Low Energy STEM of Multi-Layers and Dopant Profiles

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Dexamethasone downregulates autophagy through accelerated turn-over of the ulk-1 complex in a trabecular meshwork cells strain: Insights on steroid-induced glaucoma pathogenesis

Steroid-induced glaucoma is a severe pathological condition, sustained by a rapidly progressive increase in intraocular pressure (IOP), which is diagnosed in a subset of subjects who adhere to a glucocorticoid (GC)-based therapy. Molecular and clinical studies suggest that either natural or synthetic GCs induce a severe metabolic dysregulation of Trabecular Meshwork Cells (TMCs), an endothelial-derived histotype with phagocytic and secretive functions which lay at the iridocorneal angle in the anterior segment of the eye. Since TMCs physiologically regulate the composition and architecture of trabecular meshwork (TM), which is the main outflow pathway of aqueous humor, a fluid which shapes the eye globe and nourishes the lining cell types, GCs are supposed to trigger a pathological remodeling of the TM, inducing an IOP increase and retina mechanical compression. The metabolic dysregulation of TMCs induced by GCs exposure has never been characterized at the molecular detail. Herein, we report that, upon dexamethasone exposure, a TMCs strain develops a marked inhibition of the autophagosome biogenesis pathway through an enhanced turnover of two members of the Ulk-1 complex, the main platform for autophagy induction, through the Ubiquitin Proteasome System (UPS)

The Swift X-ray Telescope Cluster Survey II. X-ray spectral analysis

(Abridged) We present a spectral analysis of a new, flux-limited sample of 72 X-ray selected clusters of galaxies identified with the X-ray Telescope (XRT) on board the Swift satellite down to a flux limit of ~10-14 erg/s/cm2 (SWXCS, Tundo et al. 2012). We carry out a detailed X-ray spectral analysis with the twofold aim of measuring redshifts and characterizing the properties of the Intra-Cluster Medium (ICM). Optical counterparts and spectroscopic or photometric redshifts are obtained with a cross-correlation with NED. Additional photometric redshifts are computed with a dedicated follow-up program with the TNG and a cross-correlation with the SDSS. We also detect the iron emission lines in 35% of the sample, and hence obtain a robust measure of the X-ray redshift zX. We use zX whenever the optical redshift is not available. Finally, for all the sources with measured redshift, background-subtracted spectra are fitted with a mekal model. We perform extensive spectral simulations to derive an empirical formula to account for fitting bias. The bias-corrected values are then used to investigate the scaling properties of the X-ray observables. Overall, we are able to characterize the ICM of 46 sources. The sample is mostly constituted by clusters with temperatures between 3 and 10 keV, plus 14 low-mass clusters and groups with temperatures below 3 keV. The redshift distribution peaks around z~0.25 and extends up to z~1, with 60% of the sample at 0.1<z<0.4. We derive the Luminosity-Temperature relation for these 46 sources, finding good agreement with previous studies. The quality of the SWXCS sample is comparable to other samples available in the literature and obtained with much larger X-ray telescopes. Our results have interesting implications for the design of future X-ray survey telescopes, characterised by good-quality PSF over the entire field of view and low background.Comment: 27 pages, 15 figures; minor typos corrected. To be published in A&A, Volume 567, July 2014. Websites of the SWXCS project: http://www.arcetri.astro.it/SWXCS/ and http://swxcs.ustc.edu.cn

Evaluation of LENI in a case study of a retirement home

This work aims to propose a case study for the calculation of the energy performance of lighting systems in a retirement home. The proposed methodology evaluates the energy consumption of lighting systems in the presence of daytime lighting and occupancy control strategies with the Lighting Energy Numerical Indicator (LENI). The effect of natural light, the LED sources, the external obstructions, as well as building orientation and shading systems, can influence the energy consumption of the lighting systems. The case study analysed was the “Brancaccio retirement home” located in Matera (Southern part of Italy). The results of this work refer to both annual and monthly energy consumptions, and underline how important it is to evaluate the amount of energy throughout the year in the presence of control systems, given the considerable monthly variation. Furthermore, the LED source is able to significantly reduce energy consumption compared to fluorescent lamps, and this energy saving can be further increased in the presence of control systems

The role of the internal heat gains for artificial lighting on the energy performance of buildings

This paper aims to propose a procedure for calculating the energy performance indexes of buildings considering the seasonality of internal gains due to artificial lighting with a monthly quasi-steady-state energy balance. The proposed methodology evaluates the heat gains due to the integrated natural-artificial lighting system with the Lighting Energy Numerical Indicator (LENI). For the evaluation of buildings’ global energy performance and for some energy services, this contribution cannot be considered constant annually as depend strongly by climate conditions. The effect of daylighting, type of light sourcesluminaires, building orientation and shading devices could influence lighting contribution of the internal heat gains. Then, the proposed methodology evaluates the internal heat gains with monthly energy balances. This methodology was applied to the case study of the "Brancaccio" retirement home in Matera (IT) for which the values of the energy performance indexes were compared with the standard normative approach using constant internal heat gains. The results of this work underline the importance of performing a detailed analysis that considers the availability of natural light in the different months of the year, the efficiency of the different lighting systems and their power installed per unit of area as a function of the lighting comfort requirements in the different types of environments

A Left Atrial Appendage Closure Combined Procedure Review: past, present and future perspectives

Atrial fibrillation (AF) represents the most common cardiac arrhythmia worldwide; it poses a great burden in terms of quality of life reduction and yearly stroke risk. Left atrial appendage closure (LAAC) is a stroke prevention strategy that has been proven a viable alternative to anti-thrombotic regimens in non-valvular AF patients. LAAC can be performed as a stand-alone procedure or alongside a concomitant AF trans catheter ablation, in a procedure known as "Combined Procedure". Aim of this study is to summarize the scientific evidence backing this combined strategy

Somatostatin: A Novel Substrate and a Modulator of Insulin-Degrading Enzyme Activity

Insulin-degrading enzyme (IDE) is an interesting pharmacological target for Alzheimer's disease (AD), since it hydrolyzes beta-amyloid, producing non-neurotoxic fragments. It has also been shown that the somatostatin level reduction is a pathological feature of AD and that it regulates the neprilysin activity toward beta-amyloid. In this work, we report for the first time that IDE is able to hydrolyze somatostatin [k(cat) (s(-1)) = 0.38 (+/-0.05); K-m (M) = 7.5 (+/-0.9) x 10(-6)] at the Phe6-Phe7 amino acid bond. On the other hand, somatostatin modulates IDE activity, enhancing the enzymatic cleavage of a novel fluorogenic beta-amyloid through a decrease of the K-m toward this substrate, which corresponds to the 10-25 amino acid sequence of the A beta(1-40). Circular dichroism spectroscopy and surface plasmon resonance imaging experiments show that somatostatin binding to IDE brings about a concentration-dependent structural change of the secondary and tertiary structure(s) of the enzyme, revealing two possible binding sites. The higher affinity binding site disappears upon inactivation of IDE by ethylenediaminetetra acetic acid, which chelates, the catalytic Zn2+ ion. As a whole, these features suggest that the modulatory effect is due to an allosteric mechanism: somatostatin binding to the active site of one IDE subunit (where somatostatin is cleaved) induces an enhancement of IDE proteolytic activity toward fluorogenic beta-amyloid by another subunit. Therefore, this investigation on IDE-somatostatin interaction contributes to a more exhaustive knowledge about the functional and structural aspects of IDE and its pathophysiological implications in the amyloid deposition and somatostatin homeostasis in the brain. (C) 2008 Elsevier Ltd. All rights reserved