Mathematical modelling of integrin-like receptors systems

Nel presente lavoro, ho studiato e trovato le soluzioni esatte di un modello matematico applicato ai recettori cellulari della famiglia delle integrine. Nel modello le integrine sono considerate come un sistema a due livelli, attivo e non attivo. Quando le integrine si trovano nello stato inattivo possono diffondere nella membrana, mentre quando si trovano nello stato attivo risultano cristallizzate nella membrana, incapaci di diffondere. La variazione di concentrazione nella superficie cellulare di una sostanza chiamata attivatore dà luogo all’attivazione delle integrine. Inoltre, questi eterodimeri possono legare una molecola inibitrice con funzioni di controllo e regolazione, che chiameremo v, la quale, legandosi al recettore, fa aumentare la produzione della sostanza attizzatrice, che chiameremo u. In questo modo si innesca un meccanismo di retroazione positiva. L’inibitore v regola il meccanismo di produzione di u, ed assume, pertanto, il ruolo di modulatore. Infatti, grazie a questo sistema di fine regolazione il meccanismo di feedback positivo è in grado di autolimitarsi. Si costruisce poi un modello di equazioni differenziali partendo dalle semplici reazioni chimiche coinvolte. Una volta che il sistema di equazioni è impostato, si possono desumere le soluzioni per le concentrazioni dell’inibitore e dell’attivatore per un caso particolare dei parametri. Infine, si può eseguire un test per vedere cosa predice il modello in termini di integrine. Per farlo, ho utilizzato un’attivazione del tipo funzione gradino e l’ho inserita nel sistema, valutando la dinamica dei recettori. Si ottiene in questo modo un risultato in accordo con le previsioni: le integrine legate si trovano soprattutto ai limiti della zona attivata, mentre le integrine libere vengono a mancare nella zona attivata.

A mathematical model of the early visual system and border completion via subriemannian Hamiltonian geodesics

In this thesis, we aim to discuss a simple mathematical model for the edge detection mechanism and the boundary completion problem in the human brain in a differential geometry framework. We describe the columnar structure of the primary visual cortex as the fiber bundle R2 × S1, the orientation bundle, and by introducing a first vector field on it, explain the edge detection process. Edges are detected through a lift from the domain in R2 into the manifold R2 × S1 and are horizontal to a completely non-integrable distribution. Therefore, we can construct a subriemannian structure on the manifold R2 × S1, through which we retrieve perceived smooth contours as subriemannian geodesics, solutions to Hamilton’s equations. To do so, in the first chapter, we illustrate the functioning of the most fundamental structures of the early visual system in the brain, from the retina to the primary visual cortex. We proceed with introducing the necessary concepts of differential and subriemannian geometry in chapters two and three. We finally implement our model in chapter four, where we conclude, comparing our results with the experimental findings of Heyes, Fields, and Hess on the existence of an association field.

Safety factors in sheet pile wall design: considerations by using traditional methods and FEM analysis

The purpose of the work is: define and calculate a factor of collapse related to traditional method to design sheet pile walls. Furthermore, we tried to find the parameters that most influence a finite element model representative of this problem. The text is structured in this way: from chapter 1 to 5, we analyzed a series of arguments which are usefull to understanding the problem, while the considerations mainly related to the purpose of the text are reported in the chapters from 6 to 10. In the first part of the document the following arguments are shown: what is a sheet pile wall, what are the codes to be followed for the design of these structures and what they say, how can be formulated a mathematical model of the soil, some fundamentals of finite element analysis, and finally, what are the traditional methods that support the design of sheet pile walls. In the chapter 6 we performed a parametric analysis, giving an answer to the second part of the purpose of the work. Comparing the results from a laboratory test for a cantilever sheet pile wall in a sandy soil, with those provided by a finite element model of the same problem, we concluded that:in modelling a sandy soil we should pay attention to the value of cohesion that we insert in the model (some programs, like Abaqus, don’t accept a null value for this parameter), friction angle and elastic modulus of the soil, they influence significantly the behavior of the system (structure-soil), others parameters, like the dilatancy angle or the Poisson’s ratio, they don’t seem influence it. The logical path that we followed in the second part of the text is reported here. We analyzed two different structures, the first is able to support an excavation of 4 m, while the second an excavation of 7 m. Both structures are first designed by using the traditional method, then these structures are implemented in a finite element program (Abaqus), and they are pushed to collapse by decreasing the friction angle of the soil. The factor of collapse is the ratio between tangents of the initial friction angle and of the friction angle at collapse. At the end, we performed a more detailed analysis of the first structure, observing that, the value of the factor of collapse is influenced by a wide range of parameters including: the value of the coefficients assumed in the traditional method and by the relative stiffness of the structure-soil system. In the majority of cases, we found that the value of the factor of collapse is between and 1.25 and 2. With some considerations, reported in the text, we can compare the values so far found, with the value of the safety factor proposed by the code (linked to the friction angle of the soil).

