medicine.

    Science.gov (United States)

    Kotula, John R.; Digenakis, Anthony

    1985-01-01

    Underscores the need for community colleges to practice safety within the institutions and to instruct students in workplace safety procedures and requirements. Reviews Occupational Safety and Health Act (OSHA) regulations and their impact on industry and education. Looks at the legal responsibilities of colleges for safety. (DMM)

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

    Science.gov (United States)

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

    2011-02-11

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

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

    Science.gov (United States)

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

    2011-01-01

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

  13. Constantly evolving safety assessment protocols for GM foods.

    Science.gov (United States)

    Sesikeran, B; Vasanthi, Siruguri

    2008-01-01

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

  14. ON THE INVERSE MINIMUM SPANNING TREE PROBLEM WITH MINIMUM NUMBER OF PERTURBED EDGES

    Institute of Scientific and Technical Information of China (English)

    Bangyi LI; Zhaohan SHENG

    2003-01-01

    Let G= be a network with the vertex set V, the edge set E and the length vector L, andlet T* be a prior determined spanning tree of G. The inverse minimum spanning tree problem withminimum number of perturbed edges is to perturb the length vector L to L+ δ, such that T* is one ofminimum spanning trees under the length vector L+ δ and the number of perturbed edges is minimum.This paper establishes a mathematical model for this problem and transforms it into a minimumvertex covering problem in a bipartite graph Go, a path-graph. Thus a strongly polynomial algorithmwith time complexity O(mn2) can be designed by using Hungarian method.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  16. Barnidipine, a long-acting slow onset calcium antagonist.

    Science.gov (United States)

    Korstanje, C

    2000-11-01

    Barnidipine is a stereochemically pure dihydropyridine calcium antagonist with a high potency. The drug showed a slow onset and long-lasting vasorelaxating effect in vitro, and strong antihypertensive activity in hypertension models. Barnidipine was shown to have a high vasoselectivity and offered protection in cardiac and renal ischaemia models. The in vitro drug:drug interaction profile suggests a low potential for clinically relevant interactions with concomitant medication. It can be anticipated that barnidipine is an attractive calcium antagonist, offering good blood pressure control without compensatory baroreflex activity.

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

    Science.gov (United States)

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

    1982-02-01

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

  18. Minimum information about a bioactive entity (MIABE).

    Science.gov (United States)

    Orchard, Sandra; Al-Lazikani, Bissan; Bryant, Steve; Clark, Dominic; Calder, Elizabeth; Dix, Ian; Engkvist, Ola; Forster, Mark; Gaulton, Anna; Gilson, Michael; Glen, Robert; Grigorov, Martin; Hammond-Kosack, Kim; Harland, Lee; Hopkins, Andrew; Larminie, Christopher; Lynch, Nick; Mann, Romeena K; Murray-Rust, Peter; Lo Piparo, Elena; Southan, Christopher; Steinbeck, Christoph; Wishart, David; Hermjakob, Henning; Overington, John; Thornton, Janet

    2011-08-31

    Bioactive molecules such as drugs, pesticides and food additives are produced in large numbers by many commercial and academic groups around the world. Enormous quantities of data are generated on the biological properties and quality of these molecules. Access to such data - both on licensed and commercially available compounds, and also on those that fail during development - is crucial for understanding how improved molecules could be developed. For example, computational analysis of aggregated data on molecules that are investigated in drug discovery programmes has led to a greater understanding of the properties of successful drugs. However, the information required to perform these analyses is rarely published, and when it is made available it is often missing crucial data or is in a format that is inappropriate for efficient data-mining. Here, we propose a solution: the definition of reporting guidelines for bioactive entities - the Minimum Information About a Bioactive Entity (MIABE) - which has been developed by representatives of pharmaceutical companies, data resource providers and academic groups.

  19. Minimum degree condition forcing complete graph immersion

    CERN Document Server

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

    2011-01-01

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

  20. 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.

  1. Minimum Bias Measurements at the LHC

    CERN Document Server

    Kar, Deepak; The ATLAS collaboration

    2016-01-01

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

  2. Safety at CERN

    CERN Multimedia

    2009-01-01

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

  3. China's Work Safety Report

    Institute of Scientific and Technical Information of China (English)

    Liang Jiakun

    2005-01-01

    @@ General Situation of China's Work Safety in 2004 In 2004, the national work safety situation remained stable as a whole and gained momentum to improve. The totality of accidents held the line and began to drop. The safety conditions in industrial,mining, and commercial/trading enterprises improved. Progress was made in ensuring work safety in the relevant industries and fields. The safety situation in most provinces (autonomous regions, municipalities directly under the Central Government) kept stable.

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

    Directory of Open Access Journals (Sweden)

    Norman JL

    2016-07-01

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

  5. TWRS safety program plan

    Energy Technology Data Exchange (ETDEWEB)

    Calderon, L.M., Westinghouse Hanford

    1996-08-01

    Management of Nuclear Safety, Industrial Safety, Industrial Hygiene, and Fire Protection programs, functions, and field support resources for Tank Waste Remediation Systems (TWRS) has, until recently, been centralized in TWRS Safety, under the Emergency, Safety, and Quality organization. Industrial hygiene technician services were also provided to support operational needs related to safety basis compliance. Due to WHC decentralization of safety and reengineering efforts in West Tank Farms, staffing and safety responsibilities have been transferred to the facilities. Under the new structure, safety personnel for TWRS are assigned directly to East Tank Farms, West Tank Farms, and a core Safety Group in TWRS Engineering. The Characterization Project Operations (CPO) safety organization will remain in tact as it currently exists. Personnel assigned to East Tank Farms, West Tank Farms, and CPO will perform facility-specific or project-specific duties and provide field implementation of programs. Those assigned to the core group will focus on activities having a TWRS-wide or programmatic focus. Hanford-wide activities will be the responsibility of the Safety Center of Expertise. In order to ensure an effective and consistent safety program for TWRS under the new organization program functions, goals, organizational structure, roles, responsibilities, and path forward must be clearly established. The purpose of the TWRS Safety Program Plan is to define the overall safety program, responsibilities, relationships, and communication linkages for safety personnel under the new structure. In addition, issues associated with reorganization transition are addressed, including training, project ownership, records management, and dissemination of equipment. For the purpose of this document ``TWRS Safety`` refers to all safety professionals and technicians (Industrial Safety, Industrial Hygiene, Fire Protection, and Nuclear Safety) within the TWRS organization, regardless of their

  6. 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.

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

    Science.gov (United States)

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

    2011-09-01

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

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

    Directory of Open Access Journals (Sweden)

    André Maier

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

  9. Redefining the limit dates for the Maunder Minimum

    CERN Document Server

    Vaquero, J M

    2014-01-01

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

  10. Safety of ephedra: lessons learned.

    Science.gov (United States)

    Soni, Madhusudan G; Carabin, Ioana G; Griffiths, James C; Burdock, George A

    2004-04-15

    The safe use of ephedra represents the best possible outcome of a convergence of variables, some with troubling potential outcomes. Commercially used ephedra and its products is prepared from Ephedra spp. and as such is subject to a variety of influences (including differences in species and strain; growth, harvest and storage conditions) all of which may influence the content of constituents (which may, in turn, affect the absorption, distribution, and metabolism of active constituents) and taken together, influences the net pharmacological effect. Further, as a natural substance with an easily perceived and desirable (i.e. weight-loss) pharmacological effect, ephedra is also susceptible to a variety of adulterants, both economic and efficacious. All of the foregoing represent potential for misadventure before ephedra even reaches the consumer. The consumer introduces a constellation of variables as well, including, but not limited to, acute and chronic diseases, inborn errors in metabolism, simultaneous use of prescription and over-the-counter drugs, dietary supplements, alcohol, illicit substances and certain foods (e.g. chocolate, caffeinated drinks), all or some of which may exert synergistic, additive or even antagonistic influences on the desired physiologic outcome. The foregoing not withstanding, the majority of the published nonclinical and clinical studies, and history of use, support the safety of ephedra at the proposed use levels. However, the reports of adverse events submitted to FDA raise concern about the risk associated with ephedra without establishing a direct causal relationship. Given the foregoing, how best can a decision on safety be made? Should the question actually be "can ephedra be as toxic as reported?"

  11. 5-Hydroxytryptamine3 receptor antagonists and cardiac side effects

    DEFF Research Database (Denmark)

    Brygger, Louise; Herrstedt, Jørn

    2014-01-01

    INTRODUCTION: 5-Hydroxytryptamine3-receptor antagonists (5-HT3-RA) are the most widely used antiemetics in oncology, and although tolerability is high, QTC prolongation has been observed in some patients. AREAS COVERED: The purpose of this article is to outline the risk of cardiac adverse events...

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

    Directory of Open Access Journals (Sweden)

    Tanya Onushko

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

  13. 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.

  14. How Hybrid Organizations Turn Antagonistic Assets into Complementarities

    DEFF Research Database (Denmark)

    Hockerts, Kai

    2015-01-01

    This article focuses on people excluded from traditional markets as employees, producers, or consumers on the grounds that they lack the appropriate skills. It describes the processes through which these perceived liabilities can be overcome by so-called hybrid organizations. Hybrids pursue expli...... for complementarities, and by creating demands for antagonistic assets, or by using partnerships....

  15. Serotonin 2A receptor antagonists for treatment of schizophrenia

    DEFF Research Database (Denmark)

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

    2011-01-01

    Introduction: All approved antipsychotic drugs share an affinity for the dopamine 2 (D2) receptor; however, these drugs only partially ameliorate the symptoms of schizophrenia. It is, therefore, of paramount importance to identify new treatment strategies for schizophrenia. Areas covered: Preclin......Introduction: All approved antipsychotic drugs share an affinity for the dopamine 2 (D2) receptor; however, these drugs only partially ameliorate the symptoms of schizophrenia. It is, therefore, of paramount importance to identify new treatment strategies for schizophrenia. Areas covered...... 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...... antagonists appear to assume an intermediate position by being marginally superior to placebo but inferior to conventional antipsychotic drugs. Three previous 5-HT2A receptor antagonists have been discontinued after Phase II or III trials, and available Phase IIa data on the remaining 5-HT2A receptor...

  16. Facilitative and antagonistic interactions between plant viruses in mixed infections.

    Science.gov (United States)

    Syller, Jerzy

    2012-02-01

    Mixed infections of plant viruses are common in nature, and a number of important virus diseases of plants are the outcomes of interactions between causative agents. Multiple infections lead to a variety of intrahost virus-virus interactions, many of which may result in the generation of variants showing novel genetic features, and thus change the genetic structure of the viral population. Hence, virus-virus interactions in plants may be of crucial significance for the understanding of viral pathogenesis and evolution, and consequently for the development of efficient and stable control strategies. The interactions between plant viruses in mixed infections are generally categorized as synergistic or antagonistic. Moreover, mixtures of synergistic and antagonistic interactions, creating usually unpredictable biological and epidemiological consequences, are likely to occur in plants. The mechanisms of some of these are still unknown. This review aims to bring together the current knowledge on the most commonly occurring facilitative and antagonistic interactions between related or unrelated viruses infecting the same host plant. The best characterized implications of these interactions for virus-vector-host relationships are included. The terms 'synergism' and 'helper dependence' for facilitative virus-virus interactions, and 'cross-protection' and 'mutual exclusion' for antagonistic interactions, are applied in this article.

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

    NARCIS (Netherlands)

    Kooistra, Hilde Afra Margaretha

    2016-01-01

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

  18. 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.

