1,739 research outputs found

    Morals From Rationality Alone? Some Doubts

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    Contractarians aim to derive moral principles from the dictates of instrumental rationality alone. But it is well-known that contractarian moral theories struggle to identify normative principles that are both uniquely rational and morally compelling. Michael Moehler's recent book, *Minimal Morality* seeks to avoid these difficulties by developing a novel "two-level" social contract theory, which restricts the scope of contractarian morality to cases of deep and persistent moral disagreement. Yet Moehler remains ambitious, arguing that a restricted version of Kant's categorical imperative is a uniquely rational principle of conflict resolution. We develop a formal model of Moehler's informal game-theoretic argument, which reconstructs a valid argument for Moehler's conclusion. This model, in turn, enables us to expose how a successful argument for Moehler's contractarian principle rests on assumptions that can only be justified by subtle yet significant departures from the standard conception of rationality. We thus extend our understanding of familiar contractarian difficulties by showing how they arise even if we restrict the scope of contractarian morality to a domain where its application seems both promising and necessary. We show that the problem lies not in contractarians' immodest ambitions but in the modest resources rationality can offer to satisfy them

    A randomized, placebo-controlled trial of late Na current inhibition (ranolazine) in coronary microvascular dysfunction (CMD): impact on angina and myocardial perfusion reserve.

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    AimsThe mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.Materials and resultsRandomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041).ConclusionsIn this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects.Trial registrationclinicaltrials.gov Identifier: NCT01342029

    Upper Mantle Structure of Central and West Antarctica from Array Analysis of Rayleigh Wave Phase Velocities

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    The seismic velocity structure of Antarctica is important, both as a constraint on the tectonic history of the continent and for understanding solid Earth interactions with the ice sheet. We use Rayleigh wave array analysis methods applied to teleseismic data from recent temporary broadband seismograph deployments to image the upper mantle structure of central and West Antarctica. Phase velocity maps are determined using a two–plane wave tomography method and are inverted for shear velocity using a Monte Carlo approach to estimate three-dimensional velocity structure. Results illuminate the structural dichotomy between the East Antarctic Craton and West Antarctica, with West Antarctica showing thinner crust and slower upper mantle velocity. West Antarctica is characterized by a 70–100 km thick lithosphere, underlain by a low-velocity zone to depths of at least 200 km. The slowest anomalies are beneath Ross Island and the Marie Byrd Land dome and are interpreted as upper mantle thermal anomalies possibly due to mantle plumes. The central Transantarctic Mountains are marked by an uppermost mantle slow-velocity anomaly, suggesting that the topography is thermally supported. The presence of thin, higher-velocity lithosphere to depths of about 70 km beneath the West Antarctic Rift System limits estimates of the regionally averaged heat flow to less than 90 mW/m2. The Ellsworth-Whitmore block is underlain by mantle with velocities that are intermediate between those of the West Antarctic Rift System and the East Antarctic Craton. We interpret this province as Precambrian continental lithosphere that has been altered by Phanerozoic tectonic and magmatic activity

    Apatites in Gale Crater

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    ChemCam is an active remote sensing instrument suite that has operated successfully on MSL since landing Aug. 6th, 2012. It uses laser pulses to remove dust and to analyze rocks up to 7 m away. Laser-induced breakdown spectroscopy (LIBS) obtains emission spectra of materials ablated from the samples in electronically excited states. The intensities of the emission lines scale with the abundances of the related element. ChemCam is sensitive to most major rock-forming elements as well as to a set of minor and trace elements such as F, Cl, Li, P, Sr, Ba, and Rb. The measured chemical composition can then be used to infer the mineralogical composition of the ablated material. Here, we report a summary of inferred apatite detections along the MSL traverse at Gale Crater. We present the geologic settings of these findings and derive some interpretations about the formation conditions of apatite in time and space

    Upper Mantle Seismic Anisotropy Beneath the West Antarctic Rift System and Surrounding Region from Shear Wave Splitting Analysis

