Toward a multilevel representation of protein molecules: comparative approaches to the aggregation/folding propensity problem

This paper builds upon the fundamental work of Niwa et al. [34], which provides the unique possibility to analyze the relative aggregation/folding propensity of the elements of the entire Escherichia coli (E. coli) proteome in a cell-free standardized microenvironment. The hardness of the problem comes from the superposition between the driving forces of intra- and inter-molecule interactions and it is mirrored by the evidences of shift from folding to aggregation phenotypes by single-point mutations [10]. Here we apply several state-of-the-art classification methods coming from the field of structural pattern recognition, with the aim to compare different representations of the same proteins gathered from the Niwa et al. data base; such representations include sequences and labeled (contact) graphs enriched with chemico-physical attributes. By this comparison, we are able to identify also some interesting general properties of proteins. Notably, (i) we suggest a threshold around 250 residues discriminating "easily foldable" from "hardly foldable" molecules consistent with other independent experiments, and (ii) we highlight the relevance of contact graph spectra for folding behavior discrimination and characterization of the E. coli solubility data. The soundness of the experimental results presented in this paper is proved by the statistically relevant relationships discovered among the chemico-physical description of proteins and the developed cost matrix of substitution used in the various discrimination systems.Comment: 17 pages, 3 figures, 46 reference

Coherence in scale-free networks of chaotic maps

We study fully synchronized states in scale-free networks of chaotic logistic maps as a function of both dynamical and topological parameters. Three different network topologies are considered: (i) random scale-free topology, (ii) deterministic pseudo-fractal scale-free network, and (iii) Apollonian network. For the random scale-free topology we find a coupling strength threshold beyond which full synchronization is attained. This threshold scales as $k^{-\mu}$, where $k$ is the outgoing connectivity and $\mu$ depends on the local nonlinearity. For deterministic scale-free networks coherence is observed only when the coupling strength is proportional to the neighbor connectivity. We show that the transition to coherence is of first-order and study the role of the most connected nodes in the collective dynamics of oscillators in scale-free networks.Comment: 9 pages, 8 figure

Connectivity Influences on Nonlinear Dynamics in Weakly-Synchronized Networks: Insights from Rössler Systems, Electronic Chaotic Oscillators, Model and Biological Neurons

Natural and engineered networks, such as interconnected neurons, ecological and social networks, coupled oscillators, wireless terminals and power loads, are characterized by an appreciable heterogeneity in the local connectivity around each node. For instance, in both elementary structures such as stars and complex graphs having scale-free topology, a minority of elements are linked to the rest of the network disproportionately strongly. While the effect of the arrangement of structural connections on the emergent synchronization pattern has been studied extensively, considerably less is known about its influence on the temporal dynamics unfolding within each node. Here, we present a comprehensive investigation across diverse simulated and experimental systems, encompassing star and complex networks of Rössler systems, coupled hysteresis-based electronic oscillators, microcircuits of leaky integrate-and-fire model neurons, and finally recordings from in-vitro cultures of spontaneously-growing neuronal networks. We systematically consider a range of dynamical measures, including the correlation dimension, nonlinear prediction error, permutation entropy, and other information-theoretical indices. The empirical evidence gathered reveals that under situations of weak synchronization, wherein rather than a collective behavior one observes significantly differentiated dynamics, denser connectivity tends to locally promote the emergence of stronger signatures of nonlinear dynamics. In deterministic systems, transition to chaos and generation of higher-dimensional signals were observed; however, when the coupling is stronger, this relationship may be lost or even inverted. In systems with a strong stochastic component, the generation of more temporally-organized activity could be induced. These observations have many potential implications across diverse fields of basic and applied science, for example, in the design of distributed sensing systems based on wireless coupled oscillators, in network identification and control, as well as in the interpretation of neuroscientific and other dynamical data

Characterization of Neural Activity using Complex Network Theory. Application to the Identification of the Altered Neural Substrates in Schizophrenia

La esquizofrenia es un desorden psiquiátrico caracterizado por alteraciones en el pensamiento y en la capacidad de respuesta emocional. Comprende una gran variedad de síntomas, sin embargo, no está claro que todos compartan un sustrato neurológico común. Por ello, el objetivo de esta Tesis Doctoral es desarrollar un marco de referencia desde la perspectiva de la Teoría de Redes Complejas para investigar las interacciones neurales alteradas de la esquizofrenia haciendo uso de la señal electroencefalográfica. Así, dos bases de datos independientes de registros electroencefalográficos fueron registras durante una tarea cognitiva. Nuestros hallazgos son consistentes con estudios previos al tiempo que muestran una hiperactivación del intervalo de estímulo previa a una reorganización neural disminuida durante la cognición, principalmente asociado a caminos neurales secundarios. Los hallazgos de esta Tesis ponen de manifiesto la gran heterogeneidad de la esquizofrenia, posiblemente asociada a la existencia de subgrupos dentro de la misma.Departamento de Teoría de la Señal y Comunicaciones e Ingeniería TelemáticaDoctorado en Tecnologías de la Información y las Telecomunicacione

Mechanisms of Zero-Lag Synchronization in Cortical Motifs

Zero-lag synchronization between distant cortical areas has been observed in a diversity of experimental data sets and between many different regions of the brain. Several computational mechanisms have been proposed to account for such isochronous synchronization in the presence of long conduction delays: Of these, the phenomenon of "dynamical relaying" - a mechanism that relies on a specific network motif - has proven to be the most robust with respect to parameter mismatch and system noise. Surprisingly, despite a contrary belief in the community, the common driving motif is an unreliable means of establishing zero-lag synchrony. Although dynamical relaying has been validated in empirical and computational studies, the deeper dynamical mechanisms and comparison to dynamics on other motifs is lacking. By systematically comparing synchronization on a variety of small motifs, we establish that the presence of a single reciprocally connected pair - a "resonance pair" - plays a crucial role in disambiguating those motifs that foster zero-lag synchrony in the presence of conduction delays (such as dynamical relaying) from those that do not (such as the common driving triad). Remarkably, minor structural changes to the common driving motif that incorporate a reciprocal pair recover robust zero-lag synchrony. The findings are observed in computational models of spiking neurons, populations of spiking neurons and neural mass models, and arise whether the oscillatory systems are periodic, chaotic, noise-free or driven by stochastic inputs. The influence of the resonance pair is also robust to parameter mismatch and asymmetrical time delays amongst the elements of the motif. We call this manner of facilitating zero-lag synchrony resonance-induced synchronization, outline the conditions for its occurrence, and propose that it may be a general mechanism to promote zero-lag synchrony in the brain.Comment: 41 pages, 12 figures, and 11 supplementary figure