  19. 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

  20. 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

  1. Aryl biphenyl-3-ylmethylpiperazines as 5-HT7 receptor antagonists.

    Science.gov (United States)

    Kim, Jeeyeon; Kim, Youngjae; Tae, Jinsung; Yeom, Miyoung; Moon, Bongjin; Huang, Xi-Ping; Roth, Bryan L; Lee, Kangho; Rhim, Hyewhon; Choo, Il Han; Chong, Youhoon; Keum, Gyochang; Nam, Ghilsoo; Choo, Hyunah

    2013-11-01

    The 5-HT7 receptor (5-HT7 R) is a promising therapeutic target for the treatment of depression and neuropathic pain. The 5-HT7 R antagonist SB-269970 exhibited antidepressant-like activity, whereas systemic administration of the 5-HT7 R agonist AS-19 significantly inhibited mechanical hypersensitivity and thermal hyperalgesia. In our efforts to discover selective 5-HT7 R antagonists or agonists, aryl biphenyl-3-ylmethylpiperazines were designed, synthesized, and biologically evaluated against the 5-HT7 R. Among the synthesized compounds, 1-([2'-methoxy-(1,1'-biphenyl)-3-yl]methyl)-4-(2-methoxyphenyl)piperazine (28) was the best binder to the 5-HT7 R (pKi =7.83), and its antagonistic property was confirmed by functional assays. The selectivity profile of compound 28 was also recorded for the 5-HT7 R over other serotonin receptor subtypes, such as 5-HT1 R, 5-HT2 R, 5-HT3 R, and 5-HT6 R. In a molecular modeling study, the 2-methoxyphenyl moiety attached to the piperazine ring of compound 28 was proposed to be essential for the antagonistic function.

  2. 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...

  3. Does intergenerational social mobility affect antagonistic attitudes towards ethnic minorities?

    NARCIS (Netherlands)

    Tolsma, J.; Graaf, N.D. de; Quillian, L.

    2009-01-01

    Up till now, no study satisfactorily addressed the effect of social mobility on antagonistic attitudes toward ethnic minorities. In this contribution, we investigate the effect of educational and class intergenerational mobility on ethnic stereotypes, ethnic threat, and opposition to ethnic intermar

  4. 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...

  5. Occupational safety motivation

    DEFF Research Database (Denmark)

    Pedersen, Louise; Kines, Pete

    2010-01-01

    . At the same time many motivation questionnaire items are seldom founded on theory and/or do not account for the theories’ ontological and epistemological differences, e.g. of how knowledge, attitude and action are related. Present questionnaire items tap into occupational safety motivation in asking whether...... or not respondents ‘are’ motivated and whether they feel that safety is important or worthwhile. Another important aspect is ‘what’ motivates workers to comply to and participate in safety. The aim of this article is to introduce a new theory-based occupational safety motivation scale which is validated......Background: Motivation is one of the most important factors for safety behaviour and for implementing change in general. However, theoretical and psychometric studies of safety performance have traditionally treated safety motivation, safety compliance and safety participation unidimensionally...

  6. Minimum-cost quantum measurements for quantum information

    OpenAIRE

    Wallden, Petros; Dunjko, Vedran; Andersson, Erika

    2014-01-01

    Knowing about optimal quantum measurements is important for many applications in quantum information and quantum communication. However, deriving optimal quantum measurements is often difficult. We present a collection of results for minimum-cost quantum measurements, and give examples of how they can be used. Among other results, we show that a minimum-cost measurement for a set of given pure states is formally equivalent to a minimum-error measurement for certain mixed states of those same ...

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

    Science.gov (United States)

    Huijing, Peter A; Baan, Guus C

    2008-01-01

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

  8. Minimum energy design using grassed spillways

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, B. [FIE Aust, Melbourne (Australia)

    2004-09-01

    Small dams for rural communities in Australia often fail due to the Spillway or bywash, because it receives insufficient attention during the design, construction and maintenance processes. More thorough investigation and improved standards of design and construction are needed in order to resolve problems. This paper described some of the reasons for adopting grass spillways on farm dams. It compared grass and earth spillways and also discussed spillway design factors such as site conditions, peak flow estimation, and design spillway size. The factors affecting selection of spillway type and design include safety requirements, hydrological conditions, geological and site topographical conditions, and type of dam. Factors involved in grass selection in spillway design were also identified. These include climate, soils, land systems, and quality and duration of discharge, growth characteristics, hydraulic behaviour, and maintenance. It was concluded that additional research is needed regarding methods of establishing grass cover to inlets and outlet spillway. In particular, there is a need to evaluate the growth of grasses through plastic meshes and geotextiles, which could provide protection against erosion while the grass is becoming established. 10 refs., 4 tabs.

  9. Minimum Wages and Anti-Poverty Policies (Japanese)

    OpenAIRE

    Ohtake, Fumio

    2013-01-01

    This paper examines the effectiveness of minimum wages as an anti-poverty policy based on the textbook labor market model and recent empirical research. In a competitive labor market, it is well known that minimum wages either have a negative or no effect on employment. In a monopsony labor market, a rise in the minimum wage rate may increase both wages and employment. Although most of the empirical research on this topic overseas show that an increase in minimum wages decreases employment, s...

  10. 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.

  11. Carlsbad Area Office vehicle safety program

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    The Carlsbad Area Office (CAO) Vehicle Safety Program (VSP) establishes the minimum requirements for CAO personnel to safely operate government vehicles and provides direction to effectively reduce the number of vehicle accidents, reduce the severity of vehicle accidents, and minimize vehicular property damage. This Program covers the operations of Government Services Administration (GSA) vehicles, rental or leased vehicles, and special purpose vehicles used at the Waste Isolation Pilot Plant (WIPP) in the performance of work. Additionally, this Program encourages CAO employees to use safe driving habits while operating their privately owned vehicles, motorcycles, or bicycles, or, as pedestrians, to be aware of the hazards associated with traffic in and around CAO facilities. Vehicle safety is a shared responsibility in this organization. At anytime a CAO employee witnesses an unsafe act relating to the operation of a motor vehicle, it is their responsibility to notify their Team Leader (TL) or Assistant Manager (AM), or contact the CAO Safety and Occupational Health Manager (SOHM). Employees are encouraged to participate in the Carlsbad Area Office Federal Employees Safety Committee (FESC) activities and goals in order to address vehicle safety concerns. The FESC is designed to be a forum for all federal employees to improve the health and safety of the organization. The VSP is an effective method of ensuring the health and safety of CAO employees during the operation of government vehicles. The human resources of the CAO are the most valuable assets of this organization and any lost manhours are difficult to replace. Safe driving habits and defensive driving methods should always be practiced to preserve the health and safety of all employees.

  12. Accumulation of Deleterious Mutations Near Sexually Antagonistic Genes

    Directory of Open Access Journals (Sweden)

    Tim Connallon

    2016-08-01

    Full Text Available 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.

  13. Ubiquitination profiling identifies sensitivity factors for IAP antagonist treatment.

    Science.gov (United States)

    Varfolomeev, Eugene; Izrael-Tomasevic, Anita; Yu, Kebing; Bustos, Daisy; Goncharov, Tatiana; Belmont, Lisa D; Masselot, Alexandre; Bakalarski, Corey E; Kirkpatrick, Donald S; Vucic, Domagoj

    2015-02-15

    Evasion of cell death is one crucial capability acquired by tumour cells to ward-off anti-tumour therapies and represents a fundamental challenge to sustaining clinical efficacy for currently available agents. Inhibitor of apoptosis (IAP) proteins use their ubiquitin E3 ligase activity to promote cancer cell survival by mediating proliferative signalling and blocking cell death in response to diverse stimuli. Using immunoaffinity enrichment and MS, ubiquitination sites on thousands of proteins were profiled upon initiation of cell death by IAP antagonists in IAP antagonist-sensitive and -resistant breast cancer cell lines. Our analyses identified hundreds of proteins with elevated levels of ubiquitin-remnant [K-GG (Lys-Gly-Gly)] peptides upon activation of cell death by the IAP antagonist BV6. The majority of these were observed in BV6-sensitive, but not-resistant, cells. Among these were known pro-apoptotic regulators, including CYC (cytochrome c), RIP1 (receptor-interacting protein 1) and a selection of proteins known to reside in the mitochondria or regulate NF-κB (nuclear factor κB) signalling. Analysis of early time-points revealed that IAP antagonist treatment stimulated rapid ubiquitination of NF-κB signalling proteins, including TRAF2 [TNF (tumour necrosis factor) receptor-associated factor 2], HOIL-1 (haem-oxidized iron-regulatory protein 2 ubiquitin ligase-1), NEMO (NF-κB essential modifier), as well as c-IAP1 (cellular IAP1) auto-ubiquitination. Knockdown of several NF-κB pathway members reduced BV6-induced cell death and TNF production in sensitive cell lines. Importantly, RIP1 was found to be constitutively ubiquitinated in sensitive breast-cancer cell lines at higher basal level than in resistant cell lines. Together, these data show the diverse and temporally defined roles of protein ubiquitination following IAP-antagonist treatment and provide critical insights into predictive diagnostics that may enhance clinical efficacy.

  14. Safety-barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2007-01-01

    are discussed. A simple method for quantification of safety-barrier diagrams is proposed, including situations where safety barriers depend on shared common elements. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk......Safety-barrier diagrams and the related so-called "bow-tie" diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation with other methods such as fault trees and Bayesian networks...... analysis with operational safety management....

  15. Safety-in-numbers

    DEFF Research Database (Denmark)

    Elvik, Rune; Bjørnskau, Torkel

    2017-01-01

    Highlights •26 studies of the safety-in-numbers effect are reviewed. •The existence of a safety-in-numbers effect is confirmed. •Results are consistent. •Causes of the safety-in-numbers effect are incompletely known.......Highlights •26 studies of the safety-in-numbers effect are reviewed. •The existence of a safety-in-numbers effect is confirmed. •Results are consistent. •Causes of the safety-in-numbers effect are incompletely known....

  16. Beyond safety accountability

    CERN Document Server

    Geller, E Scott

    2001-01-01

    Written in an easy-to-read conversational tone, Beyond Safety Accountability explains how to develop an organizational culture that encourages people to be accountable for their work practices and to embrace a higher sense of personal responsibility. The author begins by thoroughly explaining the difference between safety accountability and safety responsibility. He then examines the need of organizations to improve safety performance, discusses why such performance improvement can be achieved through a continuous safety process, as distinguished from a safety program, and provides the practic

  17. Safety KPIs - Monitoring of safety performance

    Directory of Open Access Journals (Sweden)

    Andrej Lališ

    2014-09-01

    Full Text Available This paper aims to provide brief overview of aviation safety development focusing on modern trends represented by implementation of Safety Key Performance Indicators. Even though aviation is perceived as safe means of transport, it is still struggling with its complexity given by long-term growth and robustness which it has reached today. Thus nowadays safety issues are much more complex and harder to handle than ever before. We are more and more concerned about organizational factors and control mechanisms which have potential to further increase level of aviation safety. Within this paper we will not only introduce the concept of Key Performance Indicators in area of aviation safety as an efficient control mechanism, but also analyse available legislation and documentation. Finally we will propose complex set of indicators which could be applied to Czech Air Navigation Service Provider.

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

    OpenAIRE

    Partridge, Mark D.; 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...

  19. Design, synthesis, and structure-activity relationship of novel CCR2 antagonists.

    Science.gov (United States)

    Kothandaraman, Shankaran; Donnely, Karla L; Butora, Gabor; Jiao, Richard; Pasternak, Alexander; Morriello, Gregori J; Goble, Stephen D; Zhou, Changyou; Mills, Sander G; Maccoss, Malcolm; Vicario, Pasquale P; Ayala, Julia M; Demartino, Julie A; Struthers, Mary; Cascieri, Margaret A; Yang, Lihu

    2009-03-15

    A series of novel 1-aminocyclopentyl-3-carboxyamides incorporating substituted tetrahydropyran moieties have been synthesized and subsequently evaluated for their antagonistic activity against the human CCR2 receptor. Among them analog 59 was found to posses potent antagonistic activity.

  20. 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.

  1. Effects of Food Safety Standards on Seafood Exports to US, EU and Japan

    OpenAIRE

    Van Nguyen, Anh Thi; Wilson, Norbert L.W.

    2009-01-01

    Estimating the panel gravity model with bilateral pair and country-by-time fixed-effects separately for each seafood product, we found that food safety regulations have differential effects across seafood products. In all three industrialized markets, shrimp is most sensitive, while fish is the least sensitive to changing food safety policies. The enforcement of the US HACCP, the EU Minimum Required Performance Level and the Japanese Food Safety Basic Law caused a loss of 90.45%, 99.47%, and ...

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

    Science.gov (United States)

    Martins, José M.; Galinari, Éder; Pimentel-Filho, Natan J.; Ribeiro, José I.; Furtado, Mauro M.; Ferreira, Célia L.L.F.

    2015-01-01

    Physical, physicochemical, and microbiological changes were monitored in 256 samples of artisanal Minas cheese from eight producers from Serro region (Minas Gerais, Brazil) for 64 days of ripening to determine the minimum ripening time for the cheese to reach the safe microbiological limits established by Brazilian legislation. The cheeses were produced between dry season (April–September) and rainy season (October–March); 128 cheeses were ripened at room temperature (25 ± 4 °C), and 128 were ripened under refrigeration (8 ± 1 °C), as a control. No Listeria monocytogenes was found, but one cheese under refrigeration had Salmonella at first 15 days of ripening. However, after 22 days, the pathogen was not detected. Seventeen days was the minimum ripening time at room temperature to reduce at safe limits of total coliforms > 1000 cfu.g −1 ), Escherichia coli and Staphylococcus aureus (> 100 cfu.g −1 ) in both periods of manufacture. Otherwise under refrigeration, as expected, the minimum ripening time was longer, 33 days in the dry season and 63 days in the rainy season. To sum up, we suggest that the ripening of artisanal Minas cheese be done at room temperature, since this condition shortens the time needed to reach the microbiological quality that falls within the safety parameters required by Brazilian law, and at the same time maintain the appearance and flavor characteristics of this traditional cheese. PMID:26221111

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

    Directory of Open Access Journals (Sweden)

    José M. Martins

    2015-03-01

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

  4. Gun Safety (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Gun Safety KidsHealth > For Parents > Gun Safety Print A ... unloaded, and the ammunition should be stored separately. Guns and Pretend Play Allowing kids to play with ...

  5. Medicine safety and children

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000619.htm Medicine safety and children To use the sharing features ... especially careful if you have toddlers around. Keep Medicines out of Reach and Sight Safety tips: DO ...

  6. Water safety and drowning

    Science.gov (United States)

    ... among people of all ages. Learning and practicing water safety is important to prevent drowning accidents. ... Water safety tips for all ages include: Learn CPR Never swim alone Never dive into water unless ...

  7. Fires and Food Safety

    Science.gov (United States)

    ... Standard Forms FSIS United States Department of Agriculture Food Safety and Inspection Service About FSIS District Offices Careers ... Viewer (JSR 286) Actions ${title} Loading... Fires and Food Safety Fire! Few words can strike such terror. Residential ...

  8. 49 CFR 236.0 - Applicability, minimum requirements, and penalties.

    Science.gov (United States)

    2010-10-01

    ... requirements of subpart H of this part apply to safety-critical processor-based signal and train control... preempts the field of locomotive safety, extending to the design, the construction, and the material...

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

    Directory of Open Access Journals (Sweden)

    Changyu Pan

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  11. Electrical safety guidelines

    Energy Technology Data Exchange (ETDEWEB)

    1993-09-01

    The Electrical Safety Guidelines prescribes the DOE safety standards for DOE field offices or facilities involved in the use of electrical energy. It has been prepared to provide a uniform set of electrical safety standards and guidance for DOE installations in order to affect a reduction or elimination of risks associated with the use of electrical energy. The objectives of these guidelines are to enhance electrical safety awareness and mitigate electrical hazards to employees, the public, and the environment.

  12. Generic safety documentation model

    Energy Technology Data Exchange (ETDEWEB)

    Mahn, J.A.

    1994-04-01

    This document is intended to be a resource for preparers of safety documentation for Sandia National Laboratories, New Mexico facilities. It provides standardized discussions of some topics that are generic to most, if not all, Sandia/NM facilities safety documents. The material provides a ``core`` upon which to develop facility-specific safety documentation. The use of the information in this document will reduce the cost of safety document preparation and improve consistency of information.

  13. DOE handbook electrical safety

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-01-01

    Electrical Safety Handbook presents the Department of Energy (DOE) safety standards for DOE field offices or facilities involved in the use of electrical energy. It has been prepared to provide a uniform set of electrical safety guidance and information for DOE installations to effect a reduction or elimination of risks associated with the use of electrical energy. The objectives of this handbook are to enhance electrical safety awareness and mitigate electrical hazards to employees, the public, and the environment.

  14. Safety of probiotics

    OpenAIRE

    Gueimonde, Miguel; Ouwehand, Arthur C.; Salminen, Seppo

    2004-01-01

    The use of probiotics in foods has increased significantly and there are more and more products available with high numbers of viable probiotics. This article reviews the safety information on probiotic microorganisms. A literature search and assessment of safety data on current probiotics were undertaken. No significant safety concerns for current probiotics were observed. The available data attest to the safety of Lactobacillus and Bifidobacterium probiotics. In conclusion, current probioti...

  15. Modern technologies and food safety

    Directory of Open Access Journals (Sweden)

    Grujić Radoslav

    2003-01-01

    Full Text Available To resolve the problem of lack of food in the World within primary food production, processing and procedures of preserving, new methods have been implemented (implementation of materials for protection, medications utilization of new areas for production purposes, use of GM microorganisms plants, even animals, utilization of food additives, introduction of new procedures of preservation, etc However, these procedures do not always move in the direction of ensuring food safety. Implementation of mentioned procedures creates resistance by consumers. The opinion and the attitude about this issue are very important all over the World. According to recent research performed in last five years, most of the population of developed and semi-developed countries considers food safety a priority, as second place the presence of ingredients that can be harmful for human health and as third the content of nutrients required for normal functioning of the body. The WHO, CAC, WTO and other international institutions support these attitudes of consumers. There is more and more obvious pressure on food producers to preserve the environment, which has resulted in the introduction of production procedures known as "cleaning production".Regardless of which procedure is involved, it is necessary to implement the efficient quality control system and food safety. It is mandatory to request the compulsory implementation of different systems that are defined through the GMR GHR HACCR ISO 9000. In food production, these systems are complementary and only with full implementation of all of them in practice will if be possible to ensure the continuous production of quality and safe products. Food production must be seen as an undisturbed chain: primary production, transport, processing, storage, distribution and consumption. With strict implementation of the mentioned standards in all parts of the chain, the risk of injuries and poisoning of consumers will be decreased to

  16. Multiple Objective Minimum Cost Flow Problems: A Review

    DEFF Research Database (Denmark)

    Hamacher, H.W.; Pedersen, Christian Roed; Ruzika, S.

    2005-01-01

    In this paper, theory and algorithms for solving the multiple objective minimum cost flow problem are reviewed. For both the continuous and integer case exact and approximation algorithms are presented. In addition, a section on compromise solutions summarizes corresponding results. The reference...... list consists of all papers known to the authors which deal with the multiple objective minimum cost flow problem....

  17. 14 CFR 93.311 - Minimum terrain clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Minimum terrain clearance. 93.311 Section 93.311 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED... of Grand Canyon National Park, AZ § 93.311 Minimum terrain clearance. Except in an emergency,...

  18. 33 CFR 157.455 - Minimum under-keel clearance.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Minimum under-keel clearance. 157... § 157.455 Minimum under-keel clearance. (a) The owner or operator of a tankship, that is not fitted with... written under-keel clearance guidance that includes— (1) Factors to consider when calculating the...

  19. 77 FR 43196 - Minimum Internal Control Standards and Technical Standards

    Science.gov (United States)

    2012-07-24

    ... COMMISSION 25 CFR Parts 543 and 547 Minimum Internal Control Standards and Technical Standards AGENCY... . SUPPLEMENTARY INFORMATION: Part 543 addresses minimum internal control standards (MICS) for Class II gaming operations. The regulations require tribes to establish controls and implement procedures at least...

  20. 49 CFR 236.562 - Minimum rail current required.

    Science.gov (United States)

    2010-10-01

    ..., INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Rules and Instructions; Locomotives § 236.562 Minimum rail current required. The minimum rail current required to restore the locomotive equipment...

  1. 7 CFR 1610.5 - Minimum Bank loan.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Minimum Bank loan. 1610.5 Section 1610.5 Agriculture Regulations of the Department of Agriculture (Continued) RURAL TELEPHONE BANK, DEPARTMENT OF AGRICULTURE LOAN POLICIES § 1610.5 Minimum Bank loan. A Bank loan will not be made unless the applicant qualifies for a...

  2. State Minimum Core Curricula: Arkansas Institutions of Higher Education.

    Science.gov (United States)

    Arkansas State Dept. of Higher Education, Little Rock.

    State minimum core curricula for two-year and four-year colleges and universities have been approved by the Arkansas Board of Higher Education. Within the framework of the State Minimum Core, each state institution is required to propose 35 semester/credit hours from its institutional general education core to be recognized for purposes of the…

  3. 14 CFR 93.307 - Minimum flight altitudes.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Minimum flight altitudes. 93.307 Section 93...) AIR TRAFFIC AND GENERAL OPERATING RULES SPECIAL AIR TRAFFIC RULES Special Flight Rules in the Vicinity of Grand Canyon National Park, AZ § 93.307 Minimum flight altitudes. Except in an emergency, or...

  4. 30 CFR 77.606-1 - Rubber gloves; minimum requirements.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Rubber gloves; minimum requirements. 77.606-1... COAL MINES Trailing Cables § 77.606-1 Rubber gloves; minimum requirements. (a) Rubber gloves (lineman's... be used and tested in accordance with the provisions of §§ 77.704-6 through 77.704-8. (b)...

  5. 42 CFR 422.382 - Minimum net worth amount.

    Science.gov (United States)

    2010-10-01

    ... depreciated value of health care delivery assets (HCDAs) to satisfy the minimum net worth amount. (4) Other assets. A PSO may apply other assets not used in the delivery of health care provided that those assets... 42 Public Health 3 2010-10-01 2010-10-01 false Minimum net worth amount. 422.382 Section...

  6. 12 CFR 615.5205 - Minimum permanent capital standards.

    Science.gov (United States)

    2010-01-01

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

  7. 14 CFR 23.149 - Minimum control speed.

    Science.gov (United States)

    2010-01-01

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

  8. Solution of the Schroedinger equation for a double minimum potential

    Science.gov (United States)

    Goorvitch, D.; Galant, D. C.

    1992-01-01

    We apply Richardson's extrapolation to zero mesh size to calculate the dissociation energies and wavefunctions of a double minimum potential curve for the E,F1Sigma(+)g state of H2. We demonstrate that a double minimum potential presents no difficulties and that this extrapolation method is to be preferred over a quadratic extrapolation or the use of a basis expansion.

  9. 5 CFR 551.601 - Minimum age standards.

    Science.gov (United States)

    2010-01-01

    ... ADMINISTRATION UNDER THE FAIR LABOR STANDARDS ACT Child Labor § 551.601 Minimum age standards. (a) 16-year... subject to its child labor provisions, with certain exceptions not applicable here. (b) 18-year minimum... occupation found and declared by the Secretary of Labor to be particularly hazardous for the employment...

