Supercomputing with MPI meets the Common Workflow Language standards: an experience report

Use of standards-based workflows is still somewhat unusual by high-performance computing users. In this paper we describe the experience of using the Common Workflow Language (CWL) standards to describe the execution, in parallel, of MPI-parallelised applications. In particular, we motivate and describe the simple extension to the specification which was required, as well as our implementation of this within the CWL reference runner. We discuss some of the unexpected benefits, such as simple use of HPC-oriented performance measurement tools, and CWL software requirements interfacing with HPC module systems. We close with a request for comment from the community on how these features could be adopted within versions of the CWL standards.Comment: Submitted to 15th Workshop on Workflows in Support of Large-Scale Science (WORKS20

The nature of intraspecific and interspecific genome size variation in taxonomically complex eyebrights

Background and aims: Genome size varies considerably across the diversity of plant life. Although genome size is, by definition, affected by genetic presence/absence variants, which are ubiquitous in population sequencing studies, genome size is often treated as an intrinsic property of a species. Here, we studied intra- and interspecific genome size variation in taxonomically complex British eyebrights (Euphrasia, Orobanchaceae). Our aim is to document genome size diversity and investigate underlying evolutionary processes shaping variation between individuals, populations and species. Methods: We generated genome size data for 192 individuals of diploid and tetraploid Euphrasia and analysed genome size variation in relation to ploidy, taxonomy, population affiliation and geography. We further compared the genomic repeat content of 30 samples. Key results: We found considerable intraspecific genome size variation, and observed isolation-by-distance for genome size in outcrossing diploids. Tetraploid Euphrasia showed contrasting patterns, with genome size increasing with latitude in outcrossing Euphrasia arctica, but with little genome size variation in the highly selfing Euphrasia micrantha. Interspecific differences in genome size and the genomic proportions of repeat sequences were small. Conclusions: We show the utility of treating genome size as the outcome of polygenic variation. Like other types of genetic variation, such as single nucleotide polymorphisms, genome size variation may be affected by ongoing hybridization and the extent of population subdivision. In addition to selection on associated traits, genome size is predicted to be affected indirectly by selection due to pleiotropy of the underlying presence/absence variants.A.D.T. is supported by NERC research grants NE/L011336/1 and NE/N006739/1. The Royal Botanic Garden Edinburgh (RBGE) is supported by the Scottish Government’s Rural and Environment Science and Analytical Services Division. J.P. is supported by a Ramón y Cajal Fellowship (RYC-2017–2274) funded by the Ministerio de Ciencia y Tecnología (Gobierno de España).Issue Cover Volume 128Issue 5 8 October 2021 Article Contents Abstract INTRODUCTION METHODS The study system Population and species-level genome size variation Population sampling Genome size measurements Repeat content variation Sequence data generation Repeat content Statistical analyses Data availability RESULTS Population and species-level genome size variation Variation in genomic repeat content DISCUSSION Genome size variation mirrors population genetic patterns Genome size differences and genomic repeats Evolution of genome size variation SUPPLEMENTARY DATA ACKNOWLEDGEMENTS FUNDING LITERATURE CITED Supplementary dat

Brane/flux annihilation transitions and nonperturbative moduli stabilization

By extending the calculation of Kahler moduli stabilization to account for an embiggened antibrane, we reevaluate brane/flux annihilation in a warped throat with one stabilized Kahler modulus. We find that depending on the relative size of various fluxes three things can occur: the decay process proceeds unhindered, the anti-D3-branes are forbidden to decay classically, or the entire space decompactifies. Additionally, we show that the Kahler modulus receives a contribution from the collective 3-brane tension. This allows for a significant change in compactified volume during the transition and possibly mitigates some fine tuning otherwise required to achieve large volume.Comment: 25 pages, 6 figures, LaTeX. v2: references adde

Calcitriol suppression of parathyroid hormone fails to improve skeletal properties in an animal model of chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH. METHODS: Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality). RESULTS: PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties. CONCLUSIONS: These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton

Bone cell-independent benefits of raloxifene on the skeleton: A novel mechanism for improving bone material properties

Authors' accepted manuscript. Bone Biology Laboratory http://www.iupui.edu/~bonelab/ Department of Anatomy and Cell Biology Indiana University School of Medicine Department of Biomedical Engineering IUPUIRaloxifene is an FDA approved agent used to treat bone loss and decrease fracture risk. In clinical trials and animal studies, raloxifene reduces fracture risk and improves bone mechanical properties, but the mechanisms of action remain unclear because these benefits occur largely independent of changes to bone mass. Using a novel experimental approach, machined bone beams, both from mature male canine and human male donors, were depleted of living cells and then exposed to raloxifene ex vivo. Our data show that ex vivo exposure of non-viable bone to raloxifene improves intrinsic toughness, both in canine and human cortical bone beams tested by 4-point bending. These effects are cell-independent and appear to be mediated by an increase in matrix bound water, assessed using basic gravimetric weighing and sophisticated ultrashort echo time magnetic resonance imaging. The hydroxyl groups (-OH) on raloxifene were shown to be important in both the water and toughness increases. Wide and small angle x-ray scattering patterns during 4-pt bending show that raloxifene alters the transfer of load between the collagen matrix and the mineral crystals, placing lower strains on the mineral, and allowing greater overall deformation prior to failure. Collectively, these findings provide a possible mechanistic explanation for the therapeutic effect of raloxifene and more importantly identify a cell-independent mechanism that can be utilized for novel pharmacological approaches for enhancing bone strength.The authors would like to thank Dr. Paul K. Hansma (Department of Physics, University of California, Santa Barbara), for suggesting the soaking technique and Dr. John Okasinski, Advanced Photon Source, for helping collect the WAXS data. Raloxifene was kindly provided by Eli Lilly (Indianapolis, IN, USA) under a Material Transfer Agreement to D.B.B. Eli Lilly was not involved in the study design, analyses or interpretation of the results. We are grateful to Dr. Susan J. Gunst for sharing dog tissue. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. This work was supported by NIH grants to D.B.B. and M.R.A

