Stochastic models and dynamic measures for the characterization of bistable circuits

During the last few years, a great deal of interest has risen concerning the applications of stochastic methods to several biochemical and biological phenomena. Phenomena like gene expression, cellular memory, bet-hedging strategy in bacterial growth and many others, cannot be described by continuous stochastic models due to their intrinsic discreteness and randomness. In this thesis I have used the Chemical Master Equation (CME) technique to modelize some feedback cycles and analyzing their properties, including experimental data. In the first part of this work, the effect of stochastic stability is discussed on a toy model of the genetic switch that triggers the cellular division, which malfunctioning is known to be one of the hallmarks of cancer. The second system I have worked on is the so-called futile cycle, a closed cycle of two enzymatic reactions that adds and removes a chemical compound, called phosphate group, to a specific substrate. I have thus investigated how adding noise to the enzyme (that is usually in the order of few hundred molecules) modifies the probability of observing a specific number of phosphorylated substrate molecules, and confirmed theoretical predictions with numerical simulations. In the third part the results of the study of a chain of multiple phosphorylation-dephosphorylation cycles will be presented. We will discuss an approximation method for the exact solution in the bidimensional case and the relationship that this method has with the thermodynamic properties of the system, which is an open system far from equilibrium.In the last section the agreement between the theoretical prediction of the total protein quantity in a mouse cells population and the observed quantity will be shown, measured via fluorescence microscopy.

Comportamento dinamico fuori del piano di pareti murarie: influenza della deformabilità degli impalcati

The aim of this study was to investigate the influence of the diaphragm flexibility on the behavior of out-of-plane walls in masonry buildings. Simplified models have been developed to perform kinematic and dynamic analyses in order to compare the response of walls with different restraint conditions. Kinematic non linear analyses of assemblages of rigid blocks have been performed to obtain the acceleration-displacement curves for walls with different restraint conditions at the top. A simplified 2DOF model has been developed to analyse the dynamic response of the wall with an elastic spring at the top, following the Housner rigid behaviour hypothesis. The dissipation of energy is concentrated at every impact at the base of the wall and is modelled through the introduction of the coefficient of restitution. The sets of equations of the possible configurations of the wall, depending on the different positions of the centre of rotation at the base and at the intermediate hinge have been obtained. An algorithm for the numerical integration of the sets of the equations of motion in the time domain has been developed. Dynamic analyses of a set of walls with Gaussian impulses and recorded accelerograms inputs have been performed in order to compare the response of the simply supported wall with the one of the wall with elastic spring at the top. The influence of diaphragm stiffness Kd has been investigated determining the variation of maximum displacement demand with the value of Kd. A more regular trend has been obtained for the Gaussian input than for the recorded accelerograms.

Modeling the spatial dynamics of economic models

The advances that have been characterizing spatial econometrics in recent years are mostly theoretical and have not found an extensive empirical application yet. In this work we aim at supplying a review of the main tools of spatial econometrics and to show an empirical application for one of the most recently introduced estimators. Despite the numerous alternatives that the econometric theory provides for the treatment of spatial (and spatiotemporal) data, empirical analyses are still limited by the lack of availability of the correspondent routines in statistical and econometric software. Spatiotemporal modeling represents one of the most recent developments in spatial econometric theory and the finite sample properties of the estimators that have been proposed are currently being tested in the literature. We provide a comparison between some estimators (a quasi-maximum likelihood, QML, estimator and some GMM-type estimators) for a fixed effects dynamic panel data model under certain conditions, by means of a Monte Carlo simulation analysis. We focus on different settings, which are characterized either by fully stable or quasi-unit root series. We also investigate the extent of the bias that is caused by a non-spatial estimation of a model when the data are characterized by different degrees of spatial dependence. Finally, we provide an empirical application of a QML estimator for a time-space dynamic model which includes a temporal, a spatial and a spatiotemporal lag of the dependent variable. This is done by choosing a relevant and prolific field of analysis, in which spatial econometrics has only found limited space so far, in order to explore the value-added of considering the spatial dimension of the data. In particular, we study the determinants of cropland value in Midwestern U.S.A. in the years 1971-2009, by taking the present value model (PVM) as the theoretical framework of analysis.

