445 research outputs found

    Evaluation of seals for high-performance cryogenic turbomachines

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    An approach to computing flow and dynamic characteristics for seals or bearings is discussed. The local average velocity was strongly influenced by inlet and exit effects and fluid injection, which in turn drove zones of secondary flow. For the restricted three-dimensional model considered, the integral averaged results were in reasonable agreement with selected data. Unidirectional pressure measurements alone were insufficient to define such flow variations. However, for seal and bearing leakage correlations the principles of corresponding states were found to be useful. Also discussed are three phenomena encountered during testing of three eccentric nonrotating seal configurations for the Space Shuttle Main Engine (SSME) Program. Fluid injection, choking within a seal, and pressure profile crossover are related to postulated zones of secondary flow or separation and to direct stiffness

    Small states and the challenge of sovereignty: Commonwealth Caribbean offshore financial centers and tax competition

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    The dynamics of inter-state relations and state sovereignty have been disturbed by late-20th century globalisation. Yet the literature on the international system, globalisation and international political economy gives scant attention to the most vulnerable sovereign entities, the small and micro states. One significant exception has been the Commonwealth, with its many small state members. Another is the area of financial crime, and the role of the offshore financial centre (OFC) within global finance. This thesis analyses the efforts of several small Commonwealth states from the Caribbean to maintain their OFCs in the face of an OECD-directed campaign against tax competition. It demonstrates both the contribution made to economic development by an OFC and the successful assertion of sovereignty achieved by these small states. The case study focuses on Caribbean OFCs and the OECD campaign against harmful tax competition during 1998 - 2003. First, the argument that tax competition is a global problem is deconstructed. Three main points from the small states’ response to the OECD position are explored, along with the OECD’s rebuttal. Because the small states are individually at a disadvantage, the thesis provides an exposition of the collective response facilitated by the Commonwealth. The OFC is justified by its material contribution to the small state economy. Specific contributions made to the economies of the Bahamas, Dominica, St. Vincent and the Grenadines and the Cayman Islands are demonstrated. The pivotal impact of U.S. policy on the OECD project and on Caribbean OFCs is explored. Yet while one effect was a decline in the number of registered offshore firms, the quantity of capital transiting the Caribbean increased. This study of small states and offshore finance re-affirms the continued relevance of the sovereign state as an actor in international society, but also illustrates the importance of issue-area and geographical context

    Test Population Selection from Weibull-Based, Monte Carlo Simulations of Fatigue Life

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    Fatigue life is probabilistic and not deterministic. Experimentally establishing the fatigue life of materials, components, and systems is both time consuming and costly. As a result, conclusions regarding fatigue life are often inferred from a statistically insufficient number of physical tests. A proposed methodology for comparing life results as a function of variability due to Weibull parameters, variability between successive trials, and variability due to size of the experimental population is presented. Using Monte Carlo simulation of randomly selected lives from a large Weibull distribution, the variation in the L10 fatigue life of aluminum alloy AL6061 rotating rod fatigue tests was determined as a function of population size. These results were compared to the L10 fatigue lives of small (10 each) populations from AL2024, AL7075 and AL6061. For aluminum alloy AL6061, a simple algebraic relationship was established for the upper and lower L10 fatigue life limits as a function of the number of specimens failed. For most engineering applications where less than 30 percent variability can be tolerated in the maximum and minimum values, at least 30 to 35 test samples are necessary. The variability of test results based on small sample sizes can be greater than actual differences, if any, that exists between materials and can result in erroneous conclusions. The fatigue life of AL2024 is statistically longer than AL6061 and AL7075. However, there is no statistical difference between the fatigue lives of AL6061 and AL7075 even though AL7075 had a fatigue life 30 percent greater than AL6061

    Involvement of patients or their representatives in quality management functions in EU hospitals:implementation and impact on patient-centred care strategies

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    OBJECTIVE: The objective of this study was to describe the involvement of patients or their representatives in quality management (QM) functions and to assess associations between levels of involvement and the implementation of patient-centred care strategies. DESIGN: A cross-sectional, multilevel STUDY DESIGN: that surveyed quality managers and department heads and data from an organizational audit. SETTING: Randomly selected hospitals (n = 74) from seven European countries (The Czech Republic, France, Germany, Poland, Portugal, Spain and Turkey). PARTICIPANTS: Hospital quality managers (n = 74) and heads of clinical departments (n = 262) in charge of four patient pathways (acute myocardial infarction, stroke, hip fracture and deliveries) participated in the data collection between May 2011 and February 2012. MAIN OUTCOME MEASURES: Four items reflecting essential patient-centred care strategies based on an on-site hospital visit: (1) formal survey seeking views of patients and carers, (2) written policies on patients' rights, (3) patient information literature including guidelines and (4) fact sheets for post-discharge care. The main predictors were patient involvement in QM at the (i) hospital level and (ii) pathway level. RESULTS: Current levels of involving patients and their representatives in QM functions in European hospitals are low at hospital level (mean score 1.6 on a scale of 0 to 5, SD 0.7), but even lower at departmental level (mean 0.6, SD 0.7). We did not detect associations between levels of involving patients and their representatives in QM functions and the implementation of patient-centred care strategies; however, the smallest hospitals were more likely to have implemented patient-centred care strategies. CONCLUSIONS: There is insufficient evidence that involving patients and their representatives in QM leads to establishing or implementing strategies and procedures that facilitate patient-centred care; however, lack of evidence should not be interpreted as evidence of no effect

