Protein evolution along phylogenetic histories under structurally constrained substitution models

Motivation: Models of molecular evolution aim at describing the evolutionary processes at the molecular level. However, current models rarely incorporate information from protein structure. Conversely, structure-based models of protein evolution have not been commonly applied to simulate sequence evolution in a phylogenetic framework, and they often ignore relevant evolutionary processes such as recombination. A simulation evolutionary framework that integrates substitution models that account for protein structure stability should be able to generate more realistic in silico evolved proteins for a variety of purposes. Results: We developed a method to simulate protein evolution that combines models of protein folding stability, such that the fitness depends on the stability of the native state both with respect to unfolding and misfolding, with phylogenetic histories that can be either specified by the user or simulated with the coalescent under complex evolutionary scenarios, including recombination, demographics and migration. We have implemented this framework in a computer program called ProteinEvolver. Remarkably, comparing these models with empirical amino acid replacement models, we found that the former produce amino acid distributions closer to distributions observed in real protein families, and proteins that are predicted to be more stable. Therefore, we conclude that evolutionary models that consider protein stability and realistic evolutionary histories constitute a better approximation of the real evolutionary process.Ministerio de Ciencia e Innovación | Ref. BFU2011-24595Ministerio de Economía y Competitividad | Ref. BFU2012-40020Ministerio de Ciencia e Innovación | Ref. JCI-2011-1045

An Orion/Ares I Launch and Ascent Simulation: One Segment of the Distributed Space Exploration Simulation (DSES)

This paper describes the architecture and implementation of a distributed launch and ascent simulation of NASA's Orion spacecraft and Ares I launch vehicle. This simulation is one segment of the Distributed Space Exploration Simulation (DSES) Project. The DSES project is a research and development collaboration between NASA centers which investigates technologies and processes for distributed simulation of complex space systems in support of NASA's Exploration Initiative. DSES is developing an integrated end-to-end simulation capability to support NASA development and deployment of new exploration spacecraft and missions. This paper describes the first in a collection of simulation capabilities that DSES will support

Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies

We report the synthesis and the assessment of the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds (2-4) were obtained (45-92% yields) from the thermal reaction(PhCCPh exchange) of [Ru2Cp2(CO)(& mu;-CO){& mu;-& eta;(1):& eta;(3)-C(Ph)C(Ph)C(O)}], 1, with alkynes HCCR [R = C5H4FeCp (Fc),3-C6H4(Asp), 2-naphthyl; Cp = & eta;(5)-C5H5, Asp = OC(O)-2-C6H4C(O)Me]. Protonation of 1-3 by HBF4 afforded the corresponding & mu;-alkenyl derivatives 5-7, in 40-86% yields. All productswere characterized by IR and NMR spectroscopy; moreover, cyclic voltammetry(1, 2, 5, 7) andsingle-crystal X-ray diffraction (5, 7)analyses were performed on representative compounds. Complexes 5-7 revealed a cytotoxic activity comparableto that of cisplatin in A549 (lung adenocarcinoma), SW480 (colon adenocarcinoma),and ovarian (A2780) cancer cell lines, and 2, 5, 6, and 7 overcame cisplatin resistancein A2780cis cells. Complexes 2, 5, and 7 (but not the aspirin derivative 6) inducedan increase in intracellular ROS levels. Otherwise, 6 strongly stabilizes and elongates natural DNA (from calf thymus,CT-DNA), suggesting a possible intercalation binding mode, whereas 5 is less effective in binding CT-DNA, and 7 isineffective. This trend is reversed concerning RNA, and in particular, 7 is able to bind poly(rA)poly(rU) showing selectivity forthis nucleic acid. Complexes 5-7 caninteract with the albumin protein with a thermodynamic signature dominatedby hydrophobic interactions. Overall, we show that organometallicspecies based on the Ru2Cp2(CO)( x ) scaffold (x = 2, 3) are activeagainst cancer cells, with different incorporated fragments influencingthe interactions with nucleic acids and the production of ROS

