A genomic island present along the bacterial chromosome of the Parachlamydiaceae UWE25, an obligate amoebal endosymbiont, encodes a potentially functional F-like conjugative DNA transfer system.

BACKGROUND: The genome of Protochlamydia amoebophila UWE25, a Parachlamydia-related endosymbiont of free-living amoebae, was recently published, providing the opportunity to search for genomic islands (GIs). RESULTS: On the residual cumulative G+C content curve, a G+C-rich 19-kb region was observed. This sequence is part of a 100-kb chromosome region, containing 100 highly co-oriented ORFs, flanked by two 17-bp direct repeats. Two identical gly-tRNA genes in tandem are present at the proximal end of this genetic element. Several mobility genes encoding transposases and bacteriophage-related proteins are located within this chromosome region. Thus, this region largely fulfills the criteria of GIs. The G+C content analysis shows that several modules compose this GI. Surprisingly, one of them encodes all genes essential for F-like conjugative DNA transfer (traF, traG, traH, traN, traU, traW, and trbC), involved in sex pilus retraction and mating pair stabilization, strongly suggesting that, similarly to the other F-like operons, the parachlamydial tra unit is devoted to DNA transfer. A close relatedness of this tra unit to F-like tra operons involved in conjugative transfer is confirmed by phylogenetic analyses performed on concatenated genes and gene order conservation. These analyses and that of gly-tRNA distribution in 140 GIs suggest a proteobacterial origin of the parachlamydial tra unit. CONCLUSIONS: A GI of the UWE25 chromosome encodes a potentially functional F-like DNA conjugative system. This is the first hint of a putative conjugative system in chlamydiae. Conjugation most probably occurs within free-living amoebae, that may contain hundreds of Parachlamydia bacteria tightly packed in vacuoles. Such a conjugative system might be involved in DNA transfer between internalized bacteria. Since this system is absent from the sequenced genomes of Chlamydiaceae, we hypothesize that it was acquired after the divergence between Parachlamydiaceae and Chlamydiaceae, when the Parachlamydia-related symbiont was an intracellular bacteria. It suggests that this heterologous DNA was acquired from a phylogenetically-distant bacteria sharing an amoebal vacuole. Since Parachlamydiaceae are emerging agents of pneumonia, this GI might be involved in pathogenicity. In future, conjugative systems might be developed as genetic tools for Chlamydiales.

Long synthetic peptides for the production of vaccines and drugs: a technological platform coming of age.

Long synthetic peptides (LSPs) have a variety of important clinical uses as synthetic vaccines and drugs. Techniques for peptide synthesis were revolutionized in the 1960s and 1980s, after which efficient techniques for purification and characterization of the product were developed. These improved techniques allowed the stepwise synthesis of increasingly longer products at a faster rate, greater purity, and lower cost for clinical use. A synthetic peptide approach, coupled with bioinformatics analysis of genomes, can tremendously expand the search for clinically relevant products. In this Review, we discuss efforts to develop a malaria vaccine from LSPs, among other clinically directed work.

Conformity, upstream reciprocity and social diversity: secondary mechanisms for the evolution of cooperation

Cooperation is ubiquitous in nature: genes cooperate in genomes, cells in muti- cellular organims, and individuals in societies. In humans, division of labor and trade are key elements of most known societies, where social life is regulated by- moral systems specifying rights and duties often enforced by third party punish¬ment. Over the last decades, several primary mechanisms, such as kin selection, direct and indirect reciprocity, have been advanced to explain the evolution of cooperation from a naturalistic approach. In this thesis, I focus on the study of three secondary mechanisms which, although insufficient to allow for the evo¬lution of cooperation, have been hypothesized to further promote it when they are linked to proper primary mechanisms: conformity (the tendency to imitate common behaviors), upstream reciprocity (the tendency to help somebody once help has been received from somebody else) and social diversity (heterogeneous social contexts). I make use of mathematical and computational models in the formal framework of evolutionary game theory in order to investigate the theoret¬ical conditions under which conformity, upstream reciprocity and social diversity are able to raise the levels of cooperation attained in evolving populations. - La coopération est ubiquitaire dans la nature: les gènes coopèrent dans les génomes, les cellules dans les organismes muticellulaires, et les organismes dans les sociétés. Chez les humains, la division du travail et le commerce sont des éléments centraux de la plupart des sociétés connues, où la vie sociale est régie par des systèmes moraux établissant des droits et des devoirs, souvent renforcés par la punition. Au cours des dernières décennies, plusieurs mécanismes pri¬maires, tels que la sélection de parentèle et les réciprocités directe et indirecte, ont été avancés pour expliquer l'évolution de la coopération d'un point de vue nat¬uraliste. Dans cette thèse, nous nous concentrons sur l'étude de trois mécanismes secondaires qui, bien qu'insuffisants pour permettre l'évolution de la coopération, sont capables de la promouvoir davantage s'ils sont liés aux mécanismes primaires appropriés: la conformité (tendance à imiter des comportements en commun), la 'réciprocité en amont' (tendance à aider quelqu'un après avoir reçu l'aide de quelqu'un d'autre) et la diversité sociale (contextes sociaux hétérogènes). Nous faisons usage de modèles mathématiques et informatiques dans le cadre formel de la théorie des jeux évolutionnaires afin d'examiner les conditions théoriques dans lesquelles la conformité, la 'réciprocité en amont' et la diversité sociale sont capables d'élever le niveau de coopération des populations en évolution.

Postmodifying prepositional phrases in English and Spanish (with special reference to locative postmodifiers)

Prepositional phrases are the commonest kind of postmodification in all registers of English (Biber et al. 1999: 634). The locative ones that can be expanded into a defining relative clause (the books [which are] on the table) are usually expressed by such a construction in Spanish (los libros que están encima de la mesa) or by a phrase introduced by de (los libros de encima de la mesa). Wonder (1979) argues that Spanish allows locative phrases with prepositions other than de in the case of"situaciones"activas"" (el aterrizaje en pleno campo) as against"situaciones estáticas" (*el sofá en la sala), and if the phrase can be given an adverbial rather than, or in addition to, an adjectival interpretation (el ruido en la calle), especially if that phrase implies an alternative location for an object or contrast with another similar object (el sofá en la sala contigua). This paper further investigates this claim and looks at Spanish equivalents of English postmodifying prepositional phrases in general, while proposing an explanation for the choice of these different structures in Spanish based on considerations of lexical density. Resumen: Las frases preposicionales constituyen el tipo más frecuente de posmodificación en todos los registros del inglés (Biber et a. 1999: 634). En el español, las expresiones locativas suelen incorporar un pronombre relativo y un verbo (the books [which are] on the table > los libros que están encima de la mesa), o bien expresarse mediante una frase introducida por la preposición de (los libros de encima de la mesa). Wonder (1979) sostiene que el español permite el uso de preposiciones que no sean de en las frases locativas en el caso de"situaciones"activas"" (el aterrizaje en pleno campo) frente a"situaciones estáticas" (*el sofá en la sala), y también si la frase puede tener una función adverbial antes que, o además de, una interpretación adjetiva (el ruido en la calle), sobre todo si dicha frase encierra la idea de una posición alternativa para un objeto, o bien un contraste con otro objeto similar (el sofá en la sala contigua). El presente estudio pretende examinar este argumento y, además, explorar la posmodificación preposicional en español de un modo más general, a la par que propone una explicación sobre la elección de estructura en español que se basa en el criterio de la densidad léxica.

Fourier transform convolution integrals applied to generalized Born molecular volume.

Generalized Born methods are currently among the solvation models most commonly used for biological applications. We reformulate the generalized Born molecular volume method initially described by (Lee et al, 2003, J Phys Chem, 116, 10606; Lee et al, 2003, J Comp Chem, 24, 1348) using fast Fourier transform convolution integrals. Changes in the initial method are discussed and analyzed. Finally, the method is extensively checked with snapshots from common molecular modeling applications: binding free energy computations and docking. Biologically relevant test systems are chosen, including 855-36091 atoms. It is clearly demonstrated that, precision-wise, the proposed method performs as good as the original, and could better benefit from hardware accelerated boards.

Performance Analysis of Two Quantum Reaction Dynamics Codes: Time-Dependent and Time-Independent Strategies

The computer simulation of reaction dynamics has nowadays reached a remarkable degree of accuracy. Triatomic elementary reactions are rigorously studied with great detail on a straightforward basis using a considerable variety of Quantum Dynamics computational tools available to the scientific community. In our contribution we compare the performance of two quantum scattering codes in the computation of reaction cross sections of a triatomic benchmark reaction such as the gas phase reaction Ne + H2+ %12. NeH++ H. The computational codes are selected as representative of time-dependent (Real Wave Packet [ ]) and time-independent (ABC [ ]) methodologies. The main conclusion to be drawn from our study is that both strategies are, to a great extent, not competing but rather complementary. While time-dependent calculations advantages with respect to the energy range that can be covered in a single simulation, time-independent approaches offer much more detailed information from each single energy calculation. Further details such as the calculation of reactivity at very low collision energies or the computational effort related to account for the Coriolis couplings are analyzed in this paper.

Modelling ecological niches with support vector machines

1. The ecological niche is a fundamental biological concept. Modelling species' niches is central to numerous ecological applications, including predicting species invasions, identifying reservoirs for disease, nature reserve design and forecasting the effects of anthropogenic and natural climate change on species' ranges. 2. A computational analogue of Hutchinson's ecological niche concept (the multidimensional hyperspace of species' environmental requirements) is the support of the distribution of environments in which the species persist. Recently developed machine-learning algorithms can estimate the support of such high-dimensional distributions. We show how support vector machines can be used to map ecological niches using only observations of species presence to train distribution models for 106 species of woody plants and trees in a montane environment using up to nine environmental covariates. 3. We compared the accuracy of three methods that differ in their approaches to reducing model complexity. We tested models with independent observations of both species presence and species absence. We found that the simplest procedure, which uses all available variables and no pre-processing to reduce correlation, was best overall. Ecological niche models based on support vector machines are theoretically superior to models that rely on simulating pseudo-absence data and are comparable in empirical tests. 4. Synthesis and applications. Accurate species distribution models are crucial for effective environmental planning, management and conservation, and for unravelling the role of the environment in human health and welfare. Models based on distribution estimation rather than classification overcome theoretical and practical obstacles that pervade species distribution modelling. In particular, ecological niche models based on machine-learning algorithms for estimating the support of a statistical distribution provide a promising new approach to identifying species' potential distributions and to project changes in these distributions as a result of climate change, land use and landscape alteration.

Web Services for Bayesian Learning

In this demonstration we present our web services to perform Bayesian learning for classification tasks.

Statistical mechanics of multi-edge networks

Statistical properties of binary complex networks are well understood and recently many attempts have been made to extend this knowledge to weighted ones. There are, however, subtle yet important considerations to be made regarding the nature of the weights used in this generalization. Weights can be either continuous or discrete magnitudes, and in the latter case, they can additionally have undistinguishable or distinguishable nature. This fact has not been addressed in the literature insofar and has deep implications on the network statistics. In this work we face this problem introducing multiedge networks as graphs where multiple (distinguishable) connections between nodes are considered. We develop a statistical mechanics framework where it is possible to get information about the most relevant observables given a large spectrum of linear and nonlinear constraints including those depending both on the number of multiedges per link and their binary projection. The latter case is particularly interesting as we show that binary projections can be understood from multiedge processes. The implications of these results are important as many real-agent-based problems mapped onto graphs require this treatment for a proper characterization of their collective behavior.

Identification of HMX1 target genes: a predictive promoter model approach.

PURPOSE: A homozygous mutation in the H6 family homeobox 1 (HMX1) gene is responsible for a new oculoauricular defect leading to eye and auricular developmental abnormalities as well as early retinal degeneration (MIM 612109). However, the HMX1 pathway remains poorly understood, and in the first approach to better understand the pathway's function, we sought to identify the target genes. METHODS: We developed a predictive promoter model (PPM) approach using a comparative transcriptomic analysis in the retina at P15 of a mouse model lacking functional Hmx1 (dmbo mouse) and its respective wild-type. This PPM was based on the hypothesis that HMX1 binding site (HMX1-BS) clusters should be more represented in promoters of HMX1 target genes. The most differentially expressed genes in the microarray experiment that contained HMX1-BS clusters were used to generate the PPM, which was then statistically validated. Finally, we developed two genome-wide target prediction methods: one that focused on conserving PPM features in human and mouse and one that was based on the co-occurrence of HMX1-BS pairs fitting the PPM, in human or in mouse, independently. RESULTS: The PPM construction revealed that sarcoglycan, gamma (35kDa dystrophin-associated glycoprotein) (Sgcg), teashirt zinc finger homeobox 2 (Tshz2), and solute carrier family 6 (neurotransmitter transporter, glycine) (Slc6a9) genes represented Hmx1 targets in the mouse retina at P15. Moreover, the genome-wide target prediction revealed that mouse genes belonging to the retinal axon guidance pathway were targeted by Hmx1. Expression of these three genes was experimentally validated using a quantitative reverse transcription PCR approach. The inhibitory activity of Hmx1 on Sgcg, as well as protein tyrosine phosphatase, receptor type, O (Ptpro) and Sema3f, two targets identified by the PPM, were validated with luciferase assay. CONCLUSIONS: Gene expression analysis between wild-type and dmbo mice allowed us to develop a PPM that identified the first target genes of Hmx1.

