Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

A memetic algorithm with adaptive hill climbing strategy for dynamic optimization problems

Copyright @ Springer-Verlag 2008Dynamic optimization problems challenge traditional evolutionary algorithms seriously since they, once converged, cannot adapt quickly to environmental changes. This paper investigates the application of memetic algorithms, a class of hybrid evolutionary algorithms, for dynamic optimization problems. An adaptive hill climbing method is proposed as the local search technique in the framework of memetic algorithms, which combines the features of greedy crossover-based hill climbing and steepest mutation-based hill climbing. In order to address the convergence problem, two diversity maintaining methods, called adaptive dual mapping and triggered random immigrants, respectively, are also introduced into the proposed memetic algorithm for dynamic optimization problems. Based on a series of dynamic problems generated from several stationary benchmark problems, experiments are carried out to investigate the performance of the proposed memetic algorithm in comparison with some peer evolutionary algorithms. The experimental results show the efficiency of the proposed memetic algorithm in dynamic environments.This work was supported by the National Nature Science Foundation of China (NSFC) under Grant Nos. 70431003 and 70671020, the National Innovation Research Community Science Foundation of China under Grant No. 60521003, and the National Support Plan of China under Grant No. 2006BAH02A09 and the Engineering and Physical Sciences Research Council (EPSRC) of UK under Grant EP/E060722/01

A particle swarm optimization based memetic algorithm for dynamic optimization problems

Copyright @ Springer Science + Business Media B.V. 2010.Recently, there has been an increasing concern from the evolutionary computation community on dynamic optimization problems since many real-world optimization problems are dynamic. This paper investigates a particle swarm optimization (PSO) based memetic algorithm that hybridizes PSO with a local search technique for dynamic optimization problems. Within the framework of the proposed algorithm, a local version of PSO with a ring-shape topology structure is used as the global search operator and a fuzzy cognition local search method is proposed as the local search technique. In addition, a self-organized random immigrants scheme is extended into our proposed algorithm in order to further enhance its exploration capacity for new peaks in the search space. Experimental study over the moving peaks benchmark problem shows that the proposed PSO-based memetic algorithm is robust and adaptable in dynamic environments.This work was supported by the National Nature Science Foundation of China (NSFC) under Grant No. 70431003 and Grant No. 70671020, the National Innovation Research Community Science Foundation of China under Grant No. 60521003, the National Support Plan of China under Grant No. 2006BAH02A09 and the Ministry of Education, science, and Technology in Korea through the Second-Phase of Brain Korea 21 Project in 2009, the Engineering and Physical Sciences Research Council (EPSRC) of UK under Grant EP/E060722/01 and the Hong Kong Polytechnic University Research Grants under Grant G-YH60

Thermoelectric properties of Cu-dispersed bi0.5sb1.5te3

A novel and simple approach was used to disperse Cu nanoparticles uniformly in the Bi0.5Sb1.5Te3 matrix, and the thermoelectric properties were evaluated for the Cu-dispersed Bi0.5Sb1.5Te3. Polycrystalline Bi0.5Sb1.5Te3 powder prepared by encapsulated melting and grinding was dry-mixed with Cu(OAc)2 powder. After Cu(OAc)2 decomposition, the Cu-dispersed Bi0.5Sb1.5Te3 was hot-pressed. Cu nanoparticles were well-dispersed in the Bi0.5Sb1.5Te3 matrix and acted as effective phonon scattering centers. The electrical conductivity increased systematically with increasing level of Cu nanoparticle dispersion. All specimens had a positive Seebeck coefficient, which confirmed that the electrical charge was transported mainly by holes. The thermoelectric figure of merit was enhanced remarkably over a wide temperature range of 323-523 K

ERP evidence suggests executive dysfunction in ecstasy polydrug users

Background: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. Method: Twenty ecstasy–polydrug users, 20 non-ecstasy–polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. Results: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy–polydrug users

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study

Objectives: Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods: In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results: In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion: 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/ carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists

Nicotine patch preloading for smoking cessation (the preloading trial): study protocol for a randomized controlled trial

