MEM Resonators for RF Applications and Chemical Sensing

In this thesis modelling, design, fabrication and characterization of MEM (MicroElectroMechanical) resonators for RF applications and chemical sensing are discussed. MEM resonators allow to obtain integrated highly selective filters and low phase noise oscillators for RF applications, as well as sensors of chemical and biological species, which can be used to obtain a sensor array on a chip, leading to the possibility of very complex analysis in a very small space. Specifically, a novel RF device, namely a free-free resonator on the third mode, is presented and its basic working is demonstrated. Effect of temperature and axial stress on this device and on other flexural resonators is discussed and an equivalent circuit for free-free resonator is proposed. Furthermore, the optimized design of a bulk-mode disk resonator is presented. The goal of this optimization is the achievement of the maximum quality factor (i.e. maximizing selectivity in filter architecture or minimizing the phase noise in resonator-based oscillators) at a target resonance frequency. The maximization is based on an original strategy of estimation of the quality factor of the device through FEM simulations. Finally, the design of an innovative microbalance is presented. The main features of this device are the actuation and the sensing, which are both magnetic. The device has been fabricated with a CMOS-compatible process. The frequency response of the device was measured, showing the basic working of the device

Covariant spin-parity decomposition of the Torsion and Path Integrals

We propose a functional measure over the torsion tensor. We discuss two completely equivalent choices for the Wheeler-DeWitt supermetric for this field, the first one being based on its algebraic decomposition, the other inspired by teleparallel theories of gravity. The measure is formally defined by requiring the normalization of the Gaussian integral. To achieve such a result we split the torsion tensor into its spin-parity eigenstates by constructing a new, York-like, decomposition. Of course, such a decomposition has a wider range of applicability to any kind of tensor sharing the symmetries of the torsion. As a result of this procedure a functional Jacobian naturally arises, whose formal expression is given exactly in the phenomenologically interesting limit of maximally symmetric spaces. We also discuss the explicit computation of this Jacobian in the case of a $4$-dimensional sphere $S^4$ with particular emphasis on its logarithmic divergences.Comment: 20 pages, 1 tabl

TinderMIX : Time-dose integrated modelling of toxicogenomics data

Background: Omics technologies have been widely applied in toxicology studies to investigate the effects of different substances on exposed biological systems. A classical toxicogenomic study consists in testing the effects of a compound at different dose levels and different time points. The main challenge consists in identifying the gene alteration patterns that are correlated to doses and time points. The majority of existing methods for toxicogenomics data analysis allow the study of the molecular alteration after the exposure (or treatment) at each time point individually. However, this kind of analysis cannot identify dynamic (time-dependent) events of dose responsiveness. Results: We propose TinderMIX, an approach that simultaneously models the effects of time and dose on the transcriptome to investigate the course of molecular alterations exerted in response to the exposure. Starting from gene log fold-change, TinderMIX fits different integrated time and dose models to each gene, selects the optimal one, and computes its time and dose effect map; then a user-selected threshold is applied to identify the responsive area on each map and verify whether the gene shows a dynamic (time-dependent) and dose-dependent response; eventually, responsive genes are labelled according to the integrated time and dose point of departure. Conclusions: To showcase the TinderMIX method, we analysed 2 drugs from the Open TG-GATEs dataset, namely, cyclosporin A and thioacetamide. We first identified the dynamic dose-dependent mechanism of action of each drug and compared them. Our analysis highlights that different time- and dose-integrated point of departure recapitulates the toxicity potential of the compounds as well as their dynamic dose-dependent mechanism of action.Peer reviewe

Automatic Optimization of an in Silico Model of Human iPSC Derived Cardiomyocytes Recapitulating Calcium Handling Abnormalities

