Modelling and analysis of internally BFRP reinforced beams at elevated temperatures

The aim of the work is to conduct a finite element model analysis on a small – size concrete beam and on a full size concrete beam internally reinforced with BFRP exposed at elevated temperatures. Experimental tests performed at Kingston University have been used to compare the results from the numerical analysis for the small – size concrete beam. Once the behavior of the small – size beam at room temperature is investigated and switching to the heating phase reinforced beams are tested at 100°C, 200°C and 300°C in loaded condition. The aim of the finite element analysis is to reflect the three – point bending test adopted into the oven during the exposure of the beam at room temperature and at elevated temperatures. Performance and deformability of reinforced beams are straightly correlated to the material properties and a wide analysis on elastic modulus and coefficient of thermal expansion is given in this work. Develop a good correlation between the numerical model and the experimental test is the main objective of the analysis on the small – size concrete beam, for both modelling the aim is also to estimate which is the deterioration of the material properties due to the heating process and the influence of different parameters on the final result. The focus of the full – size modelling which involved the last part of this work is to evaluate the effect of elevated temperatures, the material deterioration and the deflection trend on a reinforced beam characterized by a different size. A comparison between the results from different modelling has been developed.

Design and fabrication of MOMS-based ultrasonic probes for minimally invasive endoscopic applications

A Micro-opto-mechanical systems (MOMS) based technology for the fabrication of ultrasonic probes on optical fiber is presented. Thanks to the high miniaturization level reached, the realization of an ultrasonic system constituted by ultrasonic generating and detecting elements, suitable for minimally invasive applications or Non Destructive Evaluation (NDE) of materials at high resolution, is demonstrated. The ultrasonic generation is realized by irradiating a highly absorbing carbon film patterned on silicon micromachined structures with a nanosecond pulsed laser source, generating a mechanical shock wave due to the thermal expansion of the film induced by optical energy conversion into heat. The short duration of the pulsed laser, together with an appropriate emitter design, assure high frequency and wide band ultrasonic generation. The acoustic detection is also realized on a MOMS device using an interferometric receiver, fabricated with a Fabry-Perot optical cavity realized by means of a patterned SU-8 and two Al metallization levels. In order to detect the ultrasonic waves, the cavity is interrogated by a laser beam measuring the reflected power with a photodiode. Various issues related to the design and fabrication of these acoustic probes are investigated in this thesis. First, theoretical models are developed to characterize the opto-acoustic behavior of the devices and estimate their expected acoustic performances. Tests structures are realized to derive the relevant physical parameters of the materials constituting the MOMS devices and determine the conditions theoretically assuring the best acoustic emission and detection performances. Moreover, by exploiting the models and the theoretical results, prototypes of acoustic probes are designed and their fabrication process developed by means of an extended experimental activity.

Design and Setup of a New HPGe Detector Based Body Counter Capable of Detecting Also Low Energy Photon Emitters

The present work describes the development of a new body-counter system based on HPGe detectors and installed at IVM of KIT. The goal, achieved, was the improvement of the ability to detect internal contaminations in the human body, especially the ones concerning low-energy emitters and multiple nuclides. The development of the system started with the characterisation of detectors purchased for this specific task, with the optimisation of the different desired measurement configurations following and ending with the installation and check of the results. A new software has been developed to handle the new detectors.

Design and implementation of a fft pruning engine for DSA-enabled cognitive radios.

This research work presents the design and implementation of a FFT pruning block, which is an extension to the FFT core for OFDM demodulation, enabling run-time 8 pruning of the FFT algorithm, without any restrictions on the distribution pattern of the active/inactive sub-carriers. The design and implementation of FFT processor core is not the part of this work. The whole design was prototyped on an ALTERA STRATIX V FPGA to evaluate the performance of the pruning engine. Synthesis and simulation results showed that the logic overhead introduced by the pruning block is limited to a 10% of the total resources utilization. Moreover, in presence of a medium-high scattering of the sub-carriers, power and energy consumption of the FFT core were reduced by a 30% factor.

Design and synthesis of multipotent drugs: application to Alzheimer's disease and benign prostatic hyperplasia

The aim of this thesis was to synthesize multipotent drugs for the treatment of Alzheimer’s disease (AD) and for benign prostatic hyperplasia (BPH), two diseases that affect the elderly. AD is a neurodegenerative disorder that is characterized, among other factors, by loss of cholinergic neurons. Selective activation of M1 receptors through an allosteric site could restore the cholinergic hypofunction, improving the cognition in AD patients. We describe here the discovery and SAR of a novel series of quinone derivatives. Among them, 1 was the most interesting, being a high M1 selective positive allosteric modulator. At 100 nM, 1 triplicated the production of cAMP induced by oxotremorine. Moreover, it inhibited AChE and it displayed antioxidant properties. Site-directed mutagenesis experiments indicated that 1 acts at an allosteric site involving residue F77. Thus, 1 is a promising drug because the M1 activation may offer disease-modifying properties that could address and reduce most of AD hallmarks. BPH is an enlargement of the prostate caused by increased cellular growth. Blockade of α1-ARs is the predominant form of medical therapy for the treatment of the symptoms associated with BPH. α1-ARs are classified into three subtypes. The α1A- and α1D-AR subtypes are predominant in the prostate, while α1B-ARs regulate the blood pressure. Herein, we report the synthesis of quinazoline-derivatives obtained replacing the piperazine ring of doxazosin and prazosin with (S)- or (R)-3-aminopiperidine. The presence of a chiral center in the 3-C position of the piperidine ring allowed us to exploit the importance of stereochemistry in the binding at α1-ARs. It turned out that the S configuration at the 3-C position of the piperidine increases the affinity of the compounds at all three α1-AR subtypes, whereas the configuration at the benzodioxole ring of doxazosin derivatives is not critical for the interaction with α1-ARs.

Design and implementation of a testbed for data distribution management

Data Distribution Management (DDM) is a core part of High Level Architecture standard, as its goal is to optimize the resources used by simulation environments to exchange data. It has to filter and match the set of information generated during a simulation, so that each federate, that is a simulation entity, only receives the information it needs. It is important that this is done quickly and to the best in order to get better performances and avoiding the transmission of irrelevant data, otherwise network resources may saturate quickly. The main topic of this thesis is the implementation of a super partes DDM testbed. It evaluates the goodness of DDM approaches, of all kinds. In fact it supports both region and grid based approaches, and it may support other different methods still unknown too. It uses three factors to rank them: execution time, memory and distance from the optimal solution. A prearranged set of instances is already available, but we also allow the creation of instances with user-provided parameters. This is how this thesis is structured. We start introducing what DDM and HLA are and what do they do in details. Then in the first chapter we describe the state of the art, providing an overview of the most well known resolution approaches and the pseudocode of the most interesting ones. The third chapter describes how the testbed we implemented is structured. In the fourth chapter we expose and compare the results we got from the execution of four approaches we have implemented. The result of the work described in this thesis can be downloaded on sourceforge using the following link: https://sourceforge.net/projects/ddmtestbed/. It is licensed under the GNU General Public License version 3.0 (GPLv3).

Treatment of knee articular cartilage defects: surgical strategies, results and analysis of factors determining the clinical outcome

Articular cartilage lesions, with their inherent limited healing potential, are hard to treat and remain a challenging problem for orthopedic surgeons. Despite the development of several treatment strategies, the real potential of each procedure in terms of clinical benefit and effects on the joint degeneration processes is not clear. Aim of this PhD project was to evaluate the results, both in terms of clinical and imaging improvement, of new promising procedures developed to address the challenging cartilage pathology. Several studies have been followed in parallel and completed over the 3-year PhD, and are reported in detail in the following pages. In particular, the studies have been focused on the evaluation of the treatment indications of a scaffold based autologous chondrocyte implantation procedure, documenting its results for the classic indication of focal traumatic lesions, as well as its use for the treatment of more challenging patients, older, with degenerative lesions, or even as salvage procedure for more advanced stages of articular degeneration. The second field of study involved the analysis of the results obtained treating lesions of the articular surface with a new biomimetic osteochondral scaffold, which showed promise for the treatment of defects where the entire osteochondral unit is involved. Finally, a new minimally invasive procedure based on the use of growth factors derived from autologous platelets has been explored, showing results and underlining indicatios for the treatment of cartilage lesions and different stages of joint degeneration. These studies shed some light on the potential of the evaluated procedures, underlining good results as well as limits, they give some indications on the most appropriate candidates for their application, and document the current knowledge on cartilage treatment procedures suggesting the limitations that need to be addressed by future studies to improve the management of cartilage lesions.

