Cortical reorganisation of cerebral networks after childhood stroke: impact on outcome.

BACKGROUND Recovery after arterial ischaemic stroke is known to largely depend on the plastic properties of the brain. The present study examines changes in the network topography of the developing brain after stroke. Effects of brain damage are best assessed by examining entire networks rather than single sites of structural lesions. Relating these changes to post-stroke neuropsychological variables and motor abilities will improve understanding of functional plasticity after stroke. Inclusion of healthy controls will provide additional insight into children's normal brain development. Resting state functional magnetic resonance imaging is a valid approach to topographically investigate the reorganisation of functional networks after a brain lesion. Transcranial magnetic stimulation provides complementary output information. This study will investigate functional reorganisation after paediatric arterial ischaemic stroke by means of resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a cross-sectional plus longitudinal study design. The general aim of this study is to better understand neuroplasticity of the developing brain after stroke in order to develop more efficacious therapy and to improve the post-stroke functional outcome. METHODS The cross-sectional part of the study will investigate the functional cerebral networks of 35 children with chronic arterial ischaemic stroke (time of the lesion >2 years). In the longitudinal part, 15 children with acute arterial ischaemic stroke (shortly after the acute phase of the stroke) will be included and investigations will be performed 3 times within the subsequent 9 months. We will also recruit 50 healthy controls, matched for age and sex. The neuroimaging and neurophysiological data will be correlated with neuropsychological and neurological variables. DISCUSSION This study is the first to combine resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a paediatric population diagnosed with arterial ischaemic stroke. Thus, this study has the potential to uniquely contribute to the understanding of neuronal plasticity in the brains of healthy children and those with acute or chronic brain injury. It is expected that the results will lead to the development of optimal interventions after arterial ischaemic stroke.

MATHEMATICAL STUDIES ON THE EVOLUTIONARY CHANGE OF DNA SEQUENCES

With the aim of understanding the mechanism of molecular evolution, mathematical problems on the evolutionary change of DNA sequences are studied. The problems studied and the results obtained are as follows: (1) Estimation of evolutionary distance between nucleotide sequences. Studying the pattern of nucleotide substitution for the case of unequal substitution rates, a new mathematical formula for estimating the average number of nucleotide substitutions per site between two homologous DNA sequences is developed. It is shown that this formula has a wider applicability than currently available formulae. A statistical method for estimating the number of nucleotide changes due to deletion and insertion is also developed. (2) Biases of the estimates of nucleotide substitutions obtained by the restriction enzyme method. The deviation of the estimate of nucleotide substitutions obtained by the restriction enzyme method from the true value is investigated theoretically. It is shown that the amount of the deviation depends on the nucleotides in the recognition sequence of the restriction enzyme used, unequal rates of substitution among different nucleotides, and nucleotide frequences, but the primary factor is the unequal rates of nucleotide substitution. When many different kinds of enzymes are used, however, the amount of average deviation is generally small. (3) Distribution of restriction fragment lengths. To see the effect of undetectable restriction fragments and fragment differences on the estimate of nucleotide differences, the theoretical distribution of fragment lengths is studied. This distribution depends on the type of restriction enzymes used as well as on the relative frequencies of four nucleotides. It is shown that undetectability of small fragments or fragment differences gives a serious underestimate of nucleotide substitutions when the length-difference method of estimation is used, but the extent of underestimation is small when the site-difference method is used. (4) Evolutionary relationships of DNA sequences in finite populations. A mathematical theory on the expected evolutionary relationships among DNA sequences (nucleons) randomly chosen from the same or different populations is developed under the assumption that the evolutionary change of nucleons is determined solely by mutation and random genetic drift. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author). UMI ^

The impact of social support networks on compliance with hypertensive therapeutic regimens among noninstitutionalized black adults

A conceptual framework based on the Health Belief Model was proposed which identified those factors most significant in the prediction of compliance behavior. The hypothesized model was applied to analyze the effects of sociodemographic characteristics, self-assessed health status, and social support networks on compliance with antihypertensive regimens, focusing on black adults.^ The study population was selected from the National Health and Examination Survey II (NHANES II) which produced a sample of 3,957 eligible persons 35-74 years of age.^ The study addressed the following research questions: (a) what is the relationship between demographic variables and self-assessed health status, (b) what is the relationship between social support network and self-assessed health status, (c) what is the compliance, (d) what factors, e.g., demographic characteristics, social support network, self-assessed health status, are most related to compliance, and (e) does the effect of these factors on compliance differ between black and white adults?^ The results of the study found that blacks: (a) had poorer health than whites, and education and income were significantly related to self-assessed health status, (b) the stronger social support networks of blacks, the better their health status, and (c) older blacks and those in poorer health were more likely to comply with recommended treatment. The hypothesized conceptual model for the prediction of compliance behavior was partially substantiated for both blacks and whites.^ Implications for the application of the conceptual model are also discussed. ^

Quantifying dispersal paths in probabilistic habitat networks: a reply to hock and mumby (2015) and an overview of recent developments and applications

Hock and Mumby (2015) describe an approach to quantify dispersal probabilities along paths in networks of habitat patches. This approach basically consists in determining the most probable (most reliable) path for movement between habitat patches by calculating the product of the dispersal probabilities in each link (step) along the paths in the network. Although the paper by Hock and Mumby (2015) has value and includes interesting analyses (see comments in section 7 below), the approach they describe is not new.

Lessons from the past: Evolutionary impacts of mass extinctions

Mass extinctions have played many evolutionary roles, involving differential survivorship or selectivity of taxa and traits, the disruption or preservation of evolutionary trends and ecosystem organization, and the promotion of taxonomic and morphological diversifications—often along unexpected trajectories—after the destruction or marginalization of once-dominant clades. The fossil record suggests that survivorship during mass extinctions is not strictly random, but it often fails to coincide with factors promoting survival during times of low extinction intensity. Although of very serious concern, present-day extinctions have not yet achieved the intensities seen in the Big Five mass extinctions of the geologic past, which each removed ≥50% of the subset of relatively abundant marine invertebrate genera. The best comparisons for predictive purposes therefore will involve factors such as differential extinction intensities among regions, clades, and functional groups, rules governing postextinction biotic interchanges and evolutionary dynamics, and analyses of the factors that cause taxa and evolutionary trends to continue unabated, to suffer setbacks but resume along the same trajectory, to survive only to fall into a marginal role or disappear (“dead clade walking”), or to undergo a burst of diversification. These issues need to be addressed in a spatially explicit framework, because the fossil record suggests regional differences in postextinction diversification dynamics and biotic interchanges. Postextinction diversifications lag far behind the initial taxonomic and morphological impoverishment and homogenization; they do not simply reoccupy vacated adaptive peaks, but explore opportunities as opened and constrained by intrinsic biotic factors and the ecological and evolutionary context of the radiation.

Disrupting evolutionary processes: The effect of habitat fragmentation on collared lizards in the Missouri Ozarks

Humans affect biodiversity at the genetic, species, community, and ecosystem levels. This impact on genetic diversity is critical, because genetic diversity is the raw material of evolutionary change, including adaptation and speciation. Two forces affecting genetic variation are genetic drift (which decreases genetic variation within but increases genetic differentiation among local populations) and gene flow (which increases variation within but decreases differentiation among local populations). Humans activities often augment drift and diminish gene flow for many species, which reduces genetic variation in local populations and prevents the spread of adaptive complexes outside their population of origin, thereby disrupting adaptive processes both locally and globally within a species. These impacts are illustrated with collared lizards (Crotaphytus collaris) in the Missouri Ozarks. Forest fire suppression has reduced habitat and disrupted gene flow in this lizard, thereby altering the balance toward drift and away from gene flow. This balance can be restored by managed landscape burns. Some have argued that, although human-induced fragmentation disrupts adaptation, it will also ultimately produce new species through founder effects. However, population genetic theory and experiments predict that most fragmentation events caused by human activities will facilitate not speciation, but local extinction. Founder events have played an important role in the macroevolution of certain groups, but only when ecological opportunities are expanding rather than contracting. The general impact of human activities on genetic diversity disrupts or diminishes the capacity for adaptation, speciation, and macroevolutionary change. This impact will ultimately diminish biodiversity at all levels.

The evolutionary impact of invasive species

Since the Age of Exploration began, there has been a drastic breaching of biogeographic barriers that previously had isolated the continental biotas for millions of years. We explore the nature of these recent biotic exchanges and their consequences on evolutionary processes. The direct evidence of evolutionary consequences of the biotic rearrangements is of variable quality, but the results of trajectories are becoming clear as the number of studies increases. There are examples of invasive species altering the evolutionary pathway of native species by competitive exclusion, niche displacement, hybridization, introgression, predation, and ultimately extinction. Invaders themselves evolve in response to their interactions with natives, as well as in response to the new abiotic environment. Flexibility in behavior, and mutualistic interactions, can aid in the success of invaders in their new environment.

Intrinsic noise in gene regulatory networks

Cells are intrinsically noisy biochemical reactors: low reactant numbers can lead to significant statistical fluctuations in molecule numbers and reaction rates. Here we use an analytic model to investigate the emergent noise properties of genetic systems. We find for a single gene that noise is essentially determined at the translational level, and that the mean and variance of protein concentration can be independently controlled. The noise strength immediately following single gene induction is almost twice the final steady-state value. We find that fluctuations in the concentrations of a regulatory protein can propagate through a genetic cascade; translational noise control could explain the inefficient translation rates observed for genes encoding such regulatory proteins. For an autoregulatory protein, we demonstrate that negative feedback efficiently decreases system noise. The model can be used to predict the noise characteristics of networks of arbitrary connectivity. The general procedure is further illustrated for an autocatalytic protein and a bistable genetic switch. The analysis of intrinsic noise reveals biological roles of gene network structures and can lead to a deeper understanding of their evolutionary origin.

Evolutionary changes in the expression pattern of a developmentally essential gene in three Drosophila species.

The hypothesis that morphological evolution may largely result from changes in gene regulation rather than gene structure has been difficult to test. Morphological differences among insects are often apparent in the cuticle structures produced. The dopa decarboxylase (Ddc) and alpha-methyldopa hypersensitive (amd) genes arose from an ancient gene duplication. In Drosophila, they have evolved nonoverlapping functions, including the production of distinct types of cuticle, and for Ddc, the production of the neurotransmitters, dopamine and serotonin. The amd gene is particularly active in the production of specialized flexible cuticles in the developing embryo. We have compared the pattern of amd expression in three Drosophila species. Several regions of expression conserved in all three species but, surprisingly, a unique domain of expression is found in Drosophila simulans that does occur in the closely related (2-5 million years) Drosophila melanogaster or in the more remote (40-50 million years) Drosophila virilis. The "sudden" appearance of a completely new and robust domain of expression provides a glimpse of evolutionary variation resulting from changes in regulation of structural gene expression.

The organization of seismicity on fault networks.

Although models of homogeneous faults develop seismicity that has a Gutenberg-Richter distribution, this is only a transient state that is followed by events that are strongly influenced by the nature of the boundaries. Models with geometrical inhomogeneities of fracture thresholds can limit the sizes of earthquakes but now favor the characteristic earthquake model for large earthquakes. The character of the seismicity is extremely sensitive to distributions of inhomogeneities, suggesting that statistical rules for large earthquakes in one region may not be applicable to large earthquakes in another region. Model simulations on simple networks of faults with inhomogeneities of threshold develop episodes of lacunarity on all members of the network. There is no validity to the popular assumption that the average rate of slip on individual faults is a constant. Intermediate term precursory activity such as local quiescence and increases in intermediate-magnitude activity at long range are simulated well by the assumption that strong weakening of faults by injection of fluids and weakening of asperities on inhomogeneous models of fault networks is the dominant process; the heat flow paradox, the orientation of the stress field, and the low average stress drop in some earthquakes are understood in terms of the asperity model of inhomogeneous faulting.

Certain observations concerning the effects of epistasis on complex traits and the evolution of genomes.

Thesis (Ph.D.)--University of Washington, 2016-05

Inter-organisational networks, value creation and the process of technology integration in research and development

Traditional methods of R&D management are no longer sufficient for embracing innovations and leveraging complex new technologies to fully integrated positions in established systems. This paper presents the view that the technology integration process is a result of fundamental interactions embedded in inter-organisational activities. Emerging industries, high technology companies and knowledge intensive organisations owe a large part of their viability to complex networks of inter-organisational interactions and relationships. R&D organisations are the gatekeepers in the technology integration process with their initial sanction and motivation to develop technologies providing the first point of entry. Networks rely on the activities of stakeholders to provide the foundations of collaborative R&D activities, business-to-business marketing and strategic alliances. Such complex inter-organisational interactions and relationships influence value creation and organisational goals as stakeholders seek to gain investment opportunities. A theoretical model is developed here that contributes to our understanding of technology integration (adoption) as a dynamic process, which is simultaneously structured and enacted through the activities of stakeholders and organisations in complex inter-organisational networks of sanction and integration.

Evolutionary economics: Foundation of liberal economic philosophy

This is a schools brief style of introduction to evolutionary economics. It addresses the nature of evolutionary theory in relation to economics, and examines why evolutionary economists argue that market-capitalism is an evolutionary system. Finally, it argues that liberal economic philosophy has much stronger and more direct relationship with evolutionary economic analysis than neoclassical economic analysis.

Evolutionary origin of Venturia canescens virus-like particles

Insect host-parasitoid interactions provide fascinating examples of evolutionary adaptations in which the parasitoid employs a variety of measures and countermeasures to overcome the immune responses of its host. Maternal factors introduced by the female wasps during egg deposition play an important role in interfering with cellular and humoral components of the host's immune defence. Some of these components actively suppress host immune components and some are believed to confer protection for the developing endoparasitoid by rather passive means. The Venturio conescens/Ephestia kuehniella parrositoid-host system is unique among other systems in that the cellular defence capacity of the host remains virtually intact after parasitization. This system raises some important questions that are discussed in this mini-review: If immune protection of the egg and the emerging larva is achieved by surface properties comprising glycoproteins and virus-like particles (VLPs) produced by the female wasp, why is the prophenoloxidose activating cascade blocked in parasitized caterpillars? Another question is the evolutionary origin of these particles, given that the functional role and structural features of V. canescens VLP proteins are more related to cellular proteins than to viruses.

Dynamics of gene expression in an artificial genome

Complex systems techniques provide a powerful tool to study the emergent properties of networks of interacting genes. In this study we extract models of genetic regulatory networks from an artificial genome, represented by a sequence of nucleotides, and analyse how variations in the connectivity and degree of inhibition of the extracted networks affects the resulting classes of behaviours. For low connectivity systems were found to be very stable. Only with higher connectivity was a significant occurrence of chaos found. Most interestingly, the peak in occurrence of chaos occurs perched on the edge of a phase transition in the occurrence of attractors.