Semi-parametric estimation of the Wilshire creep life prediction model: an application to 2.25Cr-1Mo steel

The Wilshire equation is a recent addition to the literature on safe life prediction. While the effect of temperature on creep life is reasonably understood, the effect of stress isn’t. The Wilshire equation deals with this by partitioning over sub ranges of stress, but this approximation can lead to poor life time predictions. This paper introduces a semi-parametric procedure that allows the data itself to identify the stress relationship. When applied to 2.25Cr-1Mo steel it was found that the stress relationship is non-linear, and this semi-parametric version of the Wilshire model had better predictive performance compared to any partitioned Wilshire model. This approach contains a limit to valid extrapolation and the isothermal predictions for creep life have a more realistic pattern of behaviour

An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly

ACKNOWLEDGEMENTS Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). We would also like to thank Prof. Shohei Mitani,at the National Bioresource Project for the Experimental Animal ‘Nematode C. elegans’, Japan, for FX3079. We are grateful to Prof. Tom Blumenthal (University of Colorado, Boulder) for suggestions and support of this work; and to Kathrine Wood for her contribution to the initial stages of part of this work. Author contributions. L.P., G.P., R.F., N.H., J.P. and B.M. performed experiments; B.M., J.P. and B.C. designed and lead the study; B.M. and J.P. drafted the manuscript. All authors reviewed the manuscript. FUNDING Biotechnology and Biological Sciences Research Council (BBSRC) [Project grant BB/J007137/1]; Medical Research Council (MRC) Confidence in Concept 2014 - University of Aberdeen Award(MC PC 14114v.2); University of Aberdeen Elphinstone Scholarship (to R.F.) and TET Fund support through Adekunle Ajasin University, Nigeria (to R.F.). Funding for open access charge: Biotechnology and Biological Sciences Research Council and Medical Research Council.Peer reviewedPublisher PD

Mean heart dose variation over a course of breath-holding breast cancer radiotherapy.

Objective The purpose of the work was to estimate the dose received by the heart throughout a course of breath-holding breast radiotherapy.Methods 113 cone-beam CT (CBCT) scans were acquired for 20 patients treated within the HeartSpare 1A study, in which both an active breathing control (ABC) device and a voluntary breath-hold (VBH) method were used. Predicted mean heart doses were obtained from treatment plans. CBCT scans were imported into a treatment planning system, heart outlines defined, images registered to the CT planning scan and mean heart dose recorded. Two observers outlined two cases three times each to assess interobserver and intraobserver variation.Results There were no statistically significant differences between ABC and VBH heart dose data from CT planning scans, or in the CBCT-based estimates of heart dose, and no effect from the order of the breath-hold method. Variation in mean heart dose per fraction over the three imaged fractions was <6 cGy without setup correction, decreasing to 3.3 cGy with setup correction. If scaled to 15 fractions, all differences between predicted and estimated mean heart doses were <0.5 Gy and in 80% of cases, they were <0.25 Gy.Conclusion Variation in mean heart dose was at an acceptable level over the duration of breath-holding radiotherapy and was well predicted by the planning system. Advances in knowledge: Mean heart dose was not adversely affected by fraction-to-fraction variations throughout a course of heart-sparing radiotherapy using two well-established breath-holding methods

Moyal star product approach to the Bohr-Sommerfeld approximation

The Bohr-Sommerfeld approximation to the eigenvalues of a one-dimensional quantum Hamiltonian is derived through order $\hbar^2$ (i.e., including the first correction term beyond the usual result) by means of the Moyal star product. The Hamiltonian need only have a Weyl transform (or symbol) that is a power series in $\hbar$, starting with $\hbar^0$, with a generic fixed point in phase space. The Hamiltonian is not restricted to the kinetic-plus-potential form. The method involves transforming the Hamiltonian to a normal form, in which it becomes a function of the harmonic oscillator Hamiltonian. Diagrammatic and other techniques with potential applications to other normal form problems are presented for manipulating higher order terms in the Moyal series.Comment: 27 pages, no figure

The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation

Fine control of macrophage activation is needed to prevent inflammatory disease, particularly at barrier sites such as the lungs. However, the dominant mechanisms that regulate the activation of pulmonary macrophages during inflammation are poorly understood. We found that alveolar macrophages (AlvMs) were much less able to respond to the canonical type 2 cytokine IL-4, which underpins allergic disease and parasitic worm infections, than macrophages from lung tissue or the peritoneal cavity. We found that the hyporesponsiveness of AlvMs to IL-4 depended upon the lung environment but was independent of the host microbiota or the lung extracellular matrix components surfactant protein D (SP-D) and mucin 5b (Muc5b). AlvMs showed severely dysregulated metabolism relative to that of cavity macrophages. After removal from the lungs, AlvMs regained responsiveness to IL-4 in a glycolysis-dependent manner. Thus, impaired glycolysis in the pulmonary niche regulates AlvM responsiveness during type 2 inflammation

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality

Exploiting inflammation for therapeutic gain in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with &#60;5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC

Stochastic population growth in spatially heterogeneous environments

Classical ecological theory predicts that environmental stochasticity increases extinction risk by reducing the average per-capita growth rate of populations. To understand the interactive effects of environmental stochasticity, spatial heterogeneity, and dispersal on population growth, we study the following model for population abundances in $n$ patches: the conditional law of $X_{t+dt}$ given $X_t=x$ is such that when $dt$ is small the conditional mean of $X_{t+dt}^i-X_t^i$ is approximately $[x^i\mu_i+\sum_j(x^j D_{ji}-x^i D_{ij})]dt$, where $X_t^i$ and $\mu_i$ are the abundance and per capita growth rate in the $i$-th patch respectivly, and $D_{ij}$ is the dispersal rate from the $i$-th to the $j$-th patch, and the conditional covariance of $X_{t+dt}^i-X_t^i$ and $X_{t+dt}^j-X_t^j$ is approximately $x^i x^j \sigma_{ij}dt$. We show for such a spatially extended population that if $S_t=(X_t^1+...+X_t^n)$ is the total population abundance, then $Y_t=X_t/S_t$, the vector of patch proportions, converges in law to a random vector $Y_\infty$ as $t\to\infty$, and the stochastic growth rate $\lim_{t\to\infty}t^{-1}\log S_t$ equals the space-time average per-capita growth rate \sum_i\mu_i\E[Y_\infty^i] experienced by the population minus half of the space-time average temporal variation \E[\sum_{i,j}\sigma_{ij}Y_\infty^i Y_\infty^j] experienced by the population. We derive analytic results for the law of $Y_\infty$, find which choice of the dispersal mechanism $D$ produces an optimal stochastic growth rate for a freely dispersing population, and investigate the effect on the stochastic growth rate of constraints on dispersal rates. Our results provide fundamental insights into "ideal free" movement in the face of uncertainty, the persistence of coupled sink populations, the evolution of dispersal rates, and the single large or several small (SLOSS) debate in conservation biology.Comment: 47 pages, 4 figure

Role of retinoic receptors in lung carcinogenesis

Several in vitro and in vivo studies have examined the positive and negative effects of retinoids (vitamin A analogs) in premalignant and malignant lesions. Retinoids have been used as chemopreventive and anticancer agents because of their pleiotropic regulator function in cell differentiation, growth, proliferation and apoptosis through interaction with two types of nuclear receptors: retinoic acid receptors and retinoid X receptors. Recent investigations have gradually elucidated the function of retinoids and their signaling pathways and may explain the failure of earlier chemopreventive studies

Four-electron deoxygenative reductive coupling of carbon monoxide at a single metal site

Carbon dioxide is the ultimate source of the fossil fuels that are both central to modern life and problematic: their use increases atmospheric levels of greenhouse gases, and their availability is geopolitically constrained. Using carbon dioxide as a feedstock to produce synthetic fuels might, in principle, alleviate these concerns. Although many homogeneous and heterogeneous catalysts convert carbon dioxide to carbon monoxide, further deoxygenative coupling of carbon monoxide to generate useful multicarbon products is challenging. Molybdenum and vanadium nitrogenases are capable of converting carbon monoxide into hydrocarbons under mild conditions, using discrete electron and proton sources. Electrocatalytic reduction of carbon monoxide on copper catalysts also uses a combination of electrons and protons, while the industrial Fischer–Tropsch process uses dihydrogen as a combined source of electrons and electrophiles for carbon monoxide coupling at high temperatures and pressures6. However, these enzymatic and heterogeneous systems are difficult to probe mechanistically. Molecular catalysts have been studied extensively to investigate the elementary steps by which carbon monoxide is deoxygenated and coupled, but a single metal site that can efficiently induce the required scission of carbon–oxygen bonds and generate carbon–carbon bonds has not yet been documented. Here we describe a molybdenum compound, supported by a terphenyl–diphosphine ligand, that activates and cleaves the strong carbon–oxygen bond of carbon monoxide, enacts carbon–carbon coupling, and spontaneously dissociates the resulting fragment. This complex four-electron transformation is enabled by the terphenyl–diphosphine ligand, which acts as an electron reservoir and exhibits the coordinative flexibility needed to stabilize the different intermediates involved in the overall reaction sequence. We anticipate that these design elements might help in the development of efficient catalysts for converting carbon monoxide to chemical fuels, and should prove useful in the broader context of performing complex multi-electron transformations at a single metal site