Design and Fabrication of Bond Wire Micro-Magnetics

This thesis presents a new approach for the design and fabrication of bond wire magnetics for power converter applications by using standard IC gold bonding wires and micro-machined magnetic cores. It shows a systematic design and characterization study for bond wire transformers with toroidal and race-track cores for both PCB and silicon substrates. Measurement results show that the use of ferrite cores increases the secondary self-inductance up to 315 µH with a Q-factor up to 24.5 at 100 kHz. Measurement results on LTCC core report an enhancement of the secondary self-inductance up to 23 µH with a Q-factor up to 10.5 at 1.4 MHz. A resonant DC-DC converter is designed in 0.32 µm BCD6s technology at STMicroelectronics with a depletion nmosfet and a bond wire micro-transformer for EH applications. Measures report that the circuit begins to oscillate from a TEG voltage of 280 mV while starts to convert from an input down to 330 mV to a rectified output of 0.8 V at an input of 400 mV. Bond wire magnetics is a cost-effective approach that enables a flexible design of inductors and transformers with high inductance and high turns ratio. Additionally, it supports the development of magnetics on top of the IC active circuitry for package and wafer level integrations, thus enabling the design of high density power components. This makes possible the evolution of PwrSiP and PwrSoC with reliable highly efficient magnetics.

Design and fabrication of biocompatible scaffolds for the regeneration of tissues

Regenerative medicine and tissue engineering attempt to repair or improve the biological functions of tissues that have been damaged or have ceased to perform their role through three main components: a biocompatible scaffold, cellular component and bioactive molecules. Nanotechnology provide a toolbox of innovative scaffold fabrication procedures in regenerative medicine. In fact, nanotechnology, using manufacturing techniques such as conventional and unconventional lithography, allows fabricating supports with different geometries and sizes as well as displaying physical chemical properties tunable over different length scales. Soft lithography techniques allow to functionalize the support by specific molecules that promote adhesion and control the growth of cells. Understanding cell response to scaffold, and viceversa, is a key issue; here we show our investigation of the essential features required for improving the cell-surface interaction over different scale lengths. The main goal of this thesis has been to devise a nanotechnology-based strategy for the fabrication of scaffolds for tissue regeneration. We made four types of scaffolds, which are able to accurately control cell adhesion and proliferation. For each scaffold, we chose properly designed materials, fabrication and characterization techniques.

Design and development of the new composite-material mainplane of the Dallara T12 race car

Abstract (US) Composite material components design and production techniques are discussed in the present graduation paper. In particular, this paper covers the design process and the production process of a carbon-fiber composite material component for a high performance car, more specifically, the Dallara T12 race car. This graduation paper is split in two. After a brief introduction on existing composite materials (their origins and applications), the first part of the present paper covers the main theoretical concepts behind the design of composite material components: particular focus will be given to carbon-fiber composites. The second part of the present paper covers the whole design and production process that the candidate carried out to create the new front mainplane of the Dallara T12 race car. This graduation paper is the result of a six-months-long internship that the candidate conducted as Design Office Trainee inside Dallara Automobili S.p.A. Abstract (ITA) La presente tesi di laurea discute le metodologie progettuali e produttive legate alla realizzazione di un componente in materiale composito. Nello specifico, viene discussa la progettazione e la produzione di un componente in fibra di carbonio destinato ad una vettura da competizione. La vettura in esame è la Dallara T12. Il lavoro è diviso in due parti. Nella prima parte, dopo una breve introduzione sull’origine e le tipologie di materiali compositi esistenti, vengono trattati i concetti teorici fondamentali su cui si basa la progettazione di generici componenti in materiale composito, con particolare riguardo ai materiali in fibra di carbonio. Nella seconda parte viene discusso tutto il processo produttivo che il candidato ha portato a termine per realizzare il nuovo alettone anteriore della Dallara T12. La presente tesi di laurea è il risultato del lavoro di progettazione che il candidato ha svolto presso l’Ufficio Tecnico di Dallara Automobili S.p.A. nel corso di un tirocinio formativo di sei mesi.

Modelling and analysis of thin-walled beams in the context of the Generalized Beam Theory

