Abstract This thesis describes the design, fabrication and operation of a microfluidic device for the screening of biomolecule mixture surface mediated effects. The characterisation of a surface immobilisation strategy that will allow the robust attachment of candidate biomolecules on a substrate for use in cell culture applications. This is carried out in the form of a modified and optimised layer-by-layer surface immobilisation strategy and its subsequent thorough and robust characterisation. This was achieved by compiling and critically analysing large amounts of quartz crystal microbalance with dissipation (QCM-D) data and the model utilised to provide meaningful, physical data as an output. QCM-D data was combined with surface plasmon resonance (SPR) data to validate the assumptions used within the QCM-D model package. Further evidence demonstrating the presence of the multilayer, as described by QCM-D and SPR, is achieved using x-ray photoelectron spectroscopy (XPS). These results show that the multilayer surface is robustly attached to the substrate and consists of a large amount of water whilst being able to immobilise mixtures of four proteins. A custom protocol for fabricating these two layer devices was devised and is presented. Scale limitations have been overcome to provide mixing capabilities for large extracellular matrix molecules to be immobilised on the previously described, microfluidically generated surface immobilisation strategy. The optimisation and characterisation of the mixing within this microfluidic device, affected by the incorporated staggered herring bone mixer is also shown. Using dynamic force spectroscopy (DFS) along with a custom designed force curve data processing and analysis package, the spatial localisation of a mixture of four immobilised biomolecules was determined. The aim of this study was to compare the spatial localization of a mixture of four biomolecules created by; standard cell culture protocols (adsorbed from bulk onto tissue culture polystyrene) and a surface created via microfluidic deposition on top of a previously described surface immobilisation strategy. The design and robust application of this custom analysis package allows the definition of a “Barricade of Specificity” such that interactions between an antibody functionalised AFM tip and a surface composed of a mixture of proteins, to be categorised as either a “true” specific interaction, or a non-specific interaction. The application of this Barricade of Specificity thus allows the spatial localisation of four immobilized biomolecules to be determined with a large degree of accuracy as a result of the large rage of non-specific interactions surveyed and the strict definition of a valid rupture force. The final chapter details the application of the microfluidic platform to enable high throughput screening of the effects of extracellular matrix (ECM) molecules, singly and in combination, with regards to the effect on the expression of cell surface markers on umbilical cord blood (UCB) derived CD34+ cells. Careful selection of candidate ECM molecules, cytokine and oxygen concentration has resulted in little difference in the effect on UCB derived CD34+ cells differentiation state after seven days in culture. The major effect has been the maturation towards lymphocyte and leukocyte precursors. However, of the four ECM molecules tested individually, in binary and in quaternary combinations, osteopontin (Opn) and laminin (Ln) demonstrated differences compared to other surfaces tested. In order to further assess the effect of these protein surfaces on the cell surface marker expression of UCB derived CD34+ cells, further tests are warranted for increased periods of time to enable greater discrimination in marker expression and thus increase our understanding of the fundamental biology of this rare and clinically useful cell source.

This thesis focuses on the formulation and numerical implementation of a fully coupled continuum model for deformation-diffusion in linearized elastic solids. The mathematical model takes into account the affect of the deformation on the diffusion process, and the effect of the transport of an inert chemical species on the deformation of the solid. A robust computational framework is presented for solving the proposed mathematical model, which consists of coupled non-linear partial differential equations. It should be noted that many popular numerical formulations may produce unphysical negative values for the concentration, particularly, when the diffusion process is anisotropic. The violation of the non-negative constraint by these numerical formulations is not mere numerical noise. In the proposed computational framework we employ a novel numerical formulation that will ensure that the concentration of the diffusant be always non-negative, which is one of the main contributions of this thesis. Representative numerical examples are presented to show the robustness, convergence, and performance of the proposed computational framework. Another contribution is to systematically study the affect of transport of the diffusant on the deformation of the solid and vice-versa, and their implication in modeling degradation/healing of materials. It is shown that the coupled response is both qualitatively and quantitatively different from the uncoupled response.

