Considerazioni sui casi di tumore nell’Area della Ricerca di Firenze del Consiglio Nazionale delle Ricerche

Recentemente, tra i dipendenti dell’Area della Ricerca di Firenze del Consiglio Nazionale delle Ricerche (CNR) presso il Polo Scientifico di Sesto Fiorentino si è verificato un numero preoccupante di casi di tumore. L’Azienda Sanitaria di Firenze (ASF) e l’Istituto per lo Studio e la Prevenzione Oncologica (ISPO) di Firenze, con l’interessamento dell’Azienda Regionale per la Protezione Ambientale della Toscana, hanno indagato la questione, concludendo che il numero di casi verificatisi non è statisticamente superiore alla media territoriale e che non è stata riscontrata la presenza di fattori di rischio ambientale. Questo documento evidenzia svariati aspetti critici, sia nel merito che nel metodo, dell’indagine condotta, con particolare riferimento all’approfondimento statistico. In conclusione, si ritiene che l’intervento di ASF-ISPO non costituisca un’indagine accurata e che sia stato insuffi- ciente e sbrigativo. Si raccomandano ulteriori approfondimenti e interventi di monitoraggio e prevenzione sul personale e sull’ambiente dell’Area CNR, del Polo Scientifico e della Piana in generale

Molecular dynamics of C-peptide of ribonuclease A studied by replica-exchange Monte Carlo method and diffusion theory

Generalized-ensemble algorithm and diffusion theory have been combined in order to compute the dynamical properties monitored by nuclear magnetic resonance experiments from efficient and reliable evaluation of statistical averages. Replica-exchange Monte Carlo simulations have been performed with a C-peptide analogue of ribonuclease A, and Smoluchowski diffusion equations have been applied. A fairly good agreement between the calculated and measured $^1$H-NOESY NMR cross peaks has been obtained. The combination of these advanced and continuously improving statistical tools allows the calculation of a wide variety of dynamical properties routinely obtained by experiments.Comment: 17 pages, 5 figures, (LaTeX); Chemical Physics Letters, in pres

SARS-CoV-2 virion stabilization by Zn binding

Zinc plays a crucial role in the process of virion maturation inside the host cell. The accessory Cys-rich proteins expressed in SARS-CoV-2 by genes ORF7a and ORF8 are likely involved in zinc binding and in interactions with cellular antigens activated by extensive disulfide bonds. In this report we provide a proof of concept for the feasibility of a structural study of orf7a and orf8 proteins. A conceivable hypothesis is that lack of cellular zinc, or substitution thereof, might lead to a significant slowing down of viral maturation

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

Modeling the interplay of glycine protonation and multiple histidine binding of copper in the prion protein octarepeat subdomains

The octarepeat region of the prion protein can bind Cu(2+) ions up to full occupancy (one ion per octarepeat) at neutral pH. While crystallographic data show that the HGGG octarepeat subdomain is the basic binding unit, multiple histidine coordination at lower Cu occupancy has been reported by X-ray absorption spectroscopy, EPR, and potentiometric experiments. In this paper we investigate, with first principles Car-Parrinello simulations, the first step for the formation of the Cu low-level binding mode, where four histidine side chains are coordinated to the same Cu(2+) ion. This step involves the further binding of a second histidine to an already HGGG domain bonded Cu(2+) ion. The influence of the pH on the ability of Cu to bind two histidine side chains was taken into account by simulating different protonation states of the amide N atoms of the two glycines lying nearest to the first histidine. Multiple histidine coordination is also seen to occur when glycine deprotonation occurs and the presence of the extra histidine stabilizes the Cu-peptide complex. Though the stabilization effect slightly decreases with the number of deprotonated glycines (reaching a minimum when both N atoms of the two nearest glycines are available as Cu ligands), the system is still capable of binding the second histidine in a 4N tetrahedral (though slightly distorted) coordination, whose energy is very near to that of the crystallographic square-planar 3N1O coordination. This result suggests that at low metal concentration the reorganization energy associated with Cu(II)/Cu(I) reduction is small also at pH approximately 7, when glycines are deprotonated

Low loss coatings for the VIRGO large mirrors

présentée par L. PinardThe goal of the VIRGO program is to build a giant Michelson type interferometer (3 kilometer long arms) to detect gravitational waves. Large optical components (350 mm in diameter), having extremely low loss at 1064 nm, are needed. Today, the Ion beam Sputtering is the only deposition technique able to produce optical components with such performances. Consequently, a large ion beam sputtering deposition system was built to coat large optics up to 700 mm in diameter. The performances of this coater are described in term of layer uniformity on large scale and optical losses (absorption and scattering characterization). The VIRGO interferometer needs six main mirrors. The first set was ready in June 2002 and its installation is in progress on the VIRGO site (Italy). The optical performances of this first set are discussed. The requirements at 1064 nm are all satisfied. Indeed, the absorption level is close to 1 ppm (part per million), the scattering is lower than 5 ppm and the R.M.S. wavefront of these optics is lower than 8 nm on 150 mm in diameter. Finally, some solutions are proposed to further improve these performances, especially the absorption level (lower than 0.1 ppm) and the mechanical quality factor Q of the mirrors (thermal noise reduction)

The Virgo 3 km interferometer for gravitational wave detection

Virgo, designed, constructed and developed by the French-Italian VIRGO collaboration located in Cascina (Pisa, Italy) and aiming to detect gravitational waves, is a ground-based power recycled Michelson interferometer, with 3 km long suspended Fabry-Perot cavities. The first Virgo scientific data-taking started in mid-May 2007, in coincidence with the corresponding LIGO detectors. The optical scheme of the interferometer and the various optical techniques used in the experiment, such as the laser source, control, alignment, stabilization and detection strategies are outlined. The future upgrades that are planned for Virgo from the optical point of view, especially concerning the evolution of the Virgo laser, are presented. Finally, the next generation of the gravitational wave detector (advanced Virgo) is introduced from the point of view of the laser system

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection