In vivo behaviour of human precursors into a dystrophic context

The Duchenne Muscular Dystrophy (DMD) is a lethal recessive X-linked disease caused by mutations in the dystrophin gene, no effective treatment is available up to date. The development of effective therapies requires the use of animal models both dystrophic and immunotolerant for human cells. In collaboration with James Di Santo at the Pasteur Institute, a new mutant strain of mice was created: the Rag2−Il2rb−Dmd−. This mutant lacks T and B cells, as well as NK cells. It also harbours a mutation in the dystrophin gene. This study focuses on the morphological and immunohistochemical characterization of the muscle phenotype of the new mutant mouse, its comparison with the most used DMD model (mdx) and its potential use to evaluate the regenerative potential of human myogenic progenitors. The results obtained in this thesis have shown that the dystrophic phenotype is similar between the two models. Analysis of muscle regeneration has yielded very promising results. The Rag2−Il2rb−Dmd− mouse shows a peak of spontaneous regeneration between 10 and 16 weeks, which is six weeks of intense regeneration. Results obtained after transplantation of human myoblasts have confirmed that this new model is very suitable for myogenic cells transplantation, which can effectively participate in muscle regeneration. This is very important because allows to study the behaviour of human myogenic stem cells in natural dystrophic context

Valutazione sperimentale di metodi risolutivi per problemi "master" nella generazione di colonne

Il ne di questa tesi e di presentare un confronto tra i principali metodi risolutivi per problemi di ottimizzazione. Questo confronto non sara basato su risultati teorici quanto sull'applicazione ad un problema concreto: la risoluzione di Master Problem all'interno del software per la schedulazione di veicoli ed equipaggi sviluppato dall'azienda italiana MAIOR

New insights into the [FeFe]-hydrogenase maturation pathway

The aim of my PhD project was to obtain new structural and functional insights useful to draw a more detailed overall picture of the [FeFe]-hydrogenase maturation machinery. Indeed, although during recent years advances have been made in the knowledge of this maturation pathway, significant gaps remain in the understanding of how this process occurs. In this context, my work has been developed in these topics: The resolution of the tridimensional crystal structure of HydF, the key protein of the [FeFe]-hydrogenase maturation system. The results and the analysis of the structure and its domains are contained in Chapter 1 of the thesis. The obtained informations have also opened up new scenarios that have led me to investigate further aspects of the HydF protein structure-function relationship, reported in the other two chapters. In the second Chapter I describe the work that has led to the characterization of the HydF FeS cluster binding pocket. In particular, we have analyzed the role, in the cluster coordination as well as in the hydrogenase activation, of two histidines present close to three cysteines all belonging to the highly conserved FeS cluster binding consensus sequence. Finally, in the last part of my PhD work (whose results are collected in Chapter 3) I focused my attention on the biochemical characterization of the interactions between HydF and the other components of the [FeFe]-hydrogenase maturation process, which are needed for the activity of HydF both as a scaffold and a FeS cluster carrier in this pathway. Moreover, I investigated the HydF GTPase properties, which had been previously shown to be essential for the [FeFe]-hydrogenase activation

psort: sistema di documentazione

L'elaborato presenta alcune applicazioni pratiche della documentazione di un software (nello specifico nel progetto psort). In particolare fornisce delle guide rapide per l'utilizzo di Doxygen e la creazione di una man pageopenEmbarg

A Matheuristic for Integrated Timetabling and Vehicle Scheduling

Planning a public transportation system is a complex process, which is usually broken down in several phases, performed in sequence. Most often, the trips required to cover a service with the desired frequency (headway) are decided early on, while the vehicles needed to cover these trips are determined at a later stage. This potentially leads to requiring a larger number of vehicles (and, therefore, drivers) that would be possible if the two decisions were performed simultaneously. We propose a multicommodity-flow type model for integrated timetabling and vehicle scheduling. Since the model is large-scale and cannot be solved by off-the-shelf tools with the efficiency required by planners, we propose a diving-type matheuristic approach for the problem. We report on the efficiency and effectiveness of two variants of the proposed approach, differing on how the continuous relaxation of the problem is solved, to tackle real-world instances of bus transport planning problem originating from customers of M.A.I.O.R., a leading company providing services and advanced decision-support systems to public transport authorities and operators. The results show that the approach can be used to aid even experienced planners in either obtaining better solutions, or obtaining them faster and with less effort, or both

NIGHT-Care: A Passive RFID System for Remote Monitoring and Control of Overnight Living Environment

AbstractAn Ambient Intelligence platform, NIGHTCare, for remote monitoring and control of overnight living environment is here proposed. The platform, entirely based on RFID passive technology is able to recognize nocturnal behaviors and activities, generates automatic alarms in case of anomalous or pathological events and support diagnostics. The results of a complete test in real scenario are presented, together with a numerical assessment of electromagnetic safety issues

Análisis comparativo de las alteraciones dentales encontradas en el sector anterior de la arcada superior según el tipo de fisura en pacientes con labio y paladar hendido atendidos en operación sonrisa en el período comprendido entre 2011-2017.

El propósito de esta investigación fue identificar las alteraciones encontradas en el sector anterior de la arcada superior y el tipo de fisura en pacientes con labio y paladar hendido en los pacientes que asistieron al programa de Ortodoncia de Operación Sonrisa Panamá entre los años 2011 al 2017. La misma se realizó en base a la información obtenida en las tomografía computarizadas de haz cónico. Se analizaron 23 pacientes diagnosticados con labio y paladar hendido, tanto unilateral como bilateral; se hace el estudio de 68 piezas dentales, entre incisivos centrales, laterales y caninos, tomando la longitud dental en milímetros, análisis de las imágenes identificando las anomalías en número, forma y posición dental; se mide la longitud del hueso alveolar desde la cresta alveolar a la unión cemento-esmalte desde una vista coronal y sagital, y el grosor alveolar desde una vista axial, en 3mm y 6mm de la unión cemento-esmalte. Se realizó una estadística descriptiva de todas las variables: análisis de varianza, comparación de medias y prueba de efectos inter-sujetos según el tipo de variable. Se tuvo en consideración un nivel mínimo de significacía de p < 0.05. Se llega a distintas conclusiones según el tipo de variable: la fisura puede jugar un importante rol en el deficiente desarrollo dental, las anomalías dentales en número, tamaño, forma y posición está fuertemente relaciados con el labio y paladar hendido, la distancia de la cresta alveolar a la unión cemento-esmalte excedía de 1.5 mm, encontrándose mayormente afectado en pacientes LPH Bilaterales y en cuanto al grosor alveolar, se encuentra reducido en incisivos centrales de los pacientes LPH Bilaterales y en el lado fisurado de los pacientes LPH Unilaterales

Validation of the binding stoichiometry between HCN channels and their neuronal regulator TRIP8b by single molecule measurements

Tetratricopeptide repeat–containing Rab8b-interacting (TRIP8b) protein is a brain-specific subunit of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels, a class of voltage-gated channels modulated by cyclic nucleotides. While the interaction between TRIP8b and the cytosolic C terminus of the channel has been structurally described, the HCN:TRIP8b stoichiometry is less characterized. We employed single molecule mass photometry (MP) to image HCN4 particles purified in complex with TRIP8b. Our data show that four TRIP8b subunits are bound to the tetrameric HCN4 particle, confirming a 1:1 stoichiometry