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Seismic hazard analyses require an estimate of earthquake ground motions from future events. These predictions are achieved through Ground Motion Prediction Equations, which include a prediction of the median and the standard deviation of ground motion parameters. The differences between observed and predicted ground motions, when normalized by the standard deviation, are referred to as epsilon (𝜖). For spectral accelerations, the correlation structure of normalized residuals across oscillator periods is important for guiding ground motion selection. Correlation structures for large global datasets have been studied extensively. These correlation structures reflect effects that are averaged over the entire dataset underlying the analyses. This paper considers the effects of site response, at given sites, on the correlation structure of normalized residuals. This is achieved by performing site response analyses for two hypothetical soil profiles using a set of 85 rock input motions. Results show that there is no significant difference between correlation coefficients for rock ground motions and correlation coefficients after considering the effects of site response for the chosen sites. / Master of Science

Deformational properties of soil, in terms of modulus and damping, exert a great influence on seismic response of soil sites. However, these properties for sands containing some portion of fines particles have not been systematically addressed. In addition, simultaneous modelling of the modulus and damping behaviour of soils during cyclic loading is desirable. This study presents an experimental and computational investigation into the deformational properties of sands containing fines content in the context of site response analysis. The experimental investigation is carried on sandy soils sourced from Christchurch, New Zealand using a dynamic triaxial apparatus while the computational aspect is based on the framework of total-stress one-dimensional (1D) cyclic behaviour of soil. The experimental investigation focused on a systematic study on the deformational behaviour of sand with different amounts of fines content (particle diameter ≤ 75µm) under drained conditions. The silty sands were prepared by mixing clean sand with three different percentages of fines content. A series of bender element tests at small-strain range and stress-controlled dynamic triaxial tests at medium to high-strain ranges were conducted on samples of clean sand and silty sand. This allowed measurements of linear and nonlinear deformational properties of the same specimen for a wide strain range. The testing program was designed to quantify the effects of void ratio and fines content on the low-strain stiffness of the silty sand as well as on the nonlinear stress-strain relationship and corresponding shear modulus and damping properties as a function of cyclic shear strains. Shear wave velocity, Vs, and maximum shear modulus, Gmax, of silty sand was shown to be significantly smaller than the respective values for clean sands measured at the same void ratio, e, or same relative density, Dr. However, the test results showed that the difference in the level of nonlinearity between clean sand and silty sands was small. For loose samples prepared at an identical relative density, the behaviour of clean sand was slightly less nonlinear as compared to sandy soils with higher fines content. This difference in the nonlinear behaviour of clean sand and sandy soils was negligible for dense soils. Furthermore, no systematic influence of fines content on the material damping curve was observed for sands with fines content FC = 0 to 30%. In order to normalize the effects of fines on moduli of sands, equivalent granular void ratio, e*, was employed. This was done through quantifying the participation of fines content in the force transfer chain of the sand matrix. As such, a unified framework for modelling of the variability of shear wave velocity, Vs, (or shear modulus, Gmax) with void ratio was achieved for clean sands and sands with fines, irrespective of their fines content. Furthermore, modelling of the cyclic stress-strain behaviour based on this experimental program was investigated. The modelling effort focused on developing a simple constitutive model which simultaneously models the soil modulus and damping relationships with shear strains observed in laboratory tests. The backbone curve of the cyclic model was adopted based on a modified version of Kondner and Zelasko (MKZ) hyperbolic function, with a curvature coefficient, a. In order to simulate the hysteretic cycles, the conventional Masing rules (Pyke 1979) were revised. The parameter n, in the Masing’s criteria was assumed to be a function of material damping, h, measured in the laboratory. As such the modulus and damping produced by the numerical model could match the stress-strain behaviour observed in the laboratory over the course of this study. It was shown that the Masing parameter n, is strain-dependent and generally takes values of n ≤ 2. The model was then verified through element test simulations under different cyclic loadings. It was shown that the model could accurately simulate the modulus and the damping simultaneously. The model was then incorporated within the OpenSees computational platform and was used to scrutinize the effects of damping on one-dimensional seismic site response analysis. For this purpose, several strong motion stations which recorded the Canterbury earthquake sequence were selected. The soil profiles were modelled as semi-infinite horizontally layered deposits overlying a uniform half-space subjected to vertically propagating shear waves. The advantages and limitations of the nonlinear model in terms of simulating soil nonlinearity and associated material damping were further scrutinized. It was shown that generally, the conventional Masing criteria unconservatively may underestimate some response parameters such as spectral accelerations. This was shown to be due to larger hysteretic damping modelled by using conventional Masing criteria. In addition, maximum shear strains within the soil profiles were also computed smaller in comparison to the values calculated by the proposed model. Further analyses were performed to study the simulation of backbone curve beyond the strain ranges addressed in the experimental phase of this study. A key issue that was identified was that relying only on the modulus reduction curves to simulate the stress-strain behaviour of soil may not capture the actual soil strength at larger strains. Hence, strength properties of the soil layer should also be incorporated to accurately simulate the backbone curve.

Solutions to physical problems described by Differential Equationson complex domains are in except for special cases almost impossibleto find. This turns our interest toward numerical approaches. Sincethe size of the numerical models tends to be very large when handlingcomplex problems, the area of model reduction is always a hot topic. Inthis report we look into a model reduction method called ComponentMode Synthesis. This can be described as dividing a large and complexdomain into smaller and more manageable ones. On each of thesesubdomains, we solve an eigenvalue problem and use the eigenvectorsas a reduced basis. Depending on the required accuracy we mightwant to use many or few modes in each subdomain, this opens for anadaptive selection of which subdomains that affects the solution most.We cover two numerical examples where we solve Helmholtz equationin a linear elastic problem. The first example is a truss and the othera gear wheel. In both examples we use an adaptive algorithm to refinethe reduced basis and compare the results with a uniform refinementand with a classic model reduction method called Modal Analysis. Wealso introduce a new approach when computing the coupling modesonly on the adjacent subdomains.

Numerical modeling techniques commonly used to compute the response of soil and rock media under earthquake shaking are evaluated by analyzing the observations provided by instrumented borehole arrays. The NIED Kik-Net database in Japan is selected as the main source of borehole array data for this study. The stiffness of the site and the availability of high intensity motions are the primary factors considered towards the selection of appropriate Kik-Net borehole arrays for investigation. Overall, 13 instrumented vertical arrays are investigated using over 750 recorded ground motions characterized by low (less than 0.05 g) to high (greater than 0.3 g) recorded peak ground accelerations at the downhole sensor. Based on data from the selected borehole arrays, site response predictions using 1-D linear elastic (LE) analysis, equivalent linear (EQL) analysis, equivalent linear analysis with frequency-dependent soil properties (EQL-FD), and fully nonlinear analysis (NL) are compared with the borehole observations. Initially, the low intensity motions are used to evaluate common assumptions regarding 1-D site response analysis. First, we identify the borehole wavefield best simulating the actual boundary condition at depth by comparing the theoretical linear-elastic (LE) and observed responses. Then, we identify the best-fit small-strain damping profiles that can incorporate the additional in-situ attenuation mechanisms. Finally, we assess the validity of the one-dimensional modeling assumption. Our analyses indicate that the appropriate boundary condition for analysis of a borehole array depends on the depth of the borehole sensor and that, for most of the considered vertical arrays, the one-dimensional assumption reasonably simulates the actual wave propagation pattern. In the second part of this study, we evaluate the accuracy of the EQL, EQL-FD and NL site response methods by quantifying the misfit (i.e., residual) between the simulations and observations at different levels of shaking. The evaluation of the performance of the theoretical models is made both on a site-by-site basis and in an aggregated manner. Thereafter, the variability in the predicted response from the three site response methods is assessed. Comparisons with the observed responses indicate that the misfit of simulations can be significant at short periods and large strains. Moreover, all models seem to be characterized by the same level of variability irrespectively of the level of shaking. Finally, several procedures that can be used to improve the accuracy of the one-dimensional EQL, EQL-FD and NL site response analyses, are investigated. First, an attempt to take into account the shear strength of the soil materials at large shear strains is made. Additionally, several modifications to the EQL-FD approach are proposed. The proposed modifications are evaluated against recordings from the borehole arrays. Our analyses indicate that the accuracy of the theoretical models can be, partly, increased by incorporating the proposed modifications. / text

Estimating local site effects and modifying the uncertainty in ground motion predictions are two indispensable parts of partially non-ergodic site-specific PSHA. Local site effects can be estimated using site response simulations or recorded ground motions at the site. When such predictions are available, the aleatory variability of ground motions used in PSHA can be changed to the single station sigma value. However, in these cases, the epistemic uncertainty in predicting site effects must be incorporated into the hazard analyses. This research focuses on the challenges specific to conducting partially non-ergodic site-specific PSHA using recorded ground motions or site response analysis. The main challenge in estimating local site effects using recorded data is whether ground motions collected in a relatively short time can be used to estimate site effects for long return period events. We first develop a database for recorded ground motions at the KiK-net array to investigate this question and use this database to develop a predictive model for the Fourier Amplitude Spectra of ground motions. The ground motion model (GMM) residuals are used to investigate the stability of site terms across different tectonic regimes. We observe that empirical site terms are stable across different tectonic regimes. This observation allows the use of ground motions from any tectonic regime (whether they belong to the tectonic regime that controls the hazard or not) to estimate local site effects. Moreover, in Fourier amplitude, site effects are not dependent on event magnitude and source to site distance; therefore, estimates of site effects from low magnitude events can be easily extrapolated to larger events. The Fourier amplitude GMM developed in this study adds to the library of Fourier amplitude models to be used in future partially non-ergodic site-specific PSHAs. In practice, one of the most common tools for simulating wave propagation is 1-D site response analysis. Two central assumptions in 1-D site response analysis are that the soil profile is comprised of horizontal soil layers of infinite extent and that the vertically propagating SH-waves control the horizontal component of ground motion. SH-waves tend to propagate vertically near the surface because as earthquake waves hit softer layers traveling from the source to the site, they refract until the path becomes steeply inclined. The validity of both assumptions in 1-D site response depends on the geological setting at the site and the geology between the earthquake source and the site, raising the question of which sites are suitable for 1-D site response analysis and what the model error in 1-D site response analysis is. We use the GMM developed for FAS to estimate observed and empirical site terms. The empirical site effects are then compared with the theoretical site effects to determine whether sites are amenable to 1-D site response analyses, and to quantify the model error in the analyses. / Doctor of Philosophy / It is impossible to predict future earthquake-induced ground motions due to randomness in the process and a lack of knowledge. In fact, there are significant uncertainties not only in predicting the location, time, and magnitude of a future earthquake but also in predicting the intensity of ground motion induced by a given future earthquake. Therefore, assessing the safety of the human environment against earthquake hazards requires a method that considers all sources of uncertainties. To this end, Earthquake Engineers have developed Probabilistic Seismic Hazard Analysis(PSHA) framework. Structural engineers use the results of PSHA to design a new structure or assess the safety of an existing building. The accuracy of PSHA estimations leads to designs that are both safe and cost-efficient. The distribution of possible ground motions induced by a given earthquake scenario significantly controls the result of PSHA. This distribution should consider the effect of source, source to site path, and local site effects. This research focuses on improving PSHA results by estimating local site effects using recorded ground motions or simulating wave propagation in the site. In estimating local site effects using recorded data, the local site effect observed in ground motions collected in a relatively short time window is used to estimate hazards from all scenarios. However, the collected ground motions usually belong to frequent low magnitude events that are different from large magnitude events that control the hazard. This difference requires either using a measure of local site effect that is independent of the magnitude and distance of the earthquake or considering the effect of magnitude and distance on the local site effect estimate. Moreover, since frequent events sample different sources and paths than large events, we need to make sure the local site effect is consistent across different sources and paths. This research develops Ground Motion Models(GMMs) for Fourier amplitude, a linear function of ground motion times series, using Japanese ground motions. The ratio of Fourier amplitude at the surface over bedrock is a measure of local site effect that is not dependant on magnitude and distance. The model is then used to see if the trade-off between source and site effect and path and site effect is significant or not. In practice, one of the most common tools for simulating wave propagation is 1-D site response analysis. Two central assumptions in 1-D site response analysis are that the soil profile comprises horizontal soil layers of infinite extent and that the vertically propagating horizontal shear waves (SH-waves) control the horizontal component of ground motion. SH-waves tend to propagate vertically near the surface because as earthquake waves hit softer layers traveling from the source to the site, they refract until the path becomes vertically inclined. The validity of both assumptions in 1-D site response depends on the geological setting at the site and the geology between the earthquake source and the site, raising the question of which sites are suitable for 1-D site response analysis and what the model error in 1-D site response analysis is. We use the GMM developed for FAS to estimate empirical local site effects. The empirical site effects are then compared with the theoretical site effects to determine whether sites are amenable to 1-D site response analyses and quantify the model error in the analyses.

Frequency response analysis (FRA) has emerged as the de-facto industry standard condition-monitoring tool to assess mechanical integrity of transformer windings during its service life. It the prerequisite detection sensitivity and customized portable commercial instruments are also available. Considering its importance and taking cognizance of its hidden potential, international bodies, viz., IEEE, IEC, and CIGRE have published standards/guides on its use and interpretation. In spite of all the progress witnessed over the past two decades, FRA has still not attained the status of a diagnostics tool. Probing the vast literature and research carried out in this points to the fact that lack of a rigorous mathematical basis to explain the underlying complex processes is, perhaps, one of the main reasons for the present predicament of FRA method. How-ever, it must be acknowledged that domain-knowledge is di cult to generalize in this. Having said that, the diagnostic part, which involves, the task of working back-wards starting from the FRA data to interpret a winding damage, locate it, and assess its severity, has so far remained teasingly elusive. As a consequence, FRA continues to remain as a sensitive condition-monitoring tool. Given its inherent potential, this situation seems to be a paradox, and so, calls for investigations. Once a mechanical damage has been detected by FRA, the next task is to locate its position and estimate its severity. An engineer expects FRA to provide these answers, so that corrective action, if needed, can be determined and initiated. In this context, even though FRA has attained global acceptance as a monitoring tool, it has failed as a diagnostic tool. Therefore, e orts that aim to address this issue are desirable. Driven by this motivation, the author's thesis proposes to explore a new school of thought in this direction, viz., to theoretically analyze the problem of localization of an incipient/minor mechanical damage (displacement in particular) and also assess its severity. Such an investigation seems to have not been undertaken previously. So, the goal is to establish a relationship to capture the complex interactions that exist between specific winding damages, winding parameters, and their overall in hence on the natural frequency deviations observable in the FRA data. Hence, exploring this possibility, subject to the constraint that the proposed method shall use inputs that are measurable at the terminals, becomes the primary objective of this research. In this thesis, a generalized analytical framework for handling winding displacements and FRA data has been successfully formulated. The formulation provides a general platform for localization and severity assessment of true radial and axial winding dis-placements occurring in an actual winding. An analytical solution becomes possible mainly due to manipulation of the system matrix, i.e., to consider the harmonic sum of squares of natural frequencies, instead of just the natural frequencies. This manipulation leads to an elegant closed-form expression that connects the displacement location and its severity, to changes in natural frequencies. For its implementation, short circuit natural frequencies and a few other terminal measurements are the only inputs that are necessary. This formulation is initially used in Chapter-3 to demonstrate localization of radial displacement in an isolated, actual, single, air-cored continuous-disk winding. Armed with this success, the supplicant proceeds further to show (in Chapter-4) how a minor manipulation of the formulation renders it suitable for localization of actual axial displacements as well. Extensive experimental verification was done and the results are encouraging. Accuracy of localization of radial/axial displacement is uniformly good for all positions, and so is the estimation of severity. Further details are presented in the thesis.