Multi-domain interventions for dementia prevention–a systematic review

Objectives: There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may individually or collectively be undertaken to increase one’s odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia. Design, Setting and Participants: This systematic literature review of multidomain lifestyle interventions for the prevention of cognitive decline and dementia followed the PRISMA guidelines. Clinical trials involving multidomain intervention (i.e., diet and physical activity, or without cognitive training) in older adults ( ≥ 49 years old) at higher risk of dementia were identified through 5 electronic databases (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus). A comprehensive search was performed to identify and retrieve publications until 15 November 2022. Trials were published in English. Results: The included studies (n=15) assessed change in cognition in response to a multidomain lifestyle intervention. However, the cognitive outcome measures used in these studies were heterogeneous. Despite this heterogeneity, two thirds of the studies showed improvement in cognition following a multidomain intervention (n=10 with a total of 9,439 participants). However, five studies reported no improvement in cognition following the multidomain intervention. The most common form of dietary intervention included higher amount of fruit and vegetable intake; whole-grain cereal products instead of refined; low fat options in milk and meat products; and limiting sucrose intake to less than 50 g/day. Most clinical trial studies were powered to examining the effects of multidomain interventions in cognition but were not designed to test the contribution of individual domains (i.e., dietary changes, increased physical activity, or increased cognitive stimulation alone). Conclusion: This systematic review aimed to determine the effect of multimodal lifestyle interventions on cognitive outcomes in older adults at risk of dementia. We found that participants with conditions that may increase the risk of dementia, (e.g., hypertension, cardiovascular fragility) do benefit from multi-modal lifestyle changes including diet, physical activity, and cognitive training. Two thirds of studies using multidomain lifestyle interventions showed improvements in cognitive function. Trials with a focus on cognitive training, dietary improvement, and physical activity may prevent or delay cognitive decline in older adults including those at risk of developing dementia. Future studies should consider longer follow-up periods and adequate power to be able to examine the effects of each lifestyle component in the context of multimodal interventions

Transport properties of heterogeneous materials derived from Gaussian random fields: Bounds and Simulation

We investigate the effective conductivity ($\sigma_e$) of a class of amorphous media defined by the level-cut of a Gaussian random field. The three point solid-solid correlation function is derived and utilised in the evaluation of the Beran-Milton bounds. Simulations are used to calculate $\sigma_e$ for a variety of fields and volume fractions at several different conductivity contrasts. Relatively large differences in $\sigma_e$ are observed between the Gaussian media and the identical overlapping sphere model used previously as a `model' amorphous medium. In contrast $\sigma_e$ shows little variability between different Gaussian media.Comment: 15 pages, 14 figure

Self-help educational booklets for the prevention of smoking relapse following smoking cessation treatment: a randomized controlled trial.

AIMS: Most people who quit smoking for a short term will return to smoking again in 12 months. We tested whether self-help booklets can reduce relapse in short-term quitters after receiving behavioural and pharmacological cessation treatment. DESIGN: A parallel-arm, pragmatic individually randomized controlled trial. SETTING: Smoking cessation clinics in England. Participants People who stopped smoking for 4 weeks after receiving cessation treatment in stop smoking clinics. INTERVENTION: Participants in the experimental group (n=703) were mailed eight booklets, each of which taught readers how to resist urges to smoke. Participants in the control group (n=704) received a leaflet currently used in practice. MEASUREMENTS: The primary outcome was prolonged, carbon monoxide-verified abstinence from months 4 to 12. The secondary outcomes included 7-day self-reported abstinence at 3 and 12 months. Mixed-effects logistic regression was used to estimate treatment effects and to investigate possible effect modifying variables. FINDINGS: There were no statistically significant differences between the groups in prolonged abstinence from months 4 to 12 (36.9% versus 38.6%; odds ratio 0.93, 95% confidence interval 0.75-1.16; P=0.524). In addition, there were no significant differences between the groups in any secondary outcomes. However, people who reported knowing risky situations for relapse and using strategies to handle urges to smoke were less likely to relapse. CONCLUSIONS: In people who stop smoking successfully with behavioural support, a comprehensive self-help educational programme to teach people skills to identify and respond to high-risk situations for return to smoking did not reduce relapse