725 research outputs found

    The difference between punishments and rewards in fostering moral concerns in social decision making

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    "In social decision making, punishing non-cooperation and rewarding cooperation may not only affect cooperation because of instrumental reasons. They may also evoke moral concerns regarding cooperation as they signal that cooperation is socially approved of and non-cooperation socially disapproved of. I argue that punishments do this to a greater extent than rewards as punishments communicate an obligatory rule and rewards communicate a voluntary rule. Indeed, the first experiment shows that, in a social dilemma, the concept of punishment increased cooperation and the concept of a reward did not. The second experiment showed that participants showed more disapproval towards an offender when there was a punishment for non-compliance than when there was a reward for compliance. These findings suggest that punishing non-cooperation more strongly foster moral concerns regarding cooperation than rewarding cooperation. Possible implications for internalizations are discussed." (author's abstract

    Etching suspended superconducting hybrid junctions from a multilayer

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    A novel method to fabricate large-area superconducting hybrid tunnel junctions with a suspended central normal metal part is presented. The samples are fabricated by combining photo-lithography and chemical etch of a superconductor - insulator - normal metal multilayer. The process involves few fabrication steps, is reliable and produces extremely high-quality tunnel junctions. Under an appropriate voltage bias, a significant electronic cooling is demonstrated

    The impact of dispensing fees on compliance with opioid substitution therapy: a mixed methods study

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    Background: Opioid substitution therapy (OST) programs involve the dispensing of OST medicines to patients to address their dependence on heroin and/or other opioid substances. OST medicines are subsidised by the Australian government but patients need to pay the dispensing fees. This study explored opinions from OST patients and stakeholders about the potential impact of dispensing fees on compliance and OST program retention. Current and past experiences and the potential impact of OST dispensing fees were evaluated. Methods: Mixed methodology was used to obtain data from OST patients and stakeholders. This involved 1) interviews with OST stakeholders, 2) a focus group of OST patients and 3) surveys of OST patients in Perth, Australia, between June and August 2013.Results: The majority of the eight stakeholders declared cost as the factor mostly impacting on OST compliance. Almost all of the stakeholders commented that there was a positive correlation between time on the OST program and success in terms of relapse. Most stakeholders advocated for OST fees to contribute towards the Pharmaceutical Benefits Scheme Safety Net, and for fee subsidy. Focus group themes supported stakeholder interview findings. A total of 138 surveys were completed. Survey analysis illustrated a strong correlation between patient debt and impacted lifestyle: 82.4% (p < 0.001, Chi-square test) of the 138 survey participants stated that dispensing fees impacted significantly on patients’ finances and lifestyle, specifically those patients with major debt. The cost of dispensing fees was identified by 46.3% (64/138) of survey participants as the biggest impacting factor on patient success. Logistic regression models showed that the cost of dispensing fees was also found to significantly influence both the occurrence of debt (57.7%, p < 0.0001) and lifestyle difficulties (80.0%, p = 0.0004). Conclusion: Findings provided insight into OST patients’ financial difficulties with data suggesting that dispensing fees are likely to have a negative impact on OST patients’ compliance with therapy, retention in the OST program and lifestyle. Government sponsorship of the OST dispensing fees should be considered as sponsorship would potentially increase the retention rates of income-poor OST program recipients

    On the feasibility of defect detection in composite material based on thermal periodic excitation

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    International audienceImplementation of periodic thermal excitation to identify thermal properties (conductivity, heat capacity, diffusivity) of complex composite materials at different investigation scales (from micrometer to millimetre) presents many advantages. These methods are usually based on the thermal waves phase lag observation compared to a reference signal. In fact, phase lag evolution versus distance to the heating source or versus excitation frequency is quite informative about numerous material characteristics. For example, considering that a structural defect can modify heat propagation inside a material, diagnosis can be performed from phase lag observations and comparisons between samples with and without defects. Numerous studies have been performed considering global heating (a quite large surface of the investigated composite material is heated and defect depth or size can be detected). The proposed approach is original since periodic heating is local and aims to detect defects in the periphery of the excitation. Based on a mathematical model for thermal waves propagations and introducing complex temperature for numerical resolution (finite element method), a feasibility study has allowed a sensitivity analysis. This preliminary study also provides information on the operating protocol, for heating(frequency, power, size of the source), and observation (transmission or reflection). Then, experimental device and early experimental results are briefly exposed