<p>A numerical high order difference method is developed for solution of the incompressible Navier-Stokes equations. The solution is determined on a staggered curvilinear grid in two dimensions and by a Fourier expansion in the third dimension. The description in curvilinear body-fitted coordinates is obtained by an orthogonal mapping of the equations to a rectangular grid where space derivatives are determined by compact fourth order approximations. The time derivative is discretized with a second order backward difference method in a semi-implicit scheme, where the nonlinear terms are linearly extrapolated with second order accuracy.</p><p>An approximate block factorization technique is used in an iterative scheme to solve the large linear system resulting from the discretization in each time step. The solver algorithm consists of a combination of outer and inner iterations. An outer iteration step involves the solution of two sub-systems, one for prediction of the velocities and one for solution of the pressure. No boundary conditions for the intermediate variables in the splitting are needed and second order time accurate pressure solutions can be obtained.</p><p>The method has experimentally been validated in earlier studies. Here it is validated for flow past a circular cylinder as an example of a physical test case and the fourth order method is shown to be efficient in terms of grid resolution. The method is applied to external flow past a parabolic body and internal flow in an asymmetric diffuser in order to investigate the performance in two different curvilinear geometries and to give directions for future development of the method. It is concluded that the novel formulation of boundary conditions need further investigation.</p><p>A new iterative solution method for prediction of velocities allows for larger time steps due to less restrictive convergence constraints.</p>

As a potential solution to the global energy and environmental pollution, design and synthesis of artificial photocatalysts with high activities have attracted increasing scientific interests worldwide. In recent years, the graphitic carbon nitride (g-C3N4) has shown new possible applications in the photocatalytic field due to its unique properties. However, the photocatalytic efficiency of the pristine g-C3N4 is greatly limited by the high recombination rate of the photo-induced electron-hole pairs. In this thesis, the aim is to design and fabricate efficient g-C3N4 based photocatalysts with enhanced photocatalytic activities under a visible light irradiation. In order to achieve this goal, two strategies have been employed in the present thesis. First, the as-obtained g-C3N4 was used as the host material to construct staggered-aligned composite photocatalysts by selecting semiconductors with suitable band positions. By this method, three kinds of g-C3N4-based composite photocatalysts such as g-C3N4/ZnS nanocage, g-C3N4/m-Ag2Mo2O7 and g-C3N4/MIL-88A were successfully fabricated. Second, the microstructure of the g-C3N4 was modified by the H2O2-treatment at an elevated temperature and ambient pressure. In this study, the g-C3N4 was prepared by a simple pyrolysis of urea. As for all the as-synthesized phtocatalysts, the structures, morphologies and the optical properties were carefully characterized by the following techniques: XRD, SEM, TEM, FT-IR and DRS. Also, the band edge positions of m-Ag2Mo2O7 and MIL-88A were studied by the Mott-Schottky methods. Thereafter, the photocatalytic activities were evaluated by using a solution of rhodamine B (RhB) as a target pollutant for the photodegradation experiments performed under a visible light irradiation. The results showed that all the aforementioned g-C3N4-based photocatalysts exhibited enhanced photocatalytic activities in comparison with the pristine g-C3N4. For the case of the g-C3N4-based composite photocatalysts, the enhancement factor over the pristine g-C3N4 can achieve values ranging from 2.6 to 3.4. As for the H2O2-treated g-C3N4, the degradation rate constant can be 4.6 times higher than that of the pristine g-C3N4. To understand the key factors in new materials design, we also devote a lot of efforts to elucidate the basic mechanisms during the photocatalytic degradation of organic pollutant. Based on the results of the active species trapping (AST) experiments, the main active species in each photocatalytic system were determined. In the g-C3N4/m-Ag2Mo2O7 and the g-C3N4/MIL-88A system, three kinds of active species of ·O2-, h+ and ·OH were found to be involved in the photocatalytic reaction. Among them, the ·O2- and h+ were the main active species. In the g-C3N4/ZnS and H2O2-treated g-C3N4 photocatalytic systems, the main active species was determined as the ·O2-. The reaction pathways of these active species were also demonstrated by comparing the band edge positions with the potentials of the redox couple. In addition, the relationship between the active species and the photocatalytic behaviors of N-de-ethylation and conjugated structure cleavage were studied. Finally, possible mechanisms to explain the enhanced photocatalytic activities were proposed for each photocatalytic system. The results in this thesis clearly confirm that the photocatalytic activity of the g-C3N4 based photocatalyst can efficiently be enhanced by constructions of staggered-aligned composites and by modification of the microstructure of the g-C3N4. The enhanced photocatalytic performance can mainly be ascribed to the efficient separation of the photo-induced electron-hole pairs and the increase of the active sites for the photocatalytic reaction. / <p>QC 20150909</p>

