Sensor-based evaluation of Circadian motor behavior in people with Dementia. Development and validation of analysis strategies

[ITA]La demenza consiste nel deterioramento, spesso progressivo, dello stato cognitivo di un individuo. Chi è affetto da demenza, presenta alterazioni a livello cognitivo, comportamentale e motorio, ad esempio compiendo gesti ossessivi, ripetitivi, senza uno scopo preciso. La condizione dei pazienti affetti da demenza è valutata clinicamente tramite apposite scale e le informazioni relative al comportamento vengono raccolte intervistando chi se ne occupa, come familiari, il personale infermieristico o il medico curante. Spesso queste valutazioni si rivelano inaccurate, possono essere fortemente influenzate da considerazioni soggettive, e sono dispendiose in termini di tempo. Si ha quindi l'esigenza di disporre di metodiche oggettive per valutare il comportamento motorio dei pazienti e le sue alterazioni patologiche; i sensori inerziali indossabili potrebbero costituire una valida soluzione, per questo scopo. L'obiettivo principale della presente attività di tesi è stato definire e implementare un software per una valutazione oggettiva, basata su sensori, del pattern motorio circadiano, in pazienti affetti da demenza ricoverati in un'unità di terapia a lungo termine, che potrebbe evidenziare differenze nei sintomi della malattia che interessano il comportamento motorio, come descritto in ambito clinico. Lo scopo secondario è stato quello di verificare i cambiamenti motori pre- e post-intervento in un sottogruppo di pazienti, a seguito della somministrazione di un programma sperimentale di intervento basato su esercizi fisici. --------------- [ENG]Dementia involves deterioration, often progressive, of a person's cognitive status. Those who suffer from dementia, present alterations in cognitive and motor behavior, for example performing obsessive and repetitive gestures, without a purpose. The condition of patients suffering from dementia is clinically assessed by means of specific scales and information relating to the behavior are collected by interviewing caregivers, such as the family, nurses, or the doctor. Often it turns out that these are inaccurate assessments that may be heavily influenced by subjective evaluations and are costly in terms of time. Therefore, there is the need for objective methods to assess the patients' motor behavior and the pathological changes; wearable inertial sensors may represent a viable option, so this aim. The main objective of this thesis project was to define and implement a software for a sensor-based assessment of the circadian motor pattern in patients suffering from dementia, hospitalized in a long-term care unit, which could highlight differences in the disease symptoms affecting the motor behavior, as described in the clinical setting. The secondary objective was to verify pre- and post-intervention changes in the motor patterns of a subgroup of patients, following the administration of an experimental program of intervention based on physical exercises.

Modeling and validation of the thermal behavior of buildings for the development of demand response methods

The representation of the thermal behaviour of the building is achieved through a relatively simple dynamic model that takes into account the effects due to the thermal mass of the building components. The model of a intra-floor apartment has been built in the Matlab-Simulink environment and considers the heat transmission through the external envelope, wall and windows, the internal thermal masses, (i.e. furniture, internal wall and floor slabs) and the sun gain due to opaque and see-through surfaces of the external envelope. The simulations results for the entire year have been compared and the model validated, with the one obtained with the dynamic building simulation software Energyplus.

Modeling and simulation of a synthetic genetic circuit that implements a multicelled behavior in a growing microcolony of E. coli

Synthetic Biology is a relatively new discipline, born at the beginning of the New Millennium, that brings the typical engineering approach (abstraction, modularity and standardization) to biotechnology. These principles aim to tame the extreme complexity of the various components and aid the construction of artificial biological systems with specific functions, usually by means of synthetic genetic circuits implemented in bacteria or simple eukaryotes like yeast. The cell becomes a programmable machine and its low-level programming language is made of strings of DNA. This work was performed in collaboration with researchers of the Department of Electrical Engineering of the University of Washington in Seattle and also with a student of the Corso di Laurea Magistrale in Ingegneria Biomedica at the University of Bologna: Marilisa Cortesi. During the collaboration I contributed to a Synthetic Biology project already started in the Klavins Laboratory. In particular, I modeled and subsequently simulated a synthetic genetic circuit that was ideated for the implementation of a multicelled behavior in a growing bacterial microcolony. In the first chapter the foundations of molecular biology are introduced: structure of the nucleic acids, transcription, translation and methods to regulate gene expression. An introduction to Synthetic Biology completes the section. In the second chapter is described the synthetic genetic circuit that was conceived to make spontaneously emerge, from an isogenic microcolony of bacteria, two different groups of cells, termed leaders and followers. The circuit exploits the intrinsic stochasticity of gene expression and intercellular communication via small molecules to break the symmetry in the phenotype of the microcolony. The four modules of the circuit (coin flipper, sender, receiver and follower) and their interactions are then illustrated. In the third chapter is derived the mathematical representation of the various components of the circuit and the several simplifying assumptions are made explicit. Transcription and translation are modeled as a single step and gene expression is function of the intracellular concentration of the various transcription factors that act on the different promoters of the circuit. A list of the various parameters and a justification for their value closes the chapter. In the fourth chapter are described the main characteristics of the gro simulation environment, developed by the Self Organizing Systems Laboratory of the University of Washington. Then, a sensitivity analysis performed to pinpoint the desirable characteristics of the various genetic components is detailed. The sensitivity analysis makes use of a cost function that is based on the fraction of cells in each one of the different possible states at the end of the simulation and the wanted outcome. Thanks to a particular kind of scatter plot, the parameters are ranked. Starting from an initial condition in which all the parameters assume their nominal value, the ranking suggest which parameter to tune in order to reach the goal. Obtaining a microcolony in which almost all the cells are in the follower state and only a few in the leader state seems to be the most difficult task. A small number of leader cells struggle to produce enough signal to turn the rest of the microcolony in the follower state. It is possible to obtain a microcolony in which the majority of cells are followers by increasing as much as possible the production of signal. Reaching the goal of a microcolony that is split in half between leaders and followers is comparatively easy. The best strategy seems to be increasing slightly the production of the enzyme. To end up with a majority of leaders, instead, it is advisable to increase the basal expression of the coin flipper module. At the end of the chapter, a possible future application of the leader election circuit, the spontaneous formation of spatial patterns in a microcolony, is modeled with the finite state machine formalism. The gro simulations provide insights into the genetic components that are needed to implement the behavior. In particular, since both the examples of pattern formation rely on a local version of Leader Election, a short-range communication system is essential. Moreover, new synthetic components that allow to reliably downregulate the growth rate in specific cells without side effects need to be developed. In the appendix are listed the gro code utilized to simulate the model of the circuit, a script in the Python programming language that was used to split the simulations on a Linux cluster and the Matlab code developed to analyze the data.

