Ab initio simulations of Cu binding sites in the N-terminal region of PrP

The prion protein (PrP) binds Cu2+ ions in the octarepeat domain of the N-terminal tail up to full occupancy at pH=7.4. Recent experiments show that the HGGG octarepeat subdomain is responsible for holding the metal bound in a square planar coordination. By using first principle ab initio molecular dynamics simulations of the Car-Parrinello type, the Cu coordination mode to the binding sites of the PrP octarepeat region is investigated. Simulations are carried out for a number of structured binding sites. Results for the complexes Cu(HGGGW)+(wat), Cu(HGGG) and the 2[Cu(HGGG)] dimer are presented. While the presence of a Trp residue and a H2O molecule does not seem to affect the nature of the Cu coordination, high stability of the bond between Cu and the amide Nitrogens of deprotonated Gly's is confirmed in the case of the Cu(HGGG) system. For the more interesting 2[Cu(HGGG)] dimer a dynamically entangled arrangement of the two monomers, with intertwined N-Cu bonds, emerges. This observation is consistent with the highly packed structure seen in experiments at full Cu occupancy.Comment: 4 pages, conference proceedin

A simple atomistic model for the simulation of the gel phase of lipid bilayers

In this paper we present the results of a large-scale numerical investigation of structural properties of a model of cell membrane, simulated as a bilayer of flexible molecules in vacuum. The study was performed by carrying out extensive Molecular Dynamics simulations, in the (NVE) micro-canonical ensemble, of two systems of different sizes (2x32 and 2x256 molecules), over a fairly large set of temperatures and densities, using parallel platforms and more standard serial computers. Depending on the dimension of the system, the dynamics was followed for physical times that go from few hundred of picoseconds for the largest system to 5--10 nanoseconds for the smallest one. We find that the bilayer remains stable even in the absence of water and neglecting Coulomb interactions in the whole range of temperatures and densities we have investigated. The extension of the region of physical parameters that we have explored has allowed us to study significant points in the phase diagram of the bilayer and to expose marked structural changes as density and temperature are varied, which are interpreted as the system passing from a crystal to a gel phase.Comment: 41 pages, 13 figure

Parallel computing and molecular dynamics of biological membranes

In this talk I discuss the general question of the portability of Molecular Dynamics codes for diffusive systems on parallel computers of the APE family. The intrinsic single precision arithmetics of the today available APE platforms does not seem to affect the numerical accuracy of the simulations, while the absence of integer addressing from CPU to individual nodes puts strong constraints on the possible programming strategies. Liquids can be very satisfactorily simulated using the "systolic" method. For more complex systems, like the biological ones at which we are ultimately interested in, the "domain decomposition" approach is best suited to beat the quadratic growth of the inter-molecular computational time with the number of elementary components of the system. The promising perspectives of using this strategy for extensive simulations of lipid bilayers are briefly reviewed.Comment: 4 pages LaTeX, 2 figures included, espcrc2.sty require

Multi-scale theoretical approach to X-ray absorption spectra in disordered systems: an application to the study of Zn(II) in water

We develop a multi-scale theoretical approach aimed at calculating from first principles X-ray absorption spectra of liquid solutions and disordered systems. We test the method by considering the paradigmatic case of Zn(II) in water which, besides being relevant in itself, is also of interest for biology. With the help of classical molecular dynamics simulations we start by producing bunches of configurations differing for the Zn(II)-water coordination mode. Different coordination modes are obtained by making use of the so-called dummy atoms method. From the collected molecular dynamics trajectories, snapshots of a more manageable subsystem encompassing the metal site and two solvation layers are cut out. Density functional theory is used to optimize and relax these reduced system configurations employing a uniform dielectric to mimic the surrounding bulk liquid water. On the resulting structures, fully quantum mechanical X-ray absorption spectra calculations are performed by including core-hole effects and core-level shifts. The proposed approach does not rely on any guessing or fitting of the force field or of the atomic positions of the system. The comparison of the theoretically computed spectrum with the experimental Zn K-edge XANES data unambiguously demonstrates that among the different a priori possible geometries, Zn(II) in water lives in an octahedral coordination mode.Comment: 8 pages, 3 figure