    Irrational prescribing of over-the-counter (OTC) medicines in general practice: testing the feasibility of an educational intervention among physicians in five European countries

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    Background: Irrational prescribing of over-the-counter (OTC) medicines in general practice is common in Southern Europe. Recent findings from a research project funded by the European Commission (FP7), the “OTC SOCIOMED”, conducted in seven European countries, indicate that physicians in countries in the Mediterranean Europe region prescribe medicines to a higher degree in comparison to physicians in other participating European countries. In light of these findings, a feasibility study has been designed to explore the acceptance of a pilot educational intervention targeting physicians in general practice in various settings in the Mediterranean Europe region. Methods: This feasibility study utilized an educational intervention was designed using the Theory of Planned Behaviour (TPB). It took place in geographically-defined primary care areas in Cyprus, France, Greece, Malta, and Turkey. General Practitioners (GPs) were recruited in each country and randomly assigned into two study groups in each of the participating countries. The intervention included a one-day intensive training programme, a poster presentation, and regular visits of trained professionals to the workplaces of participants. Reminder messages and email messages were, also, sent to participants over a 4-week period. A pre- and post-test evaluation study design with quantitative and qualitative data was employed. The primary outcome of this feasibility pilot intervention was to reduce GPs’ intention to provide medicines following the educational intervention, and its secondary outcomes included a reduction of prescribed medicines following the intervention, as well as an assessment of its practicality and acceptance by the participating GPs. Results: Median intention scores in the intervention groups were reduced, following the educational intervention, in comparison to the control group. Descriptive analysis of related questions indicated a high overall acceptance and perceived practicality of the intervention programme by GPs, with median scores above 5 on a 7-point Likert scale. Conclusions: Evidence from this intervention will estimate the parameters required to design a larger study aimed at assessing the effectiveness of such educational interventions. In addition, it could also help inform health policy makers and decision makers regarding the management of behavioural changes in the prescribing patterns of physicians in Mediterranean Europe, particularly in Southern European countries

    A selective p53 activator and anticancer agent to improve colorectal cancer therapy

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    Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.We thank PT national funds (FCT/MCTES , Fundação para a Ciência e a Tecnologia , and Ministério da Ciência, Tecnologia e Ensino Superior ) through grants UIDB/50006/2020 , UID/BIO/04469/2019 , UIDB/04539/2020 , and UIDP/04539/2020 ( CIBB ); BioTecNorte operation ( NORTE-01-0145-FEDER-000004 ) and Porto Neurosciences and Neurologic Disease Research Initiative at I3S ( Norte-01-0145-FEDER-000008 ) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte ; Masaryk University ( Project MUNI/A/1127/2019 ) and Ministry of Education, Youth and Sports of the Czech Republic (project nos. LQ1605 and LM2018125 ); FCT financial support through the fellowships SFRH/BD/119144/2016 (H.R.) and SFRH/BD/117949/2016 (L.R.); Fondazione AIRC ( IG#18985 , A.I.); and the Programa Operacional Potencial Humano (POCH), specifically the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences , PD/00016/2012 ). We thank Dario Rizzotto for assistance in preparing the libraries for RNA sequencing. Funding: This work was supported by PT National Funds (FCT/MCTES, Fundação para a Ciência e Tecnologia , and Ministério da Ciência, Tecnologia e Ensino Superior ) via the projects UIDB/50006/2020 ( LAQV/REQUIMTE ), UIDB/00313/2020 , and UIDP/00313/2020 , co-funded by COMPETE2020-UE

    Determination of Turbine Blade Life from Engine Field Data

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    It is probable that no two engine companies determine the life of their engines or their components in the same way or apply the same experience and safety factors to their designs. Knowing the failure mode that is most likely to occur minimizes the amount of uncertainty and simplifies failure and life analysis. Available data regarding failure mode for aircraft engine blades, while favoring low-cycle, thermal mechanical fatigue as the controlling mode of failure, are not definitive. Sixteen high-pressure turbine (HPT) T-1 blade sets were removed from commercial aircraft engines that had been commercially flown by a single airline and inspected for damage. Each set contained 82 blades. The damage was cataloged into three categories related to their mode of failure: (1) Thermal-mechanical fatigue, (2) Oxidation/Erosion, and (3) "Other." From these field data, the turbine blade life was determined as well as the lives related to individual blade failure modes using Johnson-Weibull analysis. A simplified formula for calculating turbine blade life and reliability was formulated. The L(sub 10) blade life was calculated to be 2427 cycles (11 077 hr). The resulting blade life attributed to oxidation/erosion equaled that attributed to thermal-mechanical fatigue. The category that contributed most to blade failure was Other. If there were there no blade failures attributed to oxidation/erosion and thermal-mechanical fatigue, the overall blade L(sub 10) life would increase approximately 11 to 17 percent

    Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

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    We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom
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