1,2-Dimethylindole-3-sulfonyl (MIS) as protecting group for the side chain of arginine

The protection of arginine (Arg) side chains is a crucial issue in peptide chemistry because of the propensity of the basic guanidinium group to produce side reactions. Currently, sulfonyl-type protecting groups, such as 2,2,5,7,8-pentamethylchroman (Pmc) and 2,2,4,6,7-pentamethyldihydrobenzofurane (Pbf), are the most widely used for this purpose. Nevertheless, Arg side chain protection remains problematic as a result of the acid stability of these two compounds. This issue is even more relevant in Arg-rich sequences, acid-sensitive peptides and large-scale syntheses. The 1,2-dimethylindole-3-sulfonyl (MIS) group is more acid-labile than Pmc and Pbf and can therefore be a better option for Arg side chain protection. In addition, MIS is compatible with tryptophan-containing peptides.

El desarrollo humano: perfiles y perspectivas futuras

El PNUD calcula todos los años el Índice de Desarrollo Humano (IDH). El objetivo de este trabajo es analizar los antecedentes y las perspectivas futuras del desarrollo humano a partir de los datos de este índice durante el periodo 1970-2000. Esto es, comprobar, a partir de los datos pasados, si las diferencias entre el IDH de los países del mundo están aumentando y valorar la tendencia del IDH esperada para los próximos años. En definitiva, se trata de buscar respuesta a la siguiente pregunta ¿cómo se modificarán los niveles de desarrollo humano en el futuro? Para ello, se utiliza la metodología estadística del análisis dinámico de distribución mediante las cadenas de Markov.

A web ontologies framework for digital rights management

In order to improve the management of copyright in the Internet, known as Digital Rights Management, there is the need for a shared language for copyright representation. Current approaches are based on purely syntactic solutions, i.e. a grammar that defines a rights expression language. These languages are difficult to put into practise due to the lack of explicit semantics that facilitate its implementation. Moreover, they are simple from the legal point of view because they are intended just to model the usage licenses granted by content providers to end-users. Thus, they ignore the copyright framework that lies behind and the whole value chain from creators to end-users. Our proposal is to use a semantic approach based on semantic web ontologies. We detail the development of a copyright ontology in order to put this approach into practice. It models the copyright core concepts for creation, rights and the basic kinds of actions that operate on content. Altogether, it allows building a copyright framework for the complete value chain. The set of actions operating on content are our smaller building blocks in order to cope with the complexity of copyright value chains and statements and, at the same time, guarantee a high level of interoperability and evolvability. The resulting copyright modelling framework is flexible and complete enough to model many copyright scenarios, not just those related to the economic exploitation of content. The ontology also includes moral rights, so it is possible to model this kind of situations as it is shown in the included example model for a withdrawal scenario. Finally, the ontology design and the selection of tools result in a straightforward implementation. Description Logic reasoners are used for license checking and retrieval. Rights are modelled as classes of actions, action patterns are modelled also as classes and the same is done for concrete actions. Then, to check if some right or license grants an action is reduced to check for class subsumption, which is a direct functionality of these reasoners.

Isolation and characterization of Saccharomyces cerevisiae mutants resistant to aculeacin A

Aculeacin A is a lipopeptide that inhibits ,B-glucan synthesis in yeasts. A number of Saccharomyces cerevisiae mutants resistant to this antibiotic were isolated, and four loci (ACRI, ACR2, ACR3, and ACR4) whose products are involved in the sensitivity to aculeacin A of yeast ceils were defined. Mutants containing mutations in the four loci were also resistant to echinocandin B, another member of this lipopeptide family of antibiotics. In contrast, acri, acr3, and acr4 mutants were resistant to papulacandin B (an antibiotic containing a disaccharide linked to two fatty acid chains that also inhibits P-glucan synthesis), but acr2 mutants were susceptible'to this antibiotic. This result defines common and specific steps in the entry and action of aculeacin A and papulacandin B. The analysis of double mutants revealed an epistatic effect of the acr2 mutation on the other three mutations. Cell walls of the four different mutants did not show significant alterations in composition with respect to the parental strain, and in vitro glucan synthase activity was also unaffected. However, cell surface hydrophobicity in three of the mutants was considerably decreased with respect to the parental strain.