Spezialisierung Theoretische Biologie / Obwohl die Krebstherapie im letzten Jahrhundert große Fortschritte gemacht hat, bleibt die Resistenz gegen medikamentöse Behandlungen ein großes Hindernis im Kampf gegen den Krebs. In dieser Arbeit habe ich ein R-Paket namens STASNet entwickelt, das semi-quantitative Modelle der Signaltransduktion aus Signalisierungs-Störungsantwortdaten unter Verwendung von Least Square Modular Response Analysis-Modellen generiert. Um zu untersuchen, wie gut STASNet die Aktivität von Signalwegen quantifizieren kann, haben wir Perturbationsdaten von einem Paar isogener Darmkrebszelllinien mit und ohne SHP2-Knock-out, einem bekannten Resistenzmechanismus bei dieser Krebsart, verwendet. Ich habe dann untersucht die Resistenz gegen die MEK- und ALK-Hemmung beim Neuroblastom, einem pädiatrischen Krebs mit schlechter Prognose. Ein Wirkstoffscreening zeigte, dass der MEK-Inhibitor Selumetinib ein Panel von Neuroblastom-Zelllinien in drei sensitive und sechs resistente Zelllinien trennte, dass konnte nicht mit einzelnen molekularen Markern erklärt. STASNet-Modelle zeigten, dass die starke Resistenz gegen Selumetinib durch eine starke Rückkopplung von ERK auf MEK oder eine vielschichtige Rückkopplung sowohl auf MEK als auch auf IGF1R getrieben wurde. Aus dem Modell konnte eine kombinatorische Therapie abgeleitet werden, die auf MEK in Kombination mit entweder RAF oder IGF1R abzielt, je nach Art der in der Zelllinie vorhandenen Rückkopplungen. Schließlich ergab die Untersuchung der Wirkung von NF1-KO auf die Signalübertragung, dass der Verlust von NF1 den MAPK-Weg für die Liganden-induzierte Aktivierung hypersensibilisierte, aber das ERK-RAF-Rückkopplung störte. Die Erkenntnisse aus den in dieser Arbeit entwickelten Modellen werden somit dazu beitragen, personalisierte Kombinationen von Inhibitoren zu entwerfen, die als Zweitlinientherapie nach molekularer Untersuchung der Tumorreaktion auf die Erstbehandlung eingesetzt werden könnten. / Cancer therapy has seen immense progress over the last century but resistance to drug treatments remains a major obstacle in the war against cancer. I developed an R package named STASNet to generate models of signal transduction from signalling perturbation-response data using Least Square Modular Response Analysis models. I used these models to study how differences in signal transduction relate to drug resistance and can be used to make predictions about resistance mechanisms and optimal treatments. To show how STASNet can accurately quantify the activity of signalling pathways, I used perturbation data from a pair of isogenic colon cancer cell line with and without SHP2 knock-out, a known resistance mechanism in this cancer type, which showed that MAPK signalling is more affected by SHP2 knock-out than PI3K signalling, confirming the role of SHP2 as a primary MAPK component. I investigated resistance to MEK and ALK inhibition in neuroblastoma, a pediatric cancer with a dismal prognosis. The MEK inhibitor Selumetinib separated a panel of neuroblastoma cell lines into three sensitive and six resistant cell lines that could not be explained with individual molecular markers. STASNet models trained on perturbation-response data from these cell lines revealed that the strong resistance to Selumetinib was driven by a strong feedback from ERK to MEK or a multi-layered feedback to both MEK and IGF1R. This was confirmed by phosphoproteomics and suggested a therapy targeting MEK in combination with either RAF or IGF1R depending on the type of feedback present in the cell line that was confirmed experimentally. Finally, studying the effect of NF1-KO on signalling revealed that the loss of NF1 hyper-sensitized the MAPK pathway to ligand-induced activation but disrupted the ERK-RAF feedback. Those insights to design personalized combinations of inhibitors that could be used as second line therapy after molecularly monitoring the tumor response to the initial treatment.