    When sanctions convey moral norms

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    Sanctions not only have the instrumental function of deterring people from undesired behavior but they also have the ability to convey moral norms. As such, they may create a moral motivation not to engage in the sanctioned behavior. This is desirable as this makes the success of a sanctioning system depend less on quality of enforcement. However, sanctions may not always succeed in conveying moral norms. In this paper, three conditions are highlighted that, in the psychology literature, have been empirically proven to influence whether a sanction succeeds to evoke moral norms. First, a sanction should not be regarded as a way to make up for the negative consequences of a transgression a sanction. So, they should be communicated in a retributive way rather than in a compensatory way. Second, as punishments communicate an obligatory rule and rewards communicate a voluntary rule, punishments are a better way to incur moral norms than rewards. Third, severe sanctions more strongly convey a moral norm than mild ones as long as these severe sanctions are not unreasonably severe, are installed by trustworthy authorities and in a fair way. The value of the moral expressive function of sanctions, as well as its drawbacks, are discussed

    Fluorescent Peptide Biosensor for Probing the Relative Abundance of Cyclin-Dependent Kinases in Living Cells

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    Cyclin-dependant kinases play a central role in coordinating cell growth and division, and in sustaining proliferation of cancer cells, thereby constituting attractive pharmacological targets. However, there are no direct means of assessing their relative abundance in living cells, current approaches being limited to antigenic and proteomic analysis of fixed cells. In order to probe the relative abundance of these kinases directly in living cells, we have developed a fluorescent peptide biosensor with biligand affinity for CDKs and cyclins in vitro, that retains endogenous CDK/cyclin complexes from cell extracts, and that bears an environmentally-sensitive probe, whose fluorescence increases in a sensitive fashion upon recognition of its targets. CDKSENS was introduced into living cells, through complexation with the cell-penetrating carrier CADY2 and applied to assess the relative abundance of CDK/Cyclins through fluorescence imaging and ratiometric quantification. This peptide biosensor technology affords direct and sensitive readout of CDK/cyclin complex levels, and reports on differences in complex formation when tampering with a single CDK or cyclin. CDKSENS further allows for detection of differences between different healthy and cancer cell lines, thereby enabling to distinguish cells that express high levels of these heterodimeric kinases, from cells that present decreased or defective assemblies. This fluorescent biosensor technology provides information on the overall status of CDK/Cyclin complexes which cannot be obtained through antigenic detection of individual subunits, in a non-invasive fashion which does not require cell fixation or extraction procedures. As such it provides promising perspectives for monitoring the response to therapeutics that affect CDK/Cyclin abundance, for cell-based drug discovery strategies and fluorescence-based cancer diagnostics

    Practical metrics for establishing the health benefits of research to support research prioritisation

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    Introduction : We present practical metrics for estimating the expected health benefits of specific research proposals. These can be used by research funders, researchers, and health-care decision makers within low- and middle-income countries (LMICs) to support evidence-based research prioritisation. Methods : The methods require three key assessments: (1) the current level of uncertainty around the endpoints the proposed study will measure; (2) how uncertainty impacts on the health benefits and costs of health-care programmes; and (3) the health opportunity costs imposed by programme costs. Research is valuable because it can improve health by informing the choice of which programmes should be implemented. We provide a Microsoft Excel tool to allow readers to generate estimates of the health benefits of research studies based on these three assessments. The tool can be populated using clinical studies, existing cost-effectiveness models and expert opinion. Where such evidence is not available, the tool can quantify the value of research under different assumptions. Estimates of the health benefits of research can be considered alongside research costs, and the consequences of delaying implementation until research reports, to determine whether research is worthwhile. We illustrate the method using a case study of research on HIV self-testing programmes in Malawi. This analysis combines data from the literature with outputs from the HIV synthesis model. Results : For this case study we found a costing study that could be completed and inform decision making within one year offered the highest health benefits (67,000 DALYs averted). Research on outcomes improved population health to a lesser extent (12,000 DALYs averted) and only if carried out alongside programme implementation. Conclusion : Our work provides a method for estimating the health benefits of research in a practical and timely fashion. This can be used to support accountable use of research funds