  10. 29 CFR 541.604 - Minimum guarantee plus extras.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Minimum guarantee plus extras. 541.604 Section 541.604 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS... SALES EMPLOYEES Salary Requirements § 541.604 Minimum guarantee plus extras. (a) An employer may...

  11. Minimum fatigue pre-crack extension for fracture testing

    NARCIS (Netherlands)

    Walters, C.L.; Voormeeren, L.O.

    2013-01-01

    The minimum pre-crack necessary to achieve an accurate measurement of the J-integral is examined with the use of elastic-plastic finite element analysis. This minimum pre-crack is shorter than what is specified in fracture codes ASTM E1820 and BS 7448. A variety of steel properties are considered, b

  12. 30 CFR 75.1431 - Minimum rope strength.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Minimum rope strength. 75.1431 Section 75.1431... strength. At installation, the nominal strength (manufacturer's published catalog strength) of wire ropes used for hoisting shall meet the minimum rope strength values obtained by the following formulas...

  13. 42 CFR 84.197 - Respirator containers; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Respirator containers; minimum requirements. 84.197... Cartridge Respirators § 84.197 Respirator containers; minimum requirements. Respirators shall be equipped... commercial designation of the respirator it contains and all appropriate approval labels....

  14. 42 CFR 84.1134 - Respirator containers; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Respirator containers; minimum requirements. 84..., Fume, and Mist; Pesticide; Paint Spray; Powered Air-Purifying High Efficiency Respirators and Combination Gas Masks § 84.1134 Respirator containers; minimum requirements. (a) Except as provided...

  15. 42 CFR 84.134 - Respirator containers; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Respirator containers; minimum requirements. 84.134... Respirators § 84.134 Respirator containers; minimum requirements. Supplied-air respirators shall be equipped... commercial designation of the respirator it contains, and all appropriate approval labels....

  16. 42 CFR 84.174 - Respirator containers; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Respirator containers; minimum requirements. 84.174... Air-Purifying Particulate Respirators § 84.174 Respirator containers; minimum requirements. (a) Except as provided in paragraph (b) of this section each respirator shall be equipped with a...

  17. 47 CFR 22.951 - Minimum coverage requirement.

    Science.gov (United States)

    2010-10-01

    ... MOBILE SERVICES Cellular Radiotelephone Service § 22.951 Minimum coverage requirement. Applications for... toward the minimum coverage requirement. Applications for authority to operate a new cellular system in... reefs only), except for unserved areas in the Gulf of Mexico MSA....

  18. 46 CFR 111.60-4 - Minimum cable conductor size.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Minimum cable conductor size. 111.60-4 Section 111.60-4...-GENERAL REQUIREMENTS Wiring Materials and Methods § 111.60-4 Minimum cable conductor size. Each cable conductor must be #18 AWG (0.82 mm2) or larger except— (a) Each power and lighting cable conductor must...

  19. Theoretical minimum energies to produce steel for selected conditions

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-03-01

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

  20. 12 CFR 932.8 - Minimum liquidity requirements.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Minimum liquidity requirements. 932.8 Section... CAPITAL STANDARDS FEDERAL HOME LOAN BANK CAPITAL REQUIREMENTS § 932.8 Minimum liquidity requirements. In addition to meeting the deposit liquidity requirements contained in § 965.3 of this chapter, each...

  1. The impact of minimum wages on youth employment in Portugal

    NARCIS (Netherlands)

    S.C. Pereira

    2003-01-01

    textabstractFrom January 1, 1987, the legal minimum wage for workers aged 18 and 19 in Portugal was uprated to the full adult rate, generating a 49.3% increase between 1986 and 1987 in the legal minimum wage for this age group. This shock is used as a ?natural experiment? to evaluate the impact of t

  2. Minimum Competencies in Undergraduate Motor Development. Guidance Document

    Science.gov (United States)

    National Association for Sport and Physical Education, 2004

    2004-01-01

    The minimum competency guidelines in Motor Development described herein at the undergraduate level may be gained in one or more motor development course(s) or through other courses provided in an undergraduate curriculum. The minimum guidelines include: (1) Formulation of a developmental perspective; (2) Knowledge of changes in motor behavior…

  3. 27 CFR 40.526 - Minimum manufacturing and activity requirements.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Minimum manufacturing and activity requirements. 40.526 Section 40.526 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... Manufacturers of Processed Tobacco § 40.526 Minimum manufacturing and activity requirements. A permit...

  4. 28 CFR 2.76 - Reduction in minimum sentence.

    Science.gov (United States)

    2010-07-01

    ... OF PRISONERS, YOUTH OFFENDERS, AND JUVENILE DELINQUENTS District of Columbia Code: Prisoners and... minimum term of his or her sentence may request the Commission to file an application with the sentencing... application to the sentencing court for a reduction of a prisoner's minimum term if the Commission finds...

  5. 14 CFR 135.93 - Autopilot: Minimum altitudes for use.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Autopilot: Minimum altitudes for use. 135... Operations § 135.93 Autopilot: Minimum altitudes for use. (a) Except as provided in paragraphs (b), (c), (d), and (e) of this section, no person may use an autopilot at an altitude above the terrain which is...

  6. 42 CFR 84.79 - Breathing gas; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing gas; minimum requirements. 84.79 Section...-Contained Breathing Apparatus § 84.79 Breathing gas; minimum requirements. (a) Breathing gas used to supply... respiratory tract irritating compounds. (c) Compressed, gaseous breathing air shall meet the...

  7. 42 CFR 84.122 - Breathing resistance test; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing resistance test; minimum requirements. 84... Masks § 84.122 Breathing resistance test; minimum requirements. (a) Resistance to airflow will be measured in the facepiece or mouthpiece of a gas mask mounted on a breathing machine both before and...

  8. 42 CFR 84.115 - Breathing tubes; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing tubes; minimum requirements. 84.115 Section 84.115 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL... § 84.115 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with...

  9. 42 CFR 84.72 - Breathing tubes; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing tubes; minimum requirements. 84.72...-Contained Breathing Apparatus § 84.72 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with breathing apparatus shall be designed and constructed to prevent: (a)...

  10. 42 CFR 84.203 - Breathing resistance test; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing resistance test; minimum requirements. 84.203 Section 84.203 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Chemical Cartridge Respirators § 84.203 Breathing resistance test; minimum requirements. (a) Resistance...

  11. 42 CFR 84.85 - Breathing bags; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing bags; minimum requirements. 84.85 Section...-Contained Breathing Apparatus § 84.85 Breathing bags; minimum requirements. (a) Breathing bags shall have.... (b) Breathing bags shall be constructed of materials which are flexible and resistant to...

  12. 42 CFR 84.172 - Breathing tubes; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Breathing tubes; minimum requirements. 84.172... Air-Purifying Particulate Respirators § 84.172 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with respirators shall be designed and constructed to prevent:...

  13. General safety considerations

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-09-01

    This document presents the full filling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 4 of the document contains some details about the priority to safety, financial and human resources, human factors, quality assurance, safety assessment and verification, radiation protection and emergency preparedness.

  14. General safety considerations

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-09-01

    This document presents the full filling of the Brazilian obligations under the Convention on Nuclear Safety. The Chapter 4 of the document contains some details about the priority to safety, financial and human resources, human factors, quality assurance, safety assessment and verification, radiation protection and emergency preparedness.

  15. Design and discovery of 1,3-benzodiazepines as novel dopamine antagonists.

    Science.gov (United States)

    Zhu, Zhaoning; Sun, Zhong-Yue; Ye, Yuanzan; McKittrick, Brian; Greenlee, William; Czarniecki, Michael; Fawzi, Ahmad; Zhang, Hongtao; Lachowicz, Jean E

    2009-09-01

    A series of novel 1,3-benzodiazapine based D1 antagonists was designed according to the understanding of pharmacophore models derived from SCH 23390 (1b), a potent and selective D1 antagonist. The new design features an achiral cyclic-amidine that maintains desired basicity. Solid phase synthesis was developed for SAR development of the novel dopamine antagonists.

  16. NP-Completeness Results for Minimum Planar Spanners

    Directory of Open Access Journals (Sweden)

    Ulrik Brandes

    1998-12-01

    Full Text Available For any fixed parameter t greater or equal to 1, a t-spanner of a graph G is a spanning subgraph in which the distance between every pair of vertices is at most t times their distance in G. A minimum t-spanner is a t-spanner with minimum total edge weight or, in unweighted graphs, minimum number of edges. In this paper, we prove the NP-hardness of finding minimum t-spanners for planar weighted graphs and digraphs if t greater or equal to 3, and for planar unweighted graphs and digraphs if t greater or equal to 5. We thus extend results on that problem to the interesting case where the instances are known to be planar. We also introduce the related problem of finding minimum planar t-spanners and establish its NP-hardness for similar fixed values of t.

  17. AN ANT COLONY ALGORITHM FOR MINIMUM UNSATISFIABLE CORE EXTRACTION

    Institute of Scientific and Technical Information of China (English)

    Zhang Jianmin; Shen Shengyu; Li Sikun

    2008-01-01

    Explaining the causes of infeasibility of Boolean formulas has many practical applications in electronic design automation and formal verification of hardware. Furthermore,a minimum explanation of infeasibility that excludes all irrelevant information is generally of interest. A smallest-cardinality unsatisfiable subset called a minimum unsatisfiable core can provide a succinct explanation of infea-sibility and is valuable for applications. However,little attention has been concentrated on extraction of minimum unsatisfiable core. In this paper,the relationship between maximal satisfiability and mini-mum unsatisfiability is presented and proved,then an efficient ant colony algorithm is proposed to derive an exact or ncarly exact minimum unsatisfiable core based on the relationship. Finally,ex-perimental results on practical benchmarks compared with the best known approach are reported,and the results show that the ant colony algorithm strongly outperforms the best previous algorithm.

  18. Minimum Variance Portfolios in the Brazilian Equity Market

    Directory of Open Access Journals (Sweden)

    Alexandre Rubesam

    2013-03-01

    Full Text Available We investigate minimum variance portfolios in the Brazilian equity market using different methods to estimate the covariance matrix, from the simple model of using the sample covariance to multivariate GARCH models. We compare the performance of the minimum variance portfolios to those of the following benchmarks: (i the IBOVESPA equity index, (ii an equally-weighted portfolio, (iii the maximum Sharpe ratio portfolio and (iv the maximum growth portfolio. Our results show that the minimum variance portfolio has higher returns with lower risk compared to the benchmarks. We also consider long-short 130/30 minimum variance portfolios and obtain similar results. The minimum variance portfolio invests in relatively few stocks with low βs measured with respect to the IBOVESPA index, being easily replicable by individual and institutional investors alike.

  19. Effects of protocol design on lactate minimum power.

    Science.gov (United States)

    Johnson, M A; Sharpe, G R

    2011-03-01

    The aim of this investigation was to use a validated lactate minimum test protocol and evaluate whether blood lactate responses and the lactate minimum power are influenced by the starting power (study 1) and 1 min inter-stage rest intervals (study 2) during the incremental phase. Study 1: 8 subjects performed a lactate minimum test comprising a lactate elevation phase, recovery phase, and incremental phase comprising 5 continuous 4 min stages with starting power being 40% or 45% of the maximum power achieved during the lactate elevation phase, and with power increments of 5% maximum power. Study 2: 8 subjects performed 2 identical lactate minimum tests except that during one of the tests the incremental phase included 1 min inter-stage rest intervals. The lactate minimum power was lower when the incremental phase commenced at 40% (175±29 W) compared to 45% (184±30 W) maximum power (pvalidity and therefore training status evaluation and exercise prescription.