Accurately predicting surface ground motions is critical for many earthquake engineering applications. Equivalent-linear (EQL) site response analysis is a numerical technique used to compute surface ground motions from input motions at bedrock using the site-specific dynamic soil properties. The purpose of this study was to investigate the accuracy of EQL site response analysis for stiff soil sites by comparing computed and observed transfer functions and response spectral amplification. The Kiban Kyoshin network (KiK-net) in Japan is a seismograph network consisting of downhole array sites with strong-motion accelerometers located at the ground surface and at depth. Recorded motions and shear wave velocity profiles are available for most sites. Observed transfer functions and response spectral amplification were computed for 930 individual seismic recordings at 11 stiff soil KiK-net sites. Computed transfer functions and response spectral amplification were calculated from EQL site response analysis by specifying the KiK-net base sensor motion as the input motion. Sites were characterized using the measured shear wave velocity profiles and nonlinear soil properties estimated from empirical models. Computed and observed transfer functions and response spectral amplification were compared at different levels of strain for each site. The average difference between the observed and computed response spectral amplification across the 11 sites were compared at different levels of strain. Overall, there is reasonable agreement between the computed and observed transfer functions and response spectral amplification. There is agreement between the computed and observed site periods, but with over-prediction of the computed response at the observed site periods. Higher modes often computed by the theoretical model were not always observed by the recordings. There is very good agreement between the computed and observed transfer functions and response spectral amplification for periods larger than the site periods. There is less agreement between the computed and observed transfer functions and response spectral amplification for periods less than the site periods. There is mostly over-prediction of the response spectral amplification at these periods, although some under-prediction also occurred. Across all 11 sites the predicted spectral amplification is within +/-20% at shear strains less than 0.01%. At shear strains between approximately 0.01 and 0.03%, the spectral amplification is over-predicted for these sites, in some instances by as little as 5% and in other instances by a factor of 2 or more. / text

<p>Frequency response analysis (FRA) is a method which is used to detect mechanical faults in transformers. The FRA response of a transformer is determined by its geometry and material properties, and it can be considered as the transformer’s fingerprint. If there are any mechanical changes in the transformer, for example if the windings are moved or distorted, its fingerprint will also be changed so, theoretically, mechanical changes in the transformer can be detected with FRA.</p><p>The purpose of this thesis is to partly create a simple model for the ferromagnetic material in the transformer core, and partly to investigate the high frequency part of the FRA response of the transformer winding. To be able to realize these goals, two different models are developed separately from each other. The first one is a time- and frequency domain complex permeability model for the ferromagnetic core material, and the second one is a time- and frequency domain winding model based on lumped circuits, in which the discretization is made finer and finer in three steps. Capacitances and inductances in the circuit are calculated with use of analytical expressions derived from approximated geometrical parameters.</p><p>The developed core material model and winding model are then implemented in MATLAB separately, using state space analysis for the winding model, to simulate the time- and frequency response.</p><p>The simulations are then compared to measurements to verify the correctness of the models. Measurements were performed on a magnetic material and on a winding, and were compared with obtained results from the models. It was found that the model developed for the core material predicts the behavior of the magnetic field for frequencies higher than 100 Hz, and that the model for the winding predicts the FRA response of the winding for frequencies up to 20 MHz.</p>