    The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers

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    BACKGROUND: The rhomboid family of polytopic membrane proteins shows a level of evolutionary conservation unique among membrane proteins. They are present in nearly all the sequenced genomes of archaea, bacteria and eukaryotes, with the exception of several species with small genomes. On the basis of experimental studies with the developmental regulator rhomboid from Drosophila and the AarA protein from the bacterium Providencia stuartii, the rhomboids are thought to be intramembrane serine proteases whose signaling function is conserved in eukaryotes and prokaryotes. RESULTS: Phylogenetic tree analysis carried out using several independent methods for tree constructions and the corresponding statistical tests suggests that, despite its broad distribution in all three superkingdoms, the rhomboid family was not present in the last universal common ancestor of extant life forms. Instead, we propose that rhomboids evolved in bacteria and have been acquired by archaea and eukaryotes through several independent horizontal gene transfers. In eukaryotes, two distinct, ancient acquisitions apparently gave rise to the two major subfamilies, typified by rhomboid and PARL (presenilins-associated rhomboid-like protein), respectively. Subsequent evolution of the rhomboid family in eukaryotes proceeded by multiple duplications and functional diversification through the addition of extra transmembrane helices and other domains in different orientations relative to the conserved core that harbors the protease activity. CONCLUSIONS: Although the near-universal presence of the rhomboid family in bacteria, archaea and eukaryotes appears to suggest that this protein is part of the heritage of the last universal common ancestor, phylogenetic tree analysis indicates a likely bacterial origin with subsequent dissemination by horizontal gene transfer. This emphasizes the importance of explicit phylogenetic analysis for the reconstruction of ancestral life forms. A hypothetical scenario for the origin of intracellular membrane proteases from membrane transporters is proposed

    Thermal imprint of rift-related processes in orogens as recorded in the Pyrenees

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    International audience19 The extent to which heat recorded in orogens reflects thermal conditions inherited from 20 previous rift-related processes is still debated and poorly documented. As a case study, we 21 examine the Mauléon basin in the north-western Pyrenees that experienced both extreme 22 crustal thinning and tectonic inversion within a period of ~30 Myrs. To constrain the time-23 temperature history of the basin in such a scenario, we provide new detrital zircon fission-24 track and (U-Th-Sm)/He thermochronology data. The role of rift-related processes in 25 subsequent collision is captured by inverse modeling of our thermochronological data, using 26 relationships between zircon (U-Th-Sm)/He ages and uranium content, combined with 27 thermo-kinematic models of a rift-orogen cycle. We show that the basin recorded significant 28 heating at about 100 Ma characterized by high geothermal gradients (~80°C/km). Our 29 thermo-kinematic modeling and geological constraints support the view that subcontinental 30 lithospheric mantle was exhumed at that time below the Mauléon basin. Such a high 31 geothermal gradient lasted 30 Myr after onset of convergence at ~83 Ma and was relaxed 32 during the collision phase from ~50 Ma. This study suggests that heat needed for ductile 33 shortening during convergence, is primarily inherited from extension rather than being only 34 related to tectonic and/or sedimentary burial. This should have strong implications on tectonic 35 reconstructions in many collision belts that resulted from inversion of hyper-extended rift 36 basins
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