Hypergraph-based parallel computation of passage time densities in large semi-Markov models

AbstractPassage time densities and quantiles are important performance and quality of service metrics, but their numerical derivation is, in general, computationally expensive. We present an iterative algorithm for the calculation of passage time densities in semi-Markov models, along with a theoretical analysis and empirical measurement of its convergence behaviour. In order to implement the algorithm efficiently in parallel, we use hypergraph partitioning to minimise communication between processors and to balance workloads. This enables the analysis of models with very large state spaces which could not be held within the memory of a single machine. We produce passage time densities and quantiles for very large semi-Markov models with over 15 million states and validate the results against simulation

Performance queries on Semi-Markov Stochastic Petri nets with an extended continuous Stochastic logic

Semi-Markov Stochastic Petri Nets (SM-SPNs) are a highlevel formalism for defining semi-Markov processes. We present an extended Continuous Stochastic Logic (eCSL) which provides an expressive way to articulate performance queries at the SM-SPN model level. eCSL supports queries involving steady-state, transient and passage time measures. We demonstrate this by formulating and answering eCSL queries on an SM-SPN model of a distributed voting system with up to ¢¤£¦ ¥ states.

Derivation of passage-time densities in PEPA models using ipc: the imperial PEPA compiler

We present a technique for defining and extracting passage-time densities from high-level stochastic process algebra models. Our high-level formalism is PEPA, a popular Markovian process algebra for expressing compositional performance models. We introduce ipc, a tool which can process PEPA-specified passage-time densities and models by compiling the PEPA model and passage specification into the DNAmaca formalism. DNAmaca is an established modelling language for the low-level specification of very large Markov and semi-Markov chains. We provide performance results for ipc/DNAmaca and comparisons with another tool which supports PEPA, PRISM. Finally, we generate passage-time densities and quantiles for a case study of a high-availability web server. 1

Efficacy of High Dose Vitamin D Supplements for Elite Athletes.

PURPOSE: Supplementation with dietary forms of vitamin D is commonplace in clinical medicine, elite athletic cohorts and the general population, yet the response of all major vitamin D metabolites to high doses of vitamin D is poorly characterized. We aimed to identify the responses of all major vitamin D metabolites to moderate and high dose supplemental vitamin D3. METHODS: A repeated measures design was implemented in which 46 elite professional European athletes were block randomized based on their basal 25[OH]D concentration into two treatment groups. Athletes received either 35,000 or 70,000 IU.week vitamin D3 for 12 weeks and 42 athletes completed the trial. Blood samples were collected over 18 weeks to monitor the response to supplementation and withdrawal from supplementation. RESULTS: Both doses led to significant increases in serum 25[OH]D and 1,25[OH]2D3. 70,000 IU.week also resulted in a significant increase of the metabolite 24,25[OH]2D at weeks 6 and 12 that persisted following supplementation withdrawal at week 18, despite a marked decrease in 1,25[OH]2D3. Intact PTH was decreased in both groups by week 6 and remained suppressed throughout the trial. CONCLUSIONS: High dose vitamin D3 supplementation (70,000 IU.week) may be detrimental for its intended purposes due to increased 24,25[OH]2D production. Rapid withdrawal from high dose supplementation may inhibit the bioactivity of 1,25[OH]2D3 as a consequence of sustained increases in 24,25[OH]2D that persist as 25[OH]D and 1,25[OH]2D concentrations decrease. These data imply that lower doses of vitamin D3 ingested frequently may be most appropriate and gradual withdrawal from supplementation as opposed to rapid withdrawal may be favorable

The Assessment of Total Energy Expenditure During a 14-Day In-Season Period of Professional Rugby League Players Using the Doubly Labelled Water Method

Rugby League is a high-intensity collision sport competed over 80 min. Training loads are monitored to maximize recovery and assist in the design of nutritional strategies although no data are available on the total energy expenditure (TEE) of players. We therefore assessed resting metabolic rate (RMR) and TEE in six Super League players over 2 consecutive weeks in-season including one game per week. Fasted RMR was assessed followed by a baseline urine sample before oral administration of a bolus dose of hydrogen (deuterium 2H) and oxygen (18O) stable isotopes in the form of water (2H218O). Every 24 hr thereafter, players provided urine for analysis of TEE via DLW method. Individual training load was quantified using session rating of perceived exertion (sRPE) and data were analyzed using magnitude-based inferences. There were unclear differences in RMR between forwards and backs (7.7 ± 0.5 cf. 8.0 ± 0.3 MJ, respectively). Indirect calorimetry produced RMR values most likely lower than predictive equations (7.9 ± 0.4 cf. 9.2 ± 0.4 MJ, respectively). A most likely increase in TEE from Week 1 to 2 was observed (17.9 ± 2.1 cf. 24.2 ± 3.4 MJ) explained by a most likelyincrease in weekly sRPE (432 ± 19 cf. 555 ± 22 AU), respectively. The difference in TEE between forward and backs was unclear (21.6 ± 4.2 cf. 20.5 ± 4.9 MJ, respectively). We report greater TEE than previously reported in rugby that could be explained by the ability of DLW to account for all match and training-related activities that contributes to TEE

Ultrasound Does Not Detect Acute Changes in Glycogen in Vastus Lateralis of Man.

PURPOSE: To examine the validity of ultrasound (via cloud based software that measures pixilation intensity according to a scale of 0-100) to non-invasively assess muscle glycogen in human skeletal muscle. METHODS: In Study 1, 14 professional male rugby league players competed in an 80-minute competitive rugby league game. In Study 2 (in a randomized repeated measures design), 16 recreationally active males completed an exhaustive cycling protocol to deplete muscle glycogen followed by 36 hours of HIGH or LOW carbohydrate intake (8 v 3 g.kg body mass). In both studies, muscle biopsies and ultrasound scans were obtained from the vastus lateralis (at 50% of the muscle length) before and after match play in Study 1 and at 36 h after glycogen depletion in Study 2. RESULTS: Despite match play reducing (P0.05) were present between changes in muscle glycogen concentration and changes in ultrasound scores. CONCLUSION: Data demonstrate that ultrasound (as based on measures of pixilation intensity) is not valid to measure muscle glycogen status within the physiological range (i.e. 200-500 mmol.kg dw) that is applicable to exercise-induced muscle glycogen utilization and post-exercise muscle glycogen re-synthesis

Shape-based peak identification for ChIP-Seq

We present a new algorithm for the identification of bound regions from ChIP-seq experiments. Our method for identifying statistically significant peaks from read coverage is inspired by the notion of persistence in topological data analysis and provides a non-parametric approach that is robust to noise in experiments. Specifically, our method reduces the peak calling problem to the study of tree-based statistics derived from the data. We demonstrate the accuracy of our method on existing datasets, and we show that it can discover previously missed regions and can more clearly discriminate between multiple binding events. The software T-PIC (Tree shape Peak Identification for ChIP-Seq) is available at http://math.berkeley.edu/~vhower/tpic.htmlComment: 12 pages, 6 figure

Developing and applying heterogeneous phylogenetic models with XRate

Modeling sequence evolution on phylogenetic trees is a useful technique in computational biology. Especially powerful are models which take account of the heterogeneous nature of sequence evolution according to the "grammar" of the encoded gene features. However, beyond a modest level of model complexity, manual coding of models becomes prohibitively labor-intensive. We demonstrate, via a set of case studies, the new built-in model-prototyping capabilities of XRate (macros and Scheme extensions). These features allow rapid implementation of phylogenetic models which would have previously been far more labor-intensive. XRate's new capabilities for lineage-specific models, ancestral sequence reconstruction, and improved annotation output are also discussed. XRate's flexible model-specification capabilities and computational efficiency make it well-suited to developing and prototyping phylogenetic grammar models. XRate is available as part of the DART software package: http://biowiki.org/DART .Comment: 34 pages, 3 figures, glossary of XRate model terminolog

Use of Ex Vivo Normothermic Perfusion for Quality Assessment of Discarded Human Donor Pancreases.

A significant number of pancreases procured for transplantation are deemed unsuitable due to concerns about graft quality and the associated risk of complications. However, this decision is subjective and some declined grafts may be suitable for transplantation. Ex vivo normothermic perfusion (EVNP) prior to transplantation may allow a more objective assessment of graft quality and reduce discard rates. We report ex vivo normothermic perfusion of human pancreases procured but declined for transplantation, with ABO-compatible warm oxygenated packed red blood cells for 1-2 h. Five declined human pancreases were assessed using this technique after a median cold ischemia time of 13 h 19 min. One pancreas, with cold ischemia over 30 h, did not appear viable and was excluded. In the remaining pancreases, blood flow and pH were maintained throughout perfusion. Insulin secretion was observed in all four pancreases, but was lowest in an older donation after cardiac death pancreas. Amylase levels were highest in a gland with significant fat infiltration. This is the first study to assess the perfusion, injury, as measured by amylase, and exocrine function of human pancreases using EVNP and demonstrates the feasibility of the approach, although further refinements are required.This study was financially supported by a grant from the Mason Medical Research Foundation.This is the author accepted manuscript. The final version is available via Wiley at http://onlinelibrary.wiley.com/doi/10.1111/ajt.13303/abstract