Reversible jump MCMC for nonparametric drift estimation for diffusion processes

In the context of nonparametric Bayesian estimation a Markov chain Monte Carlo algorithm is devised and implemented to sample from the posterior distribution of the drift function of a continuously or discretely observed one-dimensional diffusion. The drift is modeled by a scaled linear combination of basis functions with a Gaussian prior on the coefficients. The scaling parameter is equipped with a partially conjugate prior. The number of basis function in the drift is equipped with a prior distribution as well. For continuous data, a reversible jump Markov chain algorithm enables the exploration of the posterior over models of varying dimension. Subsequently, it is explained how data-augmentation can be used to extend the algorithm to deal with diffusions observed discretely in time. Some examples illustrate that the method can give satisfactory results. In these examples a comparison is made with another existing method as well

GLOWORM-PARA: a flexible framework to simulate the population dynamics of the parasitic phase of gastrointestinal nematodes infecting grazing livestock

Gastrointestinal (GI) nematodes are a significant threat to the economic and environmental sustainability of keeping livestock, as adequate control becomes increasingly difficult due to the development of anthelmintic resistance (AR) in some systems and climate-driven changes to infection dynamics. To mitigate any negative impacts of climate on GI nematode epidemiology and slow AR development, there is a need to develop effective, targeted control strategies that minimise the unnecessary use of anthelmintic drugs and incorporate alternative strategies such as vaccination and evasive grazing. However, the impacts climate and GI nematode epidemiology may have on the optimal control strategy are generally not considered, due to lack of available evidence to drive recommendations. Parasite transmission models can support control strategy evaluation to target field trials, thus reducing the resources and lead-time required to develop evidence-based control recommendations incorporating climate stochasticity. GI nematode population dynamics arising from natural infections have been difficult to replicate and model applications have often focussed on the free-living stages. A flexible framework is presented for the parasitic phase of GI nematodes, GLOWORM-PARA, which complements an existing model of the free-living stages, GLOWORM-FL. Longitudinal parasitological data for two species that are of major economic importance in cattle, Ostertagia ostertagi and Cooperia oncophora, were obtained from seven cattle farms in Belgium for model validation. The framework replicated the observed seasonal dynamics of infection in cattle on these farms and overall, there was no evidence of systematic under- or over-prediction of faecal egg counts (FECs). However, the model under-predicted the FECs observed on one farm with very young calves, highlighting potential areas of uncertainty that may need further investigation if the model is to be applied to young livestock. The model could be used to drive further research into alternative parasite control strategies such as vaccine development and novel treatment approaches, and to understand GI nematode epidemiology under changing climate and host management

Potential effects of oilseed rape expressing oryzacystatin-1 (OC-1) and of purified insecticidal proteins on larvae of the solitary bee Osmia bicornis

Despite their importance as pollinators in crops and wild plants, solitary bees have not previously been included in non-target testing of insect-resistant transgenic crop plants. Larvae of many solitary bees feed almost exclusively on pollen and thus could be highly exposed to transgene products expressed in the pollen. The potential effects of pollen from oilseed rape expressing the cysteine protease inhibitor oryzacystatin-1 (OC-1) were investigated on larvae of the solitary bee Osmia bicornis (= O. rufa). Furthermore, recombinant OC-1 (rOC-1), the Bt toxin Cry1Ab and the snowdrop lectin Galanthus nivalis agglutinin (GNA) were evaluated for effects on the life history parameters of this important pollinator. Pollen provisions from transgenic OC-1 oilseed rape did not affect overall development. Similarly, high doses of rOC-1 and Cry1Ab as well as a low dose of GNA failed to cause any significant effects. However, a high dose of GNA (0.1%) in the larval diet resulted in significantly increased development time and reduced efficiency in conversion of pollen food into larval body weight. Our results suggest that OC-1 and Cry1Ab expressing transgenic crops would pose a negligible risk for O. bicornis larvae, whereas GNA expressing plants could cause detrimental effects, but only if bees were exposed to high levels of the protein. The described bioassay with bee brood is not only suitable for early tier non-target tests of transgenic plants, but also has broader applicability to other crop protection products

Relocalization of Phospholipase D Activity Mediates Membrane Formation During Meiosis