In this work, the Generalized Beam Theory (GBT) is used as the main tool to analyze the mechanics of thin-walled beams. After an introduction to the subject and a quick review of some of the most well-known approaches to describe the behaviour of thin-walled beams, a novel formulation of the GBT is presented. This formulation contains the classic shear-deformable GBT available in the literature and contributes an additional description of cross-section warping that is variable along the wall thickness besides along the wall midline. Shear deformation is introduced in such a way that the classical shear strain components of the Timoshenko beam theory are recovered exactly. According to the new kinematics proposed, a reviewed form of the cross-section analysis procedure is devised, based on a unique modal decomposition. Later, a procedure for a posteriori reconstruction of all the three-dimensional stress components in the finite element analysis of thin-walled beams using the GBT is presented. The reconstruction is simple and based on the use of three-dimensional equilibrium equations and of the RCP procedure. Finally, once the stress reconstruction procedure is presented, a study of several existing issues on the constitutive relations in the GBT is carried out. Specifically, a constitutive law based on mirroring the kinematic constraints of the GBT model into a specific stress field assumption is proposed. It is shown that this method is equally valid for isotropic and orthotropic beams and coincides with the conventional GBT approach available in the literature. Later on, an analogous procedure is presented for the case of laminated beams. Lastly, as a way to improve an inherently poor description of shear deformability in the GBT, the introduction of shear correction factors is proposed. Throughout this work, numerous examples are provided to determine the validity of all the proposed contributions to the field.

Design and Synthesis of Naphthalene Diimides Based Small Molecules as Anticancer Agents: Targeting the Polyamine Transporter, G-quadruplex Structures and HDAC

Cancer is a multifactorial disease characterized by a very complex etiology. Basing on its complex nature, a promising therapeutic strategy could be based by the “Multi-Target-Directed Ligand” (MTDL) approach, based on the assumption that a single molecule could hit several targets responsible for the pathology. Several agents acting on DNA are clinically used, but the severe deriving side effects limit their therapeutic application. G-quadruplex structures are DNA secondary structures located in key zones of human genome; targeting quadruplex structures could allow obtaining an anticancer therapy more free from side effects. In the last years it has been proved that epigenetic modulation can control the expression of human genes, playing a crucial role in carcinogenesis and, in particular, an abnormal expression of histone deacetylase enzymes are related to tumor onset and progression. This thesis deals with the design and synthesis of new naphthalene diimide (NDI) derivatives endowed with anticancer activity, interacting with DNA together with other targets implicated in cancer development, such as HDACs. NDI-polyamine and NDI-polyamine-hydroxamic acid conjugates have been designed with the aim to provide potential MTDLs, in order to create molecules able simultaneously to interact with different targets involved in this pathology, specifically the G-quadruplex structures and HDAC, and to exploit the polyamine transport system to get selectively into cancer cells. Macrocyclic NDIs have been designed with the aim to improve the quadruplex targeting profile of the disubstituted NDIs. These compounds proved the ability to induce a high and selective stabilization of the quadruplex structures, together with cytotoxic activities in the micromolar range. Finally, trisubstituted NDIs have been developed as G-quadruplex-binders, potentially effective against pancreatic adenocarcinoma. In conclusion, all these studies may represent a promising starting point for the development of new interesting molecules useful for the treatment of cancer, underlining the versatility of the NDI scaffold.

Cannabinoid system combined to classic targets for a new MTDL strategy: design and synthesis of natural inspired molecules for Alzheimer's disease

In this thesis is described the design and synthesis of potential agents for the treatment of the multifactorial Alzheimer’s disease (AD). Our multi-target approach was to consider cannabinoid system involved in AD, together with classic targets. In the first project, designed modifications were performed on lead molecule in order to increase potency and obtain balanced activities on fatty acid amide hydrolase and cholinesterases. A small library of compounds was synthesized and biological results showed increased inhibitory activity (nanomolar range) related to selected target. The second project was focused on the benzofuran framework, a privileged structure being a common moiety found in many biologically active natural products and therapeutics. Hybrid molecules were designed and synthesized, focusing on the inhibition of cholinesterases, Aβ aggregation, FAAH and on the interaction with CB receptors. Preliminary results showed that several compounds are potent CB ligands, in particular the high affinity for CB2 receptors, could open new opportunities to modulate neuroinflammation. The third and the fourth project were carried out at the IMS, Aberdeen, under the supervision of Prof. Matteo Zanda. The role of the cannabinoid system in the brain is still largely unexplored and the relationship between the CB1 receptors functional modification, density and distribution and the onset of a pathological state is not well understood. For this reasons, Rimonabant analogues suitable as radioligands were synthesized. The latter, through PET, could provide reliable measurements of density and distribution of CB1 receptors in the brain. In the fifth project, in collaboration with CHyM of York, the goal was to develop arginine analogues that are target specific due to their exclusively location into NOS enzymes and could work as MRI contrasting agents. Synthesized analogues could be suitable substrate for the transfer of polarization by p-H2 molecules through SABRE technique transforming MRI a more sensitive and faster technique.