Cross-beam energy transfer in conditions relevant to direct-drive implosions on OMEGA

In cross-beam energy transfer (CBET), the interference of two laser beams ponderomotively drives an ion-acoustic wave that coherently scatters light from one beam into the other. This redirection of laser beam energy can severely inhibit the performance of direct-drive inertial confinement fusion (ICF) implosions. To assess the role of nonlinear and kinetic processes in direct-drive-relevant CBET, the energy transfer between two laser beams in the plasma conditions of an ICF implosion at the OMEGA laser facility was modeled using particle-in-cell simulations. For typical laser beam intensities, the simulations are in excellent agreement with linear kinetic theory, indicating that nonlinear processes do not play a role in direct-drive implosions. At higher intensities, CBET can be modified by pump depletion, backward stimulated Raman scattering, or ion trapping, depending on the plasma density

Unifying the analysis of high-throughput sequencing datasets: characterizing RNA-seq, 16S rRNA gene sequencing and selective growth experiments by compositional data analysis.

BACKGROUND: Experimental designs that take advantage of high-throughput sequencing to generate datasets include RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), sequencing of 16S rRNA gene fragments, metagenomic analysis and selective growth experiments. In each case the underlying data are similar and are composed of counts of sequencing reads mapped to a large number of features in each sample. Despite this underlying similarity, the data analysis methods used for these experimental designs are all different, and do not translate across experiments. Alternative methods have been developed in the physical and geological sciences that treat similar data as compositions. Compositional data analysis methods transform the data to relative abundances with the result that the analyses are more robust and reproducible. RESULTS: Data from an in vitro selective growth experiment, an RNA-seq experiment and the Human Microbiome Project 16S rRNA gene abundance dataset were examined by ALDEx2, a compositional data analysis tool that uses Bayesian methods to infer technical and statistical error. The ALDEx2 approach is shown to be suitable for all three types of data: it correctly identifies both the direction and differential abundance of features in the differential growth experiment, it identifies a substantially similar set of differentially expressed genes in the RNA-seq dataset as the leading tools and it identifies as differential the taxa that distinguish the tongue dorsum and buccal mucosa in the Human Microbiome Project dataset. The design of ALDEx2 reduces the number of false positive identifications that result from datasets composed of many features in few samples. CONCLUSION: Statistical analysis of high-throughput sequencing datasets composed of per feature counts showed that the ALDEx2 R package is a simple and robust tool, which can be applied to RNA-seq, 16S rRNA gene sequencing and differential growth datasets, and by extension to other techniques that use a similar approach

Tourist spaces and tourism policy in Spain and Portugal

Advances in Cultura, Tourism and Hospitality Research;10, 235-249This study analyses the relationship between the development of the tourism policy of Spain and Portugal and their effects on regional imbalances. Despite the proximity of the two countries and their specialisation in tourism, there are few comparative studies on tourism of the two Iberian countries. The study focuses on the two major phases of tourism policy: the period of mass tourism and post-Fordist stage. In the conclusions we refer the debate on the existence of a model of development based on tourism to the Latin countries of Southern Europe and we note the export process of the Spanish low-cost tourism model to other countries.Financiado por el Gobierno de España, Programa Fundamental de Investigación, Proyecto de I+D (CSO2012-30840) "Geografías de la crisis: análisis de los territorios urbanos y turísticos de las Islas Baleares, Costa del Sol y principales destinos del Caribe y América Central"

Phage T4 SegB protein is a homing endonuclease required for the preferred inheritance of T4 tRNA gene region occurring in co-infection with a related phage

Homing endonucleases initiate nonreciprocal transfer of DNA segments containing their own genes and the flanking sequences by cleaving the recipient DNA. Bacteriophage T4 segB gene, which is located in a cluster of tRNA genes, encodes a protein of unknown function, homologous to homing endonucleases of the GIY-YIG family. We demonstrate that SegB protein is a site-specific endonuclease, which produces mostly 3′ 2-nt protruding ends at its DNA cleavage site. Analysis of SegB cleavage sites suggests that SegB recognizes a 27-bp sequence. It contains 11-bp conserved sequence, which corresponds to a conserved motif of tRNA TψC stem-loop, whereas the remainder of the recognition site is rather degenerate. T4-related phages T2L, RB1 and RB3 contain tRNA gene regions that are homologous to that of phage T4 but lack segB gene and several tRNA genes. In co-infections of phages T4 and T2L, segB gene is inherited with nearly 100% of efficiency. The preferred inheritance depends absolutely on the segB gene integrity and is accompanied by the loss of the T2L tRNA gene region markers. We suggest that SegB is a homing endonuclease that functions to ensure spreading of its own gene and the surrounding tRNA genes among T4-related phages

Mutational analysis of human immunodeficiency virus type 1 protease suggests functional homology with aspartic proteinases.

