Fitness landscape of the cellular automata majority problem: View from the Olympus

In this paper we study cellular automata (CAs) that perform the computational Majority task. This task is a good example of what the phenomenon of emergence in complex systems is. We take an interest in the reasons that make this particular fitness landscape a difficult one. The first goal is to study the landscape as such, and thus it is ideally independent from the actual heuristics used to search the space. However, a second goal is to understand the features a good search technique for this particular problem space should possess. We statistically quantify in various ways the degree of difficulty of searching this landscape. Due to neutrality, investigations based on sampling techniques on the whole landscape are difficult to conduct. So, we go exploring the landscape from the top. Although it has been proved that no CA can perform the task perfectly, several efficient CAs for this task have been found. Exploiting similarities between these CAs and symmetries in the landscape, we define the Olympus landscape which is regarded as the ''heavenly home'' of the best local optima known (blok). Then we measure several properties of this subspace. Although it is easier to find relevant CAs in this subspace than in the overall landscape, there are structural reasons that prevent a searcher from finding overfitted CAs in the Olympus. Finally, we study dynamics and performance of genetic algorithms on the Olympus in order to confirm our analysis and to find efficient CAs for the Majority problem with low computational cost

Studying Parallel Evolutionary Algorithms: The cellular Programming Case

Parallel evolutionary algorithms, studied to some extent over the past few years, have proven empirically worthwhile—though there seems to be lacking a better understanding of their workings. In this paper we concentrate on cellular (fine-grained) models, presenting a number of statistical measures, both at the genotypic and phenotypic levels. We demonstrate the application and utility of these measures on a specific example, that of the cellular programming evolutionary algorithm, when used to evolve solutions to a hard problem in the cellular-automata domain, known as synchronization

Measure-valued differentiation for stationary Markov chains

http://staff.feweb.vu.nl/bheidergot

On RAF Sets and Autocatalytic Cycles in Random Reaction Networks

The emergence of autocatalytic sets of molecules seems to have played an important role in the origin of life context. Although the possibility to reproduce this emergence in laboratory has received considerable attention, this is still far from being achieved. In order to unravel some key properties enabling the emergence of structures potentially able to sustain their own existence and growth, in this work we investigate the probability to observe them in ensembles of random catalytic reaction networks characterized by different structural properties. From the point of view of network topology, an autocatalytic set have been defined either in term of strongly connected components (SCCs) or as reflexively autocatalytic and food-generated sets (RAFs). We observe that the average level of catalysis differently affects the probability to observe a SCC or a RAF, highlighting the existence of a region where the former can be observed, whereas the latter cannot. This parameter also affects the composition of the RAF, which can be further characterized into linear structures, autocatalysis or SCCs. Interestingly, we show that the different network topology (uniform as opposed to power-law catalysis systems) does not have a significantly divergent impact on SCCs and RAFs appearance, whereas the proportion between cleavages and condensations seems instead to play a role. A major factor that limits the probability of RAF appearance and that may explain some of the difficulties encountered in laboratory seems to be the presence of molecules which can accumulate without being substrate or catalyst of any reaction.Comment: pp 113-12

Scalar leptoquark production at TESLA and CLIC based e-gamma colliders

We study scalar leptoquark production at TESLA and CLIC based e-gamma colliders. Both direct and resolved contributions to the cross section are examined. We find that the masses of scalar leptoquarks can be probed up to about 0.9 TeV at TESLA and 2.6 TeV at CLIC.Comment: Misprints in equations are corrected. A careful spell check has been done.17 pages, 8 figure

Targeting and activation of Rac1 are mediated by the exchange factor β-Pix

Rho guanosine triphosphatases (GTPases) are critical regulators of cytoskeletal dynamics and control complex functions such as cell adhesion, spreading, migration, and cell division. It is generally accepted that localized GTPase activation is required for the proper initiation of downstream signaling events, although the molecular mechanisms that control targeting of Rho GTPases are unknown. In this study, we show that the Rho GTPase Rac1, via a proline stretch in its COOH terminus, binds directly to the SH3 domain of the Cdc42/Rac activator β-Pix (p21-activated kinase [Pak]–interacting exchange factor). The interaction with β-Pix is nucleotide independent and is necessary and sufficient for Rac1 recruitment to membrane ruffles and to focal adhesions. In addition, the Rac1–β-Pix interaction is required for Rac1 activation by β-Pix as well as for Rac1-mediated spreading. Finally, using cells deficient for the β-Pix–binding kinase Pak1, we show that Pak1 regulates the Rac1–β-Pix interaction and controls cell spreading and adhesion-induced Rac1 activation. These data provide a model for the intracellular targeting and localized activation of Rac1 through its exchange factor β-Pix

Continuation rates of alpha-blockers mono-therapy in adult men, prescribed by urologists or general practitioners:A pharmacy-based study

PURPOSE: α-Blockers are commonly used for the treatment of male lower urinary tract symptoms (LUTS). The Dutch GP guideline on male LUTS contains an advice to discontinue treatment after 3-6 months of successful treatment. The guideline for urologists does not support this advice. It is unclear if these differences lead to other patterns of (dis)continuation of α-blockers. We aim to study continuation rates of α-blockers, prescribed by a urologist or a general practitioner (GP), and to predict discontinuation after 1 year. METHODS: We conducted a retrospective inception cohort study on prescription patterns of α-blockers among Dutch men between 2006 and 2014, using the IADB.nl pharmacy prescription database from the University of Groningen. We selected men aged 30 years or older with a first α-blocker prescription between 2006 and 2013, and analysed continuation of prescriptions. RESULTS: The database included 12,191 individual patients with at least one α-blocker prescriptions from a urologist (44.5%) or a GP (55.5%). The median treatment period for patients who started in the GPs office was 210 days, compared to 150 days for patients with a prescription from a urologist. Of all patients, 60.3% (GP prescriptions) and 66.1% (urologists' prescriptions) had discontinued treatment (Chi-square p < 0.001). Discontinuation rates were age dependent with higher rates in the youngest age groups. CONCLUSION: In this study, the discontinuation rate 1 year after the initiation of treatment was high. Although Dutch GP's and urologist's guidelines differ with respect to a discontinuation advice, we could not find clinically relevant difference in (temporary) discontinuation rates