The growing importance of human induced pluripotent stem cell-derived cardiomyoyctes (hiPSC-CMs), as patient-specific and disease-specific models for studying cellular cardiac electrophysiology or for preliminary cardiotoxicity tests, generated better understanding of hiPSC-CM biophysical mechanisms and great amount of action potential and calcium transient data. In this paper, we propose a new hiPSC-CM in silico model, with particular attention to Ca2+ handling. We used (i) the hiPSC-CM Paci2013 model as starting point, (ii) a new dataset of Ca2+ transient measurements to tune the parameters of the inward and outward Ca2+ fluxes of sarcoplasmic reticulum, and (iii) an automatic parameter optimization to fit action potentials and Ca2+ transients. The Paci2018 model simulates, together with the typical hiPSC-CM spontaneous action potentials, more refined Ca2+ transients and delayed afterdepolarizations-like abnormalities, which the old Paci2013 was not able to predict due to its mathematical formulation. The Paci2018 model was validated against (i) the same current blocking experiments used to validate the Paci2013 model, and (ii) recently published data about effects of different extracellular ionic concentrations. In conclusion, we present a new and more versatile in silico model, which will provide a platform for modeling the effects of drugs or mutations that affect Ca2+ handling in hiPSC-CMs

Robot-assisted upper limb training for patients with multiple sclerosis: an evidence-based review of clinical applications and effectiveness

Upper extremities limitation is a common functional impairment in patients with Multiple Sclerosis (PwMS). Novel technological devices are increasingly used in neurorehabilitation to support motor function improvement and the quantitative assessment of motor performance during training in patients with neurological diseases. In this review, we systematically report the evidence on clinical applications and robotic-assisted arm training (RAT) in functional recovery in PwMS. PubMed/MEDLINE, the Cochrane Library, and the Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to March 2021. The 10-item PEDro scale assessed the study quality for the RCT, and the AMSTAR-2 was used to assess the quality of the systematic review. The 5-item Oxford CEBM scale was used to rate the level of evidence. A total of 10 studies (161 subjects) were included. The selected studies included one systematic review, four RCTs, one randomized crossover, and four case series. The RCTs were scored as high-quality studies, while the systematic review was determined to be of low quality. Shoulder range of motion, handgrip strength, and proximal arm impairment improved after RAT. Manual dexterity, arm function, and use in daily life also ameliorated arm function. The high clinical heterogeneity of treatment programs and the variety of robot devices affects the generalizability of the study results; therefore, we emphasize the need to standardize the intervention type in future studies that evaluate the role of robotic-assisted training in PwMS. Robot-assisted treatment seems safe and useful to increase manual dexterity and the quality of movement execution in PwMS with moderate to severe disability. Additional studies with an adequate sample size and methodological rigour are warranted to drive definite conclusion

Upper limb robotic rehabilitation for patients with cervical spinal cord injury: a comprehensive review

The upper extremities limitation represents one of the essential functional impairments in patients with cervical spinal cord injury. Electromechanics assisted devices and robots are increasingly used in neurorehabilitation to help functional improvement in patients with neurological diseases. This review aimed to systematically report the evidence-based, state-of-art on clinical applications and robotic-assisted arm training (RAT) in motor and functional recovery in subjects affected by cervical spinal cord injury. The present study has been carried out within the framework of the Italian Consensus Conference on "Rehabilitation assisted by robotic and electromechanical devices for persons with disability of neurological origin" (CICERONE). PubMed/MEDLINE, Cochrane Library, and Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to September 2021. The 10-item PEDro scale assessed the study quality for the RCT and the AMSTAR-2 for the systematic review. Two different authors rated the studies included in this review. If consensus was not achieved after discussion, a third reviewer was interrogated. The five-item Oxford CEBM scale was used to rate the level of evidence. A total of 11 studies were included. The selected studies were: two systematic reviews, two RCTs, one parallel-group controlled trial, one longitudinal intervention study and five case series. One RCT was scored as a high-quality study, while the systematic review was of low quality. RAT was reported as feasible and safe. Initial positive effects of RAT were found for arm function and quality of movement in addition to conventional therapy. The high clinical heterogeneity of treatment programs and the variety of robot devices could severely affect the generalizability of the study results. Therefore, future studies are warranted to standardize the type of intervention and evaluate the role of robotic-assisted training in subjects affected by cervical spinal cord injury

