Although the prevalence of obesity is higher among women than men, they are somewhat protected from the associated cardiometabolic consequences. The increase in cardiovascular disease risk seen after ...the menopause suggests a role for estrogens. There is also growing evidence for the importance of estrogen on body fat and metabolism in males. We hypothesized that that estrogen administration would ameliorate the adverse effects of obesity on metabolic parameters in males.
Male and female C57Bl/6 mice were fed control or obesogenic (DIO) diets from 5 weeks of age until adulthood. Glucose tolerance testing was performed at 13 weeks of age. Mice were killed at 15 weeks of age and liver and adipose tissue were collected for analysis of gene expression. A second cohort of male mice underwent the same experimental design with the addition of estradiol pellet implantation or sham surgery at 6 weeks.
DIO males had greater mesenteric adipose deposition and more severe increases in plasma glucose, insulin and lipids than females. Treatment of males with estradiol from 6 weeks of age prevented DIO-induced increases in adipose tissue mass and alterations in glucose-insulin homeostasis. We also identified sex differences in the transcript levels and activity of hepatic and adipose glucocorticoid metabolizing enzymes. Estrogen treatment feminized the pattern of DIO-induced changes in glucocorticoid metabolism, rendering males similar to females.
Thus, DIO induces sex-specific changes in glucose-insulin homeostasis, which are ameliorated in males treated with estrogen, highlighting the importance of sex steroids in metabolism. Given that altered peripheral glucocorticoid metabolism has been observed in rodent and human obesity, our results also suggest that sexually dimorphic expression and activity of glucocorticoid metabolizing enzymes may have a role in the differential metabolic responses to obesity in males and females.
Summary
The relationships of osteocalcin (OC) and C-telopeptide of type I collagen (CTX) with long-term incidence of hip fracture were examined in 1680 post-menopausal women from a population-based ...study. CTX, but not OC, levels were associated with incident hip fracture in these participants, a relationship characterized by an inverted U-shape.
Introduction
We sought to investigate the relationships of OC, a marker of bone formation, and CTX, a marker of bone resorption, with long-term incidence of hip fracture in older women.
Methods
We included 1680 women from the population-based Cardiovascular Health Study (mean SD age 74.5 5.0 years). The longitudinal association of both markers with incidence of hip fracture was examined using multivariable Cox models.
Results
During a median follow-up of 12.3 years, 288 incident hip fractures occurred. Linear spline analysis did not demonstrate an association between OC levels and incident hip fracture. By contrast, increasing levels of CTX up to the middle-upper range were associated with a significantly greater risk of hip fracture (HR = 1.52 per SD increment, 95% CI = 1.10–2.09), while further increases were associated with a marginally non-significant lower risk (HR = 0.80 per SD increment, 95% CI = 0.63–1.01), after full adjustment for potential confounders. In analyses of quartiles, CTX exhibited a similar inverted U-shaped relationship with incident fracture after adjustment, with a significant association observed only for the comparison of quartile 3 to quartile 1 (HR = 1.63, 95% CI = 1.10–2.43). In a subset with available measures, both OC and CTX were inversely associated with bone mineral density of the hip.
Conclusion
CTX, but not OC, levels were associated with incident hip fracture in post-menopausal women, a relationship characterized by an inverted U-shape. These findings highlight the complex relationship of bone turnover markers with hip fracture risk.
ABSTRACT We describe the operation and performance of the difference imaging pipeline (DiffImg) used to detect transients in deep images from the Dark Energy Survey Supernova program (DES-SN) in its ...first observing season from 2013 August through 2014 February. DES-SN is a search for transients in which ten 3 deg2 fields are repeatedly observed in the g, r, i, z passbands with a cadence of about 1 week. The observing strategy has been optimized to measure high-quality light curves and redshifts for thousands of Type Ia supernovae (SNe Ia) with the goal of measuring dark energy parameters. The essential DiffImg functions are to align each search image to a deep reference image, do a pixel-by-pixel subtraction, and then examine the subtracted image for significant positive detections of point-source objects. The vast majority of detections are subtraction artifacts, but after selection requirements and image filtering with an automated scanning program, there are ∼130 detections per deg2 per observation in each band, of which only ∼25% are artifacts. Of the ∼7500 transients discovered by DES-SN in its first observing season, each requiring a detection on at least two separate nights, Monte Carlo (MC) simulations predict that 27% are expected to be SNe Ia or core-collapse SNe. Another ∼30% of the transients are artifacts in which a small number of observations satisfy the selection criteria for a single-epoch detection. Spectroscopic analysis shows that most of the remaining transients are AGNs and variable stars. Fake SNe Ia are overlaid onto the images to rigorously evaluate detection efficiencies and to understand the DiffImg performance. The DiffImg efficiency measured with fake SNe agrees well with expectations from a MC simulation that uses analytical calculations of the fluxes and their uncertainties. In our 8 "shallow" fields with single-epoch 50% completeness depth ∼23.5, the SN Ia efficiency falls to 1/2 at redshift z 0.7; in our 2 "deep" fields with mag-depth ∼24.5, the efficiency falls to 1/2 at z 1.1. A remaining performance issue is that the measured fluxes have additional scatter (beyond Poisson fluctuations) that increases with the host galaxy surface brightness at the transient location. This bright-galaxy issue has minimal impact on the SNe Ia program, but it may lower the efficiency for finding fainter transients on bright galaxies.
•Pore shape – not just porosity – is an important control on rock strength.•Pore shape controls stress perturbation size and distribution during compression.•Variable pore shape can account for up to ...an order of magnitude strength variation.•Some void shapes are relatively stable with respect to an applied compression.•Quantifying pore shape and orientation is a critical step in rock strength studies.
The strength of rocks in the subsurface is critically important across the geosciences, with implications for fluid flow, mineralisation, seismicity, and the deep biosphere. Most studies of porous rock strength consider the scalar quantity of porosity, in which strength shows a broadly inverse relationship with total porosity, but pore shape is not explicitly defined. Here we use a combination of uniaxial compressive strength measurements of isotropic and anisotropic porous lava samples, and numerical modelling to consider the influence of pore shape on rock strength. Micro computed tomography (CT) shows that pores range from sub-spherical to elongate and flat ellipsoids. Samples that contain flat pores are weaker if compression is applied parallel to the short axis (i.e. across the minimum curvature), compared to compression applied parallel to the long axis (i.e. across the maximum curvature). Numerical models for elliptical pores show that compression applied across the minimum curvature results in relatively broad amplification of stress, compared to compression applied across the maximum curvature. Certain pore shapes may be relatively stable and remain open in the upper crust under a given remote stress field, while others are inherently weak. Quantifying the shape, orientations, and statistical distributions of pores is therefore a critical step in strength testing of rocks.
CCAT-prime is a new 6 m crossed Dragone telescope designed to characterize the cosmic microwave background (CMB) polarization and foregrounds, measure the Sunyaev–Zel’dovich effects of galaxy ...clusters, map the CII emission intensity from the epoch of reionization (EoR), and monitor accretion luminosity over multiyear timescales of hundreds of protostars in the Milky Way. CCAT-prime will make observations from a 5600-m-altitude site on Cerro Chajnantor in the Atacama Desert of northern Chile. The novel optical design of the telescope combined with high-surface-accuracy (
<
10
μ
m) mirrors and the exceptional atmospheric conditions of the site will enable sensitive broadband, polarimetric, and spectroscopic surveys at sub-millimeter to millimeter wavelengths. Prime-Cam, the first light instrument for CCAT-prime, consists of a 1.8-m-diameter cryostat that can house seven individual instrument modules. Each instrument module, optimized for a specific science goal, will use state-of-the-art kinetic inductance detector (KID) arrays operated at
∼
100
mK and Fabry–Perot interferometers (FPI) for the EoR science. Prime-Cam will be commissioned with staged deployments to populate the seven instrument modules. The full instrument will consist of 60,000 polarimetric KIDs at a combination of 220/280/350/410 GHz, 31,000 KIDS at 250/360 GHz coupled with FPIs, and 21,000 polarimetric KIDs at 850 GHz. Prime-Cam is currently being built, and the CCAT-prime telescope is designed and under construction by Vertex Antennentechnik GmbH to achieve first light in 2021. CCAT-prime is also a potential telescope platform for the future CMB Stage IV observations.
Background and purpose:
Inhibition of cholesteryl ester transfer protein (CETP) with torcetrapib in humans increases plasma high density lipoprotein (HDL) cholesterol levels but is associated with ...increased blood pressure. In a phase 3 clinical study, evaluating the effects of torcetrapib in atherosclerosis, there was an excess of deaths and adverse cardiovascular events in patients taking torcetrapib. The studies reported herein sought to evaluate off‐target effects of torcetrapib.
Experimental approach:
Cardiovascular effects of the CETP inhibitors torcetrapib and anacetrapib were evaluated in animal models.
Key results:
Torcetrapib evoked an acute increase in blood pressure in all species evaluated whereas no increase was observed with anacetrapib. The pressor effect of torcetrapib was not diminished in the presence of adrenoceptor, angiotensin II or endothelin receptor antagonists. Torcetrapib did not have a contractile effect on vascular smooth muscle suggesting its effects in vivo are via the release of a secondary mediator. Treatment with torcetrapib was associated with an increase in plasma levels of aldosterone and corticosterone and, in vitro, was shown to release aldosterone from adrenocortical cells. Increased adrenal steroid levels were not observed with anacetrapib. Inhibition of adrenal steroid synthesis did not inhibit the pressor response to torcetrapib whereas adrenalectomy prevented the ability of torcetrapib to increase blood pressure in rats.
Conclusions and implications:
Torcetrapib evoked an acute increase in blood pressure and an acute increase in plasma adrenal steroids. The acute pressor response to torcetrapib was not mediated by adrenal steroids but was dependent on intact adrenal glands.
British Journal of Pharmacology (2008) 154, 1465–1473; doi:fn2; published online 9 June 2008
When corrected for the effects of cosmic ray exposure, Mo and Ru nucleosynthetic isotope anomalies in iron meteorites from at least nine different parent bodies are strongly correlated in a manner ...consistent with variable depletion in s-process nucleosynthetic components. In contrast to prior studies, the new results show no significant deviations from a single correlation trend. In the refined Mo–Ru cosmic correlation, a distinction between the non-carbonaceous (NC) group and carbonaceous chondrite (CC) group is evident. Members of the NC group are characterized by isotope compositions reflective of variable s-process depletion. Members of the CC group analyzed here plot in a tight cluster and have the most s-process depleted Mo and Ru isotopic compositions, with Mo isotopes also slightly enriched in r- and possibly p-process contributions. This indicates that the nebular feeding zone of the NC group parent bodies was characterized by Mo and Ru with variable s-process contributions, but with the two elements always mixed in the same proportions. The CC parent bodies sampled here, by contrast, were derived from a nebular feeding zone that had been mixed to a uniform s-process depleted Mo–Ru isotopic composition.
Six molybdenite samples, four glacial diamictites, and two ocean island basalts were analyzed to provide a preliminary constraint on the average Mo isotope composition of the bulk silicate Earth (BSE). Combined results yield an average μ97Mo value of +3 ± 6. This value, coupled with a previously reported μ100Ru value of +1 ± 7 for the BSE, indicates that the isotopic composition of the BSE falls precisely on the refined Mo–Ru cosmic correlation. The overlap of the BSE with the correlation implies that there was homogeneous accretion of siderophile elements for the final accretion of 10 to 20 wt% of Earth's mass. The only known cosmochemical materials with an isotopic match to the BSE, with regard to Mo and Ru, are some members of the IAB iron meteorite complex and enstatite chondrites.
•Iron meteorite data form a precise Mo–Ru cosmic correlation.•The slope is identical to that defined by variable s-process depletion.•A Mo isotope composition of BSE is determined.•BSE plots on the correlation.•Homogeneous accretion of the final materials to Earth is implied.
The β decay of Hg208 into the one-proton hole, one neutron-particle Tl81208127 nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the ...proton-neutron interactions used, with implications for the whole of the N>126, Z
ABSTRACT
We present a sample of 151 massive (M* > 1010 M⊙) quiescent galaxies at 2 < z < 5, based on a sophisticated Bayesian spectral energy distribution fitting analysis of the CANDELS UDS and ...GOODS-South fields. Our sample includes a robust sub-sample of 61 objects for which we confidently exclude low-redshift and star-forming solutions. We identify 10 robust objects at z > 3, of which 2 are at z > 4. We report formation redshifts, demonstrating that the oldest objects formed at z > 6; however, individual ages from our photometric data have significant uncertainties, typically ∼0.5 Gyr. We demonstrate that the UVJ colours of the quiescent population evolve with redshift at z > 3, becoming bluer and more similar to post-starburst galaxies at lower redshift. Based upon this, we construct a model for the time evolution of quiescent galaxy UVJ colours, concluding that the oldest objects are consistent with forming the bulk of their stellar mass at z ∼ 6–7 and quenching at z ∼ 5. We report spectroscopic redshifts for two of our objects at z = 3.440 and 3.396, which exhibit extremely weak Ly α emission in ultra-deep VANDELS spectra. We calculate star formation rates based on these line fluxes, finding that these galaxies are consistent with our quiescent selection criteria, provided their Ly α escape fractions are >3 and >10 per cent, respectively. We finally report that our highest redshift robust object exhibits a continuum break at λ ∼ 7000 Å in a spectrum from VUDS, consistent with our photometric redshift of $z_\mathrm{phot}=4.72^{+0.06}_{-0.04}$. If confirmed as quiescent, this object would be the highest redshift known quiescent galaxy. To obtain stronger constraints on the times of the earliest quenching events, high-SNR spectroscopy must be extended to z ≳ 3 quiescent objects.
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