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.

Parallelization of the algorithm WHAM with NVIDIA CUDA.

The aim of my thesis is to parallelize the Weighting Histogram Analysis Method (WHAM), which is a popular algorithm used to calculate the Free Energy of a molucular system in Molecular Dynamics simulations. WHAM works in post processing in cooperation with another algorithm called Umbrella Sampling. Umbrella Sampling has the purpose to add a biasing in the potential energy of the system in order to force the system to sample a specific region in the configurational space. Several N independent simulations are performed in order to sample all the region of interest. Subsequently, the WHAM algorithm is used to estimate the original system energy starting from the N atomic trajectories. The parallelization of WHAM has been performed through CUDA, a language that allows to work in GPUs of NVIDIA graphic cards, which have a parallel achitecture. The parallel implementation may sensibly speed up the WHAM execution compared to previous serial CPU imlementations. However, the WHAM CPU code presents some temporal criticalities to very high numbers of interactions. The algorithm has been written in C++ and executed in UNIX systems provided with NVIDIA graphic cards. The results were satisfying obtaining an increase of performances when the model was executed on graphics cards with compute capability greater. Nonetheless, the GPUs used to test the algorithm is quite old and not designated for scientific calculations. It is likely that a further performance increase will be obtained if the algorithm would be executed in clusters of GPU at high level of computational efficiency. The thesis is organized in the following way: I will first describe the mathematical formulation of Umbrella Sampling and WHAM algorithm with their apllications in the study of ionic channels and in Molecular Docking (Chapter 1); then, I will present the CUDA architectures used to implement the model (Chapter 2); and finally, the results obtained on model systems will be presented (Chapter 3).

Mathematical models for cellular aggregation: the chemotactic instability and clustering formation

In this thesis we present a mathematical formulation of the interaction between microorganisms such as bacteria or amoebae and chemicals, often produced by the organisms themselves. This interaction is called chemotaxis and leads to cellular aggregation. We derive some models to describe chemotaxis. The first is the pioneristic Keller-Segel parabolic-parabolic model and it is derived by two different frameworks: a macroscopic perspective and a microscopic perspective, in which we start with a stochastic differential equation and we perform a mean-field approximation. This parabolic model may be generalized by the introduction of a degenerate diffusion parameter, which depends on the density itself via a power law. Then we derive a model for chemotaxis based on Cattaneo's law of heat propagation with finite speed, which is a hyperbolic model. The last model proposed here is a hydrodynamic model, which takes into account the inertia of the system by a friction force. In the limit of strong friction, the model reduces to the parabolic model, whereas in the limit of weak friction, we recover a hyperbolic model. Finally, we analyze the instability condition, which is the condition that leads to aggregation, and we describe the different kinds of aggregates we may obtain: the parabolic models lead to clusters or peaks whereas the hyperbolic models lead to the formation of network patterns or filaments. Moreover, we discuss the analogy between bacterial colonies and self gravitating systems by comparing the chemotactic collapse and the gravitational collapse (Jeans instability).

Geometrico-static modelling of continuum parallel robots

In this thesis, we explore three methods for the geometrico-static modelling of continuum parallel robots. Inspired by biological trunks, tentacles and snakes, continuum robot designs can reach confined spaces, manipulate objects in complex environments and conform to curvilinear paths in space. In addition, parallel continuum manipulators have the potential to inherit some of the compactness and compliance of continuum robots while retaining some of the precision, stability and strength of rigid-links parallel robots. Subsequently, the foundation of our work is performed on slender beam by applying the Cosserat rod theory, appropriate to model continuum robots. After that, three different approaches are developed on a case study of a planar parallel continuum robot constituted of two connected flexible links. We solve the forward and inverse geometrico-static problem namely by using (a) shooting methods to obtain a numerical solution, (b) an elliptic method to find a quasi-analytical solution, and (c) the Corde model to perform further model analysis. The performances of each of the studied methods are evaluated and their limits are highlighted. This thesis is divided as follows. Chapter one gives the introduction on the field of the continuum robotics and introduce the parallel continuum robots that is studied in this work. Chapter two describe the geometrico-static problem and gives the mathematical description of this problem. Chapter three explains the numerical approach with the shooting method and chapter four introduce the quasi-analytical solution. Then, Chapter five introduce the analytic method inspired by the Corde model and chapter six gives the conclusions of this work.

