1,720,976 research outputs found
Biophysical models for cellular dynamics: applications to metabolic pathways and microtubules kinetics
No full textGli strumenti di calcolo permettono la simulazione al calcolatore di processi biologici fornendo risultati che possono essere utilizzati per la costruzione di approcci computazionali/sperimentali per lo studio della dinamica dei processi cellulari. Nella mia Tesi di Dottorato ho descritto ed applicato metodi di calcolo per l’analisi quantitativa della dinamica di diversi processi cellulari.
Il primo capitolo descrive i metodi matematici e computazionali utilizzati poi nelle applicazioni descritte nei capitoli successivi: la prima parte descrive i modelli cinetici dettagliati basati su equazioni differenziali ordinarie (ODEs) ed i modelli topografici e stechiometrici per simulare il metabolismo cellulare di microrganismi. Particolare attenzione è data all’applicazione di un metodo ibrido proposto in letteratura: lo Structural kinetic modeling (SKM). La seconda parte descrive alcuni metodi computazionali proposti in letteratura per l’analisi di serie di immagini su cellule viventi ottenute con la tecnologia della microscopia confocale. Sono descritti i metodi di calcolo che permettono il riconoscimento e la tracciatura automatica di comete di microtubuli.
Il secondo capitolo descrive la ricerca che ho svolto con l’applicazione dei metodi quantitativi all’analisi dei percorsi metabolici cellulari di microrganismi. Si descrivono le applicazioni del metodo ODEs ed SKM e tramite simulazioni al calcolatore si analizzano le variazioni nell’output dei parametri cinetici considerando perturbazioni nell’input. Si descrive la stima di parametri attraverso il paragone tra dati sperimentali e simulati e si propone un metodo di costruzione di un indice di differenza parametrica che possa essere utile nella costruzione di un approccio computazionale/sperimentale all’analisi del metabolismo cellulare di microrganismi.
Il terzo capitolo descrive la ricerca che ho svolto sull’analisi di immagini da microscopia confocale. Si descrivono le applicazioni dei metodi computazionali di rilevazione e tracciatura applicati allo studio della dinamica dei microtubuli, determinata a partire dall'analisi della crescita delle estremità positive grazie allo studio della proteina EB3, resa fluorescente mediante fusione traduzionale con GFP. Tali metodiche sono state applicate allo studio degli effetti dell'inattivazione della proteina Citron kinase sulla dinamica dei microtubuli e sull'angolo del fuso mitotico.Computational tools allow the simulation of biological processes giving results which can be used to build computational/experimental approaches for the study of cellular processes dynamics. In my Doctoral Thesis I described and applied calculation methods for the quantitative analysis of the dynamics of different cellular processes. The first chapter describes the mathematical and computational methods then used in the applications described in the following chapters: the first part describes the detailed kinetic models based on ordinary differential equations (ODEs) and the topographic and stoichiometric models to simulate the cellular metabolism of microorganisms. Particular attention is given to the application of an hybrid method: the structural kinetic modelling (SKM). The second part describes some computational methods proposed in literature for the time-series images analysis obtained with confocal microscopy on living cells. Calculation methods described allow the automated detection and tracking of microtubules comets. The second chapter describes my research activities in the application of the quantitative methods to the analysis of metabolic pathways in microorganisms. The application of ODEs and SKM methods are described and through computational simulations the output variation in kinetic parameters are analyzed respect to the perturbations in the input kinetic parameters. The parameter estimation is described through the comparison between experimental and simulation data and a method to build a difference index of kinetic parameters is suggested for build a computational/experimental approach to the analysis of cellular metabolism of microorganisms. The third chapter describes my research activities on the analysis of images obtained from confocal microscopy. Applications of computational methods for detection and tracking of microtubules comets are described. Microtubules dynamics are determined through the analysis of the growing of the microtubules plus ends by the study of EB3 protein made fluorescently by translational fusion with GFP. These methods have been applied to the study of the effects of the inactivation of the Citron kinase protein on the microtubules dynamics and on the angle of the mitotic spindle
On some statistical issues of structural kinetics models for metabolic pathways
No full textMetabolic pathways can be analyzed through different methodologies:detailed kinetic models, topological network analysis, stoichiometric analysis, and hybrid approaches. We review the SKM methodology as an intermediate approach
considering some statistical issues and suggesting some integration on the analysis of the parameter space which describe the dynamical system
Calibration with spatial data constraints
No full textWe describe an approach that combines the calibrated estimation and the spatial data analysis. In particular we want to describe the possibility of using calibrated estimators when spatial constraints arise in the estimation process with respect to some information that were considered available instead. We describe some possible constraints that could emerge during the estimation procedure and we develop an example of a constrained situation where the constraints are on auxiliary information available and on the density of the units in the spatial domain considered
Comparing model-assisted estimators of structural variables in forest surveys
No full textWe propose a selection of common model-assisted estimators and their relative efficiencies in assessing different forest structural variables in the Italian Alps. Field measurements were coupled to remotely sensed data as ancillary information. The novelty of this approach relies in the compared estimation of several independent structural variables
Quantitative analysis of microtubule comets: differences between boundary and inside comets velocity from confocal time series images
No full textParticle tracking is a key issue in the quantitative analysis of intracellular dynamic processes and many computational algorithms have been developed to execute this task (Chenouard et al. 2014). In the computational methods used to this purpose the spatial issue is related to the detection of particle coordinates and the temporal issue is related to particles tracking by analyzing, frame by frame, the dataset of time series images.
We apply a computer algorithm (Applegate et al. 2011) to track microtubule plus ends labeled by the +tip protein EB1, producing visible comets in time series. We analyzed the descriptive statistics of the comets velocity in time series images ob-tained from confocal microscopy. Finally, we tested the speed differences of the com-ets in different zones of the cell
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