Reconstructing the free-energy landscape of Met-enkephalin using dihedral Principal Component Analysis and Well-tempered Metadynamics

Well-Tempered Metadynamics (WTmetaD) is an efficient method to enhance the reconstruction of the free-energy surface of proteins. WTmetaD guarantees a faster convergence in the long time limit in comparison with the standard metadynamics. It still suffers however from the same limitation, i.e. the non trivial choice of pertinent collective variables (CVs). To circumvent this problem, we couple WTmetaD with a set of CVs generated from a dihedral Principal Component Analysis (dPCA) on the Ramachadran dihedral angles describing the backbone structure of the protein. The dPCA provides a generic method to extract relevant CVs built from internal coordinates. We illustrate the robustness of this method in the case of the small and very diffusive Metenkephalin pentapeptide, and highlight a criterion to limit the number of CVs necessary to biased the metadynamics simulation. The free-energy landscape (FEL) of Met-enkephalin built on CVs generated from dPCA is found rugged compared with the FEL built on CVs extracted from PCA of the Cartesian coordinates of the atoms.Comment: 17 pages, 9 figures (4 in color

Effect of plasma density on diffusion rates due to wave particle interactions with chorus and plasmaspheric hiss: extreme event analysis

Wave particle interactions play an important role in controlling the dynamics of the radiation belts. The purpose of this study is to estimate how variations in the plasma density can affect diffusion rates resulting from interactions between chorus waves and plasmaspheric hiss with energetic particles and the resulting evolution of the energetic electron population. We perform a statistical analysis of the electron density derived from the plasma wave experiment on the CRRES satellite for two magnetic local time sectors corresponding to near midnight and near noon. We present the cumulative probability distribution of the electron plasma density for three levels of magnetic activity as measured by Kp. The largest densities are seen near L* = 2.5 while the smallest occur near L* = 6. The broadest distribution, corresponding to the greatest variability, occurs near L* = 4. We calculate diffusion coefficients for plasmaspheric hiss and whistler mode chorus for extreme values of the electron density and estimate the effects on the radiation belts using the Salammbô model. At L* = 4 and L* = 6, in the low density case, using the density from the 5th percentile of the cumulative distribution function, electron energy diffusion by chorus waves is strongest at 2 MeV and increases the flux by up to 3 orders of magnitude over a period of 24 h. In contrast, in the high density case, using the density from the 95th percentile, there is little acceleration at energies above 800 keV at L* = 6, and virtually no acceleration at L* = 4. In this case the strongest energy diffusion occurs at lower energies around 400 keV where the flux at L* = 6 increases 3 orders of magnitude

Mise en place d’une méthodologie d’identification et d’analyse des stérols oxygénés présents dans les kystes radiculo-dentaires

Our work has two main aims: to identify oxygenated sterols that accompany cholesterol in dental cyst and to develop effective methods for «profile» analyses of these sterols. Attention as focused on a family of products derived from cholesterol, characterized by the presence of one or more oxygenated functions.More than fifty of these oxysterols are known and find most of time in differents parts of the body. In the procedure, lipids are isolated from dental cyst, the fraction is trimethylsilylated and analysed by capillary gas chromatography. Sterols are identified by comparison with reference compounds. However, two sterols of particular interest, viz cholesterol α and β epoxides, are so easily produced from cholesterol (even when rigorous precautions are taken) that indirect methods of analysis are strongly advisable. An adequate degree of quantification is possible for sterols such as 26-Hydroxycholesterol (26OHCL), which do not arise significantly as artefacts. Even to verify the fraction which seems to be 26OHCL we used thin layer chromatography coupled with mass spectrometer.La présence de cristaux de cholestérol dans la majorité des kystes radiculo-dentaires (KRD) permet de penser qu’ils s’accompagnent d’oxystérols (OS). Ces substances agissent sur de nombreux mécanismes biologiques tels: la régulation physiologique du cholestérol, la multiplication cellulaire ou le métabolisme de l’acide arachidonique. Notre travail a pour but de mettre au point une technique de mise en évidence et de dosage des OS au sein des KRD. Les techniques utilisées sont des techniques de chromatographie en phase vapeur et de spectrométrie de masse. Cinq oxystérols sont isolés: 7OXO, 7βOH, 26OHCL, triol et époxydes α et β. L’activité biologique de certains de ces oxystérols semble favoriser le développement des kystes radiculo-dentaires, alors que d’autres semblent limiter leur extension