Activity and mechanisms of action of novel organosulfur derivatives of the HDAC inhibitor Valproic Acid in human experimental models of non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) represents the leading cause of cancer death worldwide, and 5-year survival is about 16% for patients diagnosed with advanced lung cancer and about 70-90% when the disease is diagnosed and treated at earlier stages. Treatment of NSCLC is changed in the last years with the introduction of targeted agents, such as gefitinib and erlotinib, that have dramatically changed the natural history of NSCLC patients carrying specific mutations in the EGFR gene, or crizotinib, for patients with the EML4-ALK translocation. However, such patients represent only about 15-20% of all NSCLC patients, and for the remaining individuals conventional chemotherapy represents the standard choice yet, but response rate to thise type of treatment is only about 20%. Development of new drugs and new therapeutic approaches are so needed to improve patients outcome. In this project we aimed to analyse the antitumoral activity of two compounds with the ability to inhibit histone deacethylases (ACS 2 and ACS 33), derived from Valproic Acid and conjugated with H2S, in human cancer cell lines derived from NSCLC tissues. We showed that ACS 2 represents the more promising agent. It showed strong antitumoral and pro-apoptotic activities, by inducing membrane depolarization, cytocrome-c release and caspase 3 and 9 activation. It was able to reduce the invasive capacity of cells, through inhibition of metalloproteinases expression, and to induce a reduced chromatin condensation. This last characteristic is probably responsible for the observed high synergistic activity in combination with cisplatin. In conclusion our results highlight the potential role of the ACS 2 compound as new therapeutic option for NSCLC patients, especially in combination with cisplatin. If validated in in vivo models, this compound should be worthy for phase I clinical trials.

Modelling the dynamic response of rockfall protection barriers

Mountainous areas are prone to natural hazards like rockfalls. Among the many countermeasures, rockfall protection barriers represent an effective solution to mitigate the risk. They are metallic structures designed to intercept rocks falling from unstable slopes, thus dissipating the energy deriving from the impact. This study aims at providing a better understanding of the response of several rockfall barrier types, through the development of rather sophisticated three-dimensional numerical finite elements models which take into account for the highly dynamic and non-linear conditions of such events. The models are built considering the actual geometrical and mechanical properties of real systems. Particular attention is given to the connecting details between the structural components and to their interactions. The importance of the work lies in being able to support a wide experimental activity with appropriate numerical modelling. The data of several full-scale tests carried out on barrier prototypes, as well as on their structural components, are combined with results of numerical simulations. Though the models are designed with relatively simple solutions in order to obtain a low computational cost of the simulations, they are able to reproduce with great accuracy the test results, thus validating the reliability of the numerical strategy proposed for the design of these structures. The developed models have shown to be readily applied to predict the barrier performance under different possible scenarios, by varying the initial configuration of the structures and/or of the impact conditions. Furthermore, the numerical models enable to optimize the design of these structures and to evaluate the benefit of possible solutions. Finally it is shown they can be also used as a valuable supporting tool for the operators within a rockfall risk assessment procedure, to gain crucial understanding of the performance of existing barriers in working conditions.

Stochastic foundations of dynamic trade and labor market models

This dissertation consists of three self-contained papers that are related to two main topics. In particular, the first and third studies focus on labor market modeling, whereas the second essay presents a dynamic international trade setup.rnrnIn Chapter "Expenses on Labor Market Reforms during Transitional Dynamics", we investigate the arising costs of a potential labor market reform from a government point of view. To analyze various effects of unemployment benefits system changes, this chapter develops a dynamic model with heterogeneous employed and unemployed workers.rn rnIn Chapter "Endogenous Markup Distributions", we study how markup distributions adjust when a closed economy opens up. In order to perform this analysis, we first present a closed-economy general-equilibrium industry dynamics model, where firms enter and exit markets, and then extend our analysis to the open-economy case.rn rnIn Chapter "Unemployment in the OECD - Pure Chance or Institutions?", we examine effects of aggregate shocks on the distribution of the unemployment rates in OECD member countries.rn rnIn all three chapters we model systems that behave randomly and operate on stochastic processes. We therefore exploit stochastic calculus that establishes clear methodological links between the chapters.

String inflationary models with non-monotonic slow-roll and detectable tensor modes

The first chapter of this work has the aim to provide a brief overview of the history of our Universe, in the context of string theory and considering inflation as its possible application to cosmological problems. We then discuss type IIB string compactifications, introducing the study of the inflaton, a scalar field candidated to describe the inflation theory. The Large Volume Scenario (LVS) is studied in the second chapter paying particular attention to the stabilisation of the Kähler moduli which are four-dimensional gravitationally coupled scalar fields which parameterise the size of the extra dimensions. Moduli stabilisation is the process through which these particles acquire a mass and can become promising inflaton candidates. The third chapter is devoted to the study of Fibre Inflation which is an interesting inflationary model derived within the context of LVS compactifications. The fourth chapter tries to extend the zone of slow-roll of the scalar potential by taking larger values of the field φ. Everything is done with the purpose of studying in detail deviations of the cosmological observables, which can better reproduce current experimental data. Finally, we present a slight modification of Fibre Inflation based on a different compactification manifold. This new model produces larger tensor modes with a spectral index in good agreement with the date released in February 2015 by the Planck satellite.

Fastener-Based Computational Models of Cold-Formed Steel Shear Walls

Cold-formed steel (CFS) combined with wood sheathing, such as oriented strand board (OSB), forms shear walls that can provide lateral resistance to seismic forces. The ability to accurately predict building deformations in damaged states under seismic excitations is a must for modern performance-based seismic design. However, few static or dynamic tests have been conducted on the non-linear behavior of CFS shear walls. Thus, the purpose of this research work is to provide and demonstrate a fastener-based computational model of CFS wall models that incorporates essential nonlinearities that may eventually lead to improvement of the current seismic design requirements. The approach is based on the understanding that complex interaction of the fasteners with the sheathing is an important factor in the non-linear behavior of the shear wall. The computational model consists of beam-column elements for the CFS framing and a rigid diaphragm for the sheathing. The framing and sheathing are connected with non-linear zero-length fastener elements to capture the OSB sheathing damage surrounding the fastener area. Employing computational programs such as OpenSees and MATLAB, 4 ft. x 9 ft., 8 ft. x 9 ft. and 12 ft. x 9 ft. shear wall models are created, and monotonic lateral forces are applied to the computer models. The output data are then compared and analyzed with the available results of physical testing. The results indicate that the OpenSees model can accurately capture the initial stiffness, strength and non-linear behavior of the shear walls.

Advantages and Applications of Transforming Empirical Model Input Space with Dimensional Models

Model-based calibration of steady-state engine operation is commonly performed with highly parameterized empirical models that are accurate but not very robust, particularly when predicting highly nonlinear responses such as diesel smoke emissions. To address this problem, and to boost the accuracy of more robust non-parametric methods to the same level, GT-Power was used to transform the empirical model input space into multiple input spaces that simplified the input-output relationship and improved the accuracy and robustness of smoke predictions made by three commonly used empirical modeling methods: Multivariate Regression, Neural Networks and the k-Nearest Neighbor method. The availability of multiple input spaces allowed the development of two committee techniques: a 'Simple Committee' technique that used averaged predictions from a set of 10 pre-selected input spaces chosen by the training data and the "Minimum Variance Committee" technique where the input spaces for each prediction were chosen on the basis of disagreement between the three modeling methods. This latter technique equalized the performance of the three modeling methods. The successively increasing improvements resulting from the use of a single best transformed input space (Best Combination Technique), Simple Committee Technique and Minimum Variance Committee Technique were verified with hypothesis testing. The transformed input spaces were also shown to improve outlier detection and to improve k-Nearest Neighbor performance when predicting dynamic emissions with steady-state training data. An unexpected finding was that the benefits of input space transformation were unaffected by changes in the hardware or the calibration of the underlying GT-Power model.

Non-photorealistic rendering of virtual implant models for computer-assisted fluoroscopy-based surgical procedures

Surgical navigation systems visualize the positions and orientations of surgical instruments and implants as graphical overlays onto a medical image of the operated anatomy on a computer monitor. The orthopaedic surgical navigation systems could be categorized according to the image modalities that are used for the visualization of surgical action. In the so-called CT-based systems or 'surgeon-defined anatomy' based systems, where a 3D volume or surface representation of the operated anatomy could be constructed from the preoperatively acquired tomographic data or through intraoperatively digitized anatomy landmarks, a photorealistic rendering of the surgical action has been identified to greatly improve usability of these navigation systems. However, this may not hold true when the virtual representation of surgical instruments and implants is superimposed onto 2D projection images in a fluoroscopy-based navigation system due to the so-called image occlusion problem. Image occlusion occurs when the field of view of the fluoroscopic image is occupied by the virtual representation of surgical implants or instruments. In these situations, the surgeon may miss part of the image details, even if transparency and/or wire-frame rendering is used. In this paper, we propose to use non-photorealistic rendering to overcome this difficulty. Laboratory testing results on foamed plastic bones during various computer-assisted fluoroscopybased surgical procedures including total hip arthroplasty and long bone fracture reduction and osteosynthesis are shown.