Comblike poly(a-alkyl g glutamate)s: computer simulation studies of an intermediate thermal phase.

Monte Carlo (MC) simulations have been used to study the structure of an intermediate thermal phase of poly(R-octadecyl ç,D-glutamate). This is a comblike poly(ç-peptide) able to adopt a biphasic structure that has been described as a layered arrangement of backbone helical rods immersed in a paraffinic pool of polymethylene side chains. Simulations were performed at two different temperatures (348 and 363 K), both of them above the melting point of the paraffinic phase, using the configurational bias MC algorithm. Results indicate that layers are constituted by a side-by-side packing of 17/5 helices. The organization of the interlayer paraffinic region is described in atomistic terms by examining the torsional angles and the end-to-end distances for the octadecyl side chains. Comparison with previously reported comblike poly(â-peptide)s revealed significant differences in the organization of the alkyl side chains.

Electrical signature of modern and ancient tectonic processes in the crust of the Atlas mountains of Morocco.

The Atlas Mountains in Morocco are considered as type examples of intracontinental chains, with high topography that contrasts with moderate crustal shortening and thickening. Whereas recent geological studies and geodynamic modeling have suggested the existence of dynamic topography to explain this apparent contradiction, there is a lack of modern geophysical data at the crustal scale to corroborate this hypothesis. Newly-acquired magnetotelluric data image the electrical resistivity distribution of the crust from the Middle Atlas to the Anti-Atlas, crossing the tabular Moulouya Plain and the High Atlas. All the units show different and unique electrical signatures throughout the crust reflecting the tectonic history of development of each one. In the upper crust electrical resistivity values may be associated to sediment sequences in the Moulouya and Anti-Atlas and to crustal scale fault systems in the High Atlas developed during the Cenozoic times. In the lower crust the low resistivity anomaly found below the Mouluya plain, together with other geophysical (low velocity anomaly, lack of earthquakes and minimum Bouguer anomaly) and geochemical (Neogene-Quaternary intraplate alkaline volcanic fields) evidence, infer the existence of a small degree of partial melt at the base of the lower crust. The low resistivity anomaly found below the Anti-Atlas may be associated with a relict subduction of Precambrian oceanic sediments, or to precipitated minerals during the release of fluids from the mantle during the accretion of the Anti-Atlas to the West African Supercontinent during the Panafrican orogeny ca. 685 Ma).

Reproductive morphology in Mediterranean Seirospora giraudyi (Ceramiales, Rhodophyta)

This paper presents a detailed description of the reproductive characters of Mediterranean Seirospora giraudyi based on fresh material collected in the northwestern coast of Spain. Vegetative cells are uninucleate. The plant is monoecious. Spermantangial parent’s cells are clustered on modified dwarf determinate filaments, usually situated on adaxial surfaces of branches. One to four spermatia are formed by elongation and proximal divisions of the spermatangial parent cells. Spermatium with a nucleus situated ina mec. The thallus is procarpic. The four-celled carpogonial branch is initially L-shaped, and it is situated on a periaxial supporting fertile axial cell. The mature carpogonial branch is U-shaped and the supporting cell and second periaxial cell enlarge and divide transversely to reproduce a pair uninicleate auxiliary cell. The nucleus in the ferlilized carpogonium divides twice and the carpogonium cleaves vertically into two cells that, turn, cut off a pair of uninucleate connecting cells that fuse with the auxiliary cells on opposite sides; the diploid nuclei in the connecting cells divide at the site of fusion and one of the nuclei enters the auxiliary cell white the other is extruded. Each auxiliary cell gives to a terminal primary gonimolobe initials. Gonimolobes form lax chains of carposporangia. As the gonimoblasts mature, both lobes of the foot cell which is situated on the supporting cell elongate the upper one secondary connecting with the supporting cell, and the lower one with the fertile axial cell. The gonimoblasts are subtended at maturity by one to several clusters of involucral flaments. Seirospora is currently placed in the tribe Euptiloteae; however the reproductive character of S.giraudyi is dentical to those described for the Cañllithamnieae. Molecular studies are needed to confirm the taxonomic position of S.giraudyi as well as that of the other species placed Seirospora