Enhancing quality of service in software-defined networks

Resource management is of paramount importance in network scenarios and it is a long-standing and still open issue. Unfortunately, while technology and innovation continue to evolve, our network infrastructure system has been maintained almost in the same shape for decades and this phenomenon is known as “Internet ossification”. Software-Defined Networking (SDN) is an emerging paradigm in computer networking that allows a logically centralized software program to control the behavior of an entire network. This is done by decoupling the network control logic from the underlying physical routers and switches that forward traffic to the selected destination. One mechanism that allows the control plane to communicate with the data plane is OpenFlow. The network operators could write high-level control programs that specify the behavior of an entire network. Moreover, the centralized control makes it possible to define more specific and complex tasks that could involve many network functionalities, e.g., security, resource management and control, into a single framework. Nowadays, the explosive growth of real time applications that require stringent Quality of Service (QoS) guarantees, brings the network programmers to design network protocols that deliver certain performance guarantees. This thesis exploits the use of SDN in conjunction with OpenFlow to manage differentiating network services with an high QoS. Initially, we define a QoS Management and Orchestration architecture that allows us to manage the network in a modular way. Then, we provide a seamless integration between the architecture and the standard SDN paradigm following the separation between the control and data planes. This work is a first step towards the deployment of our proposal in the University of California, Los Angeles (UCLA) campus network with differentiating services and stringent QoS requirements. We also plan to exploit our solution to manage the handoff between different network technologies, e.g., Wi-Fi and WiMAX. Indeed, the model can be run with different parameters, depending on the communication protocol and can provide optimal results to be implemented on the campus network.

Genetic patterns in recovered specimens of Caretta caretta from the Adriatic Sea

The Adriatic Sea is considered a feeding and developmental area for Mediterranean loggerhead turtles, but this area is severely threatened by human impacts. In the Adriatic Sea loggerhead turtles are often found stranded or floating, but they are also recovered as by-catch from fishing activities. Nevertheless, information about population structuring and origin of individuals found in the Adriatic Sea are still limited. Cooperation with fishermen and a good network of voluntary collaborators are essential for understanding their distribution, ecology and for developing conservation strategies in the Adriatic Sea. In this study, a comparative analysis of biometric data and DNA sequence polymorphism of the long fragment of the mitochondrial control region was carried out on ninety-three loggerheads recovered from three feeding areas in the Adriatic Sea: North-western, North-eastern and South Adriatic. Differences in turtles body sizes (e.g. Straight Carapace Length) among the three recovery areas and relationship between SCL and the type of recovery were investigated. The origin of turtles from Mediterranean rookeries and the use of the Adriatic feeding habitats by loggerheads in different life-stages were assessed to understand the migratory pathway of the species. The analysis of biometric data revealed a significant difference in turtle sizes between the Southern and the Northern Adriatic. Moreover, size of captured turtles resulted significantly different from the size of stranded and floating individuals. Actually, neritic sub-adults and adults are more affected by incidental captures than juveniles because of their feeding behavior. The Bayesian mixed-stock analysis showed a strong genetic relationship between the Adriatic aggregates and Mediterranean rookeries, while a low pro¬portion of individuals of Atlantic origin were detected in the Adriatic feeding grounds. The presence of migratory pathways towards the Adriatic Sea due to the surface current system was reinforced by the finding of individuals bearing haplotypes endemic to the nesting populations of Libya, Greece and Israel. A relatively high contribution from Turkey and Cyprus to the Northwest and South Adriatic populations was identified when the three sampled areas were analyzed independently. These results have to be taken in account in a conservative perspective, since coastal hazards, affecting the population of turtles feeding in the Adriatic Sea may also affect the nesting populations of the Eastern Mediterranean with a unique genetic pattern.