MIMAC: MIcro-tpc MAtrix of Chambers for dark matter directional detection

Directional detection of non-baryonic Dark Matter is a promising search strategy for discriminating WIMP events from neutrons, the ultimate background for dark matter direct detection. This strategy requires both a precise measurement of the energy down to a few keV and 3D reconstruction of tracks down to a few mm. The MIMAC (MIcro-tpc MAtrix of Chambers) collaboration has developed in the last years an original prototype detector based on the direct coupling of large pixelized micromegas with a special developed fast self-triggered electronics showing the feasibility of a new generation of directional detectors. The first bi-chamber prototype has been installed at Modane, underground laboratory in June 2012. The first undergournd background events, the gain stability and calibration are shown. The first spectrum of nuclear recoils showing 3D tracks coming from the radon progeny is presented.Comment: Proceedings of the 4th International Conference on Directional Dark Matter Detection CYGNUS2013, held in Toyoma (Japan), June 201

Natural Formulations Based on Olea europaea L. Fruit Extract for the Topical Treatment of HSV-1 Infections

In the present study, a hydroxytyrosol-rich Olea europaea L. fruit extract (OFE) was added to three thoroughly green formulations—hydrogel, oleogel, and cream—in order to evaluate their antiviral activity against HSV-1. The extract was characterized by different analytical techniques, i.e., FT-IR, XPS, and TGA. HPLC analyses were carried out to monitor the content and release of hydroxytyrosol in the prepared formulations. The total polyphenol content and antioxidant activity were investigated through Folin–Ciocâlteu’s reagent, DPPH, and ABTS assays. The ability of the three formulations to convey active principles to the skin was evaluated using a Franz cell, showing that the number of permeated polyphenols in the hydrogel (272.1 ± 1.8 GAE/g) was significantly higher than those in the oleogel and cream (174 ± 10 and 179.6 ± 2 GAE/g, respectively), even if a negligible amount of hydroxytyrosol crossed the membrane for all the formulations. The cell viability assay indicated that the OFE and the three formulations were not toxic to cultured Vero cells. The antiviral activity tests highlighted that the OFE had a strong inhibitory effect against HSV-1 with a 50% inhibitory concentration (IC50) at 25 µg/mL, interfering directly with the viral particles. Among the three formulations, the hydrogel exhibited the highest antiviral activity also against the acyclovir-resistant strain

Limits on the neutrino magnetic moment from the MUNU experiment

The MUNU experiment was carried out at the Bugey nuclear power reactor. The aim was the study of electron antineutrino-electron elastic scattering at low energy. The recoil electrons were recorded in a gas time projection chamber, immersed in a tank filled with liquid scintillator serving as veto detector, suppressing in particular Compton electrons. The measured electron recoil spectrum is presented. Upper limits on the neutrino magnetic moment were derived and are discussed.Comment: 9 pages, 7 figures Added reference: p.3, 1st col., TEXONO Added sentence: p.4, 1st col., electron attachement Modified sentence: p.5, 1st col., readout sequence Added sentence: p.5, 1st col., fast rise time cu

Sub MeV Particles Detection and Identification in the MUNU detector ((1)ISN, IN2P3/CNRS-UJF, Grenoble, France, (2)Institut de Physique, Neuch\^atel, Switzerland, (3) INFN, Padova Italy, (4) Physik-Institut, Z\"{u}rich, Switzerland)

We report on the performance of a 1 m$^{3}$ TPC filled with CF$_{4}$ at 3 bar, immersed in liquid scintillator and viewed by photomultipliers. Particle detection, event identification and localization achieved by measuring both the current signal and the scintillation light are presented. Particular features of $\alpha$ particle detection are also discussed. Finally, the ${54}$Mn photopeak, reconstructed from the Compton scattering and recoil angle is shown.Comment: Latex, 19 pages, 20 figure

POD\u2013Galerkin reduced order methods for combined Navier\u2013Stokes transport equations based on a hybrid FV-FE solver

The purpose of this work is to introduce a novel POD\u2013Galerkin strategy for the semi-implicit hybrid high order finite volume/finite element solver introduced in Berm\ufadez et al. (2014) and Busto et al. (2018). The interest is into the incompressible Navier\u2013Stokes equations coupled with an additional transport equation. The full order model employed in this article makes use of staggered meshes. This feature will be conveyed to the reduced order model leading to the definition of reduced basis spaces in both meshes. The reduced order model presented herein accounts for velocity, pressure, and a transport-related variable. The pressure term at both the full order and the reduced order level is reconstructed making use of a projection method. More precisely, a Poisson equation for pressure is considered within the reduced order model. Results are verified against three-dimensional manufactured test cases. Moreover a modified version of the classical cavity test benchmark including the transport of a species is analysed