From caging to rouse dynamics in polymer melts with intramolecular barriers: a critical test of the mode coupling theory

By means of computer simulations and solution of the equations of the mode coupling theory (MCT),we investigate the role of the intramolecular barriers on several dynamic aspects of nonentangled polymers. The investigated dynamic range extends from the caging regime characteristic of glass-formers to the relaxation of the chain Rouse modes. We review our recent work on this question,provide new results, and critically discuss the limitations of the theory. Solutions of the MCT for the structural relaxation reproduce qualitative trends of simulations for weak and moderate barriers. However, a progressive discrepancy is revealed as the limit of stiff chains is approached. This dis-agreement does not seem related with dynamic heterogeneities, which indeed are not enhanced by increasing barrier strength. It is not connected either with the breakdown of the convolution approximation for three-point static correlations, which retains its validity for stiff chains. These findings suggest the need of an improvement of the MCT equations for polymer melts. Concerning the relaxation of the chain degrees of freedom, MCT provides a microscopic basis for time scales from chain reorientation down to the caging regime. It rationalizes, from first principles, the observed deviations from the Rouse model on increasing the barrier strength. These include anomalous scaling of relaxation times, long-time plateaux, and nonmonotonous wavelength dependence of the mode correlators.

The differentiable chain functor is not homotopy equivalent to the continuous chain functor

Let $S_*$ and $S_*^\{infty}$ be the functors of continuous and differentiable singular chains on the category of differentiable manifolds. We prove that the natural transformation $i: S_*^\infty \rightarrow S_*$, which induces homology equivalences over each manifold, is not a natural homotopy equivalence.

The role of intramolecular barriers on the glass transition of polymers: computer simulations versus mode coupling theory

We present computer simulations of a simple bead-spring model for polymer melts with intramolecular barriers. By systematically tuning the strength of the barriers, we investigate their role on the glass transition. Dynamic observables are analyzed within the framework of the mode coupling theory (MCT). Critical nonergodicity parameters, critical temperatures, and dynamic exponents are obtained from consistent fits of simulation data to MCT asymptotic laws. The so-obtained MCT λ-exponent increases from standard values for fully flexible chains to values close to the upper limit for stiff chains. In analogy with systems exhibiting higher-order MCT transitions, we suggest that the observed large λ-values arise form the interplay between two distinct mechanisms for dynamic arrest: general packing effects and polymer-specific intramolecular barriers. We compare simulation results with numerical solutions of the MCT equations for polymer systems, within the polymer reference interaction site model (PRISM) for static correlations. We verify that the approximations introduced by the PRISM are fulfilled by simulations, with the same quality for all the range of investigated barrier strength. The numerical solutions reproduce the qualitative trends of simulations for the dependence of the nonergodicity parameters and critical temperatures on the barrier strength. In particular, the increase in the barrier strength at fixed density increases the localization length and the critical temperature. However the qualitative agreement between theory and simulation breaks in the limit of stiff chains. We discuss the possible origin of this feature.

Analysis of bulk and surface contributions in the neutron skin of nuclei

The neutron skin thickness of nuclei is a sensitive probe of the nuclear symmetry energy and has multiple implications for nuclear and astrophysical studies. However, precision measurements of this observable are difficult to obtain. The analysis of the experimental data may imply some assumptions about the bulk or surface nature of the formation of the neutron skin. Here we study the bulk or surface character of neutron skins of nuclei following from calculations with Gogny, Skyrme, and covariant nuclear mean-field interactions. These interactions are successful in describing nuclear charge radii and binding energies but predict different values for neutron skins. We perform the study by fitting two-parameter Fermi distributions to the calculated self-consistent neutron and proton densities. We note that the equivalent sharp radius is a more suitable reference quantity than the half-density radius parameter of the Fermi distributions to discern between the bulk and surface contributions in neutron skins. We present calculations for nuclei in the stability valley and for the isotopic chains of Sn and Pb.

BioSuper: A web tool for the superimposition of biomolecules and assemblies with rotational symmetry

Background Most of the proteins in the Protein Data Bank (PDB) are oligomeric complexes consisting of two or more subunits that associate by rotational or helical symmetries. Despite the myriad of superimposition tools in the literature, we could not find any able to account for rotational symmetry and display the graphical results in the web browser. Results BioSuper is a free web server that superimposes and calculates the root mean square deviation (RMSD) of protein complexes displaying rotational symmetry. To the best of our knowledge, BioSuper is the first tool of its kind that provides immediate interactive visualization of the graphical results in the browser, biomolecule generator capabilities, different levels of atom selection, sequence-dependent and structure-based superimposition types, and is the only web tool that takes into account the equivalence of atoms in side chains displaying symmetry ambiguity. BioSuper uses ICM program functionality as a core for the superimpositions and displays the results as text, HTML tables and 3D interactive molecular objects that can be visualized in the browser or in Android and iOS platforms with a free plugin. Conclusions BioSuper is a fast and functional tool that allows for pairwise superimposition of proteins and assemblies displaying rotational symmetry. The web server was created after our own frustration when attempting to superimpose flexible oligomers. We strongly believe that its user-friendly and functional design will be of great interest for structural and computational biologists who need to superimpose oligomeric proteins (or any protein). BioSuper web server is freely available to all users at http://ablab.ucsd.edu/BioSuper webcite.

Adsoption-induced restructuring of gold nanochains

The chemical properties of single-atomic chains of gold atoms are investigated using density functional calculations. The nanochains are shown to be unusually chemically active with strong chemisorption of oxygen atoms and carbon monoxide. The chemisorption energies vary significantly with the strain/stress conditions for the chain. Oxygen atoms are found to energetically prefer to get incorporated into a chain forming a new type of gold-oxygen nanochain with a conductance of one quantum unit. We suggest that the long bond lengths observed in electron microscopy investigations of gold chains can be due to oxygen incorporation.

Monoidal functors, acyclic models and chain operads

We prove that for a topological operad $P$ the operad of oriented cubical singular chains, $C^{\ord}_\ast(P)$, and the operad of simplicial singular chains, $S_\ast(P)$, are weakly equivalent. As a consequence, $C^{\ord}_\ast(P\nsemi\mathbb{Q})$ is formal if and only if $S_\ast(P\nsemi\mathbb{Q})$ is formal, thus linking together some formality results which are spread out in the literature. The proof is based on an acyclic models theorem for monoidal functors. We give different variants of the acyclic models theorem and apply the contravariant case to study the cohomology theories for simplicial sets defined by $R$-simplicial differential graded algebras.

Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells

Identification of CD8+ cytotoxic T lymphocyte (CTL) epitopes has traditionally relied upon testing of overlapping peptide libraries for their reactivity with T cells in vitro. Here, we pursued deep ligand sequencing (DLS) as an alternative method of directly identifying those ligands that are epitopes presented to CTLs by the class I human leukocyte antigens (HLA) of infected cells. Soluble class I HLA-A*11:01 (sHLA) was gathered from HIV-1 NL4-3-infected human CD4+ SUP-T1 cells. HLA-A*11:01 harvested from infected cells was immunoaffinity purified and acid boiled to release heavy and light chains from peptide ligands that were then recovered by size-exclusion filtration. The ligands were first fractionated by high-pH high-pressure liquid chromatography and then subjected to separation by nano-liquid chromatography (nano-LC)–mass spectrometry (MS) at low pH. Approximately 10 million ions were selected for sequencing by tandem mass spectrometry (MS/MS). HLA-A*11:01 ligand sequences were determined with PEAKS software and confirmed by comparison to spectra generated from synthetic peptides. DLS identified 42 viral ligands presented by HLA-A*11:01, and 37 of these were previously undetected. These data demonstrate that (i) HIV-1 Gag and Nef are extensively sampled, (ii) ligand length variants are prevalent, particularly within Gag and Nef hot spots where ligand sequences overlap, (iii) noncanonical ligands are T cell reactive, and (iv) HIV-1 ligands are derived from de novo synthesis rather than endocytic sampling. Next-generation immunotherapies must factor these nascent HIV-1 ligand length variants and the finding that CTL-reactive epitopes may be absent during infection of CD4+ T cells into strategies designed to enhance T cell immunity.