A combined experimental and computational approach to investigate emergent network dynamics based on large-scale neuronal recordings

Sviluppo di un approccio integrato computazionale-sperimentale per lo studio di reti neuronali mediante registrazioni elettrofisiologich

Noise induced processes in neural systems

Real neurons, and their networks, are far too complex to be described exactly by simple deterministic equations. Any description of their dynamics must therefore incorporate noise to some degree. It is my thesis that the nervous system is organized in such a way that its performance is optimal, subject to this constraint. I further contend that neuronal dynamics may even be enhanced by noise, when compared with their deterministic counter-parts. To support my thesis I will present and analyze three case studies. I will show how noise might (i) extend the dynamic range of mammalian cold-receptors and other cells that exhibit a temperature-dependent discharge; (ii) feature in the perception of ambiguous figures such as the Necker cube; (iii) alter the discharge pattern of single cells

A novel framework for high-quality voice source analysis and synthesis

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.The analysis, parameterization and modeling of voice source estimates obtained via inverse filtering of recorded speech are some of the most challenging areas of speech processing owing to the fact humans produce a wide range of voice source realizations and that the voice source estimates commonly contain artifacts due to the non-linear time-varying source-filter coupling. Currently, the most widely adopted representation of voice source signal is Liljencrants-Fant's (LF) model which was developed in late 1985. Due to the overly simplistic interpretation of voice source dynamics, LF model can not represent the fine temporal structure of glottal flow derivative realizations nor can it carry the sufficient spectral richness to facilitate a truly natural sounding speech synthesis. In this thesis we have introduced Characteristic Glottal Pulse Waveform Parameterization and Modeling (CGPWPM) which constitutes an entirely novel framework for voice source analysis, parameterization and reconstruction. In comparative evaluation of CGPWPM and LF model we have demonstrated that the proposed method is able to preserve higher levels of speaker dependant information from the voice source estimates and realize a more natural sounding speech synthesis. In general, we have shown that CGPWPM-based speech synthesis rates highly on the scale of absolute perceptual acceptability and that speech signals are faithfully reconstructed on consistent basis, across speakers, gender. We have applied CGPWPM to voice quality profiling and text-independent voice quality conversion method. The proposed voice conversion method is able to achieve the desired perceptual effects and the modified speech remained as natural sounding and intelligible as natural speech. In this thesis, we have also developed an optimal wavelet thresholding strategy for voice source signals which is able to suppress aspiration noise and still retain both the slow and the rapid variations in the voice source estimate

INFN What Next: Ultra-relativistic Heavy-Ion Collisions

This document was prepared by the community that is active in Italy, within INFN (Istituto Nazionale di Fisica Nucleare), in the field of ultra-relativistic heavy-ion collisions. The experimental study of the phase diagram of strongly-interacting matter and of the Quark-Gluon Plasma (QGP) deconfined state will proceed, in the next 10-15 years, along two directions: the high-energy regime at RHIC and at the LHC, and the low-energy regime at FAIR, NICA, SPS and RHIC. The Italian community is strongly involved in the present and future programme of the ALICE experiment, the upgrade of which will open, in the 2020s, a new phase of high-precision characterisation of the QGP properties at the LHC. As a complement of this main activity, there is a growing interest in a possible future experiment at the SPS, which would target the search for the onset of deconfinement using dimuon measurements. On a longer timescale, the community looks with interest at the ongoing studies and discussions on a possible fixed-target programme using the LHC ion beams and on the Future Circular Collider.Comment: 99 pages, 56 figure

A systems biology approach to axis formation during early zebrafish embryogenesis: from biophysical measurements to model inference

During early embryogenesis, secreted proteins dictate the body plan of developing individuals. The resulting patterns are thought to be imposed by a graded distribution of molecular signals. To this day, it is not fully understood how signaling gradients are formed, maintained and adjusted to body sizes of differently sized individuals. This dissertation aims to provide new insights into the biophysical underpinnings of signal molecule gradients of early embryonic patterning and propose novel mechanisms that allow for scale-invariant patterning. Two of the most important parameters controlling the range and shape of signaling gradients are the rate at which signaling molecules decay and diffuse. Despite their importance, such biophysical parameters have not been measured or have only been assessed under simplified assumptions or contexts for most developmental systems. In this dissertation I present two assays and specialized software packages that allow the assessment of these parameters in living zebrafish embryos. I then demonstrate how these tools can be used to answer long-standing questions in early embryogenesis, such as how the dorsal-ventral axis is formed. This thesis provides evidence suggesting, in contrast to current hypotheses, that the dorsal-ventral axis is formed by a simple source-sink mechanism. Moreover, I show how to use mathematical modeling equipped with parameters estimated from the biophysical measurements to describe scale-invariant patterning during germ layer patterning in zebrafish development. My model, together with a rigorous multidimensional parameter screen fitted in normal and articially size-reduced embryos, was able to identify a new mechanism that allows for scaling of the germ layers in differently-sized embryos with realistic parameter congurations. In summary, this dissertation outlines how a systems biology approach can play a crucial role to advance the understanding of classical open questions in developmental biology

Models of self-organization in biological development

Bibliography: p. 297-320.In this thesis we thus wish to consider the concept of self-organization as an overall paradigm within which various theoretical approaches to the study of development may be described and evaluated. In the process, an attempt is made to give a fair and reasonably comprehensive overview of leading modelling approaches in developmental biology, with particular reference to self-organization. The work proceeds from a physical or mathematical perspective, but not unduly so - the major mathematical derivations and results are relegated to appendices - and attempts to fill a perceived gap in the extant review literature, in its breadth and attempted impartiality of scope. A characteristic of the present account is its markedly interdisciplinary approach: it seeks to place self-organization models that have been proposed for biological pattern formation and morphogenesis both within the necessary experimentally-derived biological framework, and in the wider physical context of self-organization and the mathematical techniques that may be employed in its study. Hence the thesis begins with appropriate introductory chapters to provide the necessary background, before proceeding to a discussion of the models themselves. It should be noted that the work is structured so as to be read sequentially, from beginning to end; and that the chapters in the main text were designed to be understood essentially independently of the appendices, although frequent references to the latter are given. In view of the vastness of the available information and literature on developmental biology, a working knowledge of embryological principles must be assumed. Consequently, rather than attempting a comprehensive introduction to experimental embryology, chapter 2 presents just a few biological preliminaries, to 'set the scene', outlining some of the major issues that we are dealing with, and sketching an indication of the current status of knowledge and research on development. The chapter is aimed at furnishing the necessary biological, experimental background, in the light of which the rest of the thesis should be read, and which should indeed underpin and motivate any theoretical discussions. We encounter the different hierarchical levels of description in this chapter, as well as some of the model systems whose experimental study has proved most fruitful, some of the concepts of experimental embryology, and a brief reference to some questions that will not be addressed in this work. With chapter 3, we temporarily move away from developmental biology, and consider the wider physical and mathematical concepts related to the study of self-organization. Here we encounter physical and chemical examples of spontaneous structure formation, thermodynamic considerations, and different approaches to the description of complexity. Mathematical approaches to the dynamical study of self-organization are also introduced, with specific reference to reaction-diffusion equations, and we consider some possible chemical and biochemical realizations of self-organizing kinetics. The chapter may be read in conjunction with appendix A, which gives a somewhat more in-depth study of reaction-diffusion equations, their analysis and properties, as an example of the approach to the analysis of self-organizing dynamical systems and mathematically-formulated models. Appendix B contains a more detailed discussion of the Belousov-Zhabotinskii reaction, which provides a vivid chemical paradigm for the concepts of symmetry-breaking and self-organization. Chapter 3 concludes with a brief discussion of a model biological system, the cellular slime mould, which displays rudimentary development and has thus proved amenable to detailed study and modelling. The following two chapters form the core of the thesis, as they contain discussions of the detailed application of theoretical concepts and models, largely based on self-organization, to various developmental situations. We encounter a diversity of models which has arisen largely in the last quarter century, each of which attempts to account for some aspect of biological pattern formation and morphogenesis; an aim of the discussion is to assess the extent of the underlying unity of these models in terms of the self-organization paradigm. In chapter 4 chemical pre-patterns and positional information are considered, without the overt involvement of cells in the patterning. In chapter 5, on the other hand, cellular interactions and activities are explicitly taken into account; this chapter should be read together with appendix C, which contains a brief introduction to the mathematical formulation and analysis of some of the models discussed. The penultimate chapter, 6, considers two other approaches to the study of development; one of these has faded away, while the other is still apparently in the ascendant. The assumptions underlying catastrophe theory, the value of its applications to developmental biology and the reasons for its decline in popularity, are considered. Lastly, discrete approaches, including the recently fashionable cellular automata, are dealt with, and the possible roles of rule-based interactions, such as of the so-called L-systems, and of fractals and chaos are evaluated. Chapter 7 then concludes the thesis with a brief assessment of the value of the self-organization concept to the study of biological development