Dynamic modeling of active regeneration in catalyzed and non-catalyzed diesel particulate filters

Particulate matter (PM) emissions standards set by the US Environmental Protection Agency (EPA) have become increasingly stringent over the years. The EPA regulation for PM in heavy duty diesel engines has been reduced to 0.01 g/bhp-hr for the year 2010. Heavy duty diesel engines make use of an aftertreatment filtration device, the Diesel Particulate Filter (DPF). DPFs are highly efficient in filtering PM (known as soot) and are an integral part of 2010 heavy duty diesel aftertreatment system. PM is accumulated in the DPF as the exhaust gas flows through it. This PM needs to be removed by oxidation periodically for the efficient functioning of the filter. This oxidation process is also known as regeneration. There are 2 types of regeneration processes, namely active regeneration (oxidation of PM by external means) and passive oxidation (oxidation of PM by internal means). Active regeneration occurs typically in high temperature regions, about 500 - 600 °C, which is much higher than normal diesel exhaust temperatures. Thus, the exhaust temperature has to be raised with the help of external devices like a Diesel Oxidation Catalyst (DOC) or a fuel burner. The O2 oxidizes PM producing CO2 as oxidation product. In passive oxidation, one way of regeneration is by the use of NO2. NO2 oxidizes the PM producing NO and CO2 as oxidation products. The passive oxidation process occurs at lower temperatures (200 - 400 °C) in comparison to the active regeneration temperatures. Generally, DPF substrate walls are washcoated with catalyst material to speed up the rate of PM oxidation. The catalyst washcoat is observed to increase the rate of PM oxidation. The goal of this research is to develop a simple mathematical model to simulate the PM depletion during the active regeneration process in a DPF (catalyzed and non-catalyzed). A simple, zero-dimensional kinetic model was developed in MATLAB. Experimental data required for calibration was obtained by active regeneration experiments performed on PM loaded mini DPFs in an automated flow reactor. The DPFs were loaded with PM from the exhaust of a commercial heavy duty diesel engine. The model was calibrated to the data obtained from active regeneration experiments. Numerical gradient based optimization techniques were used to estimate the kinetic parameters of the model.

Thickness measurement of dynamic thin liquid films generated by plug-annular flow in non-wetting microchannels

Surface tension forces are significant at millimeter length-scales, causing profoundly different flow morphologies in microchannels than in macroscale flows. The existence and morphology of thin liquid films is particularly relevant for predicting performance and operational stability of devices containing microscale two phase flows. Analytical, computational, and experimental methods previously employed in the study of thin liquid films are discussed. Thicknesses before and after a novel film morphology, referred to as a `shock,' are measured with a novel film thickness measurement technique that uses confocal microscopy. Film thicknesses predicted by previous work are compared to experimental results. Methods for increasing the accuracy of the confocal film thickness measurement technique are discussed.

Landscapes of Education and the New Role of Social Work International Models of How to Combine Formal, Non-formal and Informal Education

Landscapes of education are a new topic within the debate about adequate and just education and human development for everybody. In particular, children and youths from social classes affected by poverty, a lack of prospects or minimal schooling are a focal group that should be offered new approaches and opportunities of cognitive and social development by way of these landscapes of education. It has become apparent that the traditional school alone does not suffice to meet this need. There is no doubt that competency-based orientation and employability are core areas with the help of which the generation now growing up will manage the start of its professional career. In addition and by no means less important, the development involves individual, social, cultural and societal perspectives that can be combined under the term of human development. In this context, the Capability Approach elaborated by Amartya Sen and Martha Nussbaum has developed a more extensive concept of human development and related it to empirical instruments. Using the analytic concept of individual capabilities and societal opportunities they shaped a socio-political formula that should be adapted in particular to modern social work. Moreover, the Capability Approach offers a critical foil with regard to further development and revision of institutionalised approaches in education and human development.