  20. Estimation of minimum surface temperature at stage ll (Short Communication

    Directory of Open Access Journals (Sweden)

    A. P. Dimri

    2001-04-01

    Full Text Available Forecasting minimum surface temperature at a station, Stage II, located in mountainous region requires information on the meteorological fields. An attempt has been made to develop a statistical model for forecasting minimum temperature at ground level using previous years' data. Surface data were collected at StageII (longitude 73 oB, latitude 34 oN, and altitude 2650 m. Atmospheric variables are influenced by complex orography and surface features to a great extent. In the present study, statistical relationship between atmosphere parameters and minimum temperature at the site has been established. Multivariate linear regression analysis has been used to establish the relationship to predict the minimum surface temperature for the following day. A comparison between the observed and the calculated forecast minimum temperature has been made. Most of the cases are well predicted (multiple correlation coefficient of 0.94.

  1. Leadership and safety culture. Leadership for safety

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Erwin; Nithack, Eckhard [PreussenElektra GmbH, Hannover (Germany)

    2016-08-15

    The meaning of leadership for safety in the nuclear industry is pointed out. This topic has became an increasing rank since the German ''Energiewende''. Despite the phase-out of the German NPP's nuclear safety and the belonging safety culture needs to be well maintained. A challenge for the whole organisation. Following the challenge to operate nuclear power plants towards Operational Excellence a highly skilled and motivated organisation is needed. Therefore Leadership is a valuable success factor.

  2. 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.

  3. 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.

  4. 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.

  5. Anti-antimicrobial peptides: folding-mediated host defense antagonists.

    Science.gov (United States)

    Ryan, Lloyd; Lamarre, Baptiste; Diu, Ting; Ravi, Jascindra; Judge, Peter J; Temple, Adam; Carr, Matthew; Cerasoli, Eleonora; Su, Bo; Jenkinson, Howard F; Martyna, Glenn; Crain, Jason; Watts, Anthony; Ryadnov, Maxim G

    2013-07-12

    Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance.

  6. Churg-Strauss syndrome associated with leukotriene receptor antagonists (LTRA).

    Science.gov (United States)

    Cuchacovich, R; Justiniano, M; Espinoza, L R

    2007-10-01

    Churg-Strauss syndrome (CSS) is a rare vasculitic disorder that generally occurs in patients with bronchial asthma. CSS is being increasingly recognized in asthmatic patients treated with leukotriene receptor antagonists. However, the nature of this relationship remains to be elucidated. The present report describes three asthmatic patients who developed clinical manifestations highly suggestive of CSS, although one patient lacked the presence of eosinophilia. The patient, however, exhibited biopsy-proven cutaneous necrotizing vasculitis, which improved after withdrawal of montelukast. The second patient presented with systemic constitutional signs including fever, malaise, arthralgias, clinical jaundice, peripheral blood eosinophilia, and biopsy-proven eosinophilic hepatitis. The third patient also had circulating eosinophilia, scleritis, and arthritis. All patients improved after discontinuation of the leukotriene receptor antagonist (montelukast).

  7. 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.

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

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen

    1996-01-01

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

  9. Non-imidazole histamine NO-donor H3-antagonists.

    Science.gov (United States)

    Tosco, Paolo; Bertinaria, Massimo; Di Stilo, Antonella; Cena, Clara; Fruttero, Roberta; Gasco, Alberto

    2005-01-01

    Recently a series of H3-antagonists related to Imoproxifan was realised (I); in these products the oxime substructure of the lead was constrained in NO-donor furoxan systems and in the corresponding furazan derivatives. In this paper, a new series of compounds derived from I by substituting the imidazole ring with the ethoxycarbonylpiperazino moiety present in the non-imidazole H3-ligand A-923 is described. For all the products synthesis and preliminary pharmacological characterisation, as well as their hydrophilic-lipophilic balance, are reported. The imidazole ring replacement generally results in a decreased H3-antagonist activity with respect to the analogues of series I and, in some cases, induces relaxing effects on the electrically contracted guinea-pig ileum, probably due to increased affinity for other receptor systems.

  10. Nuclear safety in perspective

    DEFF Research Database (Denmark)

    Andersson, K.; Sjöberg, B.M.D.; Lauridsen, Kurt

    2003-01-01

    The aim of the NKS/SOS-1 project has been to enhance common understanding about requirements for nuclear safety by finding improved means of communicat-ing on the subject in society. The project, which has been built around a number of seminars, wassupported by limited research in three sub......-projects: Risk assessment Safety analysis Strategies for safety management The report describes an industry in change due to societal factors. The concepts of risk and safety, safety management and systems forregulatory oversight are de-scribed in the nuclear area and also, to widen the perspective, for other...

  11. Safety survives privatisation

    Energy Technology Data Exchange (ETDEWEB)

    Cunnigham, P. [Health and Safety Executive, Sheffield (United Kingdom)

    1995-01-01

    The privatisation of British Coal will have no effect on safety standards in the industry since the new companies will still be governed by the same safety regulations. The Health and Safety Executive does not just inspect, it relies also on information exchange, in the surface mining sector particularly through the quarries National Interest Group, since good health and safety working practices save money. Future trends include compliance with the European Community directives on health and safety, although much of this is covered already. 3 figs.

  12. Safety Study in Aviation

    Directory of Open Access Journals (Sweden)

    Marek Štumper

    2016-07-01

    Full Text Available The objective of this article is to provide a brief look at safety studies, which are a necessary part of every change of system or a new system in aviation. The main focus is put on the area of air traffic management, because it affects most of the aviation stakeholders. The article begins with a description of safety and safety assessment of changes in systems. Then it discusses analysis of processes, hazard identification and risk assessment. Main part focuses on Safety studies and briefly describes the elements of the study. At the end, possible ways of safety study evaluation are mentioned.

  13. Safety in Cryogenics – Safety device sizing

    CERN Document Server

    CERN. Geneva

    2016-01-01

    The calculation is separated in three operations: o The estimation of the loads arriving on the component to protect, o The calculation of the mass flow to evacuate, o And the sizing of the safety device.

  14. Safety & Regulatory Strategy : Food Safety and Innovation

    NARCIS (Netherlands)

    Kalk, C.

    2013-01-01

    Food and feed safety is strictly regulated within the EU. Our team of toxicologists, risk assessors and consultants offers strategic advice and valuable expertise in regulatory affairs and health risk assessment.

  15. Enhanced Chronic Pain Management Utilizing Chemokine Receptor Antagonists

    Science.gov (United States)

    2016-08-01

    Center for Substance Abuse Research Lewis Katz School of Medicine at Temple University 3500 N, Broad Street Philadelphia, PA 19140 AND ADDRESS(ES) 8...processes), affect the ability of opioid drugs to counteract pain. We predicted that one way of increasing the effectiveness of the pain-relieving... drugs would be to eliminate or reduce the activity of the chemokines by administering chemokine receptor antagonists (CRAs). The blockade of one or

  16. Potent and orally efficacious benzothiazole amides as TRPV1 antagonists.

    Science.gov (United States)

    Besidski, Yevgeni; Brown, William; Bylund, Johan; Dabrowski, Michael; Dautrey, Sophie; Harter, Magali; Horoszok, Lucy; Hu, Yin; Johnson, Dean; Johnstone, Shawn; Jones, Paul; Leclerc, Sandrine; Kolmodin, Karin; Kers, Inger; Labarre, Maryse; Labrecque, Denis; Laird, Jennifer; Lundström, Therese; Martino, John; Maudet, Mickaël; Munro, Alexander; Nylöf, Martin; Penwell, Andrea; Rotticci, Didier; Slaitas, Andis; Sundgren-Andersson, Anna; Svensson, Mats; Terp, Gitte; Villanueva, Huascar; Walpole, Christopher; Zemribo, Ronald; Griffin, Andrew M

    2012-10-01

    Benzothiazole amides were identified as TRPV1 antagonists from high throughput screening using recombinant human TRPV1 receptor and structure-activity relationships were explored to pinpoint key pharmacophore interactions. By increasing aqueous solubility, through the attachment of polar groups to the benzothiazole core, and enhancing metabolic stability, by blocking metabolic sites, the drug-like properties and pharmokinetic profiles of benzothiazole compounds were sufficiently optimized such that their therapeutic potential could be verified in rat pharmacological models of pain.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    A new series of epiminocyclohepta[b]indoles with potent 5-HT(6) antagonist activity were discovered and optimized using in vitro protocols. One compound from this series was progressed to advanced pharmacokinetic (PK) studies followed by 5-HT(6) receptor occupancy studies. The compound was found...... to have excellent oral absorption, a highly favorable PK profile and demonstrated pharmacodynamic interaction with the 5-HT(6) receptor as shown by ex vivo autoradiography....

  18. Exploration of a new series of PAR1 antagonists.

    Science.gov (United States)

    Planty, Bruno; Pujol, Chantal; Lamothe, Marie; Maraval, Catherine; Horn, Clemens; Le Grand, Bruno; Perez, Michel

    2010-03-01

    Two series of new PAR1 antagonists have been identified. The first incorporates a cinnamoylpiperidine motif and the second a cinnamoylpyridine pattern. The synthesis, biological activity and structure-activity relationship of these compounds are presented. In each series, one analog showed potent in vivo antithrombotic activity in a rat AV shunt model, with up to 53% inhibition at 1.25mpk iv for compound 30.

  19. Mineralocorticoid receptor antagonists: emerging roles in cardiovascular medicine

    OpenAIRE

    Funder JW

    2013-01-01

    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 ...

  20. Pediatric safety pin ingestion.

    Science.gov (United States)

    Sarihan, H; Kaklikkaya, I; Ozcan, F

    1998-08-01

    Fifteen consecutive children with ingested safety pins were evaluated retrospectively. Eight patients were males and seven were girls. The mean age of the patients was 5.4 years ranging from 7 months to 16 years. Two of 15 patients were mentally retarded Seven safety pins ingestion were noted by parents, three older children applied with safety pin swallowing. Three infants referred with hypersalivation and swallowing difficulty. One of two mentally retarded patients had recurrent aspiration pneumonia, the other had neck abscess. These patients' lesions were detected incidentally by thoracic X-ray. Nine safety pins were at the level of the cricopharyngeus, one at the level of the aortic arch and five at the esophagogastric junction. A right esophagoscopy was used for extraction of safety pins under general anesthesia and endotracheal intubation were used. Before esophagoscopy control plain X-ray was obtained for location of safety pin. Nine safety pins were extracted by esophagoscopy. Three safety pins spontaneously and three during anesthesia induction passed through the esophagus falling down the stomach. Five of these six safety pins were spontaneously extracted without complication. However one open safety pin lodged at the duodenum and laparotomy was required. In this article, etiology and management of safety pin ingestion in children are discussed.

  1. Triangle orientation discrimination: the alternative to minimum resolvable temperature difference and minimum resolvable contrast

    Science.gov (United States)

    Bijl, Piet; Valeton, J. Mathieu

    1998-07-01

    The characterization of electro-optical system performance by means of the minimum resolvable temperature difference (MRTD) or the minimum resolvable contrast (MRC) has at least three serious disadvantages: (1) the bar pattern stimulus is theoretically and practically unsuitable for 1D or 2D spatially sampled systems such as pixel-array cameras, (2) spatial phase is not taken into account, and (3) the results depend on the observer's subjective decision criterion. We propose an adequate and easily applicable alternative: the triangle orientation discrimination (TOD) threshold. The TOD is based on an improved test pattern, a better defined observer task, and a solid psychophysical measurement procedure. The method has a large number of theoretical and practical advantages: it is suitable for pixel-array cameras, scanning systems and other electro-optical and optical imaging system sin both the thermal and visual domains, it has a close relationship to real target acquisition, and the observer task is easy. The results are free from observer bias and allow statistical significance tests. The method lends itself very well to automatic measurements, and can be extended for future sensor systems that include advanced image processing. The TOD curve can be implemented easily in a target acquisition (TA) model such as ACQUIRE. An observer performance study with real targets shows that the TOD curve better predicts TA performance than the mRC does. The method has been implemented successfully in a thermal imager field test apparatus called the thermal imager performance indicator and may be implemented in current MRTD test equipment with little effort.

