Changing patterns of West Nile virus transmission: altered vector competence and host susceptibility

West Nile virus (WNV) is a flavivirus (Flaviviridae) transmitted between Culex spp. mosquitoes and avian hosts. The virus has dramatically expanded its geographic range in the past ten years. Increases in global commerce, climate change, ecological factors and the emergence of novel viral genotypes likely play significant roles in the emergence of this virus; however, the exact mechanism and relative importance of each is uncertain. Previously WNV was primarily associated with febrile illness of children in endemic areas, but it was identified as a cause of neurological disease in humans in 1994. This modulation in disease presentation could be the result of the emergence of a more virulent genotype as well as the progression of the virus into areas in which the age structure of immunologically naïve individuals makes them more susceptible to severe neurological disease. Since its introduction to North America in 1999, a novel WNV genotype has been identified that has been demonstrated to disseminate more rapidly and with greater efficiency at elevated temperatures than the originally introduced strain, indicating the potential importance of temperature as a selective criteria for the emergence of WNV genotypes with increased vectorial capacity. Even prior to the North American introduction, a mutation associated with increased replication in avian hosts, identified to be under adaptive evolutionary pressure, has been identified, indicating that adaptation for increased replication within vertebrate hosts could play a role in increased transmission efficiency. Although stable in its evolutionary structure, WNV has demonstrated the capacity for rapidly adapting to both vertebrate hosts and invertebrate vectors and will likely continue to exploit novel ecological niches as it adapts to novel transmission foci

Estimating the number of change-points in a two-dimensional segmentation model without penalization

In computational biology, numerous recent studies have been dedicated to the analysis of the chromatin structure within the cell by two-dimensional segmentation methods. Motivated by this application, we consider the problem of retrieving the diagonal blocks in a matrix of observations. The theoretical properties of the least-squares estimators of both the boundaries and the number of blocks proposed by L\'evy-Leduc et al. [2014] are investigated. More precisely, the contribution of the paper is to establish the consistency of these estimators. A surprising consequence of our results is that, contrary to the onedimensional case, a penalty is not needed for retrieving the true number of diagonal blocks. Finally, the results are illustrated on synthetic data.Comment: 30 pages, 8 figure

Monodeurated methane in the outer solar system. 2. Its detection on Uranus at 1.6 microns

Deuterium in the atmosphere of Uranus has been studied only via measurements of the exceedingly weak dipole lines of hydrogen-deuteride (HD) seen in the visible region of the spectrum. The other sensitive indicator of deuterium in the outer solar system is monodeuterated methane (CH3D) but the two bands normally used ot study this molecule, NU sub 2 near 2200 1/cm and NU sub 6 near 1161 1/cm, have not been detected in Uranus

Engineered single nucleotide polymorphisms in the mosquito MEK docking site alter Plasmodium berghei development in Anopheles gambiae.

BackgroundSusceptibility to Plasmodium infection in Anopheles gambiae has been proposed to result from naturally occurring polymorphisms that alter the strength of endogenous innate defenses. Despite the fact that some of these mutations are known to introduce non-synonymous substitutions in coding sequences, these mutations have largely been used to rationalize knockdown of associated target proteins to query the effects on parasite development in the mosquito host. Here, we assay the effects of engineered mutations on an immune signaling protein target that is known to control parasite sporogonic development. By this proof-of-principle work, we have established that naturally occurring mutations can be queried for their effects on mosquito protein function and on parasite development and that this important signaling pathway can be genetically manipulated to enhance mosquito resistance.MethodsWe introduced SNPs into the A. gambiae MAPK kinase MEK to alter key residues in the N-terminal docking site (D-site), thus interfering with its ability to interact with the downstream kinase target ERK. ERK phosphorylation levels in vitro and in vivo were evaluated to confirm the effects of MEK D-site mutations. In addition, overexpression of various MEK D-site alleles was used to assess P. berghei infection in A. gambiae.ResultsThe MEK D-site contains conserved lysine residues predicted to mediate protein-protein interaction with ERK. As anticipated, each of the D-site mutations (K3M, K6M) suppressed ERK phosphorylation and this inhibition was significant when both mutations were present. Tissue-targeted overexpression of alleles encoding MEK D-site polymorphisms resulted in reduced ERK phosphorylation in the midgut of A. gambiae. Furthermore, as expected, inhibition of MEK-ERK signaling due to D-site mutations resulted in reduction in P. berghei development relative to infection in the presence of overexpressed catalytically active MEK.ConclusionMEK-ERK signaling in A. gambiae, as in model organisms and humans, depends on the integrity of conserved key residues within the MEK D-site. Disruption of signal transmission via engineered SNPs provides a purposeful proof-of-principle model for the study of naturally occurring mutations that may be associated with mosquito resistance to parasite infection as well as an alternative genetic basis for manipulation of this important immune signaling pathway

