A spherical model with directional interactions: I. Static properties

We introduce a simple spherical model whose structural properties are similar to the ones generated by models with directional interactions, by employing a binary mixture of large and small hard spheres, with a square-well attraction acting only between particles of different size. The small particles provide the bonds between the large ones. With a proper choice of the interaction parameters, as well as of the relative concentration of the two species, it is possible to control the effective valence. Here we focus on a specific choice of the parameters which favors tetrahedral ordering and study the equilibrium static properties of the system in a large window of densities and temperatures. Upon lowering the temperature we observe a progressive increase in local order, accompanied by the formation of a four-coordinated network of bonds. Three different density regions are observed: at low density the system phase separates into a gas and a liquid phase; at intermediate densities a network of fully bonded particles develops; at high densities -- due to the competition between excluded volume and attractive interactions -- the system forms a defective network. The very same behavior has been previously observed in numerical studies of non-spherical models for molecular liquids, such as water, and in models of patchy colloidal particles. Differently from these models, theoretical treatments devised for spherical potentials, e.g. integral equations and ideal mode coupling theory for the glass transition can be applied in the present case, opening the way for a deeper understanding of the thermodynamic and dynamic behavior of low valence molecules and particles.Comment: 11 pages, 11 figure

BCR-ABL residues interacting with ponatinib are critical to preserve the tumorigenic potential of the oncoprotein

Patients with chronic myeloid leukemia in whom tyrosine kinase inhibitors (TKIs) fail often present mutations in the BCR-ABL catalytic domain. We noticed a lack of substitutions involving 4 amino acids (E286, M318, I360, and D381) that form hydrogen bonds with ponatinib. We therefore introduced mutations in each of these residues, either preserving or altering their physicochemical properties. We found that E286, M318, I360, and D381 are dispensable for ABL and BCR-ABL protein stability but are critical for preserving catalytic activity. Indeed, only a "conservative" I360T substitution retained kinase proficiency and transforming potential. Molecular dynamics simulations of BCR-ABLI360T revealed differences in both helix αC dynamics and protein-correlated motions, consistent with a modified ATP-binding pocket. Nevertheless, this mutant remained sensitive to ponatinib, imatinib, and dasatinib. These results suggest that changes in the 4 BCR-ABL residues described here would be selected against by a lack of kinase activity or by maintained responsiveness to TKIs. Notably, amino acids equivalent to those identified in BCR-ABL are conserved in 51% of human tyrosine kinases. Hence, these residues may represent an appealing target for the design of pharmacological compounds that would inhibit additional oncogenic tyrosine kinases while avoiding the emergence of resistance due to point mutations.This work was supported by an investigator grant to P.V. from Associazione Italiana per la Ricerca sul Cancro (AIRC) and by funding from the Biotechnology and Biological Sciences Research Council (BB/I023291/1 and BB/H018409/1 to AP and FF). P.B. is the recipient of an AIRC - Marie Curie fellowship

Forces and torques on a sphere moving near a dihedral corner in creeping flow

The low-Reynolds-number flow past a sphere moving near a right dihedral corner made by a stationary and a tangentially sliding wall is considered. Using the superposition principle, the arbitrary motion of the sphere is decomposed into simple elementary motions. Fully-resolved spectral-element simulations are carried out in the frame of reference translating and rotating with the particle such that the velocity on the particle’s surface vanishes. Forces and torques on the sphere are obtained as functions of the particle position near the corner. The data obtained are fitted by closed-form expressions which take into account symmetries of the problem, exact solutions, and asymptotic solutions from lubrication theory. The correlations obtained can easily be implemented in larger-scale one-way-coupled particulate-flow simulations to correct the particle motion near dihedral corners where mere point-particle models break down

Biogenic amine in wines

International audience; Biogenic amines (BA) are a group of organic nitrogenous compounds formed and degraded by the metabolism of living organisms (microorganisms, plants and animals). The main BA associated with wine are putrescine, histamine, tyramine and cadaverine, followed by phenylethylamine, spermidine, spermine, agmatine and tryptamine. The variability in the BA content of wine could be explained on the basis of differences in the winemaking process, time and storage conditions, raw material quality, and possible microbial contamination during winery operations. BA are formed by decarboxylation of the corresponding amino acids by microorganisms through substrate-specific decarboxylase enzymes. This property is usually strain dependent. Decarboxylase enzymes are generally induced at acidic pH and therefore they have a possible role in maintaining pH homeostasis or extending the microbial growth period by detoxification of the extracellular medium. The presence of these compounds is considered by some authors a fundamental parameter for the detriment of wine

Applications of Monte Carlo methods to special radiotherapeutic techniques

Monte Carlo (MC) methods are considered one of the most powerful and precise approaches to study and solve medical physics issues. They, indeed, can be applied in all the situations where to use deterministic algorithms is infeasible or impossible. Surprising improvements in computer technology have promoted a wide diffusion of this technique, giving rise to the born of several Monte Carlo codes, such as the GEANT4 toolkit. In this paper we show some of the applications we developed using GEANT4. In particular, the simulation of two different radiotherapy techniques, such as proton/ion therapy and stereotactic radiosurgery will be discussed. In the first case we show the main features of our last public version of the GEANT4 Hadrontherapy program, also discussing the issues related to the nuclear fragmentation. In the second case, we show the procedures followed for the simulation of a Gamma Knife device, in order to validate the Treatment Planning System (TPS) used for the dose computation

Hay or silage? How the forage preservation method changes the volatile compounds and sensory properties of Caciocavallo cheese.

