Problems Associated With the Assessment of Local Site Effects Through a Multidisciplinary Integrated Study: The Case of Fivizzano’s Town (Italy)

The evaluation of local site effects, by means of ground response analyses, is a very complex and difficult task, which requires a multidisciplinary approach. This is operative philosophy expressed by VEL Project (Valutazione degli Effetti Locali), sponsored by Tuscany Region, to the aim to seismic risk characterization in the main seismic areas (i.e. Garfagnana, Lunigiana, Amiata, Valtiberina and Mugello). One of the most important urban centres, involved in the multidisciplinary activity of the VEL project, is certainly the town of Fivizzano located nearby the city of Massa, which was strongly damaged during the earthquake of September 1920 (the strongest seismic event occurred in Northern Apennines in the latest centuries). Remarkably good macroseismic information is available about the destructive impact yielded at Fivizzano by this earthquake (e.g. number of casualties, level of damage of buildings, etc). The main objective of this paper is to identify the occurrence of possible local site effects in the Fivizzano’s area following the 1920 earthquake and to quantify them by means of one and two-dimensional site response analysis. The input data required for study were obtained through a comprehensive geological survey and a multi disciplinary underground exploration of the area

Galactic chemical evolution of heavy elements: from Barium to Europium

We follow the chemical evolution of the Galaxy for elements from Ba to Eu, using an evolutionary model suitable to reproduce a large set of Galactic (local and non local) and extragalactic constraints. Input stellar yields for neutron-rich nuclei have been separated into their s-process and r-process components. The production of s-process elements in thermally pulsing asymptotic giant branch stars of low mass proceeds from the combined operation of two neutron sources: the dominant reaction 13C(alpha,n)16O, which releases neutrons in radiative conditions during the interpulse phase, and the reaction 22Ne(alpha,n)25Mg, marginally activated during thermal instabilities. The resulting s-process distribution is strongly dependent on the stellar metallicity. For the standard model discussed in this paper, it shows a sharp production of the Ba-peak elements around Z = Z_sun/4. Concerning the r-process yields, we assume that the production of r-nuclei is a primary process occurring in stars near the lowest mass limit for Type II supernova progenitors. The r-contribution to each nucleus is computed as the difference between its solar abundance and its s-contribution given by the Galactic chemical evolution model at the epoch of the solar system formation. We compare our results with spectroscopic abundances of elements from Ba to Eu at various metallicities (mainly from F and G stars) showing that the observed trends can be understood in the light of the present knowledge of neutron capture nucleosynthesis. Finally, we discuss a number of emerging features that deserve further scrutiny.Comment: 34 pages, 13 figures. accepted by Ap

The Life Span Determinant p66Shc Localizes to Mitochondria Where It Associates with Mitochondrial Heat Shock Protein 70 and Regulates Trans-membrane Potential

P66Shc regulates life span in mammals and is a critical component of the apoptotic response to oxidative stress. It functions as a downstream target of the tumor suppressor p53 and is indispensable for the ability of oxidative stress-activated p53 to induce apoptosis. The molecular mechanisms underlying the apoptogenic effect of p66Shc are unknown. Here we report the following three findings. (i) The apoptosome can be properly activated in vitro in the absence of p66Shc only if purified cytochrome c is supplied. (ii) Cytochrome c release after oxidative signals is impaired in the absence of p66Shc. (iii) p66Shc induces the collapse of the mitochondrial trans-membrane potential after oxidative stress. Furthermore, we showed that a fraction of cytosolic p66Shc localizes within mitochondria where it forms a complex with mitochondrial Hsp70. Treatment of cells with ultraviolet radiation induced the dissociation of this complex and the release of monomeric p66Shc. We propose that p66Shc regulates the mitochondrial pathway of apoptosis by inducing mitochondrial damage after dissociation from an inhibitory protein complex. Genetic and biochemical evidence suggests that mitochondria regulate life span through their effects on the energetic metabolism (mitochondrial theory of aging). Our data suggest that mitochondrial regulation of apoptosis might also contribute to life span determination

Synthesis and evaluation of new Hsp90 inhibitors based on a 1,4,5-trisubstituted 1,2,3-triazole scaffold

Abstract: Ruthenium catalyzed 1,3-cycloaddition (click chemistry) of an azido moiety installed on dihydroxycumene scaffold with differently substituted aryl propiolates, gave a new family of 1,4,5-trisubstitued triazole carboxylic acid derivatives that showed high affinity towards Hsp90 associated with cell proliferation inhibition, both in nanomolar range. The 1,5 arrangement of the resorcinol, the aryl moieties, and the presence of an alkyl (secondary) amide in position 4 of the triazole ring, were essential to get high activity. Docking simulations suggested that the triazoles penetrate the Hsp90 ATP binding site. Some 1,4,5-trisubstitued triazole carboxamides induced dramatic depletion of the examined client proteins and a very strong increase in the expression levels of the chaperone Hsp70. In vitro metabolic stability and in vivo preliminary studies on selected compounds have shown promising results comparable to the potent Hsp90 inhibitor NVP-AUY922. One of them, (compound 18; SST0287CL1) was selected for further investigation as the most promising drug candidate