Modeling of Masonry Structures at Multiple Scales

Zdivo je materiál použitý ve většině stavebních památek na celém světě. Spolehlivé nástroje pro analýzu zděných konstrukcí jsou zapotřebí nejen pro vyhodnocení jejich seismické zranitelnosti, ale také při návrhu opatření směřujících k obnovení či zvýšení únosnosti existujících budov, které si zaslouží ochranu. Zdivo je nelineární, heterogenní a anizotropní materiál, jehož vlastnosti silně závisejí na základních stavebních jednotkách, tedy blocích (cihlách) a maltě, a na jejich prostorovém uspořádání. Pro simulaci mechanického chování zděných konstrukcí byla vyvinuta řada modelů, které se liší mírou rozlišení. Pro velké konstrukce vede snaha o výpočetní efektivitu ke zjednodušeným modelům, charakterizovaným rozdělením zděných stěn na makroprvky. Významným zástupcem této skupiny modelů je metoda ekvivalentního rámu. Její podstatou je nahrazení zděné stěny idealizovaným rámem, přičemž panely jsou modelovány jako nosníky charakterizované odpovídajícím mechanickým chováním. Míra rozlišení může být zvýšena tím, že se každý makroprvek uvažuje jako homogenizované kontinuum s vlastnostmi, které reprodukují celkovou odezvu určitého výseku heterogenní mikrostruktury. Formulace vhodného konstitutivního zákona ale není lehkou úlohou. Tento zákon by měl fenomenologicky reprodukovat mechanické chování materiálu, včetně vzniku tahových trhlin, smykového pokluzu, drcení v tlaku a dalších jevů. Navíc tento přístup vyžaduje těžkopádnou identifikaci mechanických parametrů, které není vždy snadné určit na základě běžných laboratorních testů materiálu. K popisu role základních stavebních jednotek a jejich interakce může posloužit model formulovaný na mikroúrovni, který explicitně bere v úvahu jednotlivé bloky, maltu a rozhraní mezi nimi. Tato práce se zabývá zděnými konstrukcemi na několika úrovních rozlišení. Problémy s formulací modelů ekvivalentního rámu v případě nepravidelného rozmístění otvorů se zkoumají na základě porovnání výsledků pro ekvivalentní rámy s výsledky získanými metodou konečných prvků, o které lze předpokládat, že lépe postihuje skutečné chování nepravidelných stěn. Provedená parametrická analýza zděných pilířů modelovaných jako homogenizované kontinuum je zaměřena na posouzení vlivu tvaru a svislého tlakového zatížení na nelineární statické chování. Pozornost se pak přesouvá na jemnější úrovně rozlišení, na nichž se zkoumá lokalizace nepružného přetváření, která ovlivňuje konstitutivní zákony pro modelování zdiva na makro a mikroúrovni. Provádí se lokalizační analýza ortotropního makroskopického modelu formulovaného podle teorie plasticity s více plochami plasticity, v jejímž rámci jsou odvozeny analytické podmínky lokalizace potvrzené simulacemi metodou konečných prvků. V závěru je vyvinut mikromechanický model pro pravidelné zdivo a pomocí něj se na reprezentativním objemu materiálu analyzují lokalizační vlastnosti, ovlivněné velikostí tohoto objemu a předpokládanými směry periodicityMasonry represents the material used in the great majority of the world building heritage structures. Reliable tools for analysis of masonry structures are needed not only for seismic vulnerability assessment but also to properly design interventions to restore and strengthen existing buildings, which deserve to be preserved. Masonry is a nonlinear, heterogeneous, and anisotropic material whose properties strongly depend on its microstructure, typically composed of two phases, blocks and mortar, and on the way it is assembled. To simulate the mechanical behavior of masonry structures, numerous models have been developed, characterized by different detailing levels. For large structures, the need for computational efficiency leads to simplified models characterized by the subdivision of masonry walls in macro-elements. A notable example of this group of models is the equivalent-frame method, which consists of identifying the masonry wall with an ideal frame, where panels are modeled as beams characterized by proper mechanical behavior. The detailing level can be increased by considering each macro-element as a homogenized continuum, assuming that, at the scale of representation, masonry can be treated as a continuum having mechanical properties that reproduce the overall response of a certain portion of the heterogeneous microstructure. However, the formulation of a suitable constitutive law is not an easy task. It should phenomenologically reproduce the material mechanics, including tension cracking, shear sliding, compressive crushing, and many other aspects. Moreover, this approach requires a cumbersome identification of mechanical parameters that are not always easy to determine from basic experimental tests on the material. To consider the role of each constituent and the effects of their interactions, a microscale model can be set up, where blocks, mortar joints, and mortar-block interfaces are represented explicitly. In this work, masonry structures are studied at several detailing levels. An issue affecting equivalent-frame models, namely the presence of irregularity in the wall opening layout, is addressed by comparing equivalent-frame results with finite-element ones, which are assumed to better represent the actual behavior of irregular walls. A parametric analysis on masonry piers, modeled as a homogenized continuum, is carried out, aimed to assess the influence of the height-to-width ratio and the vertical compression load on the nonlinear static behavior. The focus is then shifted to finer scales. The localization analysis of an orthotropic macro-scale model in the framework of multi-surface plasticity is presented, deriving analytical localization conditions corroborated by finite element simulations. Finally, a microscale model for regular masonry is developed to analyze the localization properties of the representative volume element, also by investigating the role of its size and periodicity directions

Comparing Features of Three-Dimensional Object Models Using Registration Based on Surface Curvature Signatures

This dissertation presents a technique for comparing local shape properties for similar three-dimensional objects represented by meshes. Our novel shape representation, the curvature map, describes shape as a function of surface curvature in the region around a point. A multi-pass approach is applied to the curvature map to detect features at different scales. The feature detection step does not require user input or parameter tuning. We use features ordered by strength, the similarity of pairs of features, and pruning based on geometric consistency to efficiently determine key corresponding locations on the objects. For genus zero objects, the corresponding locations are used to generate a consistent spherical parameterization that defines the point-to-point correspondence used for the final shape comparison