Using answer set programming to integrate RNA expression with signalling pathway information to infer how mutations affect ageing.

A challenge of systems biology is to integrate incomplete knowledge on pathways with existing experimental data sets and relate these to measured phenotypes. Research on ageing often generates such incomplete data, creating difficulties in integrating RNA expression with information about biological processes and the phenotypes of ageing, including longevity. Here, we develop a logic-based method that employs Answer Set Programming, and use it to infer signalling effects of genetic perturbations, based on a model of the insulin signalling pathway. We apply our method to RNA expression data from Drosophila mutants in the insulin pathway that alter lifespan, in a foxo dependent fashion. We use this information to deduce how the pathway influences lifespan in the mutant animals. We also develop a method for inferring the largest common sub-paths within each of our signalling predictions. Our comparisons reveal consistent homeostatic mechanisms across both long- and short-lived mutants. The transcriptional changes observed in each mutation usually provide negative feedback to signalling predicted for that mutation. We also identify an S6K-mediated feedback in two long-lived mutants that suggests a crosstalk between these pathways in mutants of the insulin pathway, in vivo. By formulating the problem as a logic-based theory in a qualitative fashion, we are able to use the efficient search facilities of Answer Set Programming, allowing us to explore larger pathways, combine molecular changes with pathways and phenotype and infer effects on signalling in in vivo, whole-organism, mutants, where direct signalling stimulation assays are difficult to perform. Our methods are available in the web-service NetEffects: http://www.ebi.ac.uk/thornton-srv/software/NetEffects

Implementation of standard testbeds for numerical relativity

We discuss results that have been obtained from the implementation of the initial round of testbeds for numerical relativity which was proposed in the first paper of the Apples with Apples Alliance. We present benchmark results for various codes which provide templates for analyzing the testbeds and to draw conclusions about various features of the codes. This allows us to sharpen the initial test specifications, design a new test and add theoretical insight.Comment: Corrected versio

Partial inhibition of RNA polymerase I promotes animal health and longevity

Health and survival in old age can be improved by changes in gene expression. RNA polymerase (Pol) I is the essential, conserved enzyme whose task is to generate the pre-ribosomal RNA (rRNA). We find that reducing the levels of Pol I activity is sufficient to extend lifespan in the fruit fly. This effect can be recapitulated by partial, adult-restricted inhibition, with both enterocytes and stem cells of the adult midgut emerging as important cell types. In stem cells, Pol I appears to act in the same longevity pathway as Pol III, implicating rRNA synthesis in these cells as the key lifespan determinant. Importantly, reduction in Pol I activity delays broad, age-related impairment and pathology, improving the function of diverse organ systems. Hence, our study shows that Pol I activity in the adult drives systemic, age-related decline in animal health and anticipates mortality

Secure Real-Time Monitoring and Management of Smart Distribution Grid Using Shared Cellular Network

The electricity production and distribution is facing two major changes. First, the production is shifting from classical energy sources such as coal and nuclear power towards renewable resources such as solar and wind. Secondly, the consumption in the low voltage grid is expected to grow significantly due to expected introduction of electrical vehicles. The first step towards more efficient operational capabilities is to introduce an observability of the distribution system and allow for leveraging the flexibility of end connection points with manageable consumption, generation and storage capabilities. Thanks to the advanced measurement devices, management framework, and secure communication infrastructure developed in the FP7 SUNSEED project, the Distribution System Operator (DSO) now has full observability of the energy flows at the medium/low voltage grid. Furthermore, the prosumers are able to participate pro-actively and coordinate with the DSO and other stakeholders in the grid. The monitoring and management functionalities have strong requirements to the communication latency, reliability and security. This paper presents novel solutions and analyses of these aspects for the SUNSEED scenario, where the smart grid ICT solutions are provided through shared cellular LTE networks

Potential role of the geriatric nutritional risk index as a novel risk factor for the development of non-valvular atrial fibrillation in patients with heart failure

PURPOSE: The geriatric nutritional risk index (GNRI) is a simple and objective nutritional assessment tool for elderly patients. Lower GNRI values are associated with a worse prognosis in heart failure with reduced ejection fraction (HFrEF). Our aim is to investigate the relationship between malnutrition and follow-up cardiovascular (CV) events in HFrEF. METHODS: A retrospective study was performed on 362 patients with HFrEF. The baseline GNRI was calculated at the first visit. The patients were divided into three groups according to the GNRI: >98, no-risk group; 92 to <= 98, low risk group; 82 to <92, moderate-to-high-risk group. The study endpoint was a composite of follow-up CV events, including all-cause mortality, non-valvular atrial fibrillation (NVAF) , need for cardioverter defibrillator (ICD) therapy, HfrEF-related hospitalizations and need for percutaneous coronary interventions (PCIs). RESULTS: Follow-up data showed that the group with moderate-to-high risk had a significantly higher incidence of NVAF, PCIs and all-cause mortality compared to other groups (p0.05). Mean GNRI value was 83.3 in NVAF patients and 101.1 in patients without NVAF (p<0.001). Kaplan Meier survival analysis showed that patients from the group with moderate-to-high risk had a significantly worse survival rate (p < 0.001). In the multivariate Cox regression analysis, the group with moderate-to-high risk (HR =3.872) and ICD implantations (HR = 4.045) were associated with increased mortality. CONCLUSION: The GNRI value may have a potential role for predicting future events, especially NVAF in patients with HfrEF