Background: The use of nicotine replacement therapy before quitting smoking is called nicotine preloading. Standard smoking cessation protocols suggest commencing nicotine replacement therapy only on the first day of quitting smoking (quit day) aiming to reduce withdrawal symptoms and craving. However, other, more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after. Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward. A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed. Methods/Design: This is a study protocol for a multicenter, non-blinded, randomized controlled trial based in the United Kingdom, enrolling 1786 smokers who want to quit, funded by the National Institute for Health Research, Health Technology Assessment program, and sponsored by the University of Oxford. Participants will primarily be recruited through general practices and smoking cessation clinics, and randomized (1:1) either to use 21 mg nicotine patches, or not, for four weeks before quitting, whilst smoking as normal. All participants will be referred to receive standard smoking cessation service support. Follow-ups will take place at one week, four weeks, six months and 12 months after quit day. The primary outcome will be prolonged, biochemically verified six-month abstinence. Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration, side effects, costs of treatment, and markers of potential mediators and moderators of the preloading effect. Discussion: This large trial will add substantially to evidence on the effectiveness of nicotine preloading, but also on its cost effectiveness and potential mediators, which have not been investigated in detail previously. A range of recruitment strategies have been considered to try and compensate for any challenges encountered in recruiting the large sample, and the multicentre design means that knowledge can be shared between recruitment teams. The pragmatic study design means that results will give a realistic estimate of the success of the intervention if it were to be rolled out as part of standard smoking cessation service practice. Trial registration: Current Controlled Trials ISRCTN33031001. Registered 27 April 2012

Characteristics of children with hip displacement in cerebral palsy

<p>Abstract</p> <p>Background</p> <p>Hip dislocation in children with cerebral palsy (CP) is a common and severe problem. The dislocation can be avoided, by screening and preventive treatment of children with hips at risk. The aim of this study was to analyse the characteristics of children with CP who develop hip displacement, in order to optimise a hip surveillance programme.</p> <p>Methods</p> <p>In a total population of children with CP a standardised clinical and radiological follow-up of the hips was carried out as a part of a hip prevention programme. The present study is based on 212 children followed until 9–16 years of age.</p> <p>Results</p> <p>Of the 212 children, 38 (18%) developed displacement with Migration Percentage (MP) >40% and further 19 (9%) MP between 33 and 39%. Mean age at first registration of hip displacement was 4 years, but some hips showed MP > 40% already at two years of age. The passive range of hip motion at the time of first registration of hip displacement did not differ significantly from the findings in hips without displacement.</p> <p>The risk of hip displacement varied according to CP-subtype, from 0% in children with pure ataxia to 79% in children with spastic tetraplegia. The risk of displacement (MP > 40%) was directly related to the level of gross motor function, classified according to the gross motor function classification system, GMFCS, from 0% in children in GMFCS level I to 64% in GMFCS level V.</p> <p>Conclusion</p> <p>Hip displacement in CP often occurs already at 2–3 years of age. Range of motion is a poor indicator of hips at risk. Thus early identification and early radiographic examination of children at risk is of great importance. The risk of hip displacement varies according to both CP-subtype and GMFCS. It is sometimes not possible to determine subtype before 4 years of age, and at present several definitions and classification systems are used. GMFCS is valid and reliable from 2 years of age, and it is internationally accepted.</p> <p>We recommend a hip surveillance programme for children with CP with radiographic examinations based on the child's age and GMFCS level.</p

Thermal Properties of Graphene, Carbon Nanotubes and Nanostructured Carbon Materials

Recent years witnessed a rapid growth of interest of scientific and engineering communities to thermal properties of materials. Carbon allotropes and derivatives occupy a unique place in terms of their ability to conduct heat. The room-temperature thermal conductivity of carbon materials span an extraordinary large range - of over five orders of magnitude - from the lowest in amorphous carbons to the highest in graphene and carbon nanotubes. I review thermal and thermoelectric properties of carbon materials focusing on recent results for graphene, carbon nanotubes and nanostructured carbon materials with different degrees of disorder. A special attention is given to the unusual size dependence of heat conduction in two-dimensional crystals and, specifically, in graphene. I also describe prospects of applications of graphene and carbon materials for thermal management of electronics.Comment: Review Paper; 37 manuscript pages; 4 figures and 2 boxe