A framework for evolutionary systems biology

<p>Abstract</p> <p>Background</p> <p>Many difficult problems in evolutionary genomics are related to mutations that have weak effects on fitness, as the consequences of mutations with large effects are often simple to predict. Current systems biology has accumulated much data on mutations with large effects and can predict the properties of knockout mutants in some systems. However experimental methods are too insensitive to observe small effects.</p> <p>Results</p> <p>Here I propose a novel framework that brings together evolutionary theory and current systems biology approaches in order to quantify small effects of mutations and their epistatic interactions <it>in silico</it>. Central to this approach is the definition of fitness correlates that can be computed in some current systems biology models employing the rigorous algorithms that are at the core of much work in computational systems biology. The framework exploits synergies between the realism of such models and the need to understand real systems in evolutionary theory. This framework can address many longstanding topics in evolutionary biology by defining various 'levels' of the adaptive landscape. Addressed topics include the distribution of mutational effects on fitness, as well as the nature of advantageous mutations, epistasis and robustness. Combining corresponding parameter estimates with population genetics models raises the possibility of testing evolutionary hypotheses at a new level of realism.</p> <p>Conclusion</p> <p>EvoSysBio is expected to lead to a more detailed understanding of the fundamental principles of life by combining knowledge about well-known biological systems from several disciplines. This will benefit both evolutionary theory and current systems biology. Understanding robustness by analysing distributions of mutational effects and epistasis is pivotal for drug design, cancer research, responsible genetic engineering in synthetic biology and many other practical applications.</p

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Organ Donor Risk Stratification in Italy

The permanent gap between organ demand and supply has prompted use of organs from extended criteria donors (ECD). These carry a higher risk of disease transmission, with regard to infections and malignancies. We present herein the donor risk stratification algorithm implemented in Italy since 2004 for identification management of donor-to-recipient risk of disease transmission. The principles underlying this algorithm are: (1) the risk of disease transmission must be assessed against the potential benefit for the transplant recipient (i.e., no donor can be excluded from evaluation and their organs might benefit potential candidates); (2) patients awaiting organ transplantation must be informed that the risk of disease transmission is small but finite (standard risk); and (3) risk evaluation is an ongoing process based on information collected longitudinally after transplantation. Regional and national transplant authorities are committed to regular updating of guidelines based on clinical data derived from clinicians and on evaluation of posttransplant graft and patient survival rates

The associations between structural treatment characteristics and post-treatment functioning in compulsory residential youth care

Contains fulltext : 102944.pdf (publisher's version ) (Open Access)In 2005 a new compulsory residential treatment program was developed for adolescents in need for protection against themselves or their environment. The aim of the present study was to examine the association of structural treatment characteristics of this new residential treatment program (i.e., duration of treatment, discharge status, and group composition in terms of sex) with post-treatment functioning. Additionally, the number of pre-treatment risk factors was included in the model. A total of 301 adolescents (174 boys, 127 girls), with a mean age at time of admittance of 15.50 (SD = 1.26) participated in this study. The number of risk factors was derived from treatment files of the adolescents at time of entrance. Six months after discharge, adolescents participated in a telephone interview to measure ten post-treatment variables indicating how well they were doing. The results showed that duration of treatment was related to post-treatment living situation, in that adolescents who were in treatment for shorter durations were more likely to live on their own after treatment. For discharge status, findings suggested that adolescents who were regularly discharged had more frequent contact with their family; however, they also showed higher alcohol consumption 6 months after treatment. Group composition was related to the girls' official offending, indicating that girls placed in mixed-sex groups showed significantly fewer official police contacts than did girls in girls-only treatment groups. Overall, structural treatment characteristics were hardly related to the adolescents' functioning after treatment. Suggestions for future research are discussed.20 p