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

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

Peer Reviewe

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

Genetic Studies of Sulfadiazine-resistant and Methionine-requiring \u3cem\u3eNeisseria\u3c/em\u3e Isolated From Clinical Material

Deoxyribonucleate (DNA) preparations were extracted from Neisseria meningitidis (four isolates from spinal fluid and blood) and N. gonorrhoeae strains, all of which were resistant to sulfadiazine upon primary isolation. These DNA preparations, together with others from in vitro mutants of N. meningitidis and N. perflava, were examined in transformation tests by using as recipient a drug-susceptible strain of N. meningitidis (Ne 15 Sul-s Met+) which was able to grow in a methionine-free defined medium. The sulfadiazine resistance typical of each donor was introduced into the uniform constitution of this recipient. Production of p-aminobenzoic acid was not significantly altered thereby. Transformants elicited by DNA from the N. meningitidis clinical isolates were resistant to at least 200 μg of sulfadiazine/ml, and did not show a requirement for methionine (Sul-r Met+). DNA from six strains of N. gonorrhoeae, which were isolated during the period of therapeutic use of sulfonamides, conveyed lower degrees of resistance and, invariably, a concurrent methionine requirement (Sul-r/Met−). The requirement of these transformants, and that of in vitro mutants selected on sulfadiazine-agar, was satisfied by methionine, but not by vitamin B12, homocysteine, cystathionine, homoserine, or cysteine. Sul-r Met+ and Sul-r/Met− loci could coexist in the same genome, but were segregated during transformation. On the other hand, the dual Sul-r/Met− properties were not separated by recombination, but were eliminated together. DNA from various Sul-r/Met− clones tested against recipients having nonidentical Sul-r/Met− mutant sites yielded Sul-s Met+ transformants. The met locus involved is genetically complex, and will be a valuable tool for studies of genetic fine structure of members of Neisseria, and of genetic homology between species

GREEN: the new Global Radiation Earth ENvironment model (beta version)

GREEN (Global Radiation Earth ENvironment) is a new model (in beta version) providing fluxes at any location between L∗ =  1 and L∗ =  8, all along the magnetic field lines, for all local times and for any energy between 1 keV and 10 MeV for electrons and between 1 keV and 800 MeV for protons. This model is composed of global models (AE8 and AP8, and SPM for low energies) and local models (SLOT model, OZONE and IGE-2006 for electrons, and OPAL and IGP for protons). GREEN is not just a collection of various models; it calculates the electron and proton fluxes from the most relevant existing model for a given energy and location. Moreover, some existing models can be updated or corrected in GREEN. For examples, a new version of the SLOT model is presented here and has been integrated in GREEN. Moreover, a new model of proton flux in geostationary orbit (IGP) developed a few years ago is also detailed here and integrated in GREEN. Finally a correction of the AE8 model at high energy for L∗ &lt; 2.5 has also been implemented. The inputs of the GREEN model are the coordinates of the points and the date (year, month, day, UTC) along an orbit, the particle species (electron or proton) and the energies. Then GREEN provides fluxes all along the given orbit, depending on the solar cycle and other magnetic parameters such as L∗, Bmirror and Beq.</p