  2. Patient Safety Culture

    DEFF Research Database (Denmark)

    Kristensen, Solvejg

    Patient safety is highly prioritised in the Danish health care system, never the less, patients are still exposed to risk and harmed every day. Implementation of a patient safety culture has been suggested an effective mean to protect patients against adverse events. Working strategically...... with assessment and development of the patient safety culture is in early days in Denmark. It depends upon valid, reliable and effective methods. The patient safety culture represents a wide range of social phenomena permeating the way of life in a health care. In essence, the safety culture is an aggregation...... of health care professional’s behaviour, habits, norms, values, and basic assumptions related to patient care; it is the way things are done. The patient safety culture guides the motivation, commitment to and know-how of the safety management, and how all members of a work place interact. This thesis...

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

    Science.gov (United States)

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

    2015-01-01

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

  4. Synergistic and antagonistic drug combinations depend on network topology.

    Science.gov (United States)

    Yin, Ning; Ma, Wenzhe; Pei, Jianfeng; Ouyang, Qi; Tang, Chao; Lai, Luhua

    2014-01-01

    Drug combinations may exhibit synergistic or antagonistic effects. Rational design of synergistic drug combinations remains a challenge despite active experimental and computational efforts. Because drugs manifest their action via their targets, the effects of drug combinations should depend on the interaction of their targets in a network manner. We therefore modeled the effects of drug combinations along with their targets interacting in a network, trying to elucidate the relationships between the network topology involving drug targets and drug combination effects. We used three-node enzymatic networks with various topologies and parameters to study two-drug combinations. These networks can be simplifications of more complex networks involving drug targets, or closely connected target networks themselves. We found that the effects of most of the combinations were not sensitive to parameter variation, indicating that drug combinational effects largely depend on network topology. We then identified and analyzed consistent synergistic or antagonistic drug combination motifs. Synergistic motifs encompass a diverse range of patterns, including both serial and parallel combinations, while antagonistic combinations are relatively less common and homogenous, mostly composed of a positive feedback loop and a downstream link. Overall our study indicated that designing novel synergistic drug combinations based on network topology could be promising, and the motifs we identified could be a useful catalog for rational drug combination design in enzymatic systems.

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

    Directory of Open Access Journals (Sweden)

    Sachiko Yamada

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

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

    Science.gov (United States)

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

    2016-01-01

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

  7. Histamine H1 antagonists and clinical characteristics of febrile seizures

    Directory of Open Access Journals (Sweden)

    Zolaly MA

    2012-03-01

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

  8. Receptor discrimination and control of agonist-antagonist binding.

    Science.gov (United States)

    Tallarida, R J

    1995-08-01

    The law of mass action is the common model for the interaction of agonist and antagonist compounds with cellular receptors. Parameters of the interaction, obtained from functional and radioligand-binding studies, allow discrimination and subtyping of receptors and aid in understanding specific mechanisms. This article reviews the theory and associated mathematical models and graphical transformations of data that underlie the determination of receptor parameters. The main theory assumes that agonist and antagonist compounds bind to cells that have a fixed number of receptors and provides the framework for obtaining drug-receptor parameters from data and their graphical transformations. Conditions that produce a change in receptor number, a newer concept in pharmacology, can have an important effect on the parameter values derived in the usual way. This review concludes with a discussion of the quantitative study of receptor-mediated feedback control of endogenous ligands, a very new topic with potentially important implications for understanding antagonist effectiveness, loss of control, and chaos in regulated mass action binding.

  9. 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.

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

    Science.gov (United States)

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

    2013-05-15

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

  11. Minimum wall pressure coefficient of orifice plate energy dissipater

    Institute of Scientific and Technical Information of China (English)

    Wan-zheng Ai; Jia-hong Wang

    2015-01-01

    Orifice plate energy dissipaters have been successfully used in large-scale hydropower projects due to their simple structure, convenient construction procedure, and high energy dissipation ratio. The minimum wall pressure coefficient of an orifice plate can indirectly reflect its cavitation characteristics:the lower the minimum wall pressure coefficient is, the better the ability of the orifice plate to resist cavitation damage is. Thus, it is important to study the minimum wall pressure coefficient of the orifice plate. In this study, this coefficient and related parameters, such as the contraction ratio, defined as the ratio of the orifice plate diameter to the flood-discharging tunnel diameter;the relative thickness, defined as the ratio of the orifice plate thickness to the tunnel diameter;and the Reynolds number of the flow through the orifice plate, were theoretically analyzed, and their relationships were obtained through physical model experiments. It can be concluded that the minimum wall pressure coefficient is mainly dominated by the contraction ratio and relative thickness. The lower the contraction ratio and relative thickness are, the larger the minimum wall pressure coefficient is. The effects of the Reynolds number on the minimum wall pressure coefficient can be neglected when it is larger than 105. An empirical expression was presented to calculate the minimum wall pressure coefficient in this study.

  12. Minimum wall pressure coefficient of orifice plate energy dissipater

    Directory of Open Access Journals (Sweden)

    Wan-zheng AI

    2015-01-01

    Full Text Available Orifice plate energy dissipaters have been successfully used in large-scale hydropower projects due to their simple structure, convenient construction procedure, and high energy dissipation ratio. The minimum wall pressure coefficient of an orifice plate can indirectly reflect its cavitation characteristics: the lower the minimum wall pressure coefficient is, the better the ability of the orifice plate to resist cavitation damage is. Thus, it is important to study the minimum wall pressure coefficient of the orifice plate. In this study, this coefficient and related parameters, such as the contraction ratio, defined as the ratio of the orifice plate diameter to the flood-discharging tunnel diameter; the relative thickness, defined as the ratio of the orifice plate thickness to the tunnel diameter; and the Reynolds number of the flow through the orifice plate, were theoretically analyzed, and their relationships were obtained through physical model experiments. It can be concluded that the minimum wall pressure coefficient is mainly dominated by the contraction ratio and relative thickness. The lower the contraction ratio and relative thickness are, the larger the minimum wall pressure coefficient is. The effects of the Reynolds number on the minimum wall pressure coefficient can be neglected when it is larger than 105. An empirical expression was presented to calculate the minimum wall pressure coefficient in this study.

  13. 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......, noninferiority trial. SETTING: Twenty-five infertility centers in seven countries. PATIENT(S): Seven hundred forty-nine women. INTERVENTION(S): Controlled ovarian stimulation with hphMG or rFSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer on day 5 in one fresh or subsequent frozen......% and 38% for women treated with hphMG and rFSH, respectively (both PP and ITT). Significant differences in pharmacodynamic end points were found between the two gonadotropin preparations. CONCLUSION(S): Highly purified hMG is at least as effective as rFSH in GnRH antagonist cycles with compulsory single...

  14. Kappa opioid receptor antagonist and N-methyl-D- aspartate receptor antagonist affect dynorphin- induced spinal cord electrophysiologic impairment

    Institute of Scientific and Technical Information of China (English)

    Yu Chen; Liangbi Xiang; Jun Liu; Dapeng Zhou; Hailong Yu; Qi Wang; Wenfeng Han; Weijian Ren

    2012-01-01

    The latencies of motor- and somatosensory-evoked potentials were prolonged to different degrees, and wave amplitude was obviously decreased, after injection of dynorphin into the rat subarachnoid cavity.The wave amplitude and latencies of motor- and somatosensory-evoked potentials were significantly recovered at 7 and 14 days after combined injection of dynorphin and either the kappa opioid receptor antagonist nor-binaltorphimine or the N-methyl-D-aspartate receptor antagonist MK-801.The wave amplitude and latency were similar in rats after combined injection of dynorphin and nor-binaltorphimine or MK-801.These results suggest that intrathecal injection of dynorphin causes damage to spinal cord function.Prevention of N-methyl-D-aspartate receptor or kappa receptor activation lessened the injury to spinal cord function induced by dynorphin.

  15. Minimum Information Dominating Set for Critical Sampling over Graphs

    Science.gov (United States)

    2015-04-01

    information on IDS uniquely determines the information in the rest of the graph. The minimum vertex cover ( MVC ) [10, 11] and the mini- mum dominating set (MDS...12, 13] are related to the IDS problem. The MVC asks for a minimum subset of vertices such that each edge in the original graph is adjacent to at...vertex in this subset. The minimum IDS problem is inherently more complex than MVC and MDS. For instance, as shown in this paper, it is co-NP-complete to

  16. On minimum sum representations for weighted voting games

    CERN Document Server

    Kurz, Sascha

    2011-01-01

    A proposal in a weighted voting game is accepted if the sum of the (non-negative) weights of the "yea" voters is at least as large as a given quota. Several authors have considered representations of weighted voting games with minimum sum, where the weights and the quota are restricted to be integers. Freixas and Molinero have classified all weighted voting games without a unique minimum sum representation for up to 8 voters. Here we exhaustively classify all weighted voting games consisting of 9 voters which do not admit a unique minimum sum integer weight representation.

  17. Minimum Information about a Cardiac Electrophysiology Experiment (MICEE)

    DEFF Research Database (Denmark)

    Quinn, T A; Granite, S; Allessie, M A;

    2011-01-01

    Cardiac experimental electrophysiology is in need of a well-defined Minimum Information Standard for recording, annotating, and reporting experimental data. As a step towards establishing this, we present a draft standard, called Minimum Information about a Cardiac Electrophysiology Experiment....... It is hoped that this will enhance the integration of individual results into experimental, computational, and conceptual models. In its present form, this draft is intended for assessment and development by the research community. We invite the reader to join this effort, and, if deemed productive, implement...... the Minimum Information about a Cardiac Electrophysiology Experiment standard in their own work....

  18. Safety and the Human Factor.

    Science.gov (United States)

    Smith, Ann

    1982-01-01

    Discusses four elements of safety programs: (1) safety training; (2) safety inspections; (3) accident investigations; and (4) protective safety equipment. Also discusses safety considerations in water/wastewater treatment facilities focusing on falls, drowning hazards, trickling filters, confined space entry, collection/distribution system safety,…

  19. Role Of Biopreservation In Improving Food Safety And Storage

    Directory of Open Access Journals (Sweden)

    Swarnadyuti Nath

    2014-01-01

    Full Text Available Biopreservation refers to the use of antagonistic microorganisms or their metabolic products to inhibit or destroy undesired microorganisms in foods to enhance food safety and extend shelf life. In order to achieve improved food safety and to harmonize consumer demands with the necessary safety standards, traditional means of controlling microbial spoilage and safety hazards in foods are being replaced by combinations of innovative technologies that include biological antimicrobial systems such as lactic acid bacteria (LAB and/or their metabolites. Bacillus spp. have an antimicrobial action against Gram positive and Gram negative bacteria, as well as fungi, can therefore be used as a potential biopreservative in food processing due to its wide antimicrobial spectra. Bacteriocins are peptides or complex proteins biologically active with antimicrobial action against other bacteria, principally closely related species. Bacteriocins produced by lactic acid bacteria (LAB have received particular attention in recent years due to their potential application in food industry as natural preservatives. Bacteriocin production in Bacillus spp. has been studied over the past few decades which include Subtilin from B. subtilis, Megacin from B. megaterium and Thermacin from B. stearothermophilus. Bio-preservation may be effectively used in combination with other preservative factors (called hurdles to inhibit microbial growth and achieve food safety. Using an adequate mix of hurdles is not only economically attractive; it also serves to improve microbial stability and safety, as well as the sensory and nutritional qualities of a food.

  20. Anti free radical action of calcium antagonists and H1 and H2 receptors antagonists in neoplastic disease.

    Science.gov (United States)

    della Rovere, F; Broccio, M; Granata, A; Zirilli, A; Brugnano, L; Artemisia, A; Broccio, G

    1996-01-01

    The blood of the subjects suffering from Neoplastic Disease (ND) shows phenomena of membrane peroxidation due to the presence of Free Radicals (FRs), in a quantity much greater than the one observed in the blood of healthy subjects. This can be detected either by calculating the time necessary for the formation of "Heinz bodies" (Hbs), (p < 0.00001) after oxidative stress of the blood in vitro with acetylphenylidrazine (APH), or by calculating the methemoglobin (metHb) quantity that forms after the same treatment (P < 0.00001). The statistical analyses we carried out showed that metHb formation was not affected by age, sex, smoking habits, red blood cell number, Hb, Ht or tumor staging. In this study, by using equal parameters of investigation, we noted that the blood of the subjects with ND who were previously treated with calcium-antagonists drugs and with antagonists of H1 and H2 receptors, gave results completely superimposable on the results obtained from healthy subjects, implying that the treatment had avoided the increase of FRs. Therefore we concluded that calcium-antagonists and the antagonists of the H1 and H2 receptors behave as antioxidant substances, having decreased the FRs damaging activity on the cellular membranes, thus controlling, although to a limited degree, the pejorative evolution of the disease. It is also important to remember that investigations into the ND, even possible screenings, must take into account the above said data, submitting the subjects under investigation to a pharmacological wash out, particularly with those substances which, are considered to be scavengers of FRs. Some of these substances are investigated in this work.

  1. Conformational studies of 3-amino-1-alkyl-cyclopentane carboxamide CCR2 antagonists leading to new spirocyclic antagonists.

    Science.gov (United States)

    Pasternak, Alexander; Goble, Stephen D; Doss, George A; Tsou, Nancy N; Butora, Gabor; Vicario, Pasquale P; Ayala, Julia Marie; Struthers, Mary; Demartino, Julie A; Mills, Sander G; Yang, Lihu

    2008-02-15

    In an effort to shed light on the active binding conformation of our 3-amino-1-alkyl-cyclopentane carboxamide CCR2 antagonists, we prepared several conformationally constrained analogs resulting from backbone cyclization. Evaluation of CCR2 binding affinities for these analogs gave insight into the optimal relative positions of the piperidine and benzylamide moieties while simultaneously leading to the discovery of a new, potent lead type based upon a spirocyclic acetal scaffold.

  2. Principles of safety pharmacology.

    Science.gov (United States)

    Pugsley, M K; Authier, S; Curtis, M J

    2008-08-01

    Safety Pharmacology is a rapidly developing discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment. The aim of Safety Pharmacology is to characterize the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects using continuously evolving methodology. Unlike toxicology, Safety Pharmacology includes within its remit a regulatory requirement to predict the risk of rare lethal events. This gives Safety Pharmacology its unique character. The key issues for Safety Pharmacology are detection of an adverse effect liability, projection of the data into safety margin calculation and finally clinical safety monitoring. This article sets out to explain the drivers for Safety Pharmacology so that the wider pharmacology community is better placed to understand the discipline. It concludes with a summary of principles that may help inform future resolution of unmet needs (especially establishing model validation for accurate risk assessment). Subsequent articles in this issue of the journal address specific aspects of Safety Pharmacology to explore the issues of model choice, the burden of proof and to highlight areas of intensive activity (such as testing for drug-induced rare event liability, and the challenge of testing the safety of so-called biologics (antibodies, gene therapy and so on.).

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  4. Quantitative Comparison of Minimum Inductance and Minimum Power Algorithms for the Design of Shim Coils for Small Animal Imaging.

    Science.gov (United States)

    Hudson, Parisa; Hudson, Stephen D; Handler, William B; Scholl, Timothy J; Chronik, Blaine A

    2010-04-01

    High-performance shim coils are required for high-field magnetic resonance imaging and spectroscopy. Complete sets of high-power and high-performance shim coils were designed using two different methods: the minimum inductance and the minimum power target field methods. A quantitative comparison of shim performance in terms of merit of inductance (ML) and merit of resistance (MR) was made for shim coils designed using the minimum inductance and the minimum power design algorithms. In each design case, the difference in ML and the difference in MR given by the two design methods was inductance designs tend to feature oscillations within the current density; while minimum power designs tend to feature less rapidly varying current densities and lower power dissipation. Overall, the differences in coil performance obtained by the two methods are relatively small. For the specific case of shim systems customized for small animal imaging, the reduced power dissipation obtained when using the minimum power method is judged to be more significant than the improvements in switching speed obtained from the minimum inductance method.

  5. Formal Safety versus Real Safety: Quantitative and Qualitative Approaches to Safety Culture – Evidence from Estonia

    Directory of Open Access Journals (Sweden)

    Järvis Marina

    2016-10-01

    Full Text Available This paper examines differences between formal safety and real safety in Estonian small and medium-sized enterprises. The results reveal key issues in safety culture assessment. Statistical analysis of safety culture questionnaires showed many organisations with an outstanding safety culture and positive safety attitudes. However, qualitative data indicated some important safety weaknesses and aspects that should be included in the process of evaluation of safety culture in organisations.

  6. Evaluation of selective NK(1) receptor antagonist CI-1021 in animal models of inflammatory and neuropathic pain.

    Science.gov (United States)

    Gonzalez, M I; Field, M J; Hughes, J; Singh, L

    2000-08-01

    CI-1021 ([(2-benzofuran)-CH(2)OCO]-(R)-alpha-MeTrp-(S)-NHCH(CH (3))Ph) is a selective and competitive neurokinin-1 (NK(1)) receptor antagonist. This study examines its activity in animal models of inflammatory and neuropathic pain. In mice, CI-1021 (1-30 mg/kg, s.c.) dose dependently blocked the development of the late phase of the formalin response with a minimum effective dose (MED) of 3 mg/kg. Two chemically unrelated NK(1) receptor antagonists, CP-99,994 (3-30 mg/kg) and SR 140333 (1-100 mg/kg), also dose dependently blocked the late phase, with respective MEDs of 3 and 10 mg/kg. PD 156982, a NK(1) receptor antagonist with poor central nervous system penetration, failed to have any effect. However, when administered i. c.v., it selectively blocked the late phase of the formalin response. Chronic constrictive injury (CCI) to a sciatic nerve in the rat induced spontaneous pain, thermal and mechanical hyperalgesia, and cold, dynamic, and static allodynia. CI-1021 (10-100 mg/kg) and morphine (3 mg/kg) blocked all the responses except dynamic allodynia. Carbamazepine (100 mg/kg) was weakly effective against all the responses. Once daily administration of morphine (3 mg/kg, s. c.) in CCI rats led to the development of tolerance within 6 days. Similar administration of CI-1021 (100 mg/kg, s.c.) for up to 10 days did not induce tolerance. Moreover, the morphine tolerance failed to cross-generalize to CI-1021. CI-1021 blocked the CCI-induced hypersensitivity in the guinea pig, with a MED of 0.1 mg/kg, p.o. CI-1021 (10-100 mg/kg, s.c.) did not show sedative/ataxic action in the rat rota-rod test. It is suggested that NK(1) receptor antagonists possess a superior side effect profile to carbamazepine and morphine and may have a therapeutic use for the treatment of inflammatory and neuropathic pain.

  7. Cryostat safety tent

    Science.gov (United States)

    Millman, J. L.

    1978-01-01

    Transparent vinyl tent is designed for easy assembly with minimum use of handtools. Tent prevents toxic or explosive vapors from entering building. Frame posts are mounted on casters to allow easy mobility.

  8. Resident Assessment Instrument/Minimum Data Set (RAI/MDS)

    Data.gov (United States)

    Department of Veterans Affairs — The Resident Assessment Instrument/Minimum Data Set (RAI/MDS) is a comprehensive assessment and care planning process used by the nursing home industry since 1990 as...

  9. Parameterization of ion channeling half-angles and minimum yields

    Science.gov (United States)

    Doyle, Barney L.

    2016-03-01

    A MS Excel program has been written that calculates ion channeling half-angles and minimum yields in cubic bcc, fcc and diamond lattice crystals. All of the tables and graphs in the three Ion Beam Analysis Handbooks that previously had to be manually looked up and read from were programed into Excel in handy lookup tables, or parameterized, for the case of the graphs, using rather simple exponential functions with different power functions of the arguments. The program then offers an extremely convenient way to calculate axial and planar half-angles, minimum yields, effects on half-angles and minimum yields of amorphous overlayers. The program can calculate these half-angles and minimum yields for axes and [h k l] planes up to (5 5 5). The program is open source and available at

  10. The balanced minimum evolution problem under uncertain data

    NARCIS (Netherlands)

    Catanzaro, Daniele; Labbe, Martine; Pesenti, Raffaele

    2013-01-01

    We investigate the Robust Deviation Balanced Minimum Evolution Problem (RDBMEP), a combinatorial optimization problem that arises in computational biology when the evolutionary distances from taxa are uncertain and varying inside intervals. By exploiting some fundamental properties of the objective

  11. Minimum uncertainty and squeezing in diffusion processes and stochastic quantization

    Science.gov (United States)

    Demartino, S.; Desiena, S.; Illuminati, Fabrizo; Vitiello, Giuseppe

    1994-01-01

    We show that uncertainty relations, as well as minimum uncertainty coherent and squeezed states, are structural properties for diffusion processes. Through Nelson stochastic quantization we derive the stochastic image of the quantum mechanical coherent and squeezed states.

  12. USING GENETIC ALGORTIHM TO SOLVE STEINER MINIMUM SPANNING TREE PROBLEM

    Directory of Open Access Journals (Sweden)

    Öznur İŞÇİ

    2006-03-01

    Full Text Available Genetic algorithms (GA are a stochastic research methods, and they produce solutions that are close to optimum or near optimum. In addition to GA's successful application to traveling salesman problem, square designation, allocation, workshop table, preparation of lesson/examination schedules, planning of communication networks, assembling line balanced, minimum spanning tree type many combinatorial optimization problems it would be applicable to make the best comparison in optimization. In this study a Java program is developed to solve Steiner minimum spanning tree problem by genetic algorithm and its performance is examined. According to the tests carried out on the problems that were given before in the literature, results that are close to optimum are obtained in by GA approach that is recommended in this study. For the predetermined points in the study, length and gain are calculated for Steiner minimum spanning tree problem and minimum spanning tree problem.

  13. Procedures for Identifying and Selecting a Minimum Competency Test.

    Science.gov (United States)

    Wildemuth, Barbara

    1979-01-01

    Describes the steps that a school district should follow in the first stages of implementing a minimum competency testing program: preparatory activities, defining the project, identifying existing tests, evaluating tests, developing a local test, and sharing knowledge. (Author)

  14. 42 CFR 84.195 - Breathing tubes; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... Cartridge Respirators § 84.195 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with respirators shall be designed and constructed to prevent: (a) Restriction of free...

  15. 42 CFR 84.132 - Breathing tubes; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... Respirators § 84.132 Breathing tubes; minimum requirements. Flexible breathing tubes used in conjunction with supplied-air respirators shall be designed and constructed to prevent: (a) Restriction of free...

  16. 42 CFR 84.141 - Breathing gas; minimum requirements.

    Science.gov (United States)

    2010-10-01

    ... Respirators § 84.141 Breathing gas; minimum requirements. (a) Breathing gas used to supply supplied-air respirators shall be respirable breathing air and contain no less than 19.5 volume-percent of oxygen....

  17. The density minimum at the Earth's magnetic equator

    OpenAIRE

    1992-01-01

    Journal of Geophysical Research,Volume 97, pp. 1135-1150 Observations of the density structure in the plasmapause region reveal the existence of a local minimum in the total electron density at the magnetic equator.