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    We constrain azimuthal anisotropy in the West Antarctic upper mantle using shear wave splitting parameters obtained from teleseismic SKS, SKKS and PKS phases recorded at 37 broad-band seismometres deployed by the POLENET/ANET project. We use an eigenvalue technique to linearize the rotated and shifted shear wave horizontal particle motions and determine the fast direction and delay time for each arrival. High-quality measurements are stacked to determine the best fitting splitting parameters for each station. Overall, fast anisotropic directions are oriented at large angles to the direction of Antarctic absolute plate motion in both hotspot and no-net-rotation frameworks, showing that the anisotropy does not result from shear due to plate motion over the mantle. Further, the West Antarctic directions are substantially different from those of East Antarctica, indicating that anisotropy across the continent reflects multiple mantle regimes. We suggest that the observed anisotropy along the central Transantarctic Mountains (TAM) and adjacent West Antarctic Rift System (WARS), one of the largest zones of extended continental crust on Earth, results from asthenospheric mantle strain associated with the final pulse of western WARS extension in the late Miocene. Strong and consistent anisotropy throughout the WARS indicate fast axes subparallel to the inferred extension direction, a result unlike reports from the East African rift system and rifts within the Basin and Range, which show much greater variation. We contend that ductile shearing rather than magmatic intrusion may have been the controlling mechanism for accumulation and retention of such coherent, widespread anisotropic fabric. Splitting beneath the Marie Byrd Land Dome (MBL) is weaker than that observed elsewhere within the WARS, but shows a consistent fast direction, possibly representative of anisotropy that has been ‘frozen-in’ to remnant thicker lithosphere. Fast directions observed inland from the Amundsen Sea appear to be radial to the dome and may indicate radial horizontal mantle flow associated with an MBL plume head and low upper mantle velocities in this region, or alternatively to lithospheric features associated with the complex Cenozoic tectonics at the far-eastern end of the WARS

    "Actual" does not imply "feasible"

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    The familiar complaint that some ambitious proposal is infeasible naturally invites the following response: Once upon a time, the abolition of slavery and the enfranchisement of women seemed infeasible, yet these things were actually achieved. Presumably, then, many of those things that seem infeasible in our own time may well be achieved too and, thus, turn out to have been perfectly feasible after all. The Appeal to History, as we call it, is a bad argument. It is not true that if some desirable state of affairs was actually achieved, then it was feasible that it was achieved. “Actual” does not imply “feasible,” as we put it. Here is our objection. “Feasible” implies “not counterfactually fluky.” But “actual” does not imply “not counterfactually fluky.” So, “actual” does not imply “feasible.” While something like the Flukiness Objection is sometimes hinted at in the context of the related literature on abilities, it has not been developed in any detail, and both premises are inadequately motivated. We offer a novel articulation of the Flukiness Objection that is both more precise and better motivated. Our conclusions have important implications, not only for the admissible use of history in normative argument, but also by potentially circumscribing the normative claims that are applicable to us

    Population genomics of domestic and wild yeasts

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    The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker's yeast, _Saccharomyces cerevisiae_, and its closest relative, the wild _S. paradoxus_, which has never been associated with human activity. These were collected from numerous geographic locations and sources (including wild, clinical, baking, wine, laboratory and food spoilage). These sequences provide an unprecedented view of the population structure, natural (and artificial) selection and genome evolution in these species. Variation in gene content, SNPs, indels, copy numbers and transposable elements provide insights into the evolution of different lineages. Phenotypic variation broadly correlates with global genome-wide phylogenetic relationships however there is no correlation with source. _S. paradoxus_ populations are well delineated along geographic boundaries while the variation among worldwide _S. cerevisiae_ isolates show less differentiation and is comparable to a single _S. paradoxus_ population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of _S. cerevisiae_ shows a few well defined geographically isolated lineages and many different mosaics of these lineages, supporting the notion that human influence provided the opportunity for outbreeding and production of new combinations of pre-existing variation
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