3,218 research outputs found

    ABIM Update Latest MOC Changes: ACC Leaders Determine Next Steps

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    An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba dictyostelium discoideum

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    Mutations in either of two presenilin genes can cause familial Alzheimer's disease. Presenilins have both proteolysis-dependent functions, as components of the γ-secretase complex, and proteolysis-independent functions in signalling. In this study, we investigate a conserved function of human presenilins in the development of the simple model organism Dictyostelium discoideum. We show that the block in Dictyostelium development caused by the ablation of both Dictyostelium presenilins is rescued by the expression of human presenilin 1, restoring the terminal differentiation of multiple cell types. This developmental role is independent of proteolytic activity, because the mutation of both catalytic aspartates does not affect presenilin ability to rescue development, and the ablation of nicastrin, a γ-secretase component that is crucial for proteolytic activity, does not block development. The role of presenilins during Dictyostelium development is therefore independent of their proteolytic activity. However, presenilin loss in Dictyostelium results in elevated cyclic AMP (cAMP) levels and enhanced stimulation-induced calcium release, suggesting that presenilins regulate these intracellular signalling pathways. Our data suggest that presenilin proteins perform an ancient non-proteolytic role in regulating intracellular signalling and development, and that Dictyostelium is a useful model for analysing human presenilin function

    Effect of Long-Term Exposure to Lower Low-Density Lipoprotein Cholesterol Beginning Early in Life on the Risk of Coronary Heart Disease A Mendelian Randomization Analysis

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    ObjectivesThe purpose of this study was to estimate the effect of long-term exposure to lower plasma low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD).BackgroundLDL-C is causally related to the risk of CHD. However, the association between long-term exposure to lower LDL-C beginning early in life and the risk of CHD has not been reliably quantified.MethodsWe conducted a series of meta-analyses to estimate the effect of long-term exposure to lower LDL-C on the risk of CHD mediated by 9 polymorphisms in 6 different genes. We then combined these Mendelian randomization studies in a meta-analysis to obtain a more precise estimate of the effect of long-term exposure to lower LDL-C and compared it with the clinical benefit associated with the same magnitude of LDL-C reduction during treatment with a statin.ResultsAll 9 polymorphisms were associated with a highly consistent reduction in the risk of CHD per unit lower LDL-C, with no evidence of heterogeneity of effect (I2 = 0.0%). In a meta-analysis combining nonoverlapping data from 312,321 participants, naturally random allocation to long-term exposure to lower LDL-C was associated with a 54.5% (95% confidence interval: 48.8% to 59.5%) reduction in the risk of CHD for each mmol/l (38.7 mg/dl) lower LDL-C. This represents a 3-fold greater reduction in the risk of CHD per unit lower LDL-C than that observed during treatment with a statin started later in life (p = 8.43 × 10−19).ConclusionsProlonged exposure to lower LDL-C beginning early in life is associated with a substantially greater reduction in the risk of CHD than the current practice of lowering LDL-C beginning later in life

    Regional variation of organic functional groups in aerosol particles on four U.S. east coast platforms during the International Consortium for Atmospheric Research on Transport and Transformation 2004 campaign

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    Submicron atmospheric aerosol samples were collected during the International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) 2004 campaign on four platforms: Chebogue Point (Nova Scotia, Canada), Appledore Island (Maine), the CIRPAS Twin Otter over Ohio, and the NOAA R/V Ronald H. Brown in the Gulf of Maine. Saturated aliphatic C-C-H, unsaturated aliphatic C=C−H, aromatic C=C−H, organosulfur C-O-S, carbonyl C=O, and organic hydroxyl C-OH functional groups were measured by calibrated Fourier Transform Infrared (FTIR) spectroscopy at all four sampling platforms. The ratio of molar concentrations of carbonyl C=O to saturated aliphatic C-C-H groups was nearly constant at each sampling platform, with the Twin Otter samples having the lowest ratio at 0.1 and the three more coastal platforms having ratios of 0.4 and 0.5. Organic mass (OM) to organic carbon (OC) ratios follow similar trends for the four platforms, with the Twin Otter having the lowest ratio of 1.4 and the coastal platforms having slightly higher values typically between 1.5 and 1.6. Organosulfur compounds were occasionally observed. Collocated organic aerosol sampling with two Aerodyne aerosol mass spectrometers for OM, a Sunset Laboratory thermo-optical analysis instrument for OC, and an ion chromatography-particle into liquid sampler (IC-PILS) for speciated carboxylic acids provided comparable results for most of the project, tracking the time series of FTIR OM, OC, and carbonyl groups, respectively, and showing simultaneous peaks of similar magnitude during most of the project. The FTIR/IC-PILS comparison suggests that about 9% of the carbonyl groups found in submicron organic particles on the Twin Otter are typically associated with low molecular weight carboxylic acids