Processing of the retroviral gag and pol gene products is mediated by a viral protease. Bacterial expression systems have been developed which permit genetic analysis of the human immunodeficiency virus type 1 protease as measured by cleavage of the pol protein precursor. Deletion analysis of the pol reading frame locates the sequences required to encode a protein with appropriate proteolytic activity near the left end of the pol reading frame but largely outside the gag-pol overlap region, which is at the extreme left end of pol. Most missense mutations within an 11-amino-acid domain highly conserved among retroviral proteases and with sequence similarity to the active site of aspartic proteinases abolish appropriate processing, suggesting that the retrovirus proteases share a catalytic mechanism with aspartic proteinases. Substitution of the amino acids flanking the scissile bond at three of the processing sites encoded by pol demonstrates distinct sequence requirements for cleavage at these different sites. The inclusion of a charged amino acid at the processing site blocks cleavage. A subset of these substitutions also inhibits processing at the nonmutated sites

Estimating the evidence of selection and the reliability of inference in unigenic evolution

<p>Abstract</p> <p>Background</p> <p>Unigenic evolution is a large-scale mutagenesis experiment used to identify residues that are potentially important for protein function. Both currently-used methods for the analysis of unigenic evolution data analyze 'windows' of contiguous sites, a strategy that increases statistical power but incorrectly assumes that functionally-critical sites are contiguous. In addition, both methods require the questionable assumption of asymptotically-large sample size due to the presumption of approximate normality.</p> <p>Results</p> <p>We develop a novel approach, termed the Evidence of Selection (EoS), removing the assumption that functionally important sites are adjacent in sequence and and explicitly modelling the effects of limited sample-size. Precise statistical derivations show that the EoS score can be easily interpreted as an expected log-odds-ratio between two competing hypotheses, namely, the hypothetical presence or absence of functional selection for a given site. Using the EoS score, we then develop selection criteria by which functionally-important yet non-adjacent sites can be identified. An approximate power analysis is also developed to estimate the reliability of inference given the data. We validate and demonstrate the the practical utility of our method by analysis of the homing endonuclease <monospace>I-Bmol</monospace>, comparing our predictions with the results of existing methods.</p> <p>Conclusions</p> <p>Our method is able to assess both the evidence of selection at individual amino acid sites and estimate the reliability of those inferences. Experimental validation with <monospace>I-Bmol</monospace> proves its utility to identify functionally-important residues of poorly characterized proteins, demonstrating increased sensitivity over previous methods without loss of specificity. With the ability to guide the selection of precise experimental mutagenesis conditions, our method helps make unigenic analysis a more broadly applicable technique with which to probe protein function.</p> <p>Availability</p> <p>Software to compute, plot, and summarize EoS data is available as an open-source package called 'unigenic' for the 'R' programming language at <url>http://www.fernandes.org/txp/article/13/an-analytical-framework-for-unigenic-evolution</url>.</p

Critical perspectives on ‘consumer involvement’ in health research: epistemological dissonance and the know-do gap

Researchers in the area of health and social care (both in Australia and internationally) are encouraged to involve consumers throughout the research process, often on ethical, political and methodological grounds, or simply as ‘good practice’. This paper presents findings from a qualitative study in the UK of researchers’ experiences and views of consumer involvement in health research. Two main themes are presented in the paper. Firstly, we explore the ‘know-do gap’ which relates to the tensions between researchers’ perceptions of the potential benefits of, and their actual practices in relation to, consumer involvement. Secondly, we focus on one of the reasons for this ‘know-do gap’, namely epistemological dissonance. Findings are linked to issues around consumerism in research, lay/professional knowledges, the (re)production of professional and consumer identities and the maintenance of boundaries between consumers and researchers

Evaluation of midkine and anterior gradient 2 in a multimarker panel for the detection of ovarian cancer

The aims of this study were: to characterise and compare plasma concentrations of midkine (MDK) in normal healthy women with concentrations observed in women with ovarian cancer; and to establish and compare the performance of MDK with that of anterior gradient 2 protein (AGR2) and CA125 in the development of multi-analyte classification algorithms for ovarian cancer. Median plasma concentrations of immunoreactive MDK, AGR2 and CA125 were significantly greater in the case cohort (909 pg/ml, 765 pg/ml and 502 U/ml, respectively n = 46) than in the control cohort (383 pg/ml, 188 pg/ml and 13 U/ml, respectively n = 61) (p < 0.001). The area under the receiver operator characteristic curve (AUC) for MDK and AGR2 was not significantly different (0.734 ± 0.046 and 0.784 ± 0.049, respectively, mean ± SE) but were both significantly less than the AUC for CA125 (0.934 ± 0.030, p < 0.003). When subjected to stochastic gradient boosted logistic regression modelling, the AUC of the multi-analyte panel (MDK, AGR2 and CA125, 0.988 ± 0.010) was significantly greater than that of CA125 alone (0.934 ± 0.030, p = 0.035). The sensitivity and specificity of the multi-analyte algorithm were 95.2 and 97.7%, respectively. Within the study cohort, CA125 displayed a sensitivity and specificity of 87.0 and 94.6%, respectively. The data obtained in this study confirm that both MDK and AGR2 individually display utility as biomarkers for ovarian cancer and that in a multi-analyte panel significantly improve the diagnostic utility of CA125 in symptomatic women