Maladie mentale et stigmatisation ou Comment on devient un malade mental pour la vie

La perspective sociologique telle que présentée ici en relation avec la santé et/ou la maladie mentale est basée sur une approche interactionniste du phénomène. En effet, la société est composée d'un ensemble de normes et de valeurs, partagées par la majorité des personnes au sein d'une même culture à une époque donnée. Ces normes dont l'apprentissage commence dès la naissance de l'individu, sont issues de la génération précédente et ainsi transmises de génération en génération. Normes et valeurs constituent le tissu social, fondement de notre vie en commun. Il s'agit d'une vision de la société centrée principalement sur les rapports entre les individus et la société, et entre les individus et les institutions, ces rapports étant définis par un ensemble d'interdépendance psychologique et sociale.In this article mental illness is presented in a sociological perspective, giving prominence to social-interaction factors which, in many cases, are responsable for the permanence of this type of illness. Its thereotical base comes !form the psychology of social-interaction developped by G.H. Mead and his disciples. This perspective defines the social human being as derived from successive interactions, beginning, at birth, with maternal contacts and extending progressively to the entirety of the members of the community of which the individual is a part. This interactional network is comprised of messages, of responses, and of expectations which make up the norms and values which in turn from the basis for the distribution of roles and statuses- From these roles and statuses derive the behaviours acceptable to a given collectivity. Among other theoretical developments, interactionist sociology gave birth to formulations on deviance which became known, in american terminology as "labelling theory". In the case of mental illness many sociologists interested in the phenomenon have studied it, using the framework elaborated by the proponents of this approach to deviance. Thus, rather than considering the deviant as abnormal in himself, deviance is viewed as a process; that is, as the result of a series of interactions confronting the individual who is not, or does not behave like the collectivity as a whole and the milieu in which he lives. When the reaction of the entourage is negative, the so-called deviant is subjected to sanctions such as avoidance, rejection, exclusion, confinement, etc... This process terminates generally in stigmatization which wraps the deviant in a label from which he will probably never free himself. The studies cited demonstrate this interactional process at different stages of mental illness, these being; d) at the point of medical diagnosis, b) during hospitalisation, c) on leaving We psychiatric institution, d) and after the return to society. The conclusion leads to an appreciation of the drama experienced by psychiatric ex-patients, for most of whom the label "mentally ill" constitutes an apparently irreversible stigmatization

