14,746 research outputs found

    Hypergeometric L-functions in average polynomial time

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    We describe an algorithm for computing, for all primes pXp \leq X, the mod-pp reduction of the trace of Frobenius at pp of a fixed hypergeometric motive in time quasilinear in XX. This combines the Beukers--Cohen--Mellit trace formula with average polynomial time techniques of Harvey et al.Comment: 15 pages, 1 figure; v4 several exposition improvements as suggested the referee

    ENVIRONMENTAL LABELING OF ELECTRICITY: EFFECTS ON CONSUMER UNCERTAINTY ABOUT PRODUCT ATTRIBUTES AND LIKELIHOOD TO BUY DECISIONS

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    Using data collected by the U.S. Department of Energy we test how price and environmental marketing and labeling affects respondents' uncertainty about product attributes and about their purchase intentions.Consumer/Household Economics,

    Sketch of the life of Rev. Levi Pillsbury

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    Sketch of lifeSketch of the life of Rev. Levi Pillsbury by Alfred S. Ro

    Multidimensional HLLE Riemann solver; Application to Euler and Magnetohydrodynamic Flows

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    In this work we present a general strategy for constructing multidimensional Riemann solvers with a single intermediate state, with particular attention paid to detailing the two-dimensional Riemann solver. This is accomplished by introducing a constant resolved state between the states being considered, which introduces sufficient dissipation for systems of conservation laws. Closed form expressions for the resolved fluxes are also provided to facilitate numerical implementation. The Riemann solver is proved to be positively conservative for the density variable; the positivity of the pressure variable has been demonstrated for Euler flows when the divergence in the fluid velocities is suitably restricted so as to prevent the formation of cavitation in the flow. We also focus on the construction of multidimensionally upwinded electric fields for divergence-free magnetohydrodynamical flows. A robust and efficient second order accurate numerical scheme for two and three dimensional Euler and magnetohydrodynamic flows is presented. The scheme is built on the current multidimensional Riemann solver. The number of zones updated per second by this scheme on a modern processor is shown to be cost competitive with schemes that are based on a one-dimensional Riemann solver. However, the present scheme permits larger timesteps

    Macro-micro feedback links of water management in South Africa : CGE analyses of selected policy regimes

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    The pressure on an already stressed water situation in South Africa is predicted to increase significantly under climate change, plans for large industrial expansion, observed rapid urbanization, and government programs to provide access to water to millions of previously excluded people. The present study employed a general equilibrium approach to examine the economy-wide impacts of selected macro and water related policy reforms on water use and allocation, rural livelihoods, and the economy at large. The analyses reveal that implicit crop-level water quotas reduce the amount of irrigated land allocated to higher-value horticultural crops and create higher shadow rents for production of lower-value, water-intensive field crops, such as sugarcane and fodder. Accordingly, liberalizing local water allocation in irrigation agriculture is found to work in favor of higher-value crops, and expand agricultural production and exports and farm employment. Allowing for water trade between irrigation and non-agricultural uses fueled by higher competition for water from industrial expansion and urbanization leads to greater water shadow prices for irrigation water with reduced income and employment benefits to rural households and higher gains for non-agricultural households. The analyses show difficult tradeoffs between general economic gains and higher water prices, making irrigation subsidies difficult to justify.Water Supply and Sanitation Governance and Institutions,Town Water Supply and Sanitation,Water Supply and Systems,Water and Industry,Water Conservation

    Exploring the meaning in meaningful coincidences: an interpretative phenomenological analysis of synchronicity in therapy

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    Synchronicity experiences (SEs) are defined as psychologically meaningful connections between inner events (e.g., thought, dream or vision) and one or more external events occurring simultaneously or at a future point in time. There has been limited systematic research that has investigated the phenomenology of SEs in therapy. This study aimed to redress this by exploring the process and nature of such experiences from the perspective of the practitioner. Interpretative phenomenological analysis (IPA; Smith, Flowers, & Larkin, 2009) was used to interview a purposive sample of nine practitioners who reported SEs in their therapeutic sessions. Semi-structured face-to-face interviews were conducted with three counsellors, three psychologists and three psychotherapists, and focused on how participants make sense of their experiences of synchronicity in therapy. Three superordinate themes were identified: Sense of connectedness, therapeutic process, and professional issues. Findings suggest that SEs can serve to strengthen the therapeutic relationship and are perceived as useful harbingers of information about the therapeutic process, as well as being a means of overcoming communication difficulties, as they are seen to provide insights into the client’s experiencing of themselves and others, regardless of whether or not the SE is acknowledged by the client or disclosed by the therapist

    Crystal structure of the catalytic fragment of murine poly(ADP-ribose) polymerase-2.

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    Poly(ADP-ribose) polymerase-1 (PARP-1) has become an important pharmacological target in the treatment of cancer due to its cellular role as a 'DNA-strand break sensor', which leads in part to resistance to some existing chemo- and radiological treatments. Inhibitors have now been developed which prevent PARP-1 from synthesizing poly(ADP-ribose) in response to DNA-breaks and potentiate the cytotoxicity of DNA damaging agents. However, with the recent discoveries of PARP-2, which has a similar DNA-damage dependent catalytic activity, and additional members containing the 'PARP catalytic' signature, the isoform selectivity and resultant pharmacological effects of existing inhibitors are brought into question. We present here the crystal structure of the catalytic fragment of murine PARP-2, at 2.8 A resolution, and compare this to the catalytic fragment of PARP-1, with an emphasis on providing a possible framework for rational drug design in order to develop future isoform-specific inhibitors

    C/EBPalpha: critical at the origin of leukemic transformation

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    Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by clonal expansion of myeloid progenitor cells. A major mechanistic theme in AML biology is the extensive collaboration among fusion oncoproteins, transcription factors, and chromatin regulators to initiate and sustain a transformed cellular state. A new study in this issue describes how the C/EBPalpha transcription factor is crucial for the initiation of AML induced by MLL fusion oncoproteins, but is entirely dispensable for the maintenance of established disease. These observations provide a unique glimpse into the pioneer round of regulatory events that are critical at the origin of AML formation. Furthermore, this study implies the existence of oncogene-induced positive feedback loops capable of bypassing the continuous need for certain regulators to propagate disease

    The Mutual Orbit, Mass, and Density of Transneptunian Binary Gknhmdm (229762 2007 UK126)

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    We present high spatial resolution images of the binary transneptunian object Gkn'hmdm (229762 2007 UK126) obtained with the Hubble Space Telescope and with the Keck observatory on Mauna Kea to determine the orbit of G' hG' h, the much smaller and redder satellite. G' h orbits in a prograde sense, on a circular or near-circular orbit with a period of 11.3 days and a semimajor axis of 6000 km. Tidal evolution is expected to be slow, so it is likely that the system formed already in a low-eccentricity configuration, and possibly also with the orbit plane of the satellite in or close to the plane of Gkn'hmdm's equator. From the orbital parameters we can compute the system mass to be 1.4 10(exp 20) kg. Combined with estimates of the size of Gkn'hmdm from thermal observations and stellar occultations, we can estimate the bulk density as about 1 g cm(exp 3). This low density is indicative of an ice-rich composition, unless there is substantial internal porosity. We consider the hypothesis that the composition is not unusually ice-rich compared with larger TNOs and comet nuclei, and instead the porosity is high, suggesting that mid-sized objects in the 400 to 1000 km diameter range mark the transition between small, porous objects and larger objects that have collapsed their internal void space as a result of their much higher internal pressures and temperatures

    Co-crystalization and in vitro biological characterization of 5-Aryl-4-(5-substituted-2-4-dihydroxyphenyl)-1,2,3-thiadiazole Hsp90 inhibitors

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    A potential therapeutic strategy for targeting cancer that has gained much interest is the inhibition of the ATP binding and ATPase activity of the molecular chaperone Hsp90. We have determined the structure of the human Hsp90α N-terminal domain in complex with a series of 5-aryl-4-(5-substituted-2-4-dihydroxyphenyl)-1,2,3-thiadiazoles. The structures provide the molecular details for the activity of these inhibitors. One of these inhibitors, ICPD 34, causes a structural change that affects a mobile loop, which adopts a conformation similar to that seen in complexes with ADP, rather than the conformation generally seen with the pyrazole/isoxazole-resorcinol class of inhibitors. Competitive binding to the Hsp90 N-terminal domain was observed in a biochemical assay, and these compounds showed antiproliferative activity and induced apoptosis in the HCT116 human colon cancer cell line. These inhibitors also caused induction of the heat shock response with the upregulation of Hsp72 and Hsp27 protein expression and the depletion of Hsp90 clients, CRAF, ERBB2 and CDK4, thus confirming that antiproliferative activity was through the inhibition of Hsp90. The presence of increased levels of the cleavage product of PARP indicated apoptosis in response to Hsp90 inhibitors. This work provides a framework for the further optimization of thiadiazole inhibitors of Hsp90. Importantly, we demonstrate that the thiadiazole inhibitors display a more limited core set of interactions relative to the clinical trial candidate NVP-AUY922, and consequently may be less susceptible to resistance derived through mutations in Hsp9
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