Nutrition Strategies for Triathlon

Contemporary sports nutrition guidelines recommend that each athlete develop a personalised, periodised and practical approach to eating that allows him or her to train hard, recover and adapt optimally, stay free of illness and injury and compete at their best at peak races. Competitive triathletes undertake a heavy training programme to prepare for three different sports while undertaking races varying in duration from 20 min to 10 h. The everyday diet should be adequate in energy availability, provide CHO in varying amounts and timing around workouts according to the benefits of training with low or high CHO availability and spread high-quality protein over the day to maximise the adaptive response to each session. Race nutrition requires a targeted and well-practised plan that maintains fuel and hydration goals over the duration of the specific event, according to the opportunities provided by the race and other challenges, such as a hot environment. Supplements and sports foods can make a small contribution to a sports nutrition plan, when medical supplements are used under supervision to prevent/treat nutrient deficiencies (e.g. iron or vitamin D) or when sports foods provide a convenient source of nutrients when it is impractical to eat whole foods. Finally, a few evidence-based performance supplements may contribute to optimal race performance when used according to best practice protocols to suit the triathlete’s goals and individual responsiveness

Leaching behaviour of co-disposed steel making wastes: effects of aeration on leachate chemistry and vanadium mobilisation

Steelmaking wastes stored in landfill, such as slag and spent refractory liners, are often enriched in toxic trace metals (including V). These may become mobile in highly alkaline leachate generated during weathering. Fresh steelmaking waste was characterised using XRD, XRF, and SEM-EDX. Batch leaching tests were performed under aerated, air-excluded and acidified conditions to determine the impact of atmospheric CO2 and acid addition on leachate chemistry. Phases commonly associated with slag including dicalcium silicate, dicalcium aluminoferrite, a wüstite-like solid solution and free lime were identified, as well as a second group of phases including periclase, corundum and graphite which are representative of refractory liners. During air-excluded leaching, dissolution of free lime and dicalcium silicate results in a high pH, high Ca leachate in which the V concentration is low due to the constraint imposed by Ca3(VO4)2 solubility limits. Under aerated conditions, carbonation lowers the leachate pH and provides a sink for aqueous Ca, allowing higher concentrations of V to accumulate. Below pH 10, leachate is dominated by periclase dissolution and secondary phases including monohydrocalcite and dolomite are precipitated. Storage of waste under saturated conditions that exclude atmospheric CO2 would therefore provide the optimal environment to minimise V leaching during weathering

180x120: Designing Alternate Location Systems

Background In October 2005, Anthony Burke with Eric Paulos of Intel Labs, Berkeley were invited to design a live media installation at the San Francisco Museum of Art for an event opening. The piece was titled 180x120, drawing in a crowd of over 180 people whose presence and activity over 120 minutes created the installation itself. Contribution 40% Design, fabrication, site and contract negotiation, installation and publicity. This work was a collaboration between information technologists and architects aimed at spatially visualizing real time data of crowd behaviours. My contribution was specifically with regard to the overlap of the material and information systems, and means through which the evolving digital display could be matched to a material substrate. Significance 180x120 is an early example of a live data driven media installation, created at the invitation of the creative director of the SFMoMA in 2005. Our research aims were to interrogate the relationship between private physical location and public consumption of this now easily available information, raising issues of privacy and the extent of personal boundaries in information space. This research explicitly explores the creative possibilities between digital information and encoded material systems marking a moment of temporal, material and digital synthesis. Our research aim was to explore and understand the spatial and visual consequences of this alignment. This blending of interactive media and performance based (crowd based) art was a novel contribution to new media practice and research at the time

Ecology of a North Sea pockmark with an active methane seep

ABSTRACT: At a large North Sea pockmark, with active methane seeps, surface sediments were found to have higher insoluble sulphide concentrations than sedlments from the surrounding area. The fauna of the pockmark was characterized by 2 species which have not pi-evlously been reported from the Fladen Ground in the northern North Sea. These species were a b~valve, Thyasira sarsi (which is known to contain endosymbiotic sulphur-oxidising bacteria) and a mouthless and gutless nematode, Astomonerna sp., which also contains endosymbiotic bacteria The nematode was the dominant meiofauna species in the pockmark sediments. Both macro-lnfauna and total nematodes were in low abundance in samples taken from the base of the pockmark. Sediment samples from the pockmark contained numerous otoliths, implying that substantial winnowing of the sediment had taken place. This was supported by studies on the sulphide concentrations in the sediment which showed multiple layering of the sediments on the sides of the pockmark, suggesting displacement. The carbon isotope compositions (6I3c) of the tissues of benthic animals from in and around the pockmark were generally in the range -16 to -2O%, indicating that little methane-derived carbon was contributing to their nutrition. T sarsi had the most 13c-depleted tissues, -31.4 to -35.1 L, confirming the nutritional dependence of this species on chemoautotrophic bacteria that utilize reduced sulphur

Sparse, continuous policy representations for uniform online bin packing via regression of interpolants

Online bin packing is a classic optimisation problem, widely tackled by heuristic methods. In addition to human-designed heuristic packing policies (e.g. first- or best- fit), there has been interest over the last decade in the automatic generation of policies. One of the main limitations of some previously-used policy representations is the trade-off between locality and granularity in the associated search space. In this article, we adopt an interpolation-based representation which has the jointly-desirable properties of being sparse and continuous (i.e. exhibits good genotype-to-phenotype locality). In contrast to previous approaches, the policy space is searchable via real-valued optimization methods. Packing policies using five different interpolation methods are comprehensively compared against a range of existing methods from the literature, and it is determined that the proposed method scales to larger instances than those in the literature

Serum levels of mature microRNAs in DICER1-mutated pleuropulmonary blastoma.

DICER1 is a critical gene in the biogenesis of mature microRNAs, short non-coding RNAs that derive from either -3p or -5p precursor microRNA strands. Germline mutations of DICER1 are associated with a range of human malignancies, including pleuropulmonary blastoma (PPB). Additional somatic 'hotspot' mutations in the microRNA processing ribonuclease IIIb (RNase IIIb) domain of DICER1 are reported in cancer, and which affect microRNA biogenesis, resulting in a -3p mature microRNA strand bias. Here, in a germline (exon11 c.1806_1810insATTGA) DICER1-mutated PPB, we first confirmed the presence of an additional somatic RNase IIIb hotspot mutation (exon25 c.5425G>A [p.G1809R]) by conventional sequencing. Second, we investigated serum levels of mature microRNAs at the time of PPB diagnosis, and compared the findings with serum results from a comprehensive range of pediatric cancer patients and controls (n=52). We identified a panel of 45 microRNAs that were present at elevated levels in the serum at the time of PPB diagnosis, with a significant majority noted be derived from the -3p strand (P=0.013). In addition, we identified a subset of 10 serum microRNAs (namely miR-125a-3p, miR-125b-2-3p, miR-380-5p, miR-125b-1-3p, let-7f-2-3p, let-7a-3p, let-7b-3p, miR-708-3p, miR-138-1-3p and miR-532-3p) that were most abundant in the PPB case. Serum levels of two representative microRNAs, miR-125a-3p and miR-125b-2-3p, were not elevated in DICER1 germline-mutated relatives. In the PPB case, serum levels of miR-125a-3p and miR-125b-2-3p increased before chemotherapy, and then showed an early reduction following treatment. These microRNAs may offer future utility as serum biomarkers for screening patients with known germline DICER1 mutations for early detection of PPB, and for potential disease-monitoring in cases with confirmed PPB.We would like to thank the following for providing financial support: SPARKS (NC, MJM), Medical Research Council Fellowship (MJM), TD Bank/LDI scholarship (LdK), Alex’s Lemonade Stand Foundation (WDF), Cancer Research UK (NC) and European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement No. 310018 (MT).This is the final published version. It first appeared at http://www.nature.com/oncsis/journal/v3/n2/full/oncsis20141a.html

Safety and efficacy of an engineered hepatotropic AAV gene therapy for ornithine transcarbamylase deficiency in cynomolgus monkeys

X-linked inherited ornithine transcarbamylase deficiency (OTCD) is the most common disorder affecting the liver-based urea cycle, a pathway enabling detoxification of nitrogen waste and endogenous arginine biosynthesis. Patients develop acute hyperammonemia leading to neurological sequelae or death despite the best-accepted therapy based on ammonia scavengers and protein-restricted diet. Liver transplantation is curative but associated with procedure-related complications and lifelong immunosuppression. Adeno-associated viral (AAV) vectors have demonstrated safety and clinical benefits in a rapidly growing number of clinical trials for inherited metabolic liver diseases. Engineered AAV capsids have shown promising enhanced liver tropism. Here, we conducted a good-laboratory practice-compliant investigational new drug-enabling study to assess the safety of intravenous liver-tropic AAVLK03 gene transfer of a human codon-optimized OTC gene. Juvenile cynomolgus monkeys received vehicle and a low and high dose of vector (2 × 1012 and 2 × 1013 vector genome (vg)/kg, respectively) and were monitored for 26 weeks for in-life safety with sequential liver biopsies at 1 and 13 weeks post-vector administration. Upon completion of monitoring, animals were euthanized to study vector biodistribution, immune responses, and histopathology. The product was well tolerated with no adverse clinical events, predominant hepatic biodistribution, and sustained supra-physiological OTC overexpression. This study supports the clinical deployment of intravenous AAVLK03 for severe OTCD

Caspase-2-Mediated Cleavage of Mdm2 Creates a p53-Induced Positive Feedback Loop

Caspase-2 is an evolutionarily conserved caspase, yet its biological function and cleavage targets are poorly understood. Caspase-2 is activated by the p53 target gene product PIDD (also known as LRDD) in a complex called the Caspase-2-PIDDosome. We show that PIDD expression promotes growth arrest and chemotherapy resistance by a mechanism that depends on Caspase-2 and wild-type p53. PIDD-induced Caspase-2 directly cleaves the E3 ubiquitin ligase Mdm2 at Asp 367, leading to loss of the C-terminal RING domain responsible for p53 ubiquitination. As a consequence, N-terminally truncated Mdm2 binds p53 and promotes its stability. Upon DNA damage, p53 induction of the Caspase-2-PIDDosome creates a positive feedback loop that inhibits Mdm2 and reinforces p53 stability and activity, contributing to cell survival and drug resistance. These data establish Mdm2 as a cleavage target of Caspase-2 and provide insight into a mechanism of Mdm2 inhibition that impacts p53 dynamics upon genotoxic stress.Virginia and D.K. Ludwig Fund for Cancer Research (Postdoctoral Fellowship)Human Frontier Science Program (Strasbourg, France) (Fellowship)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD