949 resultados para Non-linear dose-response curve


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The degradation behaviour of SnO(2)-based varistors (SCNCr) due to current pulses (8/20 mu s) is reported here for the first time in comparison with the ZnO-based commercial varistors (ZnO). Puncturing and/or cracking failures were observed in ZnO-based varistors possessing inferior thermo-mechanical properties in comparison with that found in a SCNCr system free of failures. Both systems presented electric degradation related to the increase in the leakage current and decrease in the electric breakdown field, non-linear coefficient and average value of the potential barrier height. However, it was found that a more severe degradation occurred in the ZnO-based varistors concerning their non-ohmic behaviour, while in the SCNCr system, a strong non-ohmic behaviour remained after the degradation. These results indicate that the degradation in the metal oxide varistors is controlled by a defect diffusion process whose rate depends on the mobility, the concentration of meta-stable defects and the amount of electrically active interfaces. The improved behaviour of the SCNCr system is then inferred to be associated with the higher amount of electrically active interfaces (85%) and to a higher energy necessary to activate the diffusion of the specific defects.

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This work addresses the solution to the problem of robust model predictive control (MPC) of systems with model uncertainty. The case of zone control of multi-variable stable systems with multiple time delays is considered. The usual approach of dealing with this kind of problem is through the inclusion of non-linear cost constraint in the control problem. The control action is then obtained at each sampling time as the solution to a non-linear programming (NLP) problem that for high-order systems can be computationally expensive. Here, the robust MPC problem is formulated as a linear matrix inequality problem that can be solved in real time with a fraction of the computer effort. The proposed approach is compared with the conventional robust MPC and tested through the simulation of a reactor system of the process industry.

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In the present study, we investigated the involvement of beta-adrenoceptors in the medial amygdaloid nucleus (MeA) in cardiovascular responses evoked in rats submitted to an acute restraint stress. We first pretreated Wistar rats with the nonselective beta-adrenoceptor antagonist propranolol microinjected bilaterally into the MeA (10, 15, and 20 nmol/100 nL) 10 min before exposure to acute restraint. The pretreatment with propranolol did not affect the blood pressure (BP) increase evoked by restraint. However, it increased the tachycardiac response caused by acute restraint when animals were pretreated with a dose of 15 nmol, without a significant effect on the BP response. This result indicates that beta-adrenoceptors in the MeA have an inhibitory influence on restraint-evoked heart rate (HR) changes. Pretreatment with the selective beta(2)-adrenoceptor antagonist ICI 118,551 (10, 15, and 20 nmol/100 nL) significantly increased the restraint-evoked tachycardiac response after doses of 15 and 20 nmol, an effect that was similar to that observed after the pretreatment with propranolol at a dose of 15 nmol, without a significant effect on the BP response. Pretreatment of the MeA with the selective beta(1)-adrenoceptor antagonist CGP 20712 (10, 15, and 20 nmol/100 nL) caused an opposite effect on the HR response, and a significant decrease in the restraint-evoked tachycardia was observed only after the dose of 20 nmol, without a significant effect on the BP response. Because propranolol is an equipotent antagonist of both beta(1) and beta(2)-adrenoceptors, and opposite effects were observed after the treatment with the higher doses of the selective antagonists ICI 118,551 and CGP 20712, the narrow window in the dose-response to propranolol could be explained by a functional antagonism resulting from the simultaneous inhibition of beta(1) and beta(2)-adrenoceptors by the treatment with propranolol. The present results suggest that beta(2)-adrenoceptors have an inhibitory influence on the restraint-evoked tachycardiac response, whereas beta(1)-adrenoceptors have a facilitatory influence on the restraint-evoked tachycardiac response. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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Background: Since noradrenergic innervation was described in the ovarian follicle, the actions of the intraovarian catecholaminergic system have been the focus of a variety of studies. We aimed to determine the gonadotropin-independent effects of the catecholamine norepinephrine (NE) in the steroid hormone profile of a serum-free granulosa cell (GC) culture system in the context of follicular development and dominance. Methods: Primary bovine GCs were cultivated in a serum-free, chemically defined culture system supplemented with 0.1% polyvinyl alcohol. The culture features were assessed by hormone measurements and ultrastructural characteristics of GCs. Results: GCs produced increasing amounts of estradiol and pregnenolone for 144h and maintained ultrastructural features of healthy steroidogenic cells. Progesterone production was also detected, although it significantly increased only after 96h of culture. There was a highly significant positive correlation between estradiol and pregnenolone production in high E2-producing cultures. The effects of NE were further evaluated in a dose response study. The highest tested concentration of NE (10 (-7) M) resulted in a significant increase in progesterone production, but not in estradiol or pregnenolone production. The specificity of NE effects on progesterone productio n was further investigated by incubating GCs with propranolol (10 (-8) M), a non-selective beta-adrenergic antagonist. Conclusions: The present culture system represents a robust model to study the impact of intrafollicular factors, such as catecholamines, in ovarian steroidogenesis and follicular development. The results of noradrenergic effects in the steroidogenesis of GC have implications on physiological follicular fate and on certain pathological ovarian conditions such as cyst formation and anovulation.

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RATIONALE: The interaction between lungs and chest wall influences lung volume, that determines lung history during respiration cycle. In this study, the influence of chest wall mechanics on respiratory system is assessed by the evaluation of inspiration pressure-volume curve (PV curve) under three different situations: closed-chest, open-chest and isolated lung. The PV curve parameters in each situation allow us to further understand the role played by different chest wall elements in the respiratory function. Methods: Twenty-four male Wistar rats (236 ± 29 g) were used. The animals were weighted and then anesthetized with xylazine 2% (O,SmL/kg) and ketamine 10% (0,9mL/kg), exsanguinated and later tracheostomies with a metallic cannula (14 gauge).The cannula was connected to an automatic small animal insufflator. This setup was connected to a pressure transducer (32 samples/s). The 24 animals were randomly separated in three groups:(i) closed chest,(ii) open chest and (iii) isolated lung. The rats were insufflated with 20mL quasi-statically (constant speed of 0,1mUs). lnsufflated volume and measured pressure data were kept and PV curves were obtained for all animals. The PV curves were fitted (non-linear least squares) against the sigmoid equation (1) to obtain the sigmoid equation parameters (a,b,c,d). Elastance measurements were obtained from linear regression of pressure/volume measurements in a 0,8s interval before and after the calculated point. Results: The parameters a,b and c showed no significant change, but the parameter d showed a significant variation among the three groups. The initial elastance also varied between open and closed chest, indicating the need of a higher pressure for the lung expansion, as can be seen in Table 1. Conclusion: A supporting effect of the chest wall was observed at the initial moments of inspiration, observed as a higher initial elastance in open chest situations than in closed chest situations (p=0,00001). The similar initial elastance for the isolated lung and closed chest may be explained by the specific method used for the isolated lung experiment. As the isolated lung is supported by the trachea vertically, the weight of the tissue may have a similar effect of the residual negative pressure in the thorax, responsible for maintaining the residual volume.

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RATIONALE: The interaction between lungs and chest wall influences lung volume, that determines lung history during respiration cycle. In this study, the influence of chest wall mechanics on respiratory system is assessed by the evaluation of inspiration pressure-volume curve (PV curve) under three different situations: closed-chest, open-chest and isolated lung. The PV curve parameters in each situation allow us to further understand the role played by different chest wall elements in the respiratory function. Methods: Twenty-four male Wistar rats (236 ± 29 g) were used. The animals were weighted and then anesthetized with xylazine 2% (0,5mL/kg) and ketamine 10% (0,9mL/kg), exsanguinated and later tracheostomized with a metallic cannula (14 gauge). The cannula was connected to an automatic small animal insufflator. This setup was connected to a pressure transducer (32 samples/s). The 24 animals were randomly separated in three groups: (i) closed chest, (ii) open chest and (iii) isolated lung. The rats were insufflated with 20mL quasi-statically (constant speed of 0,1mL/s). Insufflated volume and measured pressure data were kept and PV curves were obtained for all animals. The PV curves were fitted (non-linear least squares) against the sigmoid equation (1) to obtain the sigmoid equation parameters (a,b,c,d). Elastance measurements were obtained from linear regression of pressure/volume measurements in a 0,8s interval before and after the calculated point. Results: The parameters a, b and c showed no significant change, but the parameter d showed a significant variation among the three groups. The initial elastance also varied between open and closed chest, indicating the need of a higher pressure for the lung expansion, as can be seen in Table 1. Table 1: Mean and Standard Deviation of parameters obtained for each protocol. Protocol: Closed Chest – a (mL) -0.35±0.33; b (mL) 13.93±0.89; c (cm H2O) 21.28±2.37; d (cm H2O) 6.17±0.84; r²** (%) 99.4±0.14; Initial Elastance* (cm H2)/mL) 12.72±6.66; Weight (g) 232.33±5.72. Open Chest - a (mL) 0.01±0.28; b (mL) 14.79±0.54; c (cm H2O) 19.47±1.41; d (cm H2O) 3.50±0.28; r²** (%) 98.8±0.34; Initial Elastance* (cm H2)/mL) 28.68±2.36; Weight (g) 217.33±7.97. Isolated Lung - a (mL) -0.09±0.46; b (mL) 14.22±0.75; c (cm H2O) 21.76±1.43; d (cm H2O) 4.24±0.50; r²** (%) 98.9±0.19; Initial Elastance* (cm H2)/mL) 7.13±8.85; Weight (g) 224.33±16.66. * Elastance measures in the 0-0,1 mL range. ** Goodness of sigmoid fit versus measured data Conclusion: A supporting effect of the chest wall was observed at the initial moments of inspiration, observed as a higher initial elastance in open chest situations than in closed chest situations (p=0,00001). The similar initial elastance for the isolated lung and closed chest may be explained by the specific method used for the isolated lung experiment. As the isolated lung is supported by the trachea vertically, the weight of the tissue may have a similar effect of the residual negative pressure in the thorax, responsible for maintaining the residual volume.

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[EN] The purpose of this investigation was to determine the contribution of muscle O(2) consumption (mVO2) to pulmonary O(2) uptake (pVO2) during both low-intensity (LI) and high-intensity (HI) knee-extension exercise, and during subsequent recovery, in humans. Seven healthy male subjects (age 20-25 years) completed a series of LI and HI square-wave exercise tests in which mVO2 (direct Fick technique) and pVO2 (indirect calorimetry) were measured simultaneously. The mean blood transit time from the muscle capillaries to the lung (MTTc-l) was also estimated (based on measured blood transit times from femoral artery to vein and vein to artery). The kinetics of mVO2 and pVO2 were modelled using non-linear regression. The time constant (tau) describing the phase II pVO2 kinetics following the onset of exercise was not significantly different from the mean response time (initial time delay + tau) for mVO2 kinetics for LI (30 +/- 3 vs 30 +/- 3 s) but was slightly higher (P < 0.05) for HI (32 +/- 3 vs 29 +/- 4 s); the responses were closely correlated (r = 0.95 and r = 0.95; P < 0.01) for both intensities. In recovery, agreement between the responses was more limited both for LI (36 +/- 4 vs 18 +/- 4 s, P < 0.05; r = -0.01) and HI (33 +/- 3 vs 27 +/- 3 s, P > 0.05; r = -0.40). MTTc-l was approximately 17 s just before exercise and decreased to 12 and 10 s after 5 s of exercise for LI and HI, respectively. These data indicate that the phase II pVO2 kinetics reflect mVO2 kinetics during exercise but not during recovery where caution in data interpretation is advised. Increased mVO2 probably makes a small contribution to during the first 15-20 s of exercise.

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This work is structured as follows: In Section 1 we discuss the clinical problem of heart failure. In particular, we present the phenomenon known as ventricular mechanical dyssynchrony: its impact on cardiac function, the therapy for its treatment and the methods for its quantification. Specifically, we describe the conductance catheter and its use for the measurement of dyssynchrony. At the end of the Section 1, we propose a new set of indexes to quantify the dyssynchrony that are studied and validated thereafter. In Section 2 we describe the studies carried out in this work: we report the experimental protocols, we present and discuss the results obtained. Finally, we report the overall conclusions drawn from this work and we try to envisage future works and possible clinical applications of our results. Ancillary studies that were carried out during this work mainly to investigate several aspects of cardiac resynchronization therapy (CRT) are mentioned in Appendix. -------- Ventricular mechanical dyssynchrony plays a regulating role already in normal physiology but is especially important in pathological conditions, such as hypertrophy, ischemia, infarction, or heart failure (Chapter 1,2.). Several prospective randomized controlled trials supported the clinical efficacy and safety of cardiac resynchronization therapy (CRT) in patients with moderate or severe heart failure and ventricular dyssynchrony. CRT resynchronizes ventricular contraction by simultaneous pacing of both left and right ventricle (biventricular pacing) (Chapter 1.). Currently, the conductance catheter method has been used extensively to assess global systolic and diastolic ventricular function and, more recently, the ability of this instrument to pick-up multiple segmental volume signals has been used to quantify mechanical ventricular dyssynchrony. Specifically, novel indexes based on volume signals acquired with the conductance catheter were introduced to quantify dyssynchrony (Chapter 3,4.). Present work was aimed to describe the characteristics of the conductancevolume signals, to investigate the performance of the indexes of ventricular dyssynchrony described in literature and to introduce and validate improved dyssynchrony indexes. Morevoer, using the conductance catheter method and the new indexes, the clinical problem of the ventricular pacing site optimization was addressed and the measurement protocol to adopt for hemodynamic tests on cardiac pacing was investigated. In accordance to the aims of the work, in addition to the classical time-domain parameters, a new set of indexes has been extracted, based on coherent averaging procedure and on spectral and cross-spectral analysis (Chapter 4.). Our analyses were carried out on patients with indications for electrophysiologic study or device implantation (Chapter 5.). For the first time, besides patients with heart failure, indexes of mechanical dyssynchrony based on conductance catheter were extracted and studied in a population of patients with preserved ventricular function, providing information on the normal range of such a kind of values. By performing a frequency domain analysis and by applying an optimized coherent averaging procedure (Chapter 6.a.), we were able to describe some characteristics of the conductance-volume signals (Chapter 6.b.). We unmasked the presence of considerable beat-to-beat variations in dyssynchrony that seemed more frequent in patients with ventricular