Answering Conjunctive Queries under Updates

We consider the task of enumerating and counting answers to $k$-ary conjunctive queries against relational databases that may be updated by inserting or deleting tuples. We exhibit a new notion of q-hierarchical conjunctive queries and show that these can be maintained efficiently in the following sense. During a linear time preprocessing phase, we can build a data structure that enables constant delay enumeration of the query results; and when the database is updated, we can update the data structure and restart the enumeration phase within constant time. For the special case of self-join free conjunctive queries we obtain a dichotomy: if a query is not q-hierarchical, then query enumeration with sublinear$^\ast$ delay and sublinear update time (and arbitrary preprocessing time) is impossible. For answering Boolean conjunctive queries and for the more general problem of counting the number of solutions of k-ary queries we obtain complete dichotomies: if the query's homomorphic core is q-hierarchical, then size of the the query result can be computed in linear time and maintained with constant update time. Otherwise, the size of the query result cannot be maintained with sublinear update time. All our lower bounds rely on the OMv-conjecture, a conjecture on the hardness of online matrix-vector multiplication that has recently emerged in the field of fine-grained complexity to characterise the hardness of dynamic problems. The lower bound for the counting problem additionally relies on the orthogonal vectors conjecture, which in turn is implied by the strong exponential time hypothesis. $^\ast)$ By sublinear we mean $O(n^{1-\varepsilon})$ for some $\varepsilon>0$, where $n$ is the size of the active domain of the current database

Beyond Worst-Case Analysis for Joins with Minesweeper

We describe a new algorithm, Minesweeper, that is able to satisfy stronger runtime guarantees than previous join algorithms (colloquially, `beyond worst-case guarantees') for data in indexed search trees. Our first contribution is developing a framework to measure this stronger notion of complexity, which we call {\it certificate complexity}, that extends notions of Barbay et al. and Demaine et al.; a certificate is a set of propositional formulae that certifies that the output is correct. This notion captures a natural class of join algorithms. In addition, the certificate allows us to define a strictly stronger notion of runtime complexity than traditional worst-case guarantees. Our second contribution is to develop a dichotomy theorem for the certificate-based notion of complexity. Roughly, we show that Minesweeper evaluates $\beta$-acyclic queries in time linear in the certificate plus the output size, while for any $\beta$-cyclic query there is some instance that takes superlinear time in the certificate (and for which the output is no larger than the certificate size). We also extend our certificate-complexity analysis to queries with bounded treewidth and the triangle query.Comment: [This is the full version of our PODS'2014 paper.

A continuous non-linear shadowing model of columnar growth

We propose the first continuous model with long range screening (shadowing) that described columnar growth in one space dimension, as observed in plasma sputter deposition. It is based on a new continuous partial derivative equation with non-linear diffusion and where the shadowing effects apply on all the different processes.Comment: Fast Track Communicatio

Evidence of Efficient Transovarial Transmission of Culex Flavivirus by Culex pipiens (Diptera: Culicidae)

This study determined the transovarial transmission (TOT) potential and tissue tropisms of Culex flavivirus (CxFV), an insect-specific flavivirus, in Culex pipiens (L.). Several hundred mosquito egg rafts were collected in the field, transferred to the insectaries, reared to the fourth larval instar, and identified using morphological characteristics. Cx. pipiens were reared to adults, allowed to oviposit in individual containers, and tested for CxFV RNA by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing. Eighteen CxFV RNA-positive females were identified from 26 females that oviposited viable egg rafts. Thirty F1 adults from each positive female were individually tested by RT-PCR for CxFV RNA. Viral RNA was detected in 526 of 540 progeny, and thus, the filial infection rate was 97.4%. Because all 18 positive females produced infected offspring, the TOT prevalence was 100%. These data indicated that efficient TOT of CxFV occurs in nature. To define the tissue tropisms of CxFV, different tissues (salivary glands, ovaries, testes, head, fat bodies, and midguts) were removed from the remainder of the F1 and tested by RT-PCR for CxFV RNA. Viral RNA was detected in all tissues. Additionally, uninfected laboratory-colonized Cx. pipiens were infected with CxFV by needle inoculation, and ovaries were collected at 4, 6, 8, and 12 d postinoculation and tested for CxFV RNA by RT-PCR. Viral RNA was detected at all time points, demonstrating that CxFV infects the ovaries as early as 4 d postinoculation. Surprisingly, however, we were unable to demonstrate transovarial transmission despite the presence of viral RNA in the ovaries. Nevertheless, the experiments performed with field-infected Cx. pipiens demonstrate that TOT is an efficient mechanism by which CxFV is maintained in mosquitoes in nature