Impact of mineral dust on short wave and long wave radiation: evaluation of different vertically resolved parameterization sin 1-D radiative transfer computations

Aerosol radiative properties are investigated in southeastern Spain during a dust event on 16–17 June 2013 in the framework of the ChArMEx/ADRIMED (Chemistry-Aerosol Mediterranean Experiment/Aerosol Direct Radiative Impact on the regional climate in the MEDiterranean region) campaign. Particle optical and microphysical properties from ground-based sun/sky photometer and lidar measurements, as well as in situ measurements on board the SAFIRE ATR 42 French research aircraft, are used to create a set of different levels of input parameterizations, which feed the 1-D radiative transfer model (RTM) GAME (Global Atmospheric ModEl). We consider three datasets: (1) a first parameterization based on the retrievals by an advanced aerosol inversion code (GRASP; Generalized Retrieval of Aerosol and Surface Properties) applied to combined photometer and lidar data, (2) a parameterization based on the photometer columnar optical properties and vertically resolved lidar retrievals with the two-component Klett–Fernald algorithm, and (3) a parameterization based on vertically resolved optical and microphysical aerosol properties measured in situ by the aircraft instrumentation. Once retrieved, the outputs of the RTM in terms of both shortwave and longwave radiative fluxes are compared against ground and in situ airborne measurements. In addition, the outputs of the model in terms of the aerosol direct radiative effect are discussed with respect to the different input parameterizations. Results show that calculated atmospheric radiative fluxes differ no more than 7 % from the measured ones. The three parameterization datasets produce a cooling effect due to mineral dust both at the surface and the top of the atmosphere. Aerosol radiative effects with differences of up to 10 W m−2 in the shortwave spectral range (mostly due to differences in the aerosol optical depth) and 2 W m−2 for the longwave spectral range (mainly due to differences in the aerosol optical depth but also to the coarse mode radius used to calculate the radiative properties) are obtained when comparing the three parameterizations. The study reveals the complexity of parameterizing 1-D RTMs as sizing and characterizing the optical properties of mineral dust is challenging. The use of advanced remote sensing data and processing, in combination with closure studies on the optical and microphysical properties from in situ aircraft measurements when available, is recommended.This work is part of the ChArMEx project supported by CNRS-INSU, ADEME, Météo-France, and CEA in the framework of the multidisciplinary program MISTRALS (Mediterranean Integrated STudies at Regional And Local Scales; http://mistrals-home.org/, last access: 15 January 2018). Lidar measurements were supported by the ACTRIS (Aerosols, Clouds, and Trace Gases Research Infrastructure Network) Research Infrastructure Project funded by the European Union's Horizon 2020 research and innovation program under grant agreement no. 654109. The Barcelona team acknowledges the Spanish Ministry of Economy and Competitiveness (project TEC2015-63832-P) and EFRD (European Fund for Regional Development); the Department of Economy and Knowledge of the Catalan autonomous government (grant 2014 SGR 583) and the Unidad de Excelencia Maria de Maeztu (project MDM-2016-0600) financed by the Spanish Agencia Estatal de Investigación. The authors also thank the Spanish Ministry of Science, Innovation and Universities (ref. CGL2017-90884-REDT). This work was also supported by the Juan de la Cierva-Formación program (grant FJCI-2015-23904). Paola Formenti and Cyrielle Denjean acknowledge the support of the French National Research Agency (ANR) through the ADRIMED program (contract ANR-11-BS56-0006)

Variation in Wolbachia cidB gene, but not cidA, is associated with cytoplasmic incompatibility mod phenotype diversity in Culex pipiens

Endosymbiotic Wolbachia bacteria are, to date, considered the most widespread symbionts in arthropods and are the cornerstone of major biological control strategies. Such a high prevalence is based on the ability of Wolbachia to manipulate their hosts' reproduction. One manipulation called cytoplasmic incompatibility (CI) is based on the death of the embryos generated by crosses between infected males and uninfected females or between individuals infected with incompatible Wolbachia strains. CI can be seen as a modification-rescue system (or mod-resc) in which paternal Wolbachia produce mod factors, inducing embryonic defects, unless the maternal Wolbachia produce compatible resc factors. Transgenic experiments in Drosophila melanogaster and Saccharomyces cerevisiae converged towards a model where the cidB Wolbachia gene is involved in the mod function while cidA is involved in the resc function. However, as cidA expression in Drosophila males was required to observe CI, it has been proposed that cidA could be involved in both resc and mod functions. A recent correlative study in natural Culex pipiens mosquito populations has revealed an association between specific cidA and cidB variations and changes in mod phenotype, also suggesting a role for both these genes in mod diversity. Here, by studying cidA and cidB genomic repertoires of individuals from newly sampled natural C. pipiens populations harbouring wPipIV strains from North Italy, we reinforce the link between cidB variation and mod phenotype variation fostering the involvement of cidB in the mod phenotype diversity. However, no association between any cidA variants or combination of cidA variants and mod phenotype variation was observed. Taken together our results in natural C. pipiens populations do not support the involvement of cidA in mod phenotype variation

The malaria parasite cyclic GMP-dependent protein kinase plays a central role in blood-stage schizogony.

A role for the Plasmodium falciparum cyclic GMP (cGMP)-dependent protein kinase (PfPKG) in gametogenesis in the malaria parasite was elucidated previously. In the present study we examined the role of PfPKG in the asexual blood-stage of the parasite life cycle, the stage that causes malaria pathology. A specific PKG inhibitor (compound 1, a trisubstituted pyrrole) prevented the progression of P. falciparum schizonts through to ring stages in erythrocyte invasion assays. Addition of compound 1 to ring-stage parasites allowed normal development up to 30 h postinvasion, and segmented schizonts were able to form. However, synchronized schizonts treated with compound 1 for > or =6 h became large and dysmorphic and were unable to rupture or liberate merozoites. To conclusively demonstrate that the effect of compound 1 on schizogony was due to its selective action on PfPKG, we utilized genetically manipulated P. falciparum parasites expressing a compound 1-insensitive PfPKG. The mutant parasites were able to complete schizogony in the presence of compound 1 but not in the presence of the broad-spectrum protein kinase inhibitor staurosporine. This shows that PfPKG is the primary target of compound 1 during schizogony and provides direct evidence of a role for PfPKG in this process. Discovery of essential roles for the P. falciparum PKG in both asexual and sexual development demonstrates that cGMP signaling is a key regulator of both of these crucial life cycle phases and defines this molecule as an exciting potential drug target for both therapeutic and transmission blocking action against malaria

Remote sensing mediante LIDAR en la UPC

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LHC Communication Infrastructure: Recommendations from the working group

The LHC Working Group for Communication Infrastructure (CIWG) was established in May 1999 with members from the accelerator sector, the LHC physics experiments, the general communication services, the technical services and other LHC working groups. It has spent a year collecting user requirements and at the same time explored and evaluated possible solutions appropriate to the LHC. A number of technical recommendations were agreed, and areas where more work is required were identified. The working group also put forward proposals for organizational changes needed to allow the design project to continue and to prepare for the installation and commissioning phase of the LHC communication infrastructure. This paper reports on the work done and explains the motivation behind the recommendations

Remote sensing mediante LIDAR en la UPC

Peer Reviewe