    The relationship between personal breastfeeding experience and the breastfeeding attitudes, knowledge, confidence and effectiveness of Australian GP registrars

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    In conjunction with other health professionals, doctors believe they play an important role in promoting breastfeeding to women. Although many have positive breastfeeding attitudes, significant knowledge deficits often limit their capacity to effectively encourage, support and assist breastfeeding women and their infants. Personal breastfeeding experience (of self or partner) may be the main source of breastfeeding knowledge and skill development and is related to improved knowledge, more positive attitudes and greater confidence. This paper describes the relationship between the cumulative length of personal breastfeeding experience and the breastfeeding knowledge and attitudes of a cohort of Australian general practice (GP) registrars, as well as their confidence and perceived effectiveness assisting breastfeeding women. The Australian Breastfeeding Knowledge and Attitude Questionnaire containing demographic items, a 20-item attitude scale and a 40-item knowledge scale was distributed between February and May 2007 to Australian GP registrars in their final year of training. Participants with more than 52-week cumulative personal (self or partner) breastfeeding experience had the highest mean knowledge score, had more positive attitudes, and were more confident and effective than all other participants. Parents with limited personal experience (≤ 26 weeks) had the poorest breast-feeding attitudes and their knowledge base was similar to participants with no personal experience. Confidence and perceived effectiveness when assisting breastfeeding women rose with increasing cumulative breastfeeding experience. Personal breastfeeding experience per se does not guarantee better breastfeeding knowledge or attitudes although increasing length of experience is related to higher knowledge, attitude, confidence and perceived effectiveness scores

    Multi-wavelength spectrophotometry of EX Hydrae

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    We present phase-resolved infrared and optical spectrophotometry of the intermediate polar EX Hya supplemented by archival ultraviolet data. The spin-modulated emission from the accretion funnel and the emission from the accretion disk or ring contain substantial optically thin components. The white dwarf dominates the unmodulated flux in the ultraviolet and is identified by numerous absorption lines. Metal absorption in the accretion curtain may add to the observed spectral features. The secondary star is of spectral type M4+-1 and is detected by its ellipsoidal modulation. We derive a distance of 65+-11 pc which makes EX Hydrae one of the closest cataclysmic variables with a known distance. The luminosity derived from the integrated overall spectral energy distribution is 3x10^32 erg/s. The accretion rate of 3x10^15 g/s (for an 0.6 Msun white dwarf) is in reasonable agreement with the rates expected from angular momentum loss by gravitational radiation and from the observed spin-up of the white dwarfComment: 15 A&A Latex, 9 Figures, accepted for publication in A&

    Interpretation of Strong Short-Term Central Perturbations in the Light Curves of Moderate-Magnification Microlensing Events

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    To improve the planet detection efficiency, current planetary microlensing experiments are focused on high-magnification events searching for planetary signals near the peak of lensing light curves. However, it is known that central perturbations can also be produced by binary companions and thus it is important to distinguish planetary signals from those induced by binary companions. In this paper, we analyze the light curves of microlensing events OGLE-2007-BLG-137/MOA-2007-BLG-091, OGLE-2007-BLG-355/MOA-2007-BLG-278, and MOA-2007-BLG-199/OGLE-2007-BLG-419, for all of which exhibit short-term perturbations near the peaks of the light curves. From detailed modeling of the light curves, we find that the perturbations of the events are caused by binary companions rather than planets. From close examination of the light curves combined with the underlying physical geometry of the lens system obtained from modeling, we find that the short time-scale caustic-crossing feature occurring at a low or a moderate base magnification with an additional secondary perturbation is a typical feature of binary-lens events and thus can be used for the discrimination between the binary and planetary interpretations.Comment: 17 pages, 4 figures, 1 tabl

    LXCat: An Open-Access, Web-Based Platform for Data Needed for Modeling Low Temperature Plasmas

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    LXCat is an open-access platform (www.lxcat.net) for curating data needed for modeling the electron and ion components of technological plasmas. The data types presently supported on LXCat are scattering cross sections and swarm/transport parameters, ion-neutral interaction potentials, and optical oscillator strengths. Twenty-four databases contributed by different groups around the world can be accessed on LXCat. New contributors are welcome; the database contributors retain ownership and are responsible for the contents and maintenance of the individual databases. This article summarizes the present status of the project. © 2016 WILEY-VCH Verlag GmbH & Co
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