dysfunction and to play a role in discriminating patients. These non-recurrent mechanical ventricular non-uniformities are probably the expression of the substantial beat-to-beat hemodynamic variations, often associated with heart failure and due to cardiopulmonary interaction and conduction disturbances. We investigated how the coherent averaging procedure may affect or refine the conductance based indexes; in addition, we proposed and tested a new set of indexes which quantify the non-periodic components of the volume signals. Using the new set of indexes we studied the acute effects of the CRT and the right ventricular pacing, in patients with heart failure and patients with preserved ventricular function. In the overall population we observed a correlation between the hemodynamic changes induced by the pacing and the indexes of dyssynchrony, and this may have practical implications for hemodynamic-guided device implantation. The optimal ventricular pacing site for patients with conventional indications for pacing remains controversial. The majority of them do not meet current clinical indications for CRT pacing. Thus, we carried out an analysis to compare the impact of several ventricular pacing sites on global and regional ventricular function and dyssynchrony (Chapter 6.c.). We observed that right ventricular pacing worsens cardiac function in patients with and without ventricular dysfunction unless the pacing site is optimized. CRT preserves left ventricular function in patients with normal ejection fraction and improves function in patients with poor ejection fraction despite no clinical indication for CRT. Moreover, the analysis of the results obtained using new indexes of regional dyssynchrony, suggests that pacing site may influence overall global ventricular function depending on its relative effects on regional function and synchrony. Another clinical problem that has been investigated in this work is the optimal right ventricular lead location for CRT (Chapter 6.d.). Similarly to the previous analysis, using novel parameters describing local synchrony and efficiency, we tested the hypothesis and we demonstrated that biventricular pacing with alternative right ventricular pacing sites produces acute improvement of ventricular systolic function and improves mechanical synchrony when compared to standard right ventricular pacing. Although no specific right ventricular location was shown to be superior during CRT, the right ventricular pacing site that produced the optimal acute hemodynamic response varied between patients. Acute hemodynamic effects of cardiac pacing are conventionally evaluated after stabilization episodes. The applied duration of stabilization periods in most cardiac pacing studies varied considerably. With an ad hoc protocol (Chapter 6.e.) and indexes of mechanical dyssynchrony derived by conductance catheter we demonstrated that the usage of stabilization periods during evaluation of cardiac pacing may mask early changes in systolic and diastolic intra-ventricular dyssynchrony. In fact, at the onset of ventricular pacing, the main dyssynchrony and ventricular performance changes occur within a 10s time span, initiated by the changes in ventricular mechanical dyssynchrony induced by aberrant conduction and followed by a partial or even complete recovery. It was already demonstrated in normal animals that ventricular mechanical dyssynchrony may act as a physiologic modulator of cardiac performance together with heart rate, contractile state, preload and afterload. The present observation, which shows the compensatory mechanism of mechanical dyssynchrony, suggests that ventricular dyssynchrony may be regarded as an intrinsic cardiac property, with baseline dyssynchrony at increased level in heart failure patients. To make available an independent system for cardiac output estimation, in order to confirm the results obtained with conductance volume method, we developed and validated a novel technique to apply the Modelflow method (a method that derives an aortic flow waveform from arterial pressure by simulation of a non-linear three-element aortic input impedance model, Wesseling et al. 1993) to the left ventricular pressure signal, instead of the arterial pressure used in the classical approach (Chapter 7.). The results confirmed that in patients without valve abnormalities, undergoing conductance catheter evaluations, the continuous monitoring of cardiac output using the intra-ventricular pressure signal is reliable. Thus, cardiac output can be monitored quantitatively and continuously with a simple and low-cost method. During this work, additional studies were carried out to investigate several areas of uncertainty of CRT. The results of these studies are briefly presented in Appendix: the long-term survival in patients treated with CRT in clinical practice, the effects of CRT in patients with mild symptoms of heart failure and in very old patients, the limited thoracotomy as a second choice alternative to transvenous implant for CRT delivery, the evolution and prognostic significance of diastolic filling pattern in CRT, the selection of candidates to CRT with echocardiographic criteria and the prediction of response to the therapy.

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This artwork reports on two different projects that were carried out during the three years of Doctor of the Philosophy course. In the first years a project regarding Capacitive Pressure Sensors Array for Aerodynamic Applications was developed in the Applied Aerodynamic research team of the Second Faculty of Engineering, University of Bologna, Forlì, Italy, and in collaboration with the ARCES laboratories of the same university. Capacitive pressure sensors were designed and fabricated, investigating theoretically and experimentally the sensor’s mechanical and electrical behaviours by means of finite elements method simulations and by means of wind tunnel tests. During the design phase, the sensor figures of merit are considered and evaluated for specific aerodynamic applications. The aim of this work is the production of low cost MEMS-alternative devices suitable for a sensor network to be implemented in air data system. The last two year was dedicated to a project regarding Wireless Pressure Sensor Network for Nautical Applications. Aim of the developed sensor network is to sense the weak pressure field acting on the sail plan of a full batten sail by means of instrumented battens, providing a real time differential pressure map over the entire sail surface. The wireless sensor network and the sensing unit were designed, fabricated and tested in the faculty laboratories. A static non-linear coupled mechanical-electrostatic simulation, has been developed to predict the pressure versus capacitance static characteristic suitable for the transduction process and to tune the geometry of the transducer to reach the required resolution, sensitivity and time response in the appropriate full scale pressure input A time dependent viscoelastic error model has been inferred and developed by means of experimental data in order to model, predict and reduce the inaccuracy bound due to the viscolelastic phenomena affecting the Mylar® polyester film used for the sensor diaphragm. The development of the two above mentioned subjects are strictly related but presently separately in this artwork.

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In Performance-Based Earthquake Engineering (PBEE), evaluating the seismic performance (or seismic risk) of a structure at a designed site has gained major attention, especially in the past decade. One of the objectives in PBEE is to quantify the seismic reliability of a structure (due to the future random earthquakes) at a site. For that purpose, Probabilistic Seismic Demand Analysis (PSDA) is utilized as a tool to estimate the Mean Annual Frequency (MAF) of exceeding a specified value of a structural Engineering Demand Parameter (EDP). This dissertation focuses mainly on applying an average of a certain number of spectral acceleration ordinates in a certain interval of periods, Sa,avg (T1,…,Tn), as scalar ground motion Intensity Measure (IM) when assessing the seismic performance of inelastic structures. Since the interval of periods where computing Sa,avg is related to the more or less influence of higher vibration modes on the inelastic response, it is appropriate to speak about improved IMs. The results using these improved IMs are compared with a conventional elastic-based scalar IMs (e.g., pseudo spectral acceleration, Sa ( T(¹)), or peak ground acceleration, PGA) and the advanced inelastic-based scalar IM (i.e., inelastic spectral displacement, Sdi). The advantages of applying improved IMs are: (i ) "computability" of the seismic hazard according to traditional Probabilistic Seismic Hazard Analysis (PSHA), because ground motion prediction models are already available for Sa (Ti), and hence it is possibile to employ existing models to assess hazard in terms of Sa,avg, and (ii ) "efficiency" or smaller variability of structural response, which was minimized to assess the optimal range to compute Sa,avg. More work is needed to assess also "sufficiency" and "scaling robustness" desirable properties, which are disregarded in this dissertation. However, for ordinary records (i.e., with no pulse like effects), using the improved IMs is found to be more accurate than using the elastic- and inelastic-based IMs. For structural demands that are dominated by the first mode of vibration, using Sa,avg can be negligible relative to the conventionally-used Sa (T(¹)) and the advanced Sdi. For structural demands with sign.cant higher-mode contribution, an improved scalar IM that incorporates higher modes needs to be utilized. In order to fully understand the influence of the IM on the seismis risk, a simplified closed-form expression for the probability of exceeding a limit state capacity was chosen as a reliability measure under seismic excitations and implemented for Reinforced Concrete (RC) frame structures. This closed-form expression is partuclarly useful for seismic assessment and design of structures, taking into account the uncertainty in the generic variables, structural "demand" and "capacity" as well as the uncertainty in seismic excitations. The assumed framework employs nonlinear Incremental Dynamic Analysis (IDA) procedures in order to estimate variability in the response of the structure (demand) to seismic excitations, conditioned to IM. The estimation of the seismic risk using the simplified closed-form expression is affected by IM, because the final seismic risk is not constant, but with the same order of magnitude. Possible reasons concern the non-linear model assumed, or the insufficiency of the selected IM. Since it is impossibile to state what is the "real" probability of exceeding a limit state looking the total risk, the only way is represented by the optimization of the desirable properties of an IM.

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CHAPTER 1:FLUID-VISCOUS DAMPERS In this chapter the fluid-viscous dampers are introduced. The first section is focused on the technical characteristics of these devices, their mechanical behavior and the latest evolution of the technology whose they are equipped. In the second section we report the definitions and the guide lines about the design of these devices included in some international codes. In the third section the results of some experimental tests carried out by some authors on the response of these devices to external forces are discussed. On this purpose we report some technical schedules that are usually enclosed to the devices now available on the international market. In the third section we show also some analytic models proposed by various authors, which are able to describe efficiently the physical behavior of the fluid-viscous dampers. In the last section we propose some cases of application of these devices on existing structures and on new-construction structures. We show also some cases in which these devices have been revealed good for aims that lies outside the reduction of seismic actions on the structures. CHAPTER 2:DESIGN METHODS PROPOSED IN LITERATURE In this chapter the more widespread design methods proposed in literature for structures equipped by fluid-viscous dampers are introduced. In the first part the response of sdf systems in the case of harmonic external force is studied, in the last part the response in the case of random external force is discussed. In the first section the equations of motion in the case of an elastic-linear sdf system equipped with a non-linear fluid-viscous damper undergoing a harmonic force are introduced. This differential problem is analytically quite complex and it’s not possible to be solved in a closed form. Therefore some authors have proposed approximate solution methods. The more widespread methods are based on equivalence principles between a non-linear device and an equivalent linear one. Operating in this way it is possible to define an equivalent damping ratio and the problem becomes linear; the solution of the equivalent problem is well-known. In the following section two techniques of linearization, proposed by some authors in literature, are described: the first technique is based on the equivalence of the energy dissipated by the two devices and the second one is based on the equivalence of power consumption. After that we compare these two techniques by studying the response of a sdf system undergoing a harmonic force. By introducing the equivalent damping ratio we can write the equation of motion of the non-linear differential problem in an implicit form, by dividing, as usual, for the mass of the system. In this way, we get a reduction of the number of variables, by introducing the natural frequency of the system. The equation of motion written in this form has two important properties: the response is linear dependent on the amplitude of the external force and the response is dependent on the ratio of the frequency of the external harmonic force and the natural frequency of the system only, and not on their single values. All these considerations, in the last section, are extended to the case of a random external force. CHAPTER 3: DESIGN METHOD PROPOSED In this chapter the theoretical basis of the design method proposed are introduced. The need to propose a new design method for structures equipped with fluid-viscous dampers arises from the observation that the methods reported in literature are always iterative, because the response affects some parameters included in the equation of motion (such as the equivalent damping ratio). In the first section the dimensionless parameterε is introduced. This parameter has been obtained from the definition of equivalent damping ratio. The implicit form of the equation of motion is written by introducing the parameter ε, instead of the equivalent damping ratio. This new implicit equation of motions has not any terms affected by the response, so that once ε is known the response can be evaluated directly. In the second section it is discussed how the parameter ε affects some characteristics of the response: drift, velocity and base shear. All the results described till this point have been obtained by keeping the non-linearity of the behavior of the dampers. In order to get a linear formulation of the problem, that is possible to solve by using the well-known methods of the dynamics of structures, as we did before for the iterative methods by introducing the equivalent damping ratio, it is shown how the equivalent damping ratio can be evaluated from knowing the value of ε. Operating in this way, once the parameter ε is known, it is quite easy to estimate the equivalent damping ratio and to proceed with a classic linear analysis. In the last section it is shown how the parameter ε could be taken as reference for the evaluation of the convenience of using non-linear dampers instead of linear ones on the basis of the type of external force and the characteristics of the system. CHAPTER 4: MULTI-DEGREE OF FREEDOM SYSTEMS In this chapter the design methods of a elastic-linear mdf system equipped with non-linear fluidviscous dampers are introduced. It has already been shown that, in the sdf systems, the response of the structure can be evaluated through the estimation of the equivalent damping ratio (ξsd) assuming the behavior of the structure elastic-linear. We would to mention that some adjusting coefficients, to be applied to the equivalent damping ratio in order to consider the actual behavior of the structure (that is non-linear), have already been proposed in literature; such coefficients are usually expressed in terms of ductility, but their treatment is over the aims of this thesis and we does not go into further. The method usually proposed in literature is based on energy equivalence: even though this procedure has solid theoretical basis, it must necessary include some iterative process, because the expression of the equivalent damping ratio contains a term of the response. This procedure has been introduced primarily by Ramirez, Constantinou et al. in 2000. This procedure is reported in the first section and it is defined “Iterative Method”. Following the guide lines about sdf systems reported in the previous chapters, it is introduced a procedure for the assessment of the parameter ε in the case of mdf systems. Operating in this way the evaluation of the equivalent damping ratio (ξsd) can be done directly without implementing iterative processes. This procedure is defined “Direct Method” and it is reported in the second section. In the third section the two methods are analyzed by studying 4 cases of two moment-resisting steel frames undergoing real accelerogramms: the response of the system calculated by using the two methods is compared with the numerical response obtained from the software called SAP2000-NL, CSI product. In the last section a procedure to create spectra of the equivalent damping ratio, affected by the parameter ε and the natural period of the system for a fixed value of exponent α, starting from the elasticresponse spectra provided by any international code, is introduced.

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The thesis studies the economic and financial conditions of Italian households, by using microeconomic data of the Survey on Household Income and Wealth (SHIW) over the period 1998-2006. It develops along two lines of enquiry. First it studies the determinants of households holdings of assets and liabilities and estimates their correlation degree. After a review of the literature, it estimates two non-linear multivariate models on the interactions between assets and liabilities with repeated cross-sections. Second, it analyses households financial difficulties. It defines a quantitative measure of financial distress and tests, by means of non-linear dynamic probit models, whether the probability of experiencing financial difficulties is persistent over time. Chapter 1 provides a critical review of the theoretical and empirical literature on the estimation of assets and liabilities holdings, on their interactions and on households net wealth. The review stresses the fact that a large part of the literature explain households debt holdings as a function, among others, of net wealth, an assumption that runs into possible endogeneity problems. Chapter 2 defines two non-linear multivariate models to study the interactions between assets and liabilities held by Italian households. Estimation refers to a pooling of cross-sections of SHIW. The first model is a bivariate tobit that estimates factors affecting assets and liabilities and their degree of correlation with results coherent with theoretical expectations. To tackle the presence of non normality and heteroskedasticity in the error term, generating non consistent tobit estimators, semi-parametric estimates are provided that confirm the results of the tobit model. The second model is a quadrivariate probit on three different assets (safe, risky and real) and total liabilities; the results show the expected patterns of interdependence suggested by theoretical considerations. Chapter 3 reviews the methodologies for estimating non-linear dynamic panel data models, drawing attention to the problems to be dealt with to obtain consistent estimators. Specific attention is given to the initial condition problem raised by the inclusion of the lagged dependent variable in the set of explanatory variables. The advantage of using dynamic panel data models lies in the fact that they allow to simultaneously account for true state dependence, via the lagged variable, and unobserved heterogeneity via individual effects specification. Chapter 4 applies the models reviewed in Chapter 3 to analyse financial difficulties of Italian households, by using information on net wealth as provided in the panel component of the SHIW. The aim is to test whether households persistently experience financial difficulties over time. A thorough discussion is provided of the alternative approaches proposed by the literature (subjective/qualitative indicators versus quantitative indexes) to identify households in financial distress. Households in financial difficulties are identified as those holding amounts of net wealth lower than the value corresponding to the first quartile of net wealth distribution. Estimation is conducted via four different methods: the pooled probit model, the random effects probit model with exogenous initial conditions, the Heckman model and the recently developed Wooldridge model. Results obtained from all estimators accept the null hypothesis of true state dependence and show that, according with the literature, less sophisticated models, namely the pooled and exogenous models, over-estimate such persistence.

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Relaxor-Ferroelektrika sind wegen ihrer möglichen technischen Anwendungen und vom Standpunkt der Grundlagenforschung als Beispiel für ungeordnete Systeme von wissenschaftlichem Interesse. Trotz zahlreicher experimenteller Untersuchungen sind die mikroskopischen Ursachen ihrer Eigenschaften aber nach wie vor ungeklärt. Im Rahmen dieser Arbeit wurde das Relaxor-Ferroelektrikum Bleimagnesiumniobat-Bleititanat (PMN-10PT) mittels linearer und nichtlinearer dielektrischer Spektroskopie untersucht. Durch Anregung mit starken elektrischen Wechselfeldern konnten mit der Methode des nichtresonanten dielektrischen Lochbrennens frequenzselektiv einzelne spektrale Bereiche aus dem verbreiterten Relaxationsspektrum herausgegriffen und deren Rückrelaxation separat verfolgt werden. Die experimentellen Ergebnisse zeigten, daß eine langlebige dynamische Heterogenität der dipolaren Reorientierung existiert. Durch ihr ausgeprägt nichtergodisches Verhalten zeigen Relaxor-Ferroelektrika starke Alterungseffekte. Die Untersuchung des Alterungsverhaltens der dielektrischen Suszeptibilität zeigte, daß ein Gedächtnis für die bei einer Alterungstemperatur eingenommene Konfiguration bestehen bleibt, sofern die Temperatur nach einer unvollständigen isothermen Alterung nur um einige Grad abgesenkt oder erhöht wurde.Außerdem wurde die induzierte Polarisation bei stochastischen dielektrischen Anregungen mit elektrischen Feldern, die in sehr guter Näherung ein weißes Rauschen darstellten, untersucht. Über die Bildung der Kreuzkorrelationsfunktion zwischen Feld und Polarisation konnte die Impulsantwortfunktion des Systems berechnet werden.Die experimentellen Ergebnisse am Relaxor-Ferroelektrikum PMN-10PT können sehr gut mit einem Modell eines ungeordneten Ferroelektrikums erklärt werden, dessen Domänenwände unordnungsbedingt an sogenannten Pinning-Zentren festhaften.

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The subject of this Ph.D. research thesis is the development and application of multiplexed analytical methods based on bioluminescent whole-cell biosensors. One of the main goals of analytical chemistry is multianalyte testing in which two or more analytes are measured simultaneously in a single assay. The advantages of multianalyte testing are work simplification, high throughput, and reduction in the overall cost per test. The availability of multiplexed portable analytical systems is of particular interest for on-field analysis of clinical, environmental or food samples as well as for the drug discovery process. To allow highly sensitive and selective analysis, these devices should combine biospecific molecular recognition with ultrasensitive detection systems. To address the current need for rapid, highly sensitive and inexpensive devices for obtaining more data from each sample,genetically engineered whole-cell biosensors as biospecific recognition element were combined with ultrasensitive bioluminescence detection techniques. Genetically engineered cell-based sensing systems were obtained by introducing into bacterial, yeast or mammalian cells a vector expressing a reporter protein whose expression is controlled by regulatory proteins and promoter sequences. The regulatory protein is able to recognize the presence of the analyte (e.g., compounds with hormone-like activity, heavy metals…) and to consequently activate the expression of the reporter protein that can be readily measured and directly related to the analyte bioavailable concentration in the sample. Bioluminescence represents the ideal detection principle for miniaturized analytical devices and multiplexed assays thanks to high detectability in small sample volumes allowing an accurate signal localization and quantification. In the first chapter of this dissertation is discussed the obtainment of improved bioluminescent proteins emitting at different wavelenghts, in term of increased thermostability, enhanced emission decay kinetic and spectral resolution. The second chapter is mainly focused on the use of these proteins in the development of whole-cell based assay with improved analytical performance. In particular since the main drawback of whole-cell biosensors is the high variability of their analyte specific response mainly caused by variations in cell viability due to aspecific effects of the sample’s matrix, an additional bioluminescent reporter has been introduced to correct the analytical response thus increasing the robustness of the bioassays. The feasibility of using a combination of two or more bioluminescent proteins for obtaining biosensors with internal signal correction or for the simultaneous detection of multiple analytes has been demonstrated by developing a dual reporter yeast based biosensor for androgenic activity measurement and a triple reporter mammalian cell-based biosensor for the simultaneous monitoring of two CYP450 enzymes activation, involved in cholesterol degradation, with the use of two spectrally resolved intracellular luciferases and a secreted luciferase as a control for cells viability. In the third chapter is presented the development of a portable multianalyte detection system. In order to develop a portable system that can be used also outside the laboratory environment even by non skilled personnel, cells have been immobilized into a new biocompatible and transparent polymeric matrix within a modified clear bottom black 384 -well microtiter plate to obtain a bioluminescent cell array. The cell array was placed in contact with a portable charge-coupled device (CCD) light sensor able to localize and quantify the luminescent signal produced by different bioluminescent whole-cell biosensors. This multiplexed biosensing platform containing whole-cell biosensors was successfully used to measure the overall toxicity of a given sample as well as to obtain dose response curves for heavy metals and to detect hormonal activity in clinical samples (PCT/IB2010/050625: “Portable device based on immobilized cells for the detection of analytes.” Michelini E, Roda A, Dolci LS, Mezzanotte L, Cevenini L , 2010). At the end of the dissertation some future development steps are also discussed in order to develop a point of care (POCT) device that combine portability, minimum sample pre-treatment and highly sensitive multiplexed assays in a short assay time. In this POCT perspective, field-flow fractionation (FFF) techniques, in particular gravitational variant (GrFFF) that exploit the earth gravitational field to structure the separation, have been investigated for cells fractionation, characterization and isolation. Thanks to the simplicity of its equipment, amenable to miniaturization, the GrFFF techniques appears to be particularly suited for its implementation in POCT devices and may be used as pre-analytical integrated module to be applied directly to drive target analytes of raw samples to the modules where biospecifc recognition reactions based on ultrasensitive bioluminescence detection occurs, providing an increase in overall analytical output.