Programming patterns and development guidelines for Semantic Sensor Grids (SemSorGrid4Env)

The web of Linked Data holds great potential for the creation of semantic applications that can combine self-describing structured data from many sources including sensor networks. Such applications build upon the success of an earlier generation of 'rapidly developed' applications that utilised RESTful APIs. This deliverable details experience, best practice, and design patterns for developing high-level web-based APIs in support of semantic web applications and mashups for sensor grids. Its main contributions are a proposal for combining Linked Data with RESTful application development summarised through a set of design principles; and the application of these design principles to Semantic Sensor Grids through the development of a High-Level API for Observations. These are supported by implementations of the High-Level API for Observations in software, and example semantic mashups that utilise the API

Corticospinal and spinal adaptations to motor skill and resistance training: Potential mechanisms and implications for motor rehabilitation and athletic development.

Optimal strategies for enhancing strength and improving motor skills are vital in athletic performance and clinical rehabilitation. Initial increases in strength and the acquisition of new motor skills have long been attributed to neurological adaptations. However, early increases in strength may be predominantly due to improvements in inter-muscular coordination rather than the force-generating capacity of the muscle. Despite the plethora of research investigating neurological adaptations from motor skill or resistance training in isolation, little effort has been made in consolidating this research to compare motor skill and resistance training adaptations. The findings of this review demonstrated that motor skill and resistance training adaptations show similar short-term mechanisms of adaptations, particularly at a cortical level. Increases in corticospinal excitability and a release in short-interval cortical inhibition occur as a result of the commencement of both resistance and motor skill training. Spinal changes show evidence of task-specific adaptations from the acquired motor skill, with an increase or decrease in spinal reflex excitability, dependant on the motor task. An increase in synaptic efficacy of the reticulospinal projections is likely to be a prominent mechanism for driving strength adaptations at the subcortical level, though more research is needed. Transcranial electric stimulation has been shown to increase corticospinal excitability and augment motor skill adaptations, but limited evidence exists for further enhancing strength adaptations from resistance training. Despite the logistical challenges, future work should compare the longitudinal adaptations between motor skill and resistance training to further optimise exercise programming

nIFTy galaxy cluster simulations - IV. Quantifying the influence of baryons on halo properties

Building on the initial results of the nIFTy simulated galaxy cluster comparison, we compare and contrast the impact of baryonic physics with a single massive galaxy cluster, run with 11 state-of-the-art codes, spanning adaptive mesh, moving mesh, classic and modern smoothed particle hydrodynamics (SPH) approaches. For each code represented we have a dark-matteronly (DM) and non-radiative (NR) version of the cluster, as well as a full physics (FP) version for a subset of the codes. We compare both radial mass and kinematic profiles, as well as global measures of the cluster (e.g. concentration, spin, shape), in the NR and FP runs with that in the DM runs. Our analysis reveals good consistency (<≈ 20 per cent) between global properties of the cluster predicted by different codes when integrated quantities are measured within the virial radius R200. However, we see larger differences for quantities within R2500, especially in the FP runs. The radial profiles reveal a diversity, especially in the cluster centre, between the NR runs, which can be understood straightforwardly from the division of codes into classic SPH and non-classic SPH (including the modern SPH, adaptive and moving mesh codes); and between the FP runs, which can also be understood broadly from the division of codes into those that include active galactic nucleus feedback and those that do not. The variation with respect to the median is much larger in the FP runs with different baryonic physics prescriptions than in the NR runs with different hydrodynamics solvers

nIFTy galaxy cluster simulations – I. Dark matter and non-radiative models

We have simulated the formation of a galaxy cluster in a Ʌ cold dark matter universe using 13 different codes modelling only gravity and non-radiative hydrodynamics (RAMSES, ART, AREPO, HYDRA and nine incarnations of GADGET). This range of codes includes particle-based, moving and fixed mesh codes as well as both Eulerian and Lagrangian fluid schemes. The various GADGET implementations span classic and modern smoothed particle hydrodynamics (SPH) schemes. The goal of this comparison is to assess the reliability of cosmological hydrodynamical simulations of clusters in the simplest astrophysically relevant case, that in which the gas is assumed to be non-radiative. We compare images of the cluster at z = 0, global properties such as mass and radial profiles of various dynamical and thermodynamical quantities. The underlying gravitational framework can be aligned very accurately for all the codes allowing a detailed investigation of the differences that develop due to the various gas physics implementations employed. As expected, the mesh-based codes RAMSES, ART and AREPO form extended entropy cores in the gas with rising central gas temperatures. Those codes employing classic SPH schemes show falling entropy profiles all the way into the very centre with correspondingly rising density profiles and central temperature inversions. We show that methods with modern SPH schemes that allow entropy mixing span the range between these two extremes and the latest SPH variants produce gas entropy profiles that are essentially indistinguishable from those obtained with grid-based methods

Mesenchymal tumor organoid models recapitulate rhabdomyosarcoma subtypes

Rhabdomyosarcomas (RMS) are mesenchyme-derived tumors and the most common childhood soft tissue sarcomas. Treatment is intense, with a nevertheless poor prognosis for high-risk patients. Discovery of new therapies would benefit from additional preclinical models. Here, we describe the generation of a collection of 19 pediatric RMS tumor organoid (tumoroid) models (success rate of 41%) comprising all major subtypes. For aggressive tumors, tumoroid models can often be established within 4-8 weeks, indicating the feasibility of personalized drug screening. Molecular, genetic, and histological characterization show that the models closely resemble the original tumors, with genetic stability over extended culture periods of up to 6 months. Importantly, drug screening reflects established sensitivities and the models can be modified by CRISPR/Cas9 with TP53 knockout in an embryonal RMS model resulting in replicative stress drug sensitivity. Tumors of mesenchymal origin can therefore be used to generate organoid models, relevant for a variety of preclinical and clinical research questions

A Genome-Wide Association Study of Female Sexual Dysfunction

PMCID: PMC3324410. CCBurri LC et al.PLOS Genet Doi:10.1371/journal.pone.0035041Female sexual dysfunction (FSD) is an important but controversial problem with serious negative impact on women's quality of life. Data from twin studies have shown a genetic contribution to the development and maintenance of FSD

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

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN