Tug of war between survival and death: exploring ATM function in cancer.

Ataxia-telangiectasia mutated (ATM) kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR). The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer

In situ observation of heat-induced degradation of perovskite solar cells

The lack of thermal stability of perovskite solar cells is hindering the progress of this technology towards adoption in the consumer market. Different pathways of thermal degradation are activated at different temperatures in these complex nanostructured hybrid composites. Thus, it is essential to explore the thermal response of the mesosuperstructured composite device to engineer materials and operating protocols. Here we produce devices according to four well-established recipes, and characterize their photovoltaic performance as they are heated within the operational range. The devices are analysed using transmission electron microscopy as they are further heated in situ, to monitor changes in morphology and chemical composition. We identify mechanisms for structural and chemical changes, such as iodine and lead migration, which appear to be correlated to the synthesis conditions. In particular, we identify a correlation between exposure of the perovskite layer to air during processing and elemental diffusion during thermal treatment. Solar cells based on lead halide perovskite composites have become increasingly popular in the past few years owing to a combination of low synthesis cost and high power conversion efficiency, with certified values in excess of 20% (refs 1,2,3,4,5). However, the stability of such devices is a concern—it is well known that heating at or above around 85 ∘C, a temperature close to those reached during normal operation in full sunlight, performance degrades rapidly, and such instability is exacerbated by exposure to moisture; systematic thermal and ageing studies are required to understand such degradation processes. Changes happen in both the organic and inorganic components of the cells; the resilience of the perovskite layer, in particular, is expected to become a limiting factor once different hole-conducting materials (or hole-conductor-free cells) are developed. To overcome this limitation, it is vital to understand the degradation pathways of the structures involved, which here are observed at nanometre-scale spatial resolution in situ, inside an analytical scanning transmission electron microscope (STEM), while the composition is monitored with elemental mapping through energy-dispersive X-ray analysis (EDX). The analysis of such devices is challenging owing to several factors. The spatial dimensions relevant to the fabrication and the operation of the cells are in the 1–100 nm range, and the materials are easily damaged by exposure to an electron beam in a TEM, requiring careful tuning of the electron dose. The system also includes organic and inorganic components in an assembly with complex chemistry and morphology. Finally, the rapid changes to the devices in air and the low degradation temperatures pose an additional challenge to the experiment, which needs to be timed appropriately and carefully executed. The monitoring of this process is made possible by combining several recent advances in TEM technology. The use of high-brightness electron guns and detectors with large collection areas allows the fast acquisition of high-quality EDX maps with limited electron dose on the sample; the signal-to-noise ratio of the maps can be further increased by applying denoising algorithms (PCA, principal components analysis) within an open-source software suite. The development of novel in situ heating holders for TEM, based on micro-heaters and featuring high stability and fast response, was also crucial—in particular, the holder used here allows very precise control (sub-degree) at values just above room temperature, as well as providing fast heating and cooling (a few seconds for the temperatures in use in this paper). The good spatial stability of the holder is crucial in acquiring EDX maps.G.D., S.C., and C.D. acknowledge funding from ERC under grant number 259619 PHOTO EM. C.D. acknowledges financial support from the EU under grant number 312483 ESTEEM2. F.M., L.C. and A.D.C. acknowledge funding from “Polo Solare Organico” Regione Lazio, the “DSSCX” MIURPRIN2010 and FP7 ITN “Destiny”. G.D and S.C. thank Dr. Francisco de la Peña and Dr. Pierre Burdet for assistance with PCA analysis.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nenergy.2015.1

Quasiclassical magnetotransport in a random array of antidots

We study theoretically the magnetoresistance $\rho_{xx}(B)$ of a two-dimensional electron gas scattered by a random ensemble of impenetrable discs in the presence of a long-range correlated random potential. We believe that this model describes a high-mobility semiconductor heterostructure with a random array of antidots. We show that the interplay of scattering by the two types of disorder generates new behavior of $\rho_{xx}(B)$ which is absent for only one kind of disorder. We demonstrate that even a weak long-range disorder becomes important with increasing $B$. In particular, although $\rho_{xx}(B)$ vanishes in the limit of large $B$ when only one type of disorder is present, we show that it keeps growing with increasing $B$ in the antidot array in the presence of smooth disorder. The reversal of the behavior of $\rho_{xx}(B)$ is due to a mutual destruction of the quasiclassical localization induced by a strong magnetic field: specifically, the adiabatic localization in the long-range Gaussian disorder is washed out by the scattering on hard discs, whereas the adiabatic drift and related percolation of cyclotron orbits destroys the localization in the dilute system of hard discs. For intermediate magnetic fields in a dilute antidot array, we show the existence of a strong negative magnetoresistance, which leads to a nonmonotonic dependence of $\rho_{xx}(B)$.Comment: 21 pages, 13 figure

Integrating urban agriculture and urban planning in Mashhad, Iran; a short survey of current status and constraints

This article addresses the role of urban and peri-urban agriculture (UPA) in Mashhad in a perspective of sustainable development. To this end the article seeks to point out the conditions that hinder this development and the factors that could favor it. The article is structured as follows: in the first section the UPA phenomenon is framed with reference to some significant planning experiences in progress in Western and Islamic countries. In the second section, an outline of Mashhad as a “city in transition” is provided highlighting its main factors of change. In the third section, the institutional framework of present urban planning in Mashhad is described, also showing the weak enforcement mechanisms of planning policy for UPA. Section four presents both a conceptual and material network of un-built areas potentially suitable for agricultural uses, articulated in three different classes. By referring to city maps and recent urban schemes, the study summarizes the physical characteristics, the ownership, and the resources of each class, from inside the compact city to its peripheral belt. The article concludes by indicating the three domains of policy, education, and social commitment as the main factors that can favor effective policies and practices for a multifunctional urban agriculture