Block shear is a limit state that should be accounted for during the design of the steel tension members. This failure mechanism combines a tension failure on one plane and a shear plane on a perpendicular plane. Although current design specifications present equations to predict block shear load capacities of the connections, they fail in predicting the failure modes. Block shear failure of a structural connection along a staggered path may be the governing failure mode. Code treatments for stagger in a block shear path are not exactly defined. A parametric study has been conducted and over a thousand finite element analyses were performed to identify the parameters affecting the block shear failure in connections with multiple bolt lines and staggered holes. The quality of the specification equations were assessed by comparing the code predictions with finite element results. In addition, based on the analytical findings new equations were developed and are presented herein.

The understanding of the physics of the Coherent Structures and their interaction with the remaining fluid motions is of paramount interest in Turbulence Research. <p>Indeed, recently had been suggested that separating and understanding the the different physical behavior of Coherent Structures and "uncoherent" background might very well be the key to understand and predict Turbulence. Available understanding of Coherent Structures shows that their size is considerably larger than the turbulent macro-scale, making permissible the application of Large Eddy Simulation to their simulation and study, with the advantage to be able to study their behavior at higher Re and more complex geometry than a Direct Numerical Simulation would normally allow. Original purpose of the present work was therefore the validation of the use of Large Eddy Simulation for the study of Coherent Structures in Shear-Layer and the its application to different flow cases to study the effect of the flow topology on the Coherent Structures nature.<p>However, during the investigation of the presence of Coherent Structures in numerically generated LES flow fields, the aging in house Large Eddy Simulation (LES) code of the Environmental & Applied Fluid Dynamics Department has shown a series of limitations and shortcomings that led to the decision of relegating it to the status of Legacy Code (from now on indicated as VKI LES legacy code and of discontinuing its development. A new natively parallel LES solver has then been developed in the VKI Environmental & Applied Fluid Dynamics Department, where all the shortcomings of the legacy code have been addressed and modern software technologies have been adopted both for the solver and the surrounding infrastructure, delivering a complete framework based exclusively on Free and Open Source Software (FOSS ) to maximize portability and avoid any dependency from commercial products. The new parallel LES solver retains some basic characteristics of the old legacy code to provide continuity with the past (Finite Differences, Staggered Grid arrangement, Multi Domain technique, grid conformity across domains), but improve in almost all the remaining aspects: the flow can now have all the three directions of inhomogeneity, against the only two of the past, the pressure equation can be solved using a three point stencil for improved accuracy, and the viscous terms and convective terms can be computed using the Computer Algebra System Maxima, to derive discretized formulas in an automatic way.<p>For the convective terms, High Resolution Central Schemes have been adapted to the three-dimensional Staggered Grid Arrangement from a collocated bi-dimensional one, and a system of Master-Slave simulations has been developed to run in parallel a Slave simulation (on 1 Processing Element) for generating the inlet data for the Master simulation (n - 1 Processing Elements). The code can perform Automatic Run-Time Load Balancing, Domain Auto-Partitioning, has embedded documentation (doxygen), has a CVS repository (version managing) for ease of use of new and old developers.<p>As part of the new Frame Work, a set of Visual Programs have been provided for IBM Open Data eXplorer (OpenDX), a powerful FOSS Flow visualization and analysis tool, aimed as a replacement for the commercial TecplotTM, and a bug tracking mechanism via Bugzilla and cooperative forum resources (phpBB) for developers and users alike. The new M.i.O.m.a. (MiOma) Solver is ready to be used again for Coherent Structures analysis in the near future. / Doctorat en sciences appliquées / info:eu-repo/semantics/nonPublished

