Weighted Modal Transition Systems

Specification theories as a tool in model-driven development processes of component-based software systems have recently attracted a considerable attention. Current specification theories are however qualitative in nature, and therefore fragile in the sense that the inevitable approximation of systems by models, combined with the fundamental unpredictability of hardware platforms, makes it difficult to transfer conclusions about the behavior, based on models, to the actual system. Hence this approach is arguably unsuited for modern software systems. We propose here the first specification theory which allows to capture quantitative aspects during the refinement and implementation process, thus leveraging the problems of the qualitative setting. Our proposed quantitative specification framework uses weighted modal transition systems as a formal model of specifications. These are labeled transition systems with the additional feature that they can model optional behavior which may or may not be implemented by the system. Satisfaction and refinement is lifted from the well-known qualitative to our quantitative setting, by introducing a notion of distances between weighted modal transition systems. We show that quantitative versions of parallel composition as well as quotient (the dual to parallel composition) inherit the properties from the Boolean setting.Comment: Submitted to Formal Methods in System Desig

Pits and fissures: Relative space contribution in fissures from sealants, prophylaxis pastes and organic remnants

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Previous studies by the authors have looked at the nature of the fissure system of human permanent molars and premolars, and has provided evidence for the presence of a prismless layer of enamel. It was noted during these studies that the fissure spaces were often occupied by material other than the fissure sealant. The aim of this study was to define these materials and to look at the percentage contribution of each to the sealed fissure space. MethodS: A sample of teeth, both molars and premolars, were sealed with an unfilled fissure sealant after prophylaxis with a coloured prophylaxis paste. In one group, the crown of the tooth was removed by dissolution in hydrochloric acid following placement of the sealant. This revealed a negative image of the fissure system and its contents. The second group of teeth was sectioned following sealing, and the contents of the fissure space were analyzed. Results: The negative image of the fissure system displayed the fissure contents by colour and the sectioned teeth were able to be computer analyzed to establish the relative contribution of sealant, prophylaxis paste and organic material to the fissure space. Conclusions: Sealant contribution was in the range of 14- 96 per cent, prophylaxis paste from 0-50 per cent and organic remnants 0-55 per cent. The presence of these last two components could contribute to sealant loss

Cyclebase.org: version 2.0, an updated comprehensive, multi-species repository of cell cycle experiments and derived analysis results

Cell division involves a complex series of events orchestrated by thousands of molecules. To study this process, researchers have employed mRNA expression profiling of synchronously growing cell cultures progressing through the cell cycle. These experiments, which have been carried out in several organisms, are not easy to access, combine and evaluate. Complicating factors include variation in interdivision time between experiments and differences in relative duration of each cell-cycle phase across organisms. To address these problems, we created Cyclebase, an online resource of cell-cycle-related experiments. This database provides an easy-to-use web interface that facilitates visualization and download of genome-wide cell-cycle data and analysis results. Data from different experiments are normalized to a common timescale and are complimented with key cell-cycle information and derived analysis results. In Cyclebase version 2.0, we have updated the entire database to reflect changes to genome annotations, included information on cyclin-dependent kinase (CDK) substrates, predicted degradation signals and loss-of-function phenotypes from genome-wide screens. The web interface has been improved and provides a single, gene-centric graph summarizing the available cell-cycle experiments. Finally, key information and links to orthologous and paralogous genes are now included to further facilitate comparison of cell-cycle regulation across species. Cyclebase version 2.0 is available at http://www.cyclebase.org

ENVIRONMENTS and EOL : identification of Environment Ontology terms in text and the annotation of the Encyclopedia of Life

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Bioinformatics 31 (2015): 1872-1874, doi:10.1093/bioinformatics/btv045.The association of organisms to their environments is a key issue in exploring biodiversity patterns. This knowledge has traditionally been scattered, but textual descriptions of taxa and their habitats are now being consolidated in centralized resources. However, structured annotations are needed to facilitate large-scale analyses. Therefore, we developed ENVIRONMENTS, a fast dictionary-based tagger capable of identifying Environment Ontology (ENVO) terms in text. We evaluate the accuracy of the tagger on a new manually curated corpus of 600 Encyclopedia of Life (EOL) species pages. We use the tagger to associate taxa with environments by tagging EOL text content monthly, and integrate the results into the EOL to disseminate them to a broad audience of users.The Encyclopedia Of Life Rubenstein Fellows Program [CRDF EOL-33066-13/E33066], the LifeWatchGreece Research Infrastructure [384676-94/GSRT/ NSRF(C&E)] and the Novo Nordisk Foundation Center for Protein Research [NNF14CC0001]

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

On the complexity of resource-bounded logics

We revisit decidability results for resource-bounded logics and use decision problems for vector addition systems with states (VASS) to characterise the complexity of (decidable) model-checking problems. We show that the model-checking problem for the logic RB+-ATL is 2EXPTIME-complete by using recent results on alternating VASS. In addition, we establish that the model-checking problem for RBTL is decidable and has the same complexity as for RBTL* (the extension of RBTL with arbitrary path formulae), namely EXPSPACE-complete, proving a new decidability result as a by-product of the approach. Finally, we establish that the model-checking problem for RB+-ATL* is decidable by a reduction to parity games, and show how to synthesise values for resource parameters

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