Simulated-annealing-based conditional simulation for the local-scale characterization of heterogeneous aquifers

Simulated-annealing-based conditional simulations provide a flexible means of quantitatively integrating diverse types of subsurface data. Although such techniques are being increasingly used in hydrocarbon reservoir characterization studies, their potential in environmental, engineering and hydrological investigations is still largely unexploited. Here, we introduce a novel simulated annealing (SA) algorithm geared towards the integration of high-resolution geophysical and hydrological data which, compared to more conventional approaches, provides significant advancements in the way that large-scale structural information in the geophysical data is accounted for. Model perturbations in the annealing procedure are made by drawing from a probability distribution for the target parameter conditioned to the geophysical data. This is the only place where geophysical information is utilized in our algorithm, which is in marked contrast to other approaches where model perturbations are made through the swapping of values in the simulation grid and agreement with soft data is enforced through a correlation coefficient constraint. Another major feature of our algorithm is the way in which available geostatistical information is utilized. Instead of constraining realizations to match a parametric target covariance model over a wide range of spatial lags, we constrain the realizations only at smaller lags where the available geophysical data cannot provide enough information. Thus we allow the larger-scale subsurface features resolved by the geophysical data to have much more due control on the output realizations. Further, since the only component of the SA objective function required in our approach is a covariance constraint at small lags, our method has improved convergence and computational efficiency over more traditional methods. Here, we present the results of applying our algorithm to the integration of porosity log and tomographic crosshole georadar data to generate stochastic realizations of the local-scale porosity structure. Our procedure is first tested on a synthetic data set, and then applied to data collected at the Boise Hydrogeophysical Research Site.

Stochastic inversion of tracer test and electrical geophysical data to estimate hydraulic conductivities.

Quantifying the spatial configuration of hydraulic conductivity (K) in heterogeneous geological environments is essential for accurate predictions of contaminant transport, but is difficult because of the inherent limitations in resolution and coverage associated with traditional hydrological measurements. To address this issue, we consider crosshole and surface-based electrical resistivity geophysical measurements, collected in time during a saline tracer experiment. We use a Bayesian Markov-chain-Monte-Carlo (McMC) methodology to jointly invert the dynamic resistivity data, together with borehole tracer concentration data, to generate multiple posterior realizations of K that are consistent with all available information. We do this within a coupled inversion framework, whereby the geophysical and hydrological forward models are linked through an uncertain relationship between electrical resistivity and concentration. To minimize computational expense, a facies-based subsurface parameterization is developed. The Bayesian-McMC methodology allows us to explore the potential benefits of including the geophysical data into the inverse problem by examining their effect on our ability to identify fast flowpaths in the subsurface, and their impact on hydrological prediction uncertainty. Using a complex, geostatistically generated, two-dimensional numerical example representative of a fluvial environment, we demonstrate that flow model calibration is improved and prediction error is decreased when the electrical resistivity data are included. The worth of the geophysical data is found to be greatest for long spatial correlation lengths of subsurface heterogeneity with respect to wellbore separation, where flow and transport are largely controlled by highly connected flowpaths.

Textual autocorrelation : formalism and illustrations

Abstract Textual autocorrelation is a broad and pervasive concept, referring to the similarity between nearby textual units: lexical repetitions along consecutive sentences, semantic association between neighbouring lexemes, persistence of discourse types (narrative, descriptive, dialogal...) and so on. Textual autocorrelation can also be negative, as illustrated by alternating phonological or morpho-syntactic categories, or the succession of word lengths. This contribution proposes a general Markov formalism for textual navigation, and inspired by spatial statistics. The formalism can express well-known constructs in textual data analysis, such as term-document matrices, references and hyperlinks navigation, (web) information retrieval, and in particular textual autocorrelation, as measured by Moran's I relatively to the exchange matrix associated to neighbourhoods of various possible types. Four case studies (word lengths alternation, lexical repulsion, parts of speech autocorrelation, and semantic autocorrelation) illustrate the theory. In particular, one observes a short-range repulsion between nouns together with a short-range attraction between verbs, both at the lexical and semantic levels. Résumé: Le concept d'autocorrélation textuelle, fort vaste, réfère à la similarité entre unités textuelles voisines: répétitions lexicales entre phrases successives, association sémantique entre lexèmes voisins, persistance du type de discours (narratif, descriptif, dialogal...) et ainsi de suite. L'autocorrélation textuelle peut être également négative, comme l'illustrent l'alternance entre les catégories phonologiques ou morpho-syntaxiques, ou la succession des longueurs de mots. Cette contribution propose un formalisme markovien général pour la navigation textuelle, inspiré par la statistique spatiale. Le formalisme est capable d'exprimer des constructions bien connues en analyse des données textuelles, telles que les matrices termes-documents, les références et la navigation par hyperliens, la recherche documentaire sur internet, et, en particulier, l'autocorélation textuelle, telle que mesurée par le I de Moran relatif à une matrice d'échange associée à des voisinages de différents types possibles. Quatre cas d'étude illustrent la théorie: alternance des longueurs de mots, répulsion lexicale, autocorrélation des catégories morpho-syntaxiques et autocorrélation sémantique. On observe en particulier une répulsion à courte portée entre les noms, ainsi qu'une attraction à courte portée entre les verbes, tant au niveau lexical que sémantique.

En torno a los efectos de la edad en el aprendizaje escolar de una lengua extrangera

The purpose of this article is to treat a currently much debated issue, the effects of age on second language learning. To do so, we contrast data collected by our research team from over one thousand seven hundred young and adult learners with four popular beliefs or generalizations, which, while deeply rooted in this society, are not always corroborated by our data.Two of these generalizations about Second Language Acquisition (languages spoken in the social context) seem to be widely accepted: a) older children, adolescents and adults are quicker and more efficient at the first stages of learning than are younger learners; b) in a natural context children with an early start are more liable to attain higher levels of proficiency. However, in the context of Foreign Language Acquisition, the context in which we collect the data, this second generalization is difficult to verify due to the low number of instructional hours (a maximum of some 800 hours) and the lower levels of language exposure time provided. The design of our research project has allowed us to study differences observed with respect to the age of onset (ranging from 2 to 18+), but in this article we focus on students who began English instruction at the age of 8 (LOGSE Educational System) and those who began at the age of 11 (EGB). We have collected data from both groups after a period of 200 (Time 1) and 416 instructional hours (Time 2), and we are currently collecting data after a period of 726 instructional hours (Time 3). We have designed and administered a variety of tests: tests on English production and reception, both oral and written, and within both academic and communicative oriented approaches, on the learners' L1 (Spanish and Catalan), as well as a questionnaire eliciting personal and sociolinguistic information. The questions we address and the relevant empirical evidence are as follows: 1. "For young children, learning languages is a game. They enjoy it more than adults."Our data demonstrate that the situation is not quite so. Firstly, both at the levels of Primary and Secondary education (ranging from 70.5% in 11-year-olds to 89% in 14-year-olds) students have a positive attitude towards learning English. Secondly, there is a difference between the two groups with respect to the factors they cite as responsible for their motivation to learn English: the younger students cite intrinsic factors, such as the games they play, the methodology used and the teacher, whereas the older students cite extrinsic factors, such as the role of their knowledge of English in the achievement of their future professional goals. 2 ."Young children have more resources to learn languages." Here our data suggest just the opposite. The ability to employ learning strategies (actions or steps used) increases with age. Older learners' strategies are more varied and cognitively more complex. In contrast, younger learners depend more on their interlocutor and external resources and therefore have a lower level of autonomy in their learning. 3. "Young children don't talk much but understand a lot"This third generalization does seem to be confirmed, at least to a certain extent, by our data in relation to the analysis of differences due to the age factor and productive use of the target language. As seen above, the comparably slower progress of the younger learners is confirmed. Our analysis of interpersonal receptive abilities demonstrates as well the advantage of the older learners. Nevertheless, with respect to passive receptive activities (for example, simple recognition of words or sentences) no great differences are observed. Statistical analyses suggest that in this test, in contrast to the others analyzed, the dominance of the subjects' L1s (reflecting a cognitive capacity that grows with age) has no significant influence on the learning process. 4. "The sooner they begin, the better their results will be in written language"This is not either completely confirmed in our research. First of all, we perceive that certain compensatory strategies disappear only with age, but not with the number of instructional hours. Secondly, given an identical number of instructional hours, the older subjects obtain better results. With respect to our analysis of data from subjects of the same age (12 years old) but with a different number of instructional hours (200 and 416 respectively, as they began at the ages of 11 and 8), we observe that those who began earlier excel only in the area of lexical fluency. In conclusion, the superior rate of older learners appears to be due to their higher level of cognitive development, a factor which allows them to benefit more from formal or explicit instruction in the school context. Younger learners, however, do not benefit from the quantity and quality of linguistic exposure typical of a natural acquisition context in which they would be allowed to make use of implicit learning abilities. It seems clear, then, that the initiative in this country to begin foreign language instruction earlier will have positive effects only if it occurs in combination with either higher levels of exposure time to the foreign language, or, alternatively, with its use as the language of instruction in other areas of the curriculum.