Supercontinuum radiation for ultra-high sensitivity liquid-phase sensing

The real-time detection of trace species is key to a wide range of applications such as on-line chemical process analysis, medical diagnostics, identification of environmentally toxic species and atmospheric pollutant sensing. There is a growing demand for suitable techniques that are not only sensitive, but also simple to operate, fast and versatile. Most currently available techniques, such as spectrophotometry, are neither sensitive enough nor fast enough for kinetic studies, whilst other techniques are too complex to be operated by the non-specialist. This thesis presents two techniques that have been developed for and applied to liquid-phase analysis, with supercontinuum (SC) radiation used for liquid-phase absorption for the first time. Firstly, supercontinuum cavity enhanced absorption spectroscopy (SC-CEAS) was used for the kinetic measurement of chemical species in the liquid phase using a linear optical cavity. This technique is simple to implement, robust and achieves a sensitivity of 9.1 × 10−7 cm−1 Hz−1/2 at a wavelength of 550nm for dye species dissolved in water. SC-CEAS is not calibration-free and for this purpose a second technique, a time-resolved variant called broadband cavity ring-down spectroscopy (BB-CRDS), was successfully developed. Use of a novel single-photon avalanche diode (SPAD) array enabled the simultaneous detection of ring-down events at multiple spectral positions for BB-CRDS measurements. The performance of both techniques is demonstrated through a number of applications that included the monitoring of an oscillating (Belousov-Zhabotinsky) reaction, detection of commercially important photoluminescent metal complexes (europium(III)) at trace level concentration, and the analysis of biomedical species (whole and lysed blood) and proteins (amyloids). Absorption spectra covering the entire visible wavelength range can be acquired in fractions of a second using sample volumes measuring only 1.0mL. Most alternative devices capable of achieving similar sensitivity have, up until now, been restricted to single wavelength measurements. This has limited speed and number of species that can be measured at once. The work presented here exemplifies the potential of these techniques as analytical tools for research scientists, healthcare practitioners and process engineers alike

Numerical resistive relativistic magnetohydrodynamics

La presente tesis se desarrollada dentro del marco de la Magnetohidrodinámica Resistiva Relativistica (RRMHD; por sus siglas en inglés) y uno de sus principales objetivos es el caracterizar las condiciones físicas que optimizan la disipación de campos magnéticos en plasmas relativistas, especialmente en aquellos que son de interés astrofísico. Para alcanzar este objetivo, realizamos el estudio de los denominados modos de ruptura dobles, bajo condiciones ideales (IDTMs; por sus siglas en inglés) que maximizan sus tasas de crecimiento. Se demuestra que en el régimen relativista los IDTMs pueden crecer en escalas de tiempo de unos pocos tiempos característicos de Alfvén, desarrollando regímenes explosivos, incluso si las condiciones en las que se desarrollan no son estrictamente ideales. Ello nos permite concluir que los IDTMs relativistas pueden utilizarse para explicar los fenómenos de reconexión astrofísicos más violentos, como por ejemplo los que se cree que acontecen en la magnetosferas de estrellas de neutrones. Para lograr este objetivo, piedra angular de la tesis, se construyó un nuevo código RRMHD, apto para ser usado en el estudio de plasmas en el contexto astrofísico. Este nuevo código denominado CUEVA , se basa en una formulación conservativa de volúmenes finitos de las ecuaciones de RRMHD. La evolución de un estado inicial dado se realiza mediante la técnica conocida como método de líneas. Dado que en el régimen ideal el sistema de ecuaciones de la RRMHD es matemáticamente rígido, la integración temporal se lleva a cabo con métodos parcialmente implícitos. En C UEVA se implementan dos familias principales de integradores de tiempo: los métodos denominados RKIMEX y MIRK. Como un subproducto de esta tesis, hemos desarrollado un resolvedor aproximado del tipo HLLC. El nuevo resolvedor captura de forma exacta discontinuidades de contacto estacionarias. En combinación con técnicas de reconstrucción espacial de orden ultra-alto, en esta tesis caracterizamos la resistividad y la viscosidad numérica de CUEVA de manera exhaustiva. Ello nos ha permitido delimitar con claridad que el desarrollo de los IDTMs es de origen físico y no un artefacto numérico.The main goal of this thesis is the study of magnetic reconnection in relativistic plasma of astrophysical interest. We pay special attention to the dynamical effects that the resistive dissipation of magnetic fields may have in such process. Thus, our approach to the study is numerical, i.e. we developed numerical models that mimic as closely as possible the physical conditionsunder which reconnection happens in relativistic astrophysical plasma. The goals of this thesis can be grouped in two sets: computational and physical. Considering that we aim to obtain physical results (ideally) indepen-dent of the numerical methods that we employ, we pursue the development of a new multidimensional RRMHD code for astrophysical applications. The code include, different numerical algorithms for the time-evolution, for the solution of the Riemann problem and for the intercell reconstruction. Only in this way we may calibrate the impact of the numerical methods on the results. Therefore, concerning the physics of reconnection in astro-physical plasma, our first and foremost goal is to understand the dependenceof the growth rate of resistive instabilities (such as TM instabilities) on the physical properties of the plasma. We shall consider specifically the case of relativistic ideal double tearing modes (RIDTMs), where the adjective ideal refers to the fact that the instability develops at a timescale of the order of the MHD timescale (i.e. Alfvén crossing time) and its growth rate is independent of the resistivity (and thus, it does not diverge in the ideal RMHD regime). This is an unexplored and interesting setup where two parallel current sheets may interact as TMs develop yielding an explosive reconnection episode, where the reconnection time scales are so small that may be of interest for explaining a number of astrophysical objects