A numerical high order difference method is developed for solution of the incompressible Navier-Stokes equations. The solution is determined on a staggered curvilinear grid in two dimensions and by a Fourier expansion in the third dimension. The description in curvilinear body-fitted coordinates is obtained by an orthogonal mapping of the equations to a rectangular grid where space derivatives are determined by compact fourth order approximations. The time derivative is discretized with a second order backward difference method in a semi-implicit scheme, where the nonlinear terms are linearly extrapolated with second order accuracy. An approximate block factorization technique is used in an iterative scheme to solve the large linear system resulting from the discretization in each time step. The solver algorithm consists of a combination of outer and inner iterations. An outer iteration step involves the solution of two sub-systems, one for prediction of the velocities and one for solution of the pressure. No boundary conditions for the intermediate variables in the splitting are needed and second order time accurate pressure solutions can be obtained. The method has experimentally been validated in earlier studies. Here it is validated for flow past a circular cylinder as an example of a physical test case and the fourth order method is shown to be efficient in terms of grid resolution. The method is applied to external flow past a parabolic body and internal flow in an asymmetric diffuser in order to investigate the performance in two different curvilinear geometries and to give directions for future development of the method. It is concluded that the novel formulation of boundary conditions need further investigation. A new iterative solution method for prediction of velocities allows for larger time steps due to less restrictive convergence constraints. / QC 20101221

This thesis investigates the impacts of user choice in Swedish elderly care on quality and cost as well as the impact of marketisation on the Covid-19 death toll. In the last three decades welfare service provision in Sweden has been increasingly marketised. Since 2009, Swedish municipalities have been able to introduce user choice in elderly care and it has been widely adopted in home care. To investigate the impact of introducing user choice, new insights from econometrics literature is used to estimate a staggered Difference-in-Difference model, using panel data for the years 2003-2019 and the 290 Swedish municipalities. The impact of marketisation on the Covid-19 death toll is estimated through Ordinary Least Squares using a cross-sectional data set. There are three main findings of this thesis. (i) The impact on quality and cost of the introduction of user choice has had heterogeneous effects across adoption groups, calendar time, and exposure length of treatment, and hence, the standard Difference- in-Difference approach is likely to provide biased estimates in this setting. (ii) The introduction of user choice has no clear effect on non-contractible quality measured by mortality rate and fall accidents, nor on cost. However, user choice has increased subjective quality, as measured by user satisfaction. (iii) A higher degree of marketisation in home care is associated with a higher Covid-19 death toll amongst those which had home care.

We examine 102 share lockup agreements following IPOs on the Swedish stock market and whether any abnormal returns exist in the days surrounding the expiration of lockup agreements. We also test three potential explanatory variables based on previous research, the length of the lockup agreement, the type of pre-IPO ownership for the firm (if it is backed by private equity or not), and if the lockup has multiple expiration dates (staggered lockup) or only one. Our results are unable to prove that there are abnormal returns surrounding the expiration lockups, and our variables fail to provide any explanation for the cumulative abnormal return (CAR). One variable that could prove interesting in future research is the change of free float, which we add in a robustness test and find a significant increase in explanatory power.

In this thesis, the impact of conservation banking on biodiversity is assessed by examining the bird species richness in U.S. counties that have implemented the policy. Conservation banking is a market-based instrument designed for developers who need to comply with the Endangered Species Act for the negative environmental impacts that their projects have made. Conservation banking aims to “protect and recover imperilled species and the ecosystems upon which they depend” (USFWS 2013, p. 1). In this thesis, a staggered difference-in-difference with differential timing by Goodman-Bacon (2018) and further developed by Callaway and Sant’Anna (2021) is used to estimate the effect of conservation banks on biodiversity. Data for biodiversity, bird species richness are collected from U.S. Geological Survey's data from the North American Breeding Bird Survey (BBS). Information on conservation banks is gathered from the Regulatory In-lieu fee and Bank Information Tracking System (RIBITS). This thesis focuses on 107 conservation banks in 53 counties in the U.S. established between 2005 and 2016. The main results from this study indicate a positive impact of the introduction of conservation banks, with an increase in biodiversity of 4,1%. Consequently, this confirms the positive effect of the policy intervention. Despite these results, it is vital to consider caution regarding this market-based instrument. Market-based instruments that commodify elements of nature into the market are a new frontier in capitalist expansion. This approach may exclude areas from the natural evolutionary selection process, leading to potential long-term ecological imbalances. Current payment structures in conservation banking can lead to misallocation of taxpayers’ money at the same time as biodiversity outcomes are not optimized. Therefore, the most fundamental recommendation for this policy is to change to outcome-based payments.