Intensity-dependent reductions in resting blood pressure following short-term isometric exercise training

To reduce resting blood pressure, a minimum isometric exercise training (IET) intensity has been suggested, but this is not known for short-term IET programmes. We therefore compared the effects of moderate- and low-intensity IET programmes on resting blood pressure. Forty normotensive participants (22.3 ± 3.4 years; 69.5 ± 15.5 kg; 170.2 ± 8.7 cm) were randomly assigned to groups of differing training intensities [20%EMGpeak (~23%MVC, maximum voluntary contraction, or 30%EMGpeak (~34%MVC)] or control group; 3 weeks of IET at 30%EMGpeak resulted in significant reductions in resting mean arterial pressure (e.g. −3.9 ± 1.0 mmHg, P 0.05). Moreover, after pooling all female versus male participants, IET induced a 6.9-mmHg reduction in systolic blood pressure in female participants, but only a 1.5-mmHg reduction in systolic blood pressure in male participants, although the difference was not significant. An IET intensity between 20%EMGpeak and 30%EMGpeak is sufficient to elicit significant resting blood pressure reductions in a short-term training period (3 weeks). In addition, sexual dimorphism may exist in the magnitude of reductions, but further work is required to confirm this possibility, which could be important in understanding the mechanisms responsible

Monopiles subjected to uni- and multi-lateral cyclic loading

Offshore wind turbines are subjected to significant environmental loads from a combination of current, wind and wave action. Under such conditions, the directions of these environmental loads vary over the service life of the structure and therefore the cyclic lateral loading on the foundation also changes direction. The work reported in this paper examines the effects of multi-directional loading on the performance of offshore wind turbine monopile foundations. Tests were carried out in a model sand bed and a mobile loading platform was manufactured to apply loading on the pile in various directions. Tests were also carried out where the cyclic loading was applied under both one-way and two-way loading. The observations indicate significant differences in the stiffness of monopiles between uni-directional and multi-directional lateral cyclic loading. Multi-directional lateral cyclic loading generally results in higher displacements and lower stiffness compared to uni-directional loading, most likely due to shear deformation of a larger volume of soil mass adjacent to the pile

Stocktake and analysis of legume evaluation for tropical pastures in Australia

There has been a large effort dedicated to the evaluation of a wide variety of sub-tropical and tropical pasture legumes in the past. This large body of information is very valuable for guiding any future legume development activities, yet much of this information was at risk of being lost. This project aimed to collate and store this tropical legume evaluation data and use this and knowledge from past researchers to recommend priority R&D approaches and activities for future pasture legume development. Together with retired pasture researchers, legume evaluation datasets were identified, prioritised, and collated into a database which captured over 180 000 data records collected from 567 sites across northern Australia. Using this large integrated dataset, high power statistical approaches were used to identify legume species which performed well across this large range of evaluation sites. Several species and genera were identified which warrant further investigation and further in-depth analysis of the database in species or genera of interest would be valuable. A gap analysis of commercially proven, underused and prospective legumes was conducted across the key production regions of northern Australia. A range of material was identified which could offer potential improvements in seed production, cold, drought or grazing tolerance compared to the current released varieties

Predictive sensorimotor control in autism

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this recordAutism Spectrum Disorder has been characterised by atypicalities in how predictions and sensory information are processed in the brain. To shed light on this relationship in the context of sensorimotor control we assessed prediction-related measures of cognition, perception, gaze and motor functioning in a large general population (n = 92; experiment one) and in clinicallydiagnosed autistic people (n = 29; experiment two). In both these experiments perception and action were strongly driven by prior expectations of object weight, with large items typically predicted to weigh more than equally-weighted smaller ones. Interestingly, these predictive action models were employed comparably at a sensorimotor level in both autistic and neurotypical individuals with varying levels of autistic-like traits. Specifically, initial fingertip force profiles and resulting action kinematics were both scaled according to participants’ prelift heaviness estimates, and generic visual sampling behaviours were notably consistent across groups. These results suggest that the weighting of prior information is not chronically underweighted in autism, as proposed by simple Bayesian accounts of the disorder. Instead, our results cautiously implicate context-sensitive processing mechanisms, such as precision modulation and hierarchical volatility inference. Together, these findings present novel implications for both future scientific investigations and the applied autism community.Economic and Social Research Council (ESRC

C13orf31 (FAMIN) is a central regulator of immunometabolic function.

Single-nucleotide variations in C13orf31 (LACC1) that encode p.C284R and p.I254V in a protein of unknown function (called 'FAMIN' here) are associated with increased risk for systemic juvenile idiopathic arthritis, leprosy and Crohn's disease. Here we set out to identify the biological mechanism affected by these coding variations. FAMIN formed a complex with fatty acid synthase (FASN) on peroxisomes and promoted flux through de novo lipogenesis to concomitantly drive high levels of fatty-acid oxidation (FAO) and glycolysis and, consequently, ATP regeneration. FAMIN-dependent FAO controlled inflammasome activation, mitochondrial and NADPH-oxidase-dependent production of reactive oxygen species (ROS), and the bactericidal activity of macrophages. As p.I254V and p.C284R resulted in diminished function and loss of function, respectively, FAMIN determined resilience to endotoxin shock. Thus, we have identified a central regulator of the metabolic function and bioenergetic state of macrophages that is under evolutionary selection and determines the risk of inflammatory and infectious disease.Supported by the European Research Council under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement 260961, the Wellcome Trust (investigator award 106260/Z/14/Z; a PhD fellowship for clinicians; and a Career Re-Entry Fellowship), the Wellcome Trust Sanger Institute, the US National Institutes of Health (5U420D011174 and 5U54HG006348), the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research Cambridge Biomedical Research Centre, the European Crohn’s and Colitis Organisation and the Swedish Medical Research Council and the Olle Engkvist foundation.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ni.353

Exploring The Architectures Of Planetary Systems That Form In Thermally Evolving Viscous Disc Models

PhDThe diversity in observed planets and planetary systems has raised the question of whether they can be explained by a single model of planet formation or whether multiple models are required. The work presented in this thesis aims to examine the oligarchic growth scenario, to determine whether the core accretion model, where planets form bottom-up, can recreate the observed diversity. I begin by exploring how changing model parameters such as disc mass and metallicity influence the types of planetary systems that emerge. I show that rapid inward migration leads to very few planets with masses mp > 10M⊕ surviving, with surviving planetary systems typically containing numerous low-mass planets. I examine what conditions are required for giant planets to form and survive migration, finding that for a planet similar to Jupiter to form and survive, it must form at an orbital radius rp > 10 au. In the second project in this thesis, I update the physical models before examining whether a broader range of parameters can produce planetary systems similar to those observed. I find that compact systems of low-mass planets form in simulations if there is sufficient solid material in the disc or if planetesimals are small, thus having increased mobility. I also find that giant planets can form when the solid abundance and mobility of planetesimals are high, however they all undergo largescale migration into the magnetospheric cavity located close to the star. For the final project of this thesis, I examined the effects that disc radial structuring has on the formation of giant planets. I find that by including radial structures, numerous giant planets are able to form at large orbital radii and survive migration. The observed period valley between 10–100 days is also recreated, of which I attribute to disc dispersal late in the disc’s lifetime.STFC PhD studentship

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts