Population Fluctuation Promotes Cooperation in Networks

We consider the problem of explaining the emergence and evolution of cooperation in dynamic network-structured populations. Building on seminal work by Poncela et al, which shows how cooperation (in one-shot prisoner's dilemma) is supported in growing populations by an evolutionary preferential attachment (EPA) model, we investigate the effect of fluctuations in the population size. We find that the fluctuating model is more robust than Poncela et al's in that cooperation flourishes for a wide variety of initial conditions. In terms of both the temptation to defect, and the types of strategies present in the founder network, the fluctuating population is found to lead more securely to cooperation. Further, we find that this model will also support the emergence of cooperation from pre-existing non-cooperative random networks. This model, like Poncela et al's, does not require agents to have memory, recognition of other agents, or other cognitive abilities, and so may suggest a more general explanation of the emergence of cooperation in early evolutionary transitions, than mechanisms such as kin selection, direct and indirect reciprocity.Comment: Published in Nature Scientific Reports 201

Genetic Testing and Risk Scores: Impact on Familial Hypercholesterolemia

Familial Hypercholesterolemia (FH) is an inherited lipid disorder affecting 1 in 220 individuals resulting in highly elevated low-density lipoprotein levels and risk of premature coronary disease. Pathogenic variants causing FH typically involve the LDL receptor (LDLR), apolipoprotein B-100 (APOB), and proprotein convertase subtulisin/kexin type 9 genes (PCSK9) and if identified convey a risk of early onset coronary artery disease (ASCVD) of 3- to 10-fold vs. the general population depending on the severity of the mutation. Identification of monogenic FH within a family has implications for family-based testing (cascade screening), risk stratification, and potentially management, and it has now been recommended that such testing be offered to all potential FH patients. Recently, robust genome wide association studies (GWAS) have led to the recognition that the accumulation of common, small effect alleles affecting many LDL-c raising genes can result in a clinical phenotype largely indistinguishable from monogenic FH (i.e., a risk of early onset ASCVD of ~3-fold) in those at the extreme tail of the distribution for these alleles (i.e., the top 8% of the population for a polygenic risk score). The incorporation of these genetic risk scores into clinical practice for non-FH patients may improve risk stratification but is not yet widely performed due to a less robust evidence base for utility. Here, we review the current status of FH genetic testing, potential future applications as well as challenges and pitfalls

Genetic Modifiers of Atherosclerosis in Mice

Atherosclerosis is a complex, multifactorial disease with both genetic and environmental determinants. Experimental investigation of the effects of these determinants on the development and progression of atherosclerosis has been greatly facilitated by the use of targeted mouse models of the disease, particularly those resulting from the absence of functional genes for apolipoprotein E or the low density lipoprotein receptor (LDLR). This review focuses on the influence on atherosclerosis of combining apoE or LDLR deficiencies with factors affecting atherogenesis, including (1) inflammatory processes, (2) glucose metabolism, (3) blood pressure, and (4) coagulation and fibrinolysis. We also discuss the general problem of using the mouse to test the effects on atherogenesis of human polymorphic variations and future ways of enhancing the usefulness of these mouse models

Statistical analysis of activation and reaction energies with quasi-variational coupled-cluster theory

The performance of quasi-variational coupled-cluster (QV) theory applied to the calculation of activation and reaction energies has been investigated. A statistical analysis of results obtained for six different sets of reactions has been carried out, and the results have been compared to those from standard single-reference methods. In general, the QV methods lead to increased activation energies and larger absolute reaction energies compared to those obtained with traditional coupled-cluster theory

Comparing Multi-objective and Threshold-moving ROC Curve Generation for a Prototype-based Classifier

Proceedings of: GECCO 2013: 15th International Conference on Genetic and Evolutionary Computation Conference (Amsterdam, The Netherlands, July 06-10, 2013): a recombination of the 22nd International Conference on Genetic Algorithms (ICGA) and the 18th Annual Genetic Programming Conference (GP), Amsterdam, The Netherlands, July 06-10, 2013Receiver Operating Characteristics (ROC) curves represent the performance of a classifier for all possible operating con-ditions, i.e., for all preferences regarding the tradeoff be-tween false positives and false negatives. The generation of a ROC curve generally involves the training of a single classifier for a given set of operating conditions, with the subsequent use of threshold-moving to obtain a complete ROC curve. Recent work has shown that the generation of ROC curves may also be formulated as a multi-objective optimization problem in ROC space: the goals to be min-imized are the false positive and false negative rates. This technique also produces a single ROC curve, but the curve may derive from operating points for a number of different classifiers. This paper aims to provide an empirical compar-ison of the performance of both of the above approaches, for the specific case of prototype-based classifiers. Results on synthetic and real domains shows a performance advantage for the multi-objective approach.GECCO 2013 Presentation slidesThis work has been funded by the Spanish Ministry of Science under contract TIN2011-28336 (MOVES project)En prens

Artefacts and biases affecting the evaluation of scoring functions on decoy sets for protein structure prediction

Motivation: Decoy datasets, consisting of a solved protein structure and numerous alternative native-like structures, are in common use for the evaluation of scoring functions in protein structure prediction. Several pitfalls with the use of these datasets have been identified in the literature, as well as useful guidelines for generating more effective decoy datasets. We contribute to this ongoing discussion an empirical assessment of several decoy datasets commonly used in experimental studies