Information Theory in Molecular Evolution: From Models to Structures and Dynamics

This Special Issue collects novel contributions from scientists in the interdisciplinary field of biomolecular evolution. Works listed here use information theoretical concepts as a core but are tightly integrated with the study of molecular processes. Applications include the analysis of phylogenetic signals to elucidate biomolecular structure and function, the study and quantification of structural dynamics and allostery, as well as models of molecular interaction specificity inspired by evolutionary cues

Linear and nonlinear approaches to unravel dynamics and connectivity in neuronal cultures

[eng] In the present thesis, we propose to explore neuronal circuits at the mesoscale, an approach in which one monitors small populations of few thousand neurons and concentrates in the emergence of collective behavior. In our case, we carried out such an exploration both experimentally and numerically, and by adopting an analysis perspective centered on time series analysis and dynamical systems. Experimentally, we used neuronal cultures and prepared more than 200 of them, which were monitored using fluorescence calcium imaging. By adjusting the experimental conditions, we could set two basic arrangements of neurons, namely homogeneous and aggregated. In the experiments, we carried out two major explorations, namely development and disintegration. In the former we investigated changes in network behavior as it matured; in the latter we applied a drug that reduced neuronal interconnectivity. All the subsequent analyses and modeling along the thesis are based on these experimental data. Numerically, the thesis comprised two aspects. The first one was oriented towards a simulation of neuronal connectivity and dynamics. The second one was oriented towards the development of linear and nonlinear analysis tools to unravel dynamic and connectivity aspects of the measured experimental networks. For the first aspect, we developed a sophisticated software package to simulate single neuronal dynamics using a quadratic integrate–and–fire model with adaptation and depression. This model was plug into a synthetic graph in which the nodes of the network are neurons, and the edges connections. The graph was created using spatial embedding and realistic biology. We carried out hundreds of simulations in which we tuned the density of neurons, their spatial arrangement and the characteristics of the fluorescence signal. As a key result, we observed that homogeneous networks required a substantial number of neurons to fire and exhibit collective dynamics, and that the presence of aggregation significantly reduced the number of required neurons. For the second aspect, data analysis, we analyzed experiments and simulations to tackle three major aspects: network dynamics reconstruction using linear descriptions, dynamics reconstruction using nonlinear descriptors, and the assessment of neuronal connectivity from solely activity data. For the linear study, we analyzed all experiments using the power spectrum density (PSD), and observed that it was sufficiently good to describe the development of the network or its disintegration. PSD also allowed us to distinguish between healthy and unhealthy networks, and revealed dynamical heterogeneities across the network. For the nonlinear study, we used techniques in the context of recurrence plots. We first characterized the embedding dimension m and the time delay δ for each experiment, built the respective recurrence plots, and extracted key information of the dynamics of the system through different descriptors. Experimental results were contrasted with numerical simulations. After analyzing about 400 time series, we concluded that the degree of dynamical complexity in neuronal cultures changes both during development and disintegration. We also observed that the healthier the culture, the higher its dynamic complexity. Finally, for the reconstruction study, we first used numerical simulations to determine the best measure of ‘statistical interdependence’ among any two neurons, and took Generalized Transfer Entropy. We then analyzed the experimental data. We concluded that young cultures have a weak connectivity that increases along maturation. Aggregation increases average connectivity, and more interesting, also the assortativity, i.e. the tendency of highly connected nodes to connect with other highly connected node. In turn, this assortativity may delineates important aspects of the dynamics of the network. Overall, the results show that spatial arrangement and neuronal dynamics are able to shape a very rich repertoire of dynamical states of varying complexity.[cat] L’habilitat dels teixits neuronals de processar i transmetre informació de forma eficient depèn de les propietats dinàmiques intrínseques de les neurones i de la connectivitat entre elles. La present tesi proposa explorar diferents tècniques experimentals i de simulació per analitzar la dinàmica i connectivitat de xarxes neuronals corticals de rata embrionària. Experimentalment, la gravació de l’activitat espontània d’una població de neurones en cultiu, mitjançant una càmera ràpida i tècniques de fluorescència, possibilita el seguiment de forma controlada de l’activitat individual de cada neurona, així com la modificació de la seva connectivitat. En conjunt, aquestes eines permeten estudiar el comportament col.lectiu emergent de la població neuronal. Amb l’objectiu de simular els patrons observats en el laboratori, hem implementat un model mètric aleatori de creixement neuronal per simular la xarxa física de connexions entre neurones, i un model quadràtic d’integració i dispar amb adaptació i depressió per modelar l’ampli espectre de dinàmiques neuronals amb un cost computacional reduït. Hem caracteritzat la dinàmica global i individual de les neurones i l’hem correlacionat amb la seva estructura subjacent mitjançant tècniques lineals i no–lineals de series temporals. L’anàlisi espectral ens ha possibilitat la descripció del desenvolupament i els canvis en connectivitat en els cultius, així com la diferenciació entre cultius sans dels patològics. La reconstrucció de la dinàmica subjacent mitjançant mètodes d’incrustació i l’ús de gràfics de recurrència ens ha permès detectar diferents transicions dinàmiques amb el corresponent guany o pèrdua de la complexitat i riquesa dinàmica del cultiu durant els diferents estudis experimentals. Finalment, a fi de reconstruir la connectivitat interna hem testejat, mitjançant simulacions, diferents quantificadors per mesurar la dependència estadística entre neurona i neurona, seleccionant finalment el mètode de transferència d’entropia gereralitzada. Seguidament, hem procedit a caracteritzar les xarxes amb diferents paràmetres. Malgrat presentar certs tres de xarxes tipus ‘petit món’, els nostres cultius mostren una distribució de grau ‘exponencial’ o ‘esbiaixada’ per, respectivament, cultius joves i madurs. Addicionalment, hem observat que les xarxes homogènies presenten la propietat de disassortativitat, mentre que xarxes amb un creixent nivell d’agregació espaial presenten assortativitat. Aquesta propietat impacta fortament en la transmissió, resistència i sincronització de la xarxa

Ecohydrological Footprints:Quantitative Response of Ecosystems to Changes in their Hydrological Drivers

Ecohydrological footprints are defined as the response of ecosystem functions or services to changes in their hydrologic drivers. In this thesis, several diverse footprints are addressed: noise-driven effects on storage-discharge relations and catchment streamflow distributions, that are important drivers of biodiversity; soil salinization and its ecohydrological implications; topological effects of the ecological interaction networks on living communities (e.g. on their species persistence); and form and function of the global virtual water trade network. The coherence of the conceptual framework is provided by the study of drivers and controls of ecohydrological variability using methodological approaches based on statistical mechanics. In fact, this thesis work outlines a significant portion of environmental statistical mechanics, an overarching discipline that is emerging in recent years, which applies mathematical tools from statistical mechanics to model several ecohydrological processes. The proposed relevance of this thesis lies in the major effects of hydrologic drivers on ecological process. The view that emerges from current research in ecohydrology, that this thesis supports, is that there exists a definite need for an integrated understanding of ecological and hydrological processes. Because stochasticity is intrinsic to environmental and ecohydrological variability, noise plays an important and constructive role in ecohydrological processes. In this thesis, a stochastic approach is applied to analyze different ecohydrological processes, ranging from green and blue water flows in river basins (part I), ecosystem dynamics affected by the directional dispersal provided by river networks (part II) to water footprints of human society (part III).Methods range from novel exact solutions to stochastic differential equations to random graph theory applications, and imply the analysis of suitable field data. An analytical framework for quantitative analysis is laid out to tackle complex problems and to estimate the effects of environmental change on the interaction of the hydrologic processes with the biota. The main results of this thesis are: i) the achievement of exact solutions for the probability distribution of catchment streamflow, that takes in account stochastic fluctuations in the storage-discharge relation and for the condition of a noise induced phenomena to the streamflows regimes; ii) the stationary solutions of soil salinity under stochastic hydrologic forcing; iii) a novel solution of the Ito-Stratonovich problem in multiplicative Poisson processes; iv) the proper framework for species' persistence time distributions, as a function of topological constraints on the ecosystem, and its connection with other important macroecological laws. A related length-bias sampling problem is also solved. v) A statistical analysis of the global virtual trade network and a semi-analytical model that is able to describe most of the observed properties

Model based forecasting for demand response strategies

The incremental deployment of decentralized renewable energy sources in the distribution grid is triggering a paradigm change for the power sector. This shift from a centralized structure with big power plants to a decentralized scenario of distributed energy resources, such as solar and wind, calls for a more active management of the distribution grid. Conventional distribution grids were passive systems, in which the power was flowing unidirectionally from upstream to downstream. Nowadays, and increasingly in the future, the penetration of distributed generation (DG), with its stochastic nature and lack of controllability, represents a major challenge for the stability of the network, especially at the distribution level. In particular, the power flow reversals produced by DG cause voltage excursions, which must be compensated. This poses an obstacle to the energy transition towards a more sustainable energy mix, which can however be mitigated by using a more active approach towards the control of the distribution networks. Demand side management (DSM) offers a possible solution to the problem, allowing to actively control the balance between generation, consumption and storage, close to the point of generation. An active energy management implies not only the capability to react promptly in case of disturbances, but also to ability to anticipate future events and take control actions accordingly. This is usually achieved through model predictive control (MPC), which requires a prediction of the future disturbances acting on the system. This thesis treat challenges of distributed DSM, with a particular focus on the case of a high penetration of PV power plants. The first subject of the thesis is the evaluation of the performance of models for forecasting and control with low computational requirements, of distributed electrical batteries. The proposed methods are compared by means of closed loop deterministic and stochastic MPC performance. The second subject of the thesis is the development of model based forecasting for PV power plants, and methods to estimate these models without the use of dedicated sensors. The third subject of the thesis concerns strategies for increasing forecasting accuracy when dealing with multiple signals linked by hierarchical relations. Hierarchical forecasting methods are introduced and a distributed algorithm for reconciling base forecasters is presented. At the same time, a new methodology for generating aggregate consistent probabilistic forecasts is proposed. This method can be applied to distributed stochastic DSM, in the presence of high penetration of rooftop installed PV systems. In this case, the forecasts' errors become mutually dependent, raising difficulties in the control problem due to the nontrivial summation of dependent random variables. The benefits of considering dependent forecasting errors over considering them as independent and uncorrelated, are investigated. The last part of the thesis concerns models for distributed energy markets, relying on hierarchical aggregators. To be effective, DSM requires a considerable amount of flexible load and storage to be controllable. This generates the need to be able to pool and coordinate several units, in order to reach a critical mass. In a real case scenario, flexible units will have different owners, who will have different and possibly conflicting interests. In order to recruit as much flexibility as possible, it is therefore importan