Bilinear models for spatio-temporal point distribution analysis: application to extrapolation of left ventricular, biventricular and whole heart cardiac dynamics

In this work we describe the usage of bilinear statistical models as a means of factoring the shape variability into two components attributed to inter-subject variation and to the intrinsic dynamics of the human heart. We show that it is feasible to reconstruct the shape of the heart at discrete points in the cardiac cycle. Provided we are given a small number of shape instances representing the same heart atdifferent points in the same cycle, we can use the bilinearmodel to establish this. Using a temporal and a spatial alignment step in the preprocessing of the shapes, around half of the reconstruction errors were on the order of the axial image resolution of 2 mm, and over 90% was within 3.5 mm. From this, weconclude that the dynamics were indeed separated from theinter-subject variability in our dataset.

Dynamics of fluorescence fluctuations in green fluorescent protein observed by fluorescence correlation spectroscopy

We have investigated the pH dependence of the dynamics of conformational fluctuations of green fluorescent protein mutants EGFP (F64L/S65T) and GFP-S65T in small ensembles of molecules in solution by using fluorescence correlation spectroscopy (FCS). FCS utilizes time-resolved measurements of fluctuations in the molecular fluorescence emission for determination of the intrinsic dynamics and thermodynamics of all processes that affect the fluorescence. Fluorescence excitation of a bulk solution of EGFP decreases to zero at low pH (pKa = 5.8) paralleled by a decrease of the absorption at 488 nm and an increase at 400 nm. Protonation of the hydroxyl group of Tyr-66, which is part of the chromophore, induces these changes. When FCS is used the fluctuations in the protonation state of the chromophore are time resolved. The autocorrelation function of fluorescence emission shows contributions from two chemical relaxation processes as well as diffusional concentration fluctuations. The time constant of the fast, pH-dependent chemical process decreases with pH from 300 μs at pH 7 to 45 μs at pH 5, while the time-average fraction of molecules in a nonfluorescent state increases to 80% in the same range. A second, pH-independent, process with a time constant of 340 μs and an associated fraction of 13% nonfluorescent molecules is observed between pH 8 and 11, possibly representing an internal proton transfer process and associated conformational rearrangements. The FCS data provide direct measures of the dynamics and the equilibrium properties of the protonation processes. Thus FCS is a convenient, intrinsically calibrated method for pH measurements in subfemtoliter volumes with nanomolar concentrations of EGFP.

Patterns in the situated activity of substance use in the careers of elite doping athletes

Objectives This article presents a psychological approach to substance use in sport using a dynamic and situated activity framework. The aim was to analyze the various relationships between activity and the consumption of substances during the sporting life course of athletes who recognized doping violation. Design Data were collected from secondary sources and biographical and self-confrontational interviews to build traces of the past activity. Method Twelve doping athletes or those admitting to having used banned substances volunteered to participate. The data were coded and compared to identify typical activities and their intrinsic dynamics. Results Six activities were identified: "Agree to use," "Drop out of a non-viable state," Return to a former state," "Prevent a potential deficiency," "Maintain an acquired state," and "Balance the sporting life with substance use," comprising 11 patterns. Conclusions The athletes' activity embedded substance use in reciprocal relationships that consisted of freezing, exploring and exploiting fields of possible actions created and offered by the situation dynamics. Recommendations for situated and dynamic prevention are provided.

Synchronization in a lattice model of pulse-coupled oscillators

We analyze the collective behavior of a lattice model of pulse-coupled oscillators. By means of computer simulations we find the relation between the intrinsic dynamics of each member of the population and their mutual interactions that ensures, in a general context, the existence of a fully synchronized regime. This condition turns out to be the same as that obtained for the globally coupled population. When the condition is not completely satisfied we find different spatial structures. This also gives some hints about self-organized criticality.

Real-time monitoring of protein conformational changes using a nano-mechanical sensor.

Proteins can switch between different conformations in response to stimuli, such as pH or temperature variations, or to the binding of ligands. Such plasticity and its kinetics can have a crucial functional role, and their characterization has taken center stage in protein research. As an example, Topoisomerases are particularly interesting enzymes capable of managing tangled and supercoiled double-stranded DNA, thus facilitating many physiological processes. In this work, we describe the use of a cantilever-based nanomotion sensor to characterize the dynamics of human topoisomerase II (Topo II) enzymes and their response to different kinds of ligands, such as ATP, which enhance the conformational dynamics. The sensitivity and time resolution of this sensor allow determining quantitatively the correlation between the ATP concentration and the rate of Topo II conformational changes. Furthermore, we show how to rationalize the experimental results in a comprehensive model that takes into account both the physics of the cantilever and the dynamics of the ATPase cycle of the enzyme, shedding light on the kinetics of the process. Finally, we study the effect of aclarubicin, an anticancer drug, demonstrating that it affects directly the Topo II molecule inhibiting its conformational changes. These results pave the way to a new way of studying the intrinsic dynamics of proteins and of protein complexes allowing new applications ranging from fundamental proteomics to drug discovery and development and possibly to clinical practice.