Effects of robotic upper limb treatment after stroke on cognitive patterns: A systematic review

Background: Robotic therapy (RT) has been internationally recognized for the motor rehabilitation of the upper limb. Although it seems that RT can stimulate and promote neuroplasticity, the effectiveness of robotics in restoring cognitive deficits has been considered only in a few recent studies. Objective: To verify whether, in the current state of the literature, cognitive measures are used as inclusion or exclusion criteria and/or outcomes measures in robotic upper limb rehabilitation in stroke patients. Methods: The systematic review was conducted according to PRISMA guidelines. Studies eligible were identified through PubMed/MEDLINE and Web of Science from inception to March 2021. Results: Eighty-one studies were considered in this systematic review. Seventy-three studies have at least a cognitive inclusion or exclusion criteria, while only seven studies assessed cognitive outcomes. Conclusion: Despite the high presence of cognitive instruments used for inclusion/exclusion criteria their heterogeneity did not allow the identification of a guideline for the evaluation of patients in different stroke stages. Therefore, although the heterogeneity and the low percentage of studies that included cognitive outcomes, seemed that the latter were positively influenced by RT in post-stroke rehabilitation. Future larger RCTs are needed to outline which cognitive scales are most suitable and their cut-off, as well as what cognitive outcome measures to use in the various stages of post-stroke rehabilitation

Application of AFT Fathom code to steady-state thermal-hydraulics analysis of ITER Primary Heat Transfer Systems

The ITER Tokamak Cooling Water System (TCWS) is comprised of four (3) primary heat transfer systems and their supporting sub-systems; these primary heat transfer systems include First Wall Blanket and Divertor PHTS, Neutral Beam Injector PHTS, Vacuum Vessel PHTS. The TCWS provides the cooling water to ITER tokamak client systems for heat removal during plasma operations and provides the primary confinement barrier for the radioactive substances (Activated Corrosion Products (ACPs) and tritium) that become entrained in the cooling water. The TCWS PHTSs have specific functional design criteria for meeting the thermal-hydraulic parameters for heat removal, pressure, and temperature at the supply and return headers and at the tokamak in-vessel components. These parameters need to be carefully assessed in order to select key components that comprise the physical system including pumps, heat exchangers, valves, pipe and balancing orifices. AFT FathomTM code is a graphical platform for modeling incompressible flow in pipe networks. The main features of the code include the modeling network flow, pressure, and temperature at all node points in the system based on the Process Flow Diagram (PFD) and the input data (Workspace Window) and provide the analysis results (Visual Report Window) in a graphical form. FATHOMTM permits the definition of geometric properties of the circuit and includes pipe length, fittings, and components elevations. These characteristics are utilized to verify the correspondence of physical the geometry of the model with the analog PFD and hence provide a good approximation of the actual hydraulic circuit. The various models of the PHTSs performed using FATHOMTM permits the prediction of the various thermal-hydraulics characteristics during the steady-state performance of the TCWS

Modeling and characterization of three kinds of MEMS resonators fabricated with a thick polysilicon technology

Three different kinds of two-port flexural res nators, with both clamped and free ends, and with nominal resonance frequencies between 5 MHz and 50 MHz, were designed and fabricated. Among them, a novel free-free third-mode resonator, as well as a tunable free-free resonator, designed to maintain a high quality factor despite its tunability, are presented. Because of reduced energy loss in the clamps, higher quality factors are expected from free-free devices. To estimate the resonators performance, the effect of temperature and axial stresses on the resonators is investigated:for the clamped-clamped resonator, a theoretical model is also presented. FEM simulations are performed for the three geometries and the results are discussed.info:eu-repo/semantics/publishe