The Linac Coherent Light Source (LCLS) is an X-ray free-electron laser at the SLAC National Accelerator Laboratory, which has been operating since 2009 for a wide range of scientific research. The ...free-electron laser process at LCLS is based on self-amplified spontaneous emission (SASE) where spontaneous emission from the initial electron beam shot noise is amplified by its interaction with the electrons over a long magnetic undulator. Although SASE is very effective, producing tremendously powerful, ultrashort X-ray beams, the start-up from noise leaves poor temporal coherence and a broad, noisy spectrum. We present experimental results of a new method, suggested by colleagues at DESY, allowing self-seeding using X-rays from the first half of the undulator to seed the second half through a diamond-based monochromator, producing near Fourier-transform-limited X-ray pulses with 0.4-0.5 eV bandwidth at 8-9 keV. These results demonstrate self-seeding at ångstrom wavelengths with a relative bandwidth reduction of 40-50 with respect to SASE.
Global tropospheric ozone distributions, budgets, and radiative forcings from an ensemble of 26 state‐of‐the‐art atmospheric chemistry models have been intercompared and synthesized as part of a ...wider study into both the air quality and climate roles of ozone. Results from three 2030 emissions scenarios, broadly representing “optimistic,” “likely,” and “pessimistic” options, are compared to a base year 2000 simulation. This base case realistically represents the current global distribution of tropospheric ozone. A further set of simulations considers the influence of climate change over the same time period by forcing the central emissions scenario with a surface warming of around 0.7K. The use of a large multimodel ensemble allows us to identify key areas of uncertainty and improves the robustness of the results. Ensemble mean changes in tropospheric ozone burden between 2000 and 2030 for the 3 scenarios range from a 5% decrease, through a 6% increase, to a 15% increase. The intermodel uncertainty (±1 standard deviation) associated with these values is about ±25%. Model outliers have no significant influence on the ensemble mean results. Combining ozone and methane changes, the three scenarios produce radiative forcings of −50, 180, and 300 mW m−2, compared to a CO2 forcing over the same time period of 800–1100 mW m−2. These values indicate the importance of air pollution emissions in short‐ to medium‐term climate forcing and the potential for stringent/lax control measures to improve/worsen future climate forcing. The model sensitivity of ozone to imposed climate change varies between models but modulates zonal mean mixing ratios by ±5 ppbv via a variety of feedback mechanisms, in particular those involving water vapor and stratosphere‐troposphere exchange. This level of climate change also reduces the methane lifetime by around 4%. The ensemble mean year 2000 tropospheric ozone budget indicates chemical production, chemical destruction, dry deposition and stratospheric input fluxes of 5100, 4650, 1000, and 550 Tg(O3) yr−1, respectively. These values are significantly different to the mean budget documented by the Intergovernmental Panel on Climate Change (IPCC) Third Assessment Report (TAR). The mean ozone burden (340 Tg(O3)) is 10% larger than the IPCC TAR estimate, while the mean ozone lifetime (22 days) is 10% shorter. Results from individual models show a correlation between ozone burden and lifetime, and each model's ozone burden and lifetime respond in similar ways across the emissions scenarios. The response to climate change is much less consistent. Models show more variability in the tropics compared to midlatitudes. Some of the most uncertain areas of the models include treatments of deep tropical convection, including lightning NOx production; isoprene emissions from vegetation and isoprene's degradation chemistry; stratosphere‐troposphere exchange; biomass burning; and water vapor concentrations.
Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have ...been implicated in myelin health
, it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1-TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease
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The Linac Coherent Light Source has added a self-seeding capability to the soft x-ray range using a grating monochromator system. We report the demonstration of soft x-ray self-seeding with a ...measured resolving power of 2000-5000, wavelength stability of 10(-4), and an increase in peak brightness by a factor of 2-5 across the photon energy range of 500-1000 eV. By avoiding the need for a monochromator at the experimental station, the self-seeded beam can deliver as much as 50-fold higher brightness to users.
Identification of ALK in Thinness Orthofer, Michael; Valsesia, Armand; Mägi, Reedik ...
Cell,
06/2020, Letnik:
181, Številka:
6
Journal Article
Recenzirano
Odprti dostop
There is considerable inter-individual variability in susceptibility to weight gain despite an equally obesogenic environment in large parts of the world. Whereas many studies have focused on ...identifying the genetic susceptibility to obesity, we performed a GWAS on metabolically healthy thin individuals (lowest 6th percentile of the population-wide BMI spectrum) in a uniquely phenotyped Estonian cohort. We discovered anaplastic lymphoma kinase (ALK) as a candidate thinness gene. In Drosophila, RNAi mediated knockdown of Alk led to decreased triglyceride levels. In mice, genetic deletion of Alk resulted in thin animals with marked resistance to diet- and leptin-mutation-induced obesity. Mechanistically, we found that ALK expression in hypothalamic neurons controls energy expenditure via sympathetic control of adipose tissue lipolysis. Our genetic and mechanistic experiments identify ALK as a thinness gene, which is involved in the resistance to weight gain.
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•GWAS in the EGCUT biobank identifies ALK as a candidate thinness gene•Knockdown of Alk in Drosophila results in reduced triglyceride levels•Alk mutant mice exhibit resistance to diet- and leptin-mutation-induced obesity•ALK controls energy expenditure via sympathetic tone to the adipose organ
Genetic association studies in an Estonian biobank implicate ALK in the regulation of thinness. Studies in Drosophila and mice show that ALK functions as a regulator of sympathetic tone and loss of ALK leads to resistance to weight gain.
We analyze present‐day and future carbon monoxide (CO) simulations in 26 state‐of‐the‐art atmospheric chemistry models run to study future air quality and climate change. In comparison with ...near‐global satellite observations from the MOPITT instrument and local surface measurements, the models show large underestimates of Northern Hemisphere (NH) extratropical CO, while typically performing reasonably well elsewhere. The results suggest that year‐round emissions, probably from fossil fuel burning in east Asia and seasonal biomass burning emissions in south‐central Africa, are greatly underestimated in current inventories such as IIASA and EDGAR3.2. Variability among models is large, likely resulting primarily from intermodel differences in representations and emissions of nonmethane volatile organic compounds (NMVOCs) and in hydrologic cycles, which affect OH and soluble hydrocarbon intermediates. Global mean projections of the 2030 CO response to emissions changes are quite robust. Global mean midtropospheric (500 hPa) CO increases by 12.6 ± 3.5 ppbv (16%) for the high‐emissions (A2) scenario, by 1.7 ± 1.8 ppbv (2%) for the midrange (CLE) scenario, and decreases by 8.1 ± 2.3 ppbv (11%) for the low‐emissions (MFR) scenario. Projected 2030 climate changes decrease global 500 hPa CO by 1.4 ± 1.4 ppbv. Local changes can be much larger. In response to climate change, substantial effects are seen in the tropics, but intermodel variability is quite large. The regional CO responses to emissions changes are robust across models, however. These range from decreases of 10–20 ppbv over much of the industrialized NH for the CLE scenario to CO increases worldwide and year‐round under A2, with the largest changes over central Africa (20–30 ppbv), southern Brazil (20–35 ppbv) and south and east Asia (30–70 ppbv). The trajectory of future emissions thus has the potential to profoundly affect air quality over most of the world's populated areas.
Air quality, ecosystem exposure to nitrogen deposition, and climate change are intimately coupled problems: we assess changes in the global atmospheric environment between 2000 and 2030 using 26 ...state-of-the-art global atmospheric chemistry models and three different emissions scenarios. The first (CLE) scenario reflects implementation of current air quality legislation around the world, while the second (MFR) represents a more optimistic case in which all currently feasible technologies are applied to achieve maximum emission reductions. We contrast these scenarios with the more pessimistic IPCC SRES A2 scenario. Ensemble simulations for the year 2000 are consistent among models and show a reasonable agreement with surface ozone, wet deposition, and NO2 satellite observations. Large parts of the world are currently exposed to high ozone concentrations and high deposition of nitrogen to ecosystems. By 2030, global surface ozone is calculated to increase globally by 1.5 ± 1.2 ppb (CLE) and 4.3 ± 2.2 ppb (A2), using the ensemble mean model results and associated ±1 σ standard deviations. Only the progressive MFR scenario will reduce ozone, by −2.3 ± 1.1 ppb. Climate change is expected to modify surface ozone by −0.8 ± 0.6 ppb, with larger decreases over sea than over land. Radiative forcing by ozone increases by 63 ± 15 and 155 ± 37 mW m-2 for CLE and A2, respectively, and decreases by −45 ± 15 mW m-2 for MFR. We compute that at present 10.1% of the global natural terrestrial ecosystems are exposed to nitrogen deposition above a critical load of 1 g N m-2 yr-1. These percentages increase by 2030 to 15.8% (CLE), 10.5% (MFR), and 25% (A2). This study shows the importance of enforcing current worldwide air quality legislation and the major benefits of going further. Nonattainment of these air quality policy objectives, such as expressed by the SRES-A2 scenario, would further degrade the global atmospheric environment.
Exercise training produces enhanced nitric oxide (NO)-dependent, endothelium-mediated vasodilator responses of porcine coronary arterioles but not conduit coronary arteries. The purpose of this study ...was to test the hypothesis that exercise training increases the amount of endothelial NO synthase (eNOS) in the coronary arterial microcirculation but not in the conduit coronary arteries. Miniature swine were either exercise trained or remained sedentary for 16--20 wk. Exercise-trained pigs exhibited increased skeletal muscle oxidative capacity, exercise tolerance, and heart weight-to-body weight ratios. Content of eNOS protein was determined with immunoblot analysis in conduit coronary arteries (2- to 3-mm ID), small arteries (301- to 1,000-microm ID), resistance arteries (151- to 300-microm ID), and three sizes of coronary arterioles large (101- to 150-microm ID), intermediate (51- to 100-microm ID), and small (<50-microm ID). Immunoblots revealed increased eNOS protein in some sizes of coronary arteries and arterioles but not in others. Content of eNOS was increased by 60--80% in small and large arterioles, resistance arteries, and small arteries; was increased by 10--20% in intermediate-sized arterioles; and was not changed or decreased in conduit arteries. Immunohistochemistry revealed that eNOS was located in the endothelial cells in all sizes of coronary artery. We conclude that exercise training increases eNOS protein expression in a nonuniform manner throughout the coronary arterial tree. Regional differences in shear stress and intraluminal pressures during exercise training bouts may be responsible for the distribution of increased eNOS protein content in the coronary arterial tree.
Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we ...report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the alpha 2 delta family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 ( alpha 2 delta 3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, alpha 2 delta 3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in alpha 2 delta 3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in alpha 2 delta 3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.
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