Abstract platforms of computation

Computational formalisms have been pushing the boundaries of the field of computing for the last 80 years and much debate has surrounded what computing entails; what it is, and what it is not. This paper seeks to explore the boundaries of the ideas of computation and provide a framework for enabling a constructive discussion of computational ideas. First, a review of computing is given, ranging from Turing Machines to interactive computing. Then, a variety of natural physical systems are considered for their computational qualities. From this exploration, a framework is presented under which all dynamical systems can be considered as instances of the class of abstract computational platforms. An abstract computational platform is defined by both its intrinsic dynamics and how it allows computation that is meaningful to an external agent through the configuration of constraints upon those dynamics. It is asserted that a platform’s computational expressiveness is directly related to the freedom with which constraints can be placed. Finally, the requirements for a formal constraint description language are considered and it is proposed that Abstract State Machines may provide a reasonable basis for such a language.

Efeitos da informação comportamental na dinâmica intrínseca do controle postural

Esse estudo teve como objetivo examinar possíveis alterações na dinâmica intrínseca de crianças e adultos decorrentes de informações externas na realização de uma tarefa de manutenção da postura ereta. Participaram do estudo dez crianças de 8 anos de idade e dez adultos jovens de ambos os gêneros. Eles permaneceram na posição ereta dentro de uma sala móvel que foi movimentada continuamente para frente e para trás. Os participantes recebiam informação sobre o movimento da sala e eram solicitados a não oscilar ou a oscilar junto com o movimento da mesma. Os resultados mostraram que a manipulação da informação visual induziu oscilação corporal correspondente (dinâmica intrínseca) em crianças e adultos. Informação sobre o movimento da sala e solicitação de uma ação (informação comportamental) alteraram o relacionamento entre informação visual e oscilação corporal. Crianças apresentaram mais dificuldades em alterar a dinâmica intrínseca do que adultos, indicando que elas são mais dependentes da dinâmica intrínseca do que adultos. Esses resultados trazem implicações importantes para a situação de ensino-aprendizagem, pois indica que aprendizagem envolvendo crianças deve ser estruturada propiciando condições mais favoráveis para alterações na dinâmica intrínseca para que os objetivos da mesma sejam alcançados.

Efeitos da informação comportamental na dinâmica intrínseca do controle postural

Esse estudo teve como objetivo examinar possíveis alterações na dinâmica intrínseca de crianças e adultos decorrentes de informações externas na realização de uma tarefa de manutenção da postura ereta. Participaram do estudo dez crianças de 8 anos de idade e dez adultos jovens de ambos os gêneros. Eles permaneceram na posição ereta dentro de uma sala móvel que foi movimentada continuamente para frente e para trás. Os participantes recebiam informação sobre o movimento da sala e eram solicitados a não oscilar ou a oscilar junto com o movimento da mesma. Os resultados mostraram que a manipulação da informação visual induziu oscilação corporal correspondente (dinâmica intrínseca) em crianças e adultos. Informação sobre o movimento da sala e solicitação de uma ação (informação comportamental) alteraram o relacionamento entre informação visual e oscilação corporal. Crianças apresentaram mais dificuldades em alterar a dinâmica intrínseca do que adultos, indicando que elas são mais dependentes da dinâmica intrínseca do que adultos. Esses resultados trazem implicações importantes para a situação de ensino-aprendizagem, pois indica que aprendizagem envolvendo crianças deve ser estruturada propiciando condições mais favoráveis para alterações na dinâmica intrínseca para que os objetivos da mesma sejam alcançados.

Efeitos da informação comportamental na dinâmica intrínseca do controle postural

Esse estudo teve como objetivo examinar possíveis alterações na dinâmica intrínseca de crianças e adultos decorrentes de informações externas na realização de uma tarefa de manutenção da postura ereta. Participaram do estudo dez crianças de 8 anos de idade e dez adultos jovens de ambos os gêneros. Eles permaneceram na posição ereta dentro de uma sala móvel que foi movimentada continuamente para frente e para trás. Os participantes recebiam informação sobre o movimento da sala e eram solicitados a não oscilar ou a oscilar junto com o movimento da mesma. Os resultados mostraram que a manipulação da informação visual induziu oscilação corporal correspondente (dinâmica intrínseca) em crianças e adultos. Informação sobre o movimento da sala e solicitação de uma ação (informação comportamental) alteraram o relacionamento entre informação visual e oscilação corporal. Crianças apresentaram mais dificuldades em alterar a dinâmica intrínseca do que adultos, indicando que elas são mais dependentes da dinâmica intrínseca do que adultos. Esses resultados trazem implicações importantes para a situação de ensino-aprendizagem, pois indica que aprendizagem envolvendo crianças deve ser estruturada propiciando condições mais favoráveis para alterações na dinâmica intrínseca para que os objetivos da mesma sejam alcançados.

Optimization and Machine Learning Frameworks for Complex Network Analysis

Thesis (Ph.D.)--University of Washington, 2016-06

Intrinsic fractal dynamics in the respiratory system by means of pressure-volume loops

This contribution presents novel concepts for analysis of pressure–volume curves, which offer information about the time domain dynamics of the respiratory system. The aim is to verify whether a mapping of the respiratory diseases can be obtained, allowing analysis of (dis)similarities between the dynamical pattern in the breathing in children. The groups investigated here are children, diagnosed as healthy, asthmatic, and cystic fibrosis. The pressure–volume curves have been measured by means of the noninvasive forced oscillation technique during breathing at rest. The geometrical fractal dimension is extracted from the pressure–volume curves and a power-law behavior is observed in the data. The power-law model coefficients are identified from the three sets and the results show that significant differences are present between the groups. This conclusion supports the idea that the respiratory system changes with disease in terms of airway geometry, tissue parameters, leading in turn to variations in the fractal dimension of the respiratory tree and its dynamics.

Memory from the dynamics of intrinsic membrane currents

Almost all theoretical and experimental studies of the mechanisms underlying learning and memory focus on synaptic efficacy and make the implicit assumption that changes in synaptic efficacy are both necessary and sufficient to account for learning and memory. However, network dynamics depends on the complex interaction between intrinsic membrane properties and synaptic strengths and time courses. Furthermore, neuronal activity itself modifies not only synaptic efficacy but also the intrinsic membrane properties of neurons. This paper presents examples demonstrating that neurons with complex temporal dynamics can provide short-term “memory” mechanisms that rely solely on intrinsic neuronal properties. Additionally, we discuss the potential role that activity may play in long-term modification of intrinsic neuronal properties. While not replacing synaptic plasticity as a powerful learning mechanism, these examples suggest that memory in networks results from an ongoing interplay between changes in synaptic efficacy and intrinsic membrane properties.

Intrinsic compressibility and volume compression in solvated proteins by molecular dynamics simulation at high pressure.

Constant pressure and temperature molecular dynamics techniques have been employed to investigate the changes in structure and volumes of two globular proteins, superoxide dismutase and lysozyme, under pressure. Compression (the relative changes in the proteins' volumes), computed with the Voronoi technique, is closely related with the so-called protein intrinsic compressibility, estimated by sound velocity measurements. In particular, compression computed with Voronoi volumes predicts, in agreement with experimental estimates, a negative bound water contribution to the apparent protein compression. While the use of van der Waals and molecular volumes underestimates the intrinsic compressibilities of proteins, Voronoi volumes produce results closer to experimental estimates. Remarkably, for two globular proteins of very different secondary structures, we compute identical (within statistical error) protein intrinsic compressions, as predicted by recent experimental studies. Changes in the protein interatomic distances under compression are also investigated. It is found that, on average, short distances compress less than longer ones. This nonuniform contraction underlines the peculiar nature of the structural changes due to pressure in contrast with temperature effects, which instead produce spatially uniform changes in proteins. The structural effects observed in the simulations at high pressure can explain protein compressibility measurements carried out by fluorimetric and hole burning techniques. Finally, the calculation of the proteins static structure factor shows significant shifts in the peaks at short wavenumber as pressure changes. These effects might provide an alternative way to obtain information concerning compressibilities of selected protein regions.

Role of noise in population dynamics cycles

Noise is an intrinsic feature of population dynamics and plays a crucial role in oscillations called phase-forgetting quasicycles by converting damped into sustained oscillations. This function of noise becomes evident when considering Langevin equations whose deterministic part yields only damped oscillations. We formulate here a consistent and systematic approach to population dynamics, leading to a Fokker-Planck equation and the associate Langevin equations in accordance with this conceptual framework, founded on stochastic lattice-gas models that describe spatially structured predator-prey systems. Langevin equations in the population densities and predator-prey pair density are derived in two stages. First, a birth-and-death stochastic process in the space of prey and predator numbers and predator-prey pair number is obtained by a contraction method that reduces the degrees of freedom. Second, a van Kampen expansion in the inverse of system size is then performed to get the Fokker-Planck equation. We also study the time correlation function, the asymptotic behavior of which is used to characterize the transition from the cyclic coexistence of species to the ordinary coexistence.