New target tracking and monitoring guidance laws for UAV

A pursuer UAV tracking and loitering around a target is the problem analyzed in this thesis. The UAV is assumed to be a fixed-wing vehicle and constant airspeed together with bounded lateral accelerations are the main constraints of the problem. Three different guidance laws are designed for ensuring a continuos overfly on the target. Different proofs are presented to demonstrate the stability properties of the laws. All the algorithms are tested on a 6DoF Pioneer software simulator. Classic control design methods have been adopted to develop autopilots for implementig the simulation platform used for testing the guidance laws.

Shape memory and elastoplastic materials: from constitutive and numerical to fatigue modeling

Shape memory materials (SMMs) represent an important class of smart materials that have the ability to return from a deformed state to their original shape. Thanks to such a property, SMMs are utilized in a wide range of innovative applications. The increasing number of applications and the consequent involvement of industrial players in the field have motivated researchers to formulate constitutive models able to catch the complex behavior of these materials and to develop robust computational tools for design purposes. Such a research field is still under progress, especially in the prediction of shape memory polymer (SMP) behavior and of important effects characterizing shape memory alloy (SMA) applications. Moreover, the frequent use of shape memory and metallic materials in biomedical devices, particularly in cardiovascular stents, implanted in the human body and experiencing millions of in-vivo cycles by the blood pressure, clearly indicates the need for a deeper understanding of fatigue/fracture failure in microsize components. The development of reliable stent designs against fatigue is still an open subject in scientific literature. Motivated by the described framework, the thesis focuses on several research issues involving the advanced constitutive, numerical and fatigue modeling of elastoplastic and shape memory materials. Starting from the constitutive modeling, the thesis proposes to develop refined phenomenological models for reliable SMA and SMP behavior descriptions. Then, concerning the numerical modeling, the thesis proposes to implement the models into numerical software by developing implicit/explicit time-integration algorithms, to guarantee robust computational tools for practical purposes. The described modeling activities are completed by experimental investigations on SMA actuator springs and polyethylene polymers. Finally, regarding the fatigue modeling, the thesis proposes the introduction of a general computational approach for the fatigue-life assessment of a classical stent design, in order to exploit computer-based simulations to prevent failures and modify design, without testing numerous devices.

Sanctions and public enforcement of insider trading laws in Europe

The recent financial crisis triggered an increasing demand for financial regulation to counteract the potential negative economic effects of the evermore complex operations and instruments available on financial markets. As a result, insider trading regulation counts amongst the relatively recent but particularly active regulation battles in Europe and overseas. Claims for more transparency and equitable securities markets proliferate, ranging from concerns about investor protection to global market stability. The internationalization of the world’s securities market has challenged traditional notions of regulation and enforcement. Considering that insider trading is currently forbidden all over Europe, this study follows a law and economics approach in identifying how this prohibition should be enforced. More precisely, the study investigates first whether criminal law is necessary under all circumstances to enforce insider trading; second, if it should be introduced at EU level. This study provides evidence of law and economics theoretical logic underlying the legal mechanisms that guide sanctioning and public enforcement of the insider trading prohibition by identifying optimal forms, natures and types of sanctions that effectively induce insider trading deterrence. The analysis further aims to reveal the economic rationality that drives the potential need for harmonization of criminal enforcement of insider trading laws within the European environment by proceeding to a comparative analysis of the current legislations of height selected Member States. This work also assesses the European Union’s most recent initiative through a critical analysis of the proposal for a Directive on criminal sanctions for Market Abuse. Based on the conclusions drawn from its close analysis, the study takes on the challenge of analyzing whether or not the actual European public enforcement of the laws prohibiting insider trading is coherent with the theoretical law and economics recommendations, and how these enforcement practices could be improved.

The constitutive activation of the DNA damage response pathway is a novel therapeutic target in aggressive B-cell lymphoma

The recent finding that MYC-driven cancers are sensitive to inhibition of the DNA damage response (DDR) pathway, prompted us to investigate the role of DDR pathway as therapeutic target in diffuse large B-cell lymphoma (DLBCL), which frequently overexpresses the MYC oncogene. In a preliminary immunohistochemical study conducted on 99 consecutive DLBCL patients, we found that about half of DLBCLs showed constitutive expression of the phosphorylated forms of checkpoint kinases (CHK) and CDC25c, markers of DDR activation, and of phosphorylated histone H2AX (γH2AX), marker of DNA damage and genomic instability. Constitutive γH2AX expression correlated with c-MYC levels and DDR activation, and defined a subset of tumors characterised by poor outcome. Next, we used the CHK inhibitor PF-0477736 as a tool to investigate whether the inhibition of the DDR pathway might represent a novel therapeutic approach in DLBCL. Submicromolar concentrations of PF-0477736 hindered proliferation in DLBCL cell lines with activated DDR pathway. These results were fully recapitulated with a different CHK inhibitor (AZD-7762). Inhibition of checkpoint kinases induced rapid DNA damage accumulation and apoptosis in DLBCL cell lines and primary cells. These data suggest that pharmacologic inhibition of DDR through targeting of CHK kinases may represent a novel therapeutic strategy in DLBCL. The second part of this work is the clinical, molecular and functional description of a paradigmatic case of primary refractory Burkitt lymphoma characterized by spatial intratumor heterogeneity for the TP53 mutational status, high expression levels of genomic instability and DDR activation markers, primary resistance to chemotherapy and exquisite sensitivity to DDR inhibitors.