  18. Minimum Population Search, an Application to Molecular Docking

    Directory of Open Access Journals (Sweden)

    Antonio Bolufé-Röhler

    2014-08-01

    Full Text Available Computer modeling of protein-ligand interactions is one of the most important phases in a drug design process. Part of the process involves the optimization of highly multi-modal objective (scoring functions. This research presents the Minimum Population Search heuristic as an alternative for solving these global unconstrained optimization problems. To determine the effectiveness of Minimum Population Search, a comparison with seven state-of-the-art search heuristics is performed. Being specifically designed for the optimization of large scale multi-modal problems, Minimum Population Search achieves excellent results on all of the tested complexes, especially when the amount of available function evaluations is strongly reduced. A first step is also made toward the design of hybrid algorithms based on the exploratory power of Minimum Population Search. Computational results show that hybridization leads to a further improvement in performance.

  19. 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

  20. Safety advice sheets

    CERN Multimedia

    HSE Unit

    2013-01-01

    You never know when you might be faced with questions such as: when/how should I dispose of a gas canister? Where can I find an inspection report? How should I handle/store/dispose of a chemical substance…?   The SI section of the DGS/SEE Group is primarily responsible for safety inspections, evaluating the safety conditions of equipment items, premises and facilities. On top of this core task, it also regularly issues “Safety Advice Sheets” on various topics, designed to be of assistance to users but also to recall and reinforce safety rules and procedures. These clear and concise sheets, complete with illustrations, are easy to display in the appropriate areas. The following safety advice sheets have been issued so far: Other sheets will be published shortly. Suggestions are welcome and should be sent to the SI section of the DGS/SEE Group. Please send enquiries to general-safety-visits.service@cern.ch.

  1. Safety objectives for 2014

    CERN Multimedia

    HSE Unit

    2014-01-01

    This is the third year in which the CERN Management has presented annual safety objectives for the Organization, the “HSE Objectives”.   The HSE objectives for 2014, which were announced by the Director-General at his traditional New Year’s address to the staff and were presented at the first Enlarged Directorate meeting of the year, have been drawn up and agreed in close collaboration between the DSOs, the HSE Unit and the DG himself. From safety in the workplace to radiation and environmental protection, the document emphasises that “Safety is a priority for CERN” and that safety policy is a key element in how the Organization is run. And, like all policies, it generates objectives that “serve as a general framework for action”. The HSE objectives are broken down into the following fields: occupational health and safety on sites and in the workplace, radiation protection, radiation safety, environmental protection, emerge...

  2. Reliability and safety engineering

    CERN Document Server

    Verma, Ajit Kumar; Karanki, Durga Rao

    2016-01-01

    Reliability and safety are core issues that must be addressed throughout the life cycle of engineering systems. Reliability and Safety Engineering presents an overview of the basic concepts, together with simple and practical illustrations. The authors present reliability terminology in various engineering fields, viz.,electronics engineering, software engineering, mechanical engineering, structural engineering and power systems engineering. The book describes the latest applications in the area of probabilistic safety assessment, such as technical specification optimization, risk monitoring and risk informed in-service inspection. Reliability and safety studies must, inevitably, deal with uncertainty, so the book includes uncertainty propagation methods: Monte Carlo simulation, fuzzy arithmetic, Dempster-Shafer theory and probability bounds. Reliability and Safety Engineering also highlights advances in system reliability and safety assessment including dynamic system modeling and uncertainty management. Cas...

  3. Minimum Orders of Eulerian Oriented Digraphs with Given Diameter

    Institute of Scientific and Technical Information of China (English)

    Yoomi RHO; Byeong Moon KIM; Woonjae HWANG; Byung Chul SONG

    2014-01-01

    A digraph D is oriented if it does not contain 2-cycles. If an oriented digraph D has a directed eulerian path, it is an oriented eulerian digraph. In this paper, when an oriented eulerian digraph D has minimum out-degree 2 and a diameter d, we find the minimum order of D. In addition, when D is 2-regular with diameter 4m (m≥2), we classify the extremal cases.

  4. Decoding Reed-Solomon Codes beyond half the minimum distance

    DEFF Research Database (Denmark)

    Høholdt, Tom; Nielsen, Rasmus Refslund

    1999-01-01

    We describe an efficient implementation of M.Sudan"s algorithm for decoding Reed-Solomon codes beyond half the minimum distance. Furthermore we calculate an upper bound of the probabilty of getting more than one codeword as output......We describe an efficient implementation of M.Sudan"s algorithm for decoding Reed-Solomon codes beyond half the minimum distance. Furthermore we calculate an upper bound of the probabilty of getting more than one codeword as output...

  5. Minimum emittance of isochronus rings for synchrotron light source

    CERN Document Server

    Shoji, Y

    1999-01-01

    Theoretically achievable minimum emittances of isochronus rings for synchrotron light source are calculated. The rings discussed in this paper consist of isochronus and achromatic bending cells, isochronus TBA (triple bend achromat) cells with negative dispersion, isochronus TBA cells with inverse bends or isochronus QBA (four bend achromat) cells. We show that the minimum emittances of these rings are roughly 2 or 3 times of those of the optimized non-isochronus rings.

  6. SOLVING MINIMUM SPANNING TREE PROBLEM WITH DNA COMPUTING

    Institute of Scientific and Technical Information of China (English)

    Liu Xikui; Li Yan; Xu Jin

    2005-01-01

    Molecular programming is applied to minimum spanning problem whose solution requires encoding of real values in DNA strands. A new encoding scheme is proposed for real values that is biologically plausible and has a fixed code length. According to the characteristics of the problem, a DNA algorithm solving the minimum spanning tree problem is given. The effectiveness of the proposed method is verified by simulation. The advantages and disadvantages of this algorithm are discussed.

  7. Minimum entropy production of neutrino radiation in the steady state

    Energy Technology Data Exchange (ETDEWEB)

    Essex, C.; Kennedy, D.C.

    1997-08-01

    A thermodynamical minimum principle valid for photon radiation is shown to hold for arbitrary geometries. It is successfully extended to neutrinos, in the zero mass and chemical potential case, following a parallel development of photon and neutrino statistics. This minimum principle stems more from that of Planck than that of classical Onsager-Prigogine irreversible thermodynamics. Its extension from bosons to fermions suggests that it may have a still wider validity. 14 refs.

  8. Minimum cost network flows: Problems, algorithms, and software

    Directory of Open Access Journals (Sweden)

    Sifaleras Angelo

    2013-01-01

    Full Text Available We present a wide range of problems concerning minimum cost network flows, and give an overview of the classic linear single-commodity Minimum Cost Network Flow Problem (MCNFP and some other closely related problems, either tractable or intractable. We also discuss state-of-the-art algorithmic approaches and recent advances in the solution methods for the MCNFP. Finally, optimization software packages for the MCNFP are presented.

  9. Informality and minimum wages by cohort in Colombia

    Directory of Open Access Journals (Sweden)

    Jhon James Mora

    2014-12-01

    Full Text Available This article aims to analyze the effect of minimum wage levels on the decision to join the informal job sector. We estimated a pseudo panel model of engagement in the informal sector using an IV-probit. Our results show that an increased wage gap-the relative difference between observed and minimum wage-has not only a disincentive effect on the probability of joining informality, but also leads to a substitution effect between younger and older cohorts.

  10. Distributed consensus on minimum time rendezvous via cyclic alternating projection

    OpenAIRE

    Hu, Chunhe; Chen, Zongji

    2014-01-01

    In this paper, we propose a distributed algorithm to solve planar minimum time multi-vehicle rendezvous problem with non-identical velocity constraints on cyclic digraph (topology). Motivated by the cyclic alternating projection method that can compute a point's projection on the intersection of some convex sets, we transform the minimum time rendezvous problem into finding the distance between the position plane and the intersection of several second-order cones in position-time space. The d...

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  12. Hydrogen Technologies Safety Guide

    Energy Technology Data Exchange (ETDEWEB)

    Rivkin, C. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Burgess, R. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Buttner, W. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2015-01-01

    The purpose of this guide is to provide basic background information on hydrogen technologies. It is intended to provide project developers, code officials, and other interested parties the background information to be able to put hydrogen safety in context. For example, code officials reviewing permit applications for hydrogen projects will get an understanding of the industrial history of hydrogen, basic safety concerns, and safety requirements.

  13. Principles of electrical safety

    CERN Document Server

    Sutherland, Peter E

    2015-01-01

    Principles of Electrical Safety discusses current issues in electrical safety, which are accompanied by series' of practical applications that can be used by practicing professionals, graduate students, and researchers. .  Provides extensive introductions to important topics in electrical safety Comprehensive overview of inductance, resistance, and capacitance as applied to the human body Serves as a preparatory guide for today's practicing engineers

  14. Thermal reactor safety

    Energy Technology Data Exchange (ETDEWEB)

    1980-06-01

    Information is presented concerning new trends in licensing; seismic considerations and system structural behavior; TMI-2 risk assessment and thermal hydraulics; statistical assessment of potential accidents and verification of computational methods; issues with respect to improved safety; human factors in nuclear power plant operation; diagnostics and activities in support of recovery; LOCA transient analysis; unresolved safety issues and other safety considerations; and fission product transport.

  15. Food Safety & Standards

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ An increasing number of people have realized that food safety is an important issue for public health. It not only concerns public health and safety, but also has direct influence on national economic progress and social development. The development and implementation of food safety standards play a vital role in protecting public health, as well as in standardizing and facilitating the sound development of food production and business.

  16. Improved safety at CERN

    CERN Multimedia

    2006-01-01

    As announced in Weekly Bulletin No. 43/2006, a new approach to the implementation of Safety at CERN has been decided, which required taking some managerial decisions. The guidelines of the new approach are described in the document 'New approach to Safety implementation at CERN', which also summarizes the main managerial decisions I have taken to strengthen compliance with the CERN Safety policy and Rules. To this end I have also reviewed the mandates of the Safety Commission and the Safety Policy Committee (SAPOCO). Some details of the document 'Safety Policy at CERN' (also known as SAPOCO42) have been modified accordingly; its essential principles, unchanged, remain the basis for the safety policy of the Organisation. I would also like to inform you that I have appointed Dr M. Bona as the new Head of the Safety Commission until 31.12.2008, and that I will proceed soon to the appointment of the members of the new Safety Policy Committee. All members of the personnel are deemed to have taken note of the d...

  17. Light water reactor safety

    CERN Document Server

    Pershagen, B

    2013-01-01

    This book describes the principles and practices of reactor safety as applied to the design, regulation and operation of light water reactors, combining a historical approach with an up-to-date account of the safety, technology and operating experience of both pressurized water reactors and boiling water reactors. The introductory chapters set out the basic facts upon which the safety of light water reactors depend. The central section is devoted to the methods and results of safety analysis. The accidents at Three Mile Island and Chernobyl are reviewed and their implications for light wate

  18. Older Consumers Safety Test

    Science.gov (United States)

    ... Certification Import Safety International Recall Guidance Civil and Criminal Penalties Federal Court Orders & Decisions Research & Statistics Research & Statistics Technical Reports Injury Statistics NEISS Injury ...

  19. Bathroom safety - children

    Science.gov (United States)

    ... sure your child's daycare also follows these guidelines. Images Child safety References American Academy of Pediatrics: Committee on Injury, Violence, and Poison Prevention. Policy statement -- prevention of drowning. ...

  20. Safety Study in Aviation

    OpenAIRE

    2016-01-01

    The objective of this article is to provide a brief look at safety studies, which are a necessary part of every change of system or a new system in aviation. The main focus is put on the area of air traffic management, because it affects most of the aviation stakeholders. The article begins with a description of safety and safety assessment of changes in systems. Then it discusses analysis of processes, hazard identification and risk assessment. Main part focuses on Safety studies and briefly...