The aim of this study was to determine the effect of the forage preservation method (silage vs. hay) on volatile compounds and sensory properties of a traditional Caciocavallo cheese during ripening. A brown-midrib sudangrass hybrid was cultivated on a 7-ha field and at harvesting it was half ensiled in plastic silo bags and half dried to hay. Forty-four lactating cows were equally allotted into 2 groups fed a isonitrogenous and isoenergetic total mixed ration containing as the sole forage either sorghum hay (H group) or sorghum silage (S group). Milk from the 2 groups was used to produce 3 batches/diet of Caciocavallo ripened for 30, 60, and 90 d. Milk yield and composition as well as cheese chemical and fatty acid composition were not markedly affected by the diet treatment and ripening time. By contrast, ripening induced increased levels of the appearance attribute "yellowness," along with the "overall flavor," the odor/flavor attributes "butter" and "hay," the "salty," "bitter," and "umami" tastes, and the texture attribute "oiliness," whereas the appearance attribute "uniformity" and the texture attribute "elasticity" were reduced. The silage-based diet induced higher perceived intensities of several attributes such as "yellowness"; "overall flavor"; "butter"; "grass" and "hay" odor/flavors; "salty," "bitter," and "umami" tastes; and "tenderness" and "oiliness" textures. In S cheese we also observed higher amounts of ketones and fatty acids. Conversely, H cheese showed the terpene α-pinene, which was not detected in S cheese, and a higher intensity of the appearance attribute "uniformity." These differences allowed the trained panel to discriminate the products, determined an increased consumer liking for 90-d ripened cheese, and tended to increase consumer liking for hay cheese

Charged particle's flux measurement from PMMA irradiated by 80 MeV/u carbon ion beam

Hadrontherapy is an emerging technique in cancer therapy that uses beams of charged particles. To meet the improved capability of hadrontherapy in matching the dose release with the cancer position, new dose monitoring techniques need to be developed and introduced into clinical use. The measurement of the fluxes of the secondary particles produced by the hadron beam is of fundamental importance in the design of any dose monitoring device and is eagerly needed to tune Monte Carlo simulations. We report the measurements done with charged secondary particles produced from the interaction of a 80 MeV/u fully stripped carbon ion beam at the INFN Laboratori Nazionali del Sud, Catania, with a Poly-methyl methacrylate target. Charged secondary particles, produced at 90$\degree$ with respect to the beam axis, have been tracked with a drift chamber, while their energy and time of flight has been measured by means of a LYSO scintillator. Secondary protons have been identified exploiting the energy and time of flight information, and their emission region has been reconstructed backtracking from the drift chamber to the target. Moreover a position scan of the target indicates that the reconstructed emission region follows the movement of the expected Bragg peak position. Exploting the reconstruction of the emission region, an accuracy on the Bragg peak determination in the submillimeter range has been obtained. The measured differential production rate for protons produced with $E^{\rm Prod}_{\rm kin} >$ 83 MeV and emitted at 90$\degree$ with respect to the beam line is: $dN_{\rm P}/(dN_{\rm C}d\Omega)(E^{\rm Prod}_{\rm kin} > 83 {\rm ~MeV}, \theta=90\degree)= (2.69\pm 0.08_{\rm stat} \pm 0.12_{\rm sys})\times 10^{-4} sr^{-1}$.Comment: 13 pages, 9 figure

ELIMED: MEDICAL APPLICATION AT ELI-BEAMLINES. STATUS OF THE COLLABORATION AND FIRST RESULTS

ELI-Beamlines is one of the four pillars of the ELI (Extreme Light Infrastructure) pan-European project. It will be an ultrahigh-intensity, high repetition-rate, femtosecond laser facility whose main goal is to generate and apply high-brightness X-ray sources and accelerated charged particles. In particular, medical applications are treated by the ELIMED task force, which has been launched by collaboration between ELI and INFN researchers. ELIMED aims to demonstrate the clinical applicability of laser accelerated ions. In this article, the state of the ELIMED project and the first scientific results are reported. The design and realisation of a preliminary beam handling system and of an advanced spectrometer for diagnostics of high energy (multi-MeV) laser-accelerated ion beams will also be briefly presented