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

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

The development and validation of a disease-specific quality of life measure in hyperhidrosis : the Hyperhidrosis Quality of Life Index (HidroQOL©)

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original authors and the source are credited.PURPOSE: To develop and validate a new disease-specific quality of life measure in hyperhidrosis for use in both routine clinical practice and clinical research. METHODS: Interviews and focus group discussions with hyperhidrosis patients, reported elsewhere, provided the content for the measure validated in this study (n = 71). A panel of dermatologists (n = 5) and patients (n = 7) carried out content validation. Further, item reduction and the initial construct validation were carried out in a cross-sectional study (n = 595), using the unidimensional Rasch analysis and exploratory factor analysis. Subsequently, the construct validity, reliability and responsiveness of the revised measure were assessed in a longitudinal study (n = 260). Data collection for the item reduction and the final validation phases was entirely carried out online. RESULTS: The expert panels judged the HidroQoL as content valid. Rasch analysis supported the revision of response options from five to three. Following removal of misfitting items, a set of 15 items showed optimal fit to the model (chi-squared statistic = 159.64, p = 0.07). Three additional items were retained on consideration of their importance to patients, resulting in an 18-item instrument. The items were grouped into two subscales, daily life activities and psychosocial life domains, based on results of the factor analysis. In subsequent construct validation, the HidroQoL correlated with the DLQI (r s = 0.6, p < 0.01). Reliability was high (internal consistency, Cronbach's alpha: overall scale = 0.9; test-retest reliability, Intra-class correlation = 0.9). The HidroQoL scores were sensitive to change in patients' disease severity (score change from baseline to follow-up after 15-35 days, Cohen's ES = 0.47). CONCLUSION: This study has provided the initial evidence supporting measurement properties and the use of the HidroQoL instrument in both routine clinical practice and in research, for assessing quality of life impacts in hyperhidrosis.Peer reviewedFinal Published versio

Nuova architettura per l’Università Bocconi, Roberto Collovà

Progetto di concorso per l'ampliamento dell'università Bocconi, Milano 200