Dust from AGBs: relevant factors and modelling uncertainties

The dust formation process in the winds of Asymptotic Giant Branch stars is discussed, based on full evolutionary models of stars with mass in the range $1$M$_{\odot} \leq$M$\leq 8$M$_{\odot}$, and metallicities $0.001 < Z <0.008$. Dust grains are assumed to form in an isotropically expanding wind, by growth of pre--existing seed nuclei. Convection, for what concerns the treatment of convective borders and the efficiency of the schematization adopted, turns out to be the physical ingredient used to calculate the evolutionary sequences with the highest impact on the results obtained. Low--mass stars with M$\leq 3$M$_{\odot}$ produce carbon type dust with also traces of silicon carbide. The mass of solid carbon formed, fairly independently of metallicity, ranges from a few $10^{-4}$M$_{\odot}$, for stars of initial mass $1-1.5$M$_{\odot}$, to $\sim 10^{-2}$M$_{\odot}$ for M$\sim 2-2.5$M$_{\odot}$; the size of dust particles is in the range $0.1 \mu$m$\leq a_C \leq 0.2\mu$m. On the contrary, the production of silicon carbide (SiC) depends on metallicity. For $10^{-3} \leq Z \leq 8\times 10^{-3}$ the size of SiC grains varies in the range $0.05 \mu {\rm m} < {\rm a_{SiC}} < 0.1 \mu$m, while the mass of SiC formed is $10^{-5}{\rm M}_{\odot} < {\rm M_{SiC}} < 10^{-3}{\rm M}_{\odot}$. Models of higher mass experience Hot Bottom Burning, which prevents the formation of carbon stars, and favours the formation of silicates and corundum. In this case the results scale with metallicity, owing to the larger silicon and aluminium contained in higher--Z models. At Z=$8\times 10^{-3}$ we find that the most massive stars produce dust masses $m_d \sim 0.01$M$_{\odot}$, whereas models of smaller mass produce a dust mass ten times smaller. The main component of dust are silicates, although corundum is also formed, in not negligible quantities ($\sim 10-20\%$).Comment: Paper accepted for publication in Monthly Notices of the Royal Astronomical Society Main Journal (2014 January 4

Masters and students in italian physics between the 19th and the 20th centuries: the Felici-Bartoli-Stracciati-Corbino case

In the second half of the 19th century, a special practice of research and training in physics took shape in Pisa, characterized by a particular attention to theoretical studies and to combining experimental activity with a profound mastery of mathematical tools. This peculiar approach, started by Carlo Matteucci and Ottaviano Mossotti, continued and spread by Riccardo Felici, Enrico Betti, Adolfo Bartoli and Vito Volterra, was quite an exception in the framework generally marked by strict experimentalism and positivist empiricism of the Italian physics cabinets of the time. The present paper highlights a special path connecting this tradition of the Pisan school to the scientific environment that was formed in the early years of the 20th century at the Royal Physical Institute in Via Panisperna in Rome, through the interaction of Orso Mario Corbino with Volterra on one side, and the imprinting left on Corbino by Adolfo Bartoli and his student and collaborator Enrico Stracciati

CLINICIAN-PATIENT RELATIONSHIP AND ADHERENCE TO TREATMENT

PATIENT'S ADHERENCE TO TREATMENT IS STRONGLY RELATED TO CLINICIAN'S ABILITY.ROLE OF EMPATHY, OF COMMUNICATION'S SKILLS ARE NOT INVESTIGATED ENOUGH, EVEN IF ACCORDING TO PATIENT'S OPINION THESE ABILITY ARE MORE IMPORTANT OF TECHNICAL SKILLS