Development of Optimal Energy Management Strategies for a Hybrid Boat

The present work proposes different approaches to extend the mathematical methods of supervisory energy management used in terrestrial environments to the maritime sector, that diverges in constraints, variables and disturbances. The aim is to find the optimal real-time solution that includes the minimization of a defined track time, while maintaining the classical energetic approach. Starting from analyzing and modelling the powertrain and boat dynamics, the energy economy problem formulation is done, following the mathematical principles behind the optimal control theory. Then, an adaptation aimed in finding a winning strategy for the Monaco Energy Boat Challenge endurance trial is performed via ECMS and A-ECMS control strategies, which lead to a more accurate knowledge of energy sources and boat’s behaviour. The simulations show that the algorithm accomplishes fuel economy and time optimization targets, but the latter adds huge tuning and calculation complexity. In order to assess a practical implementation on real hardware, the knowledge of the previous approaches has been translated into a rule-based algorithm, that let it be run on an embedded CPU. Finally, the algorithm has been tuned and tested in a real-world race scenario, showing promising results.

Hardware-In-The Loop setup and test of an air spring control system

In this work, a Hardware-in-the-loop test bench is designed. The bench is used to test the behaviour of an electronic control unit used in Maserati to control the dynamics of an air spring system. First the mathematical model of the plant has been defined, then the simulation enviroment and the test environment have been set up. The performed tests succesfully highlighted some bugs in the device under test.

Experimental characterization of a planar jet by hot-wire anemometry

The study of turbulence is also nowadays a problem that does not have solution from the mathematical point of view due to the lack of solution to link the mean part of the flow with the fluctuating one. To solve this problem, in the CICLoPE laboratory of Predappio, experiments on different type of jets are performed in order to derive a closure model able to close our mathematical model. One of the most interesting type of jet that could be studied is the planar turbulent free jet which is a two dimensional canonical jet characterized by the self-similarity condition of the velocity profiles. To study this particular jet, a new facility was built. The aim of this project is to characterize the jet at different distances from the nozzle exit, for different values of Reynolds number, to demonstrate that the self-similarity condition is respected. To do that, the evaluation of quantities such as spreading rate, centerline velocity decay and relation between fluctuations and mean part of the flow has to be obtain. All these parameters could be detected thanks to the use of single and X hot-wire anemometry with which it is possible to analyzed the fluctuating behaviour of the flow by associating to an electric signal a physical variable expressed in terms of velocity. To justify the data obtain by the measures, a comparison with results coming from the literature has to be shown.

Modeling and Model Predictive Control of an Industrial Hydraulic System

This thesis aims to illustrate the construction of a mathematical model of a hydraulic system, oriented to the design of a model predictive control (MPC) algorithm. The modeling procedure starts with the basic formulation of a piston-servovalve system. The latter is a complex non linear system with some unknown and not measurable effects that constitute a challenging problem for the modeling procedure. The first level of approximation for system parameters is obtained basing on datasheet informations, provided workbench tests and other data from the company. Then, to validate and refine the model, open-loop simulations have been made for data matching with the characteristics obtained from real acquisitions. The final developed set of ODEs captures all the main peculiarities of the system despite some characteristics due to highly varying and unknown hydraulic effects, like the unmodeled resistive elements of the pipes. After an accurate analysis, since the model presents many internal complexities, a simplified version is presented. The latter is used to linearize and discretize correctly the non linear model. Basing on that, a MPC algorithm for reference tracking with linear constraints is implemented. The results obtained show the potential of MPC in this kind of industrial applications, thus a high quality tracking performances while satisfying state and input constraints. The increased robustness and flexibility are evident with respect to the standard control techniques, such as PID controllers, adopted for these systems. The simulations for model validation and the controlled system have been carried out in a Python code environment.

Modeling, simulation, and control of a formation of multirotor aircraft for cooperative transportation of suspended loads

The work presented in this thesis aims to contribute to innovation in the Urban Air Mobility and Delivery sector and represents a solid starting point for air logistics and its future scenarios. The dissertation focuses on modeling, simulation, and control of a formation of multirotor aircraft for cooperative load transportation, with particular attention to environmental sustainability. First, a simulation and test environment is developed to assess technologies for suspended load stabilization. Starting from the mathematical model of two identical multirotors, formation-flight-keeping and collision-avoidance algorithms are analyzed. This approach guarantees both the safety of the vehicles within the formation and that of the payload, which may be made of people in the very near future. Afterwards, a mathematical model for the suspended load is implemented, as well as an active controller for its stabilization. The key focus of this part is represented by both analysis and control of payload oscillatory motion, by thoroughly investigating load kinetic energy decay. At this point, several test cases were introduced, in order to understand which strategy is the most effective and safe in terms of future applications in the field of air logistics.