Phospholipase D (PLD) enzymes catalyze the hydrolysis of phosphatidylcholine and are involved in membrane trafficking and cytoskeletal reorganization. The Saccharomyces cerevisiae SPO14 gene encodes a PLD that is essential for meiosis. We have analyzed the role of PLD in meiosis by examining two mutant proteins, one with a point mutation in a conserved residue (Spo14pK→ H) and one with an amino-terminal deletion (Spo14pΔN), neither of which can restore meiosis in a spo14 deletion strain. Spo14pK→ H is enzymatically inactive, indicating that PLD activity is required, whereas Spo14pΔN retains PLD catalytic activity in vitro, indicating that PLD activity is not sufficient for meiosis. To explore other aspects of Spo14 function, we followed the localization of the enzyme during meiosis. Spo14p is initially distributed throughout the cell, becomes concentrated at the spindle pole bodies after the meiosis I division, and at meiosis II localizes to the new spore membrane as it surrounds the nuclei and then expands to encapsulate the associated cytoplasm during the formation of spores. The catalytically inactive protein also undergoes relocalization during meiosis; however, in the absence of PLD activity, no membrane is formed. In contrast, Spo14pΔN does not relocalize properly, indicating that the failure of this protein to complement a spo14 mutant is due to its inability to localize its PLD activity. Furthermore, we find that Spo14p movement is correlated with phosphorylation of the protein. These experiments indicate that PLD participates in regulated membrane formation during meiosis, and that both its catalytic activity and subcellular redistribution are essential for this function

Health economic evaluation of a web-based intervention for depression: the EVIDENT-trial, a randomized controlled study.

Gräfe V, Berger T, Hautzinger M, et al. Health economic evaluation of a web-based intervention for depression: the EVIDENT-trial, a randomized controlled study. Health economics review. 2019;9(1): 16.BACKGROUND: Depression often remains undiagnosed or treated inadequately. Web-based interventions for depression may improve accessibility of treatment and reduce disease-related costs. This study aimed to examine the potential of the web-based cognitive behavioral intervention "deprexis" in reducing disease-related costs.; METHODS: Participants with mild to moderate depressive symptoms were recruited and randomized to either a 12-week web-based intervention (deprexis) in addition to care as usual (intervention group) or care as usual (control group). Outcome measures were health-related resource use, use of medication and incapacity to work as well as relating direct health care costs. Outcomes were assessed on patients' self-report at baseline, three months and six months.; RESULTS: A total of 1013 participants were randomized. In both groups total direct health care costs decreased during the study period, but changes from baseline did not significantly differ between study groups. Numeric differences between study groups existed in outpatient treatment costs. They could be attributed to differences in changes of costs for psychotherapeutic treatment from baseline. Whereas costs for psychotherapeutic treatment decreased in the intervention group, costs increased in the control group (-16.8% (80) vs. +14.7% (60)) (tdf=685=2.57; p=0.008).; CONCLUSION: The study indicates the health economic potential of innovative e-mental-health programs. There is evidence to suggest that the use of deprexis over a period of 12weeks leads to a decrease in outpatient treatment cost, especially in those related to different types of psychotherapeutic treatment

A flexible loop in yeast ribosomal protein L11 coordinates P-site tRNA binding

High-resolution structures reveal that yeast ribosomal protein L11 and its bacterial/archael homologs called L5 contain a highly conserved, basically charged internal loop that interacts with the peptidyl-transfer RNA (tRNA) T-loop. We call this the L11 ‘P-site loop’. Chemical protection of wild-type ribosome shows that that the P-site loop is inherently flexible, i.e. it is extended into the ribosomal P-site when this is unoccupied by tRNA, while it is retracted into the terminal loop of 25S rRNA Helix 84 when the P-site is occupied. To further analyze the function of this structure, a series of mutants within the P-site loop were created and analyzed. A mutant that favors interaction of the P-site loop with the terminal loop of Helix 84 promoted increased affinity for peptidyl-tRNA, while another that favors its extension into the ribosomal P-site had the opposite effect. The two mutants also had opposing effects on binding of aa-tRNA to the ribosomal A-site, and downstream functional effects were observed on translational fidelity, drug resistance/hypersensitivity, virus maintenance and overall cell growth. These analyses suggest that the L11 P-site loop normally helps to optimize ribosome function by monitoring the occupancy status of the ribosomal P-site

Cell wall proteins: a new insight through proteomics

Cell wall proteins are essential constituents of plant cell walls; they are involved in modifications of cell wall components, wall structure, signaling and interactions with plasma membrane proteins at the cell surface. The application of proteomic approaches to the cell wall compartment raises important questions: are there technical problems specific to cell wall proteomics? What kinds of proteins can be found in Arabidopsis walls? Are some of them unexpected? What sort of post-translational modifications have been characterized in cell wall proteins to date? The purpose of this review is to discuss the experimental results obtained to date using proteomics, as well as some of the new questions challenging future research

New potentials for multiscale simulations of liquid metals

We present the technique and results for finding norm-conserving pseudopotentials and EAM potentials that can be used to recover atomic and electronic structure of liquid iron at and above the melting point. Pseudopotentials were found by minimizing the energy differences of our results with all-electron reference methods; EAM potentials — by the modified hybridization method proposed earlier by Belashchenko. We show that these potentials are at least as accurate in describing liquid iron as the established potentials in the field

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured