Nutritional and tissue-specific regulation of cytochrome P450 CYP711A MAX1 homologues and strigolactone biosynthesis in wheat

Strigolactones (SLs) are a class of phytohormones regulating branching/tillering, and their biosynthesis has been associated with nutritional signals and plant adaptation to nutrient-limiting conditions. The enzymes in the SL biosynthetic pathway downstream of carlactone are of interest as they are responsible for structural diversity in SLs, particularly cytochrome P450 CYP711A subfamily members, such as MORE AXILLARY GROWTH1 (MAX1) in Arabidopsis. We identified 13 MAX1 homologues in wheat, clustering in four clades and five homoeologous subgroups. The utilization of RNA-sequencing data revealed a distinct expression pattern of MAX1 homologues in above- and below-ground tissues, providing insights into the distinct roles of MAX1 homologues in wheat. In addition, a transcriptional analysis showed that SL biosynthetic genes were systematically regulated by nitrogen supply. Nitrogen limitation led to larger transcriptional changes in the basal nodes than phosphorus limitation, which was consistent with the observed tillering suppression, as wheat showed higher sensitivity to nitrogen. The opposite was observed in roots, with phosphorus limitation leading to stronger induction of most SL biosynthetic genes compared with nitrogen limitation. The observed tissue-specific regulation of SL biosynthetic genes in response to nutritional signals is likely to reflect the dual role of SLs as rhizosphere signals and branching inhibitors

Measurement and RANS modelling of large-scale under-expanded CO2 releases for CCS applications

The deployment of a complete carbon-capture and storage chain requires a focus upon the hazards posed by the operation of CO2 pipelines, and the consequences of accidental release must be considered as an integral part of the design process. Presented are results from the application of a shock-capturing numerical scheme to the solution of the Favre-averaged Navier-Stokes fluid-flow equations, coupled with a compressibility-corrected turbulence model, and a novel equation of state for CO2. Comparisons are made with a series of as-yet unreported experimental observations of field-scale, high-pressure CO2 releases. The effects of corrections to the solenoidal turbulence energy dissipation are tested, with conclusions drawn, and recommendations made for future developments

Phase IIa Global Study Evaluating Rituximab for the Treatment of Pediatric Patients With Granulomatosis With Polyangiitis or Microscopic Polyangiitis

OBJECTIVE: To assess the safety, tolerability, pharmacokinetics, and efficacy of rituximab (RTX) in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). METHODS: The Pediatric Polyangiitis Rituximab Study was a phase IIa, international, open-label, single-arm study. During the initial 6-month remission-induction phase, patients received intravenous infusions of RTX (375 mg/m2 body surface area) and glucocorticoids once per week for 4 weeks. During the follow-up period, patients could receive further treatment, including RTX, for GPA or MPA. The safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy outcomes with RTX were evaluated. RESULTS: Twenty-five pediatric patients with new-onset or relapsing disease were enrolled at 11 centers (19 with GPA [76%] and 6 with MPA [24%]). The median age was 14 years (range 6-17 years). All patients completed the remission-induction phase. During the overall study period (≤4.5 years), patients received between 4 and 28 infusions of RTX. All patients experienced ≥1 adverse event (AE), mostly grade 1 or grade 2 primarily infusion-related reactions. Seven patients experienced 10 serious AEs, and 17 patients experienced 31 infection-related AEs. No deaths were reported. RTX clearance correlated with body surface area. The body surface area-adjusted RTX dosing regimen resulted in similar exposure in both pediatric and adult patients with GPA or MPA. Remission, according to the Pediatric Vasculitis Activity Score, was achieved in 56%, 92%, and 100% of patients by months 6, 12, and 18, respectively. CONCLUSION: In pediatric patients with GPA or MPA, RTX is well tolerated and effective, with an overall safety profile comparable to that observed in adult patients with GPA or MPA who receive treatment with RTX. RTX is associated with a positive risk/benefit profile in pediatric patients with active GPA or MPA

CO2PipeHaz: Quantitative hazard assessment for next generation CO2 pipelines

Without a clear understanding of the hazards associated with the failure of CO2 pipelines, carbon capture and storage (CCS) cannot be considered as a viable proposition for tackling the effects of global warming. Given that CO2 is an asphyxiant at high concentrations, the development of reliable validated pipeline outflow and dispersion models are central to addressing this challenge. This information is pivotal to quantifying all the hazard consequences associated with the failure of CO2 transportation pipelines, which forms the basis for emergency response planning and determining minimum safe distances to populated areas. This paper presents an overview of the main findings of the recently completed CO2PipeHaz project [1] which focussed on the hazard assessment of CO2 pipelines to be employed as an integral part of CCS. Funded by the European Commission FP7 Energy programme, the project's main objective was to address this fundamentally important issue

In Silico Investigation of Potential Src Kinase Ligands from Traditional Chinese Medicine

Src kinase is an attractive target for drug development based on its established relationship with cancer and possible link to hypertension. The suitability of traditional Chinese medicine (TCM) compounds as potential drug ligands for further biological evaluation was investigated using structure-based, ligand-based, and molecular dynamics (MD) analysis. Isopraeroside IV, 9alpha-hydroxyfraxinellone-9-O-beta-D-glucoside (9HFG) and aurantiamide were the top three TCM candidates identified from docking. Hydrogen bonds and hydrophobic interactions were the primary forces governing docking stability. Their stability with Src kinase under a dynamic state was further validated through MD and torsion angle analysis. Complexes formed by TCM candidates have lower total energy estimates than the control Sacaratinib. Four quantitative-structural activity relationship (QSAR) in silico verifications consistently suggested that the TCM candidates have bioactive properties. Docking conformations of 9HFG and aurantiamide in the Src kinase ATP binding site suggest potential inhibitor-like characteristics, including competitive binding at the ATP binding site (Lys295) and stabilization of the catalytic cleft integrity. The TCM candidates have significantly lower ligand internal energies and are estimated to form more stable complexes with Src kinase than Saracatinib. Structure-based and ligand-based analysis support the drug-like potential of 9HFG and aurantiamide and binding mechanisms reveal the tendency of these two candidates to compete for the ATP binding site

Methadone, Buprenorphine, and Street Drug Interactions with Antiretroviral Medications

While street drugs appear unlikely to alter the metabolism of antiretroviral (ARV) medications, several ARVs may induce or inhibit metabolism of various street drugs. However, research on these interactions is limited. Case reports have documented life-threatening overdoses of ecstasy and gamma-hydroxybutyrate after starting ritonavir, an ARV that inhibits several metabolic enzymes. For opioid addiction, methadone or buprenorphine are the treatments of choice. Because a number of ARVs decrease or increase methadone levels, patients should be monitored for methadone withdrawal or toxicity when they start or stop ARVs. Most ARVs do not cause buprenorphine withdrawal or toxicity, even if they alter buprenorphine levels, with rare exceptions to date including atazanavir/ritonavir associated with significant increases in buprenorphine and adverse events related to sedation and mental status changes in some cases. There are newer medications yet to be studied with methadone or buprenorphine. Further, there are many frequently used medications in treatment of complications of HIV disease that have not been studied. There is need for continuing research to define these drug interactions and their clinical significance

Analytical and computational modelling for wave energy systems:the example of oscillating wave surge converters

This is an Open Access Article. It is published by Springer under the Creative Commons Attribution 4.0 International Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/The development of new wave energy converters has shed light on a number of unanswered questions in fluid mechanics, but has also identified a number of new issues of importance for their future deployment. The main concerns relevant to the practical use of wave energy converters are sustainabiliy, survivability, and maintainability. And of course, it is also necessary to maximize the capture per unit area of the structure as well as to minimize the cost. In this review, we consider some of the questions related to the topics of sustainability, survivability, and maintenance access, with respect to sea conditions, for generic wave energy converters with an emphasis on the oscillating wave surge converter (OWSC). New analytical models that have been developed are a topic of particular discussion. It is also shown how existing numerical models have been pushed to their limits to provide answers to open questions relating to the operation and characteristics of wave energy converters

Carbon capture: Whole system experimental and theoretical modeling investigation of the optimal CO<inf>2</inf> stream composition in the carbon capture and sequestration chain

Rapid increase in emissions of greenhouse gases (GHGs) has become a major concern to the global community. This is associated with the rapid growth in population and corresponding increase in energy demand. Combustion of fossil fuels accounts for the majority of CO2 emissions. Coal is used mostly for electricity generation, for instance, about 85.5% of coal (produced and imported) in the United 459Kingdom was used for electricity generation in 2011 [1]. Coal-fired power plants are therefore the largest stationary source of CO2

Experimental measurement and Reynolds-averaged Navier-Stokes modelling of the near-field structure of multi-phase CO jet releases

The deployment of a complete carbon capture and storage chain requires a focus upon the hazards posed by the operation of CO pipelines and intermediate storage vessels, and the consequences of accidental release. The aim of this work is the construction of a computational fluid dynamic model capable of accurately representing the complex physics observed in such a release, essential if dispersion phenomena are to be accurately predicted. The interacting thermo-physical processes observed include those associated with the rapid expansion of a highly under-expanded jet, leading to an associated sonic flow structure. In such a release, it is also possible for three phases to be present due to the expansion and subsequent Joule-Thomson cooling, and a suitable equation of state is required to elucidate a system's composition. The primary objective of this work is the consideration of these physical processes, and their integration into a suitable numerical framework which can be used as a tool for quantifying associated hazards. This also incorporates the validation of such a model using data available in the literature and also using that recently obtained, and presented here for the first time. Overall, the model has provided an excellent level of agreement with experimental data in terms of fluid and sonic structure and temperature measurements, and good agreement with respect to composition data