<p>The mechanical behavior of tissues at the macroscale is tightly coupled to cellular activity at the microscale and tuned by microstructure at the mesoscale. Dermal wound healing is a prominent example of a complex system in which multiscale mechanics regulate restoration of tissue form and function. In cutaneous wound healing, a fibrin matrix is populated by fibroblasts migrating in from a surrounding tissue made mostly out of collagen. Fibroblasts both respond to mechanical cues such as fiber alignment and stiffness as well as exert active stresses needed for wound closure. </p> <p>To model wound healing mechanobiology, we first develop a multiscale model with a two-way coupling between a microscale cell adhesion model and a macroscale tissue mechanics model. Starting from the well-known model of adhesion kinetics proposed by Bell, we extend the formulation to account for nonlinear mechanics of fibrin and collagen and show how this nonlinear response naturally captures stretch-driven mechanosensing. We then embed the new nonlinear adhesion model into a custom finite element implementation of tissue mechanical equilibrium. Strains and stresses at the tissue level are coupled with the solution of the microscale adhesion model at each integration point of the finite element mesh. In addition, solution of the adhesion model is coupled with the active contractile stress of the cell population. The multiscale model successfully captures the mechanical response of biopolymer fibers and gels, contractile stresses generated by fibroblasts, and stress-strain contours observed during wound healing. We anticipate this framework will not only increase our understanding of how mechanical cues guide cellular behavior in cutaneous wound healing, but will also be helpful in the study of mechanobiology, growth, and remodeling in other tissues. </p> <p>Next, we develop another multiscale model with a bidirectional coupling between a microscale cell adhesion model and a mesoscale microstructure mechanics model. By mimicking the generation of fibrous network in experiment, we established a discrete fiber network model to simulate the microstructure of biopolymer gels. We then coupled the cell adhesion model to the discrete model to obtain the solution of microstructure equilibrium. This multiscale model was able to recover the volume loss of fibrous gels and the contraction from cells in the networks observed in experiment. We examined the influence of RVE size, stiffness of single fibers and stretch of the gels. We expect this work will help bridge the activity of cell to the microstructure and then to the tissue mechanics especially in wound healing. We hope this work will provide more rigorous understanding in the study of mechanobiology.</p> <p>At last, we established a computational model to accurately capture the mechanical response of fibrin gels which is a naturally occurring protein network that forms a temporary structure to enable remodeling during wound healing and a common tissue engineering scaffold due to the controllable structural properties. We formulated a strategy to quantify both the macroscale (1–10 mm) stress-strain response and the deformation of the mesoscale (10–1000 microns) network structure during unidirectional tensile tests. Based on the experimental data, we successfully predict the strain fields that were observed experimentally within heterogenous fibrin gels with spatial variations in material properties by developing a hyper-viscoelastic model with non-affined evolution under stretching. This model is also potential to predict the macroscale mechanics and mesoscale network organization of other heterogeneous biological tissues and matrices.</p>

Hypoplastic left heat syndrome (HLHS) is a complex cardiac malformation in neonates suffering from congenital heart disease and occurs in nearly 1 per 5000 births. HLHS is uniformly fatal within the first hours or days after birth as the severly malformed anatomies of the left ventricle, mitral, and aortic valves, and ascending aorta are not compatable with life. The regularly implemented treatment, the Norwood operation, is a complex open heart procedure that attempts to establish univenticular circulation by removing the atrial septum ( communicating the right and left ventricle), reconstructing the malformed aortic arch, and connecting the main pulmonary artery into the reconstructed arch to allow direct perfusion from the right ventricle into the systemic circulation. A relatively new treatment being utilized,the Hybrid Norwood procedure, involves a less invasive strategy to establish univentricular circulation that avoids a cardiopulmonary bypass (heart-lung machine), deliberate cardiac arrest, and circulatroy arrest of the patient during the procedure. The resulting systemic-pulmonary circulation is unconventional; blood is pumped simotaneously and in parallel to the systemic and pulmonary arteries after the procedure. Cardiac surgeons are deeply interested in understanding the global and local hemodynamics of this anotomical configuration. To this end, a multiscale model of the entire circulatory system was developed utilizing an electrical lumped parameter model for the peripheralor distal circulation coupled with a #D Computational Fluid Dynamics (CFD) model to understand the local hemodynamics. The lumped parameter (LP) model is mainly a closed loop circut comprised of RLC comartments that model cardiac function as well as the viscous drag, flow intertia, and compliance of the different atrial and venous beds in the body. A system of 32 first-order differential equations is formulated and solved for the LP model using a fourth-order adaptive Runge-Kutta solver. The output pressure and flow waveforms obtained from the LP model are imposed as boundary conditions on the CFD model. Coupling of the two models is done through an iterative process where the parameters in the LP model are adjusted to match the CFD solution. The CFD model domain is a representative HLHS anatomy of an infant after undergoing the Hybrid Norwood procedure and is comprised of the neo-aorta, pulmonary roots, aortic arch with branching arteries, and pulmonary arteries. The flow field is solved over several cardiac cycles using an implicit-unsteady RANS equation solver with the k-epsilon turbulence model.; Hypoplastic left heart syndrome (HLHS) is a complex cardiac malformation in neonates suffering from congenital heart disease and occurs in nearly 1 per 5000 births. HLHS is uniformly fatal within the first hours or days after birth as the severely malformed anatomies of the left ventricle, mitral and aortic valves, and ascending aorta are not compatible with life. The regularly implemented treatment, the Norwood operation, is a complex open heart procedure that attempts to establish univentricular circulation by removing the atrial septum (communicating the right and left ventricle), reconstructing the malformed aortic arch, and connecting the main pulmonary artery into the reconstructed arch to allow direct perfusion from the right ventricle into the systemic circulation. A relatively new treatment being utilized, the Hybrid Norwood procedure, involves a less invasive strategy to establish univentricular circulation that avoids a cardiopulmonary bypass (heart-lung machine), deliberate cardiac arrest, and circulatory arrest of the patient during the procedure. The resulting systemic-pulmonary circulation is unconventional; blood is pumped simultaneously and in parallel to the systemic and pulmonary arteries after the procedure. Cardiac surgeons are deeply interested in understanding the global and local hemodynamics of this anatomical configuration. To this end, a multiscale model of the entire circulatory system was developed utilizing an electrical lumped parameter model for the peripheral or distal circulation coupled with a 3D Computational Fluid Dynamics (CFD) model to understand the local hemodynamics. The lumped parameter (LP) model is mainly a closed loop circuit comprised of RLC compartments that model cardiac function as well as the viscous drag, flow inertia, and compliance of the different arterial and venous beds in the body.

Many machine learning problems involve dealing with a large amount of high-dimensional data across diverse domains. In addition, annotating or labeling the data is expensive as it involves significant human effort. This dissertation explores a joint solution to both these problems by exploiting the property that high-dimensional data in real-world application domains often lies on a lower-dimensional structure, whose geometry can be modeled as a graph or manifold. In particular, we propose a set of novel manifold-alignment based approaches for transfer learning. The proposed approaches transfer knowledge across different domains by finding low-dimensional embeddings of the datasets to a common latent space, which simultaneously match corresponding instances while preserving local or global geometry of each input dataset. We develop a novel two-step transfer learning method called Procrustes alignment. Procrustes alignment first maps the datasets to low-dimensional latent spaces reflecting their intrinsic geometries and then removes the translational, rotational and scaling components from one set so that the optimal alignment between the two sets can be achieved. This approach can preserve either global geometry or local geometry depending on the dimensionality reduction approach used in the first step. We propose a general one-step manifold alignment framework called manifold projections that can find alignments, both across instances as well as across features, while preserving local domain geometry. We develop and mathematically analyze several extensions of this framework to more challenging situations, including (1) when no correspondences across domains are given; (2) when the global geometry of each input domain needs to be respected; (3) when label information rather than correspondence information is available. A final contribution of this thesis is the study of multiscale methods for manifold alignment. Multiscale alignment automatically generates alignment results at different levels by discovering the shared intrinsic multilevel structures of the given datasets, providing a common representation across all input datasets.

Iron-based ferritic alloys are used for a plethora of industrial applications. These alloys contain foreign atoms purposely employed to improve certain properties as well as some unwanted impurities introduced during fabrication. Materials properties are decisively influenced by diffusion processes. Very often diffusion cannot be avoided during fabrication and application. Therefore, many efforts are made to understand the underlying atomic-level mechanisms by both experimental and theoretical investigations. In this thesis work a multiscale modelling approach is used to study oxygen and vacancy diffusion in dilute ferritic iron alloys. Due to the extremely low solubility of oxygen the measurement of oxygen diffusion in iron is difficult. Only few experimental data are available. Experimental investigation of vacancy migration is still more complicated. The lack of reliable experimental data is therefore an important motivation for theoretical investigations. Gaining fundamental data on oxygen and vacancy diffusion in dilute iron alloys is essential for many applications. Oxygen plays a crucial role in the corrosion of iron-based alloys. Oxygen and the vacancy are also important in the formation and evolution of Y-Ti-O nanoclusters in oxide dispersion strengthened ferritic Fe-Cr alloys, which are considered as promising candidates for structural materials of future fusion and fission reactors. Furthermore, vacancies are formed during neutron and ion irradiation and their diffusion affects radiation-induced nanostructure formation in ferritic alloys. In the first part of this thesis work, the diffusion of interstitial oxygen under the influence of substitutional atoms or solutes (Al, Si, P, S, Ti, Cr, Mn, Ni, Y, Mo and W) in bcc Fe is investigated by the combination of Density Functional Theory (DFT) and Atomistic Kinetic Monte Carlo (AKMC) simulations. The substitutional atoms are assumed to be immobile because oxygen diffusion is much faster than that of the solutes. DFT is applied to gain data on binding energies between interstitial oxygen and the substitutional foreign atoms, and to calculate the migration barriers for oxygen in the environment of the solutes. Using the migration barriers obtained by DFT, the diffusion coefficient of oxygen is determined by AKMC simulation. It is found that Si, P, Ni, Mo, and W have negligible influence on the oxygen diffusion coefficient. Al, Cr, Mn, S, Ti, and Y cause a considerable reduction of oxygen mobility. In these cases, the temperature dependence of oxygen diffusivity shows deviations from Arrhenius behavior. This is explained in detail by the significant temperature dependence of the ratio between residence times in the respective states. In the second part of the work a method is presented which allows for an efficient calculation of the diffusion coefficient of oxygen and other interstitial atoms in dilute alloys. The method is applied to examples considered in the first part of the work. The calculation procedure is based on the separation of the diffusion path into a contribution related to migration in the interaction region between the mobile interstitial and the substitutional solute and another part related to diffusion in perfect bcc Fe. In this manner AKMC simulation must be performed only for one concentration of the substitutional solute, and the obtained results can be employed to obtain data for other concentrations using analytical expressions containing binding energies between the interstitial and the substitutional solute. The focus of third part of the work is on the mutual dependence of oxygen and vacancy diffusion in bcc Fe and dilute iron alloys. Here both O and v must be considered as mobile while the substitutional atoms are assumed to be immobile. DFT is applied to determine the binding energy between O and v for different distances, the migration barriers for O in the environment of v, and the corresponding barriers of v in the vicinity of O. In agreement with previous work O and v have a very strong binding at the 1st neighbor distance. On the other hand, the calculations show that the Ov pair at the 6th neighbor distance is instable. The newly found simultaneous or coupled jumps of both O and v compensate the lack of jump paths that would occur due to this instability. The DFT results are employed to determine the diffusion coefficient of O and v using the scheme of the AKMC-based calculation method presented in the second part of the thesis work. At first a model system with fixed O and v concentrations is studied. It is found that a small v content of some ppm can already lead to a strong reduction of the O diffusivity. A similar effect is obtained for v diffusion under the influence of O. Furthermore, investigations on the interdependence of O and v diffusion during thermal processing of oxide dispersion strengthened iron alloys are performed, and the influence of the substitutional atoms Y and Ti is studied. A simple thermodynamic model is employed to determine the concentration of O, Y, and Ti monomers as well as the total v concentration, for a typical total content of O, Y, and Ti. These results are used in calculations of the diffusion coefficients of O and v. Not only a strong mutual dependence but also a significant influence of Y on O diffusion is found. Finally, O and v diffusivities in a system with a total O content close to the thermal solubility are calculated. The monomer O concentration as well as the total v concentration was determined using two different models considering equilibrium of O and v with Ov, or equilibrium of O and v with Ov and O2v or Ov2. Despite the very small value of thermal solubility of O in bcc Fe, both the O and v diffusion coefficient are very different from that in pure iron. Even for such a low amount of O in the alloy the diffusion coefficients differ strongly from those in perfect bcc Fe. The results of the present work have important consequences for planning and performing new experiments on O and v diffusion in dilute iron alloys. In particular, a very precise knowledge of the concentrations of O and v, as well as of other foreign atoms and traps such as dislocations is required.

Biomineralized lattice materials with have high mineral contents (~ 99 wt%), usually "conceal" multiscale structural arrangements for unique mechanical or functional performance, such as the remarkable damage tolerance despite of the brittle nature of the constituents (e.g., biogenic silica and calcite). However, the quantitative explorations of the structure-mechanics relationships in multiscale of biomineralized lattices remain insufficient and hence hinder the leverage of the functional benefits to design architected cellular materials. In this dissertation, I selected two groups of marine animals (i.e., Hexactinellid sponges and Echinoderms) for systematic structural-mechanical study. Their biomineralized lattice skeletons exhibit three representative types of multiscale structures: 1) multiscale hierarchical structure: skeleton of Hexactinellid sponge such as Euplectella aspergillum; 2) multiscale functionally graded structure: spine of sea urchin Heterocentrotus mammillatus; and 3) dual-scale (atomic and microlattice scales) periodic structure: ossicle of starfish Protoreaster nodosus. This dissertation develops quantitatively the structural-mechanical/functional correlations in biomineralized cellular materials for bio-inspired material design. Four different species of Hexactinellid sponges have been studied with particular focus on the species E. aspergillum. As an example of the multiscale hierarchical biomineralized lattice, the extremely lightweight skeleton (~99% porosity) of E. aspergillum exhibits 1) amorphous nanoparticular biogenic silica; 2) micron-sized fibrous spicule with cylindrically laminated silica layers separated by organic interfaces; 3) spicule bundles where the individual spicules merged by secondary silica deposition; 4) a centimeter-sized Voronoi-like cellular dome known as sieve plate; and 5) a centimeter-sized cylindrically arranged rectangular lattice with double-diagonal reinforcement and external helical ridge. Here, we discovered a series of mechanical or functional properties or formation process of structures in different length scales: 1) for the biogenic silica in three different species of Hexactinellid sponge, consistent modulus and hardness of the biogenic silica throughout the cross section of the spicule are found via substantial correlation between the measured values and locations; 2) for the sieve plate, the Voronoi-like cellular dome constructed by porous branch with increased height achieves balance between improved mechanical stiffness and large pore opening for sponge's current pumping mechanism; 3) via microstructural study, the formation process of the sieve plate is proposed; and 4) for the cylindrical skeletal body, the double-diagonal configuration and the ridge structure are found to provide tendency to optimize torsional rigidity, and enhanced radial stiffening and improved permeability, respectively. The cellular structure in the spine of the H. mammillatus (i.e., stereom) made of ~99wt% of single-crystalline calcite shows a multiscale functionally graded structure. We developed and optimized a cellular network analysis workflow on the large-volume 3D lattice structure obtained from the synchrotron-based micro-Computed Tomography scan. The analysis provides quantitative descriptions of the branch, ring structure, and septum which reveals a functionally graded structure in multiscale from the center region to the edge region of the spine: 1) in microscale, the branch thickness and length increases, resulting in a significantly decreased porosity; and 2) in macroscale, the center region of the spine with galleried stereom of highly aligned branches transits to the edge region with laminar stereom of radially arranged septa and interconnecting branches. The multiscale structural variations lead to the mechanical variations the increased elastic modulus and mechanical isotropy from the center to the edge of the spine. This provides a biological pathway for designing the lightweight, strong, and tough beam with multiscale structural gradient. In previous work, we discovered that ossicle in starfish P. nodosus possesses a unique dual-scale periodic lattice structure, which means periodic single crystal calcite in nanoscale and diamond triply periodic minimal surface (diamond-TPMS) lattice in microscale. It has three unique structural features: 1) microlattice dislocations in ossicles similar to those found in crystals with diamond cubic lattice; 2) a diamond-TPMS microlattice with ca. 50% relative density; and 3) dual-scale crystallographic coalignment between c-axis of the single-crystalline constituent calcite and the [111] direction of the diamond-TPMS microlattice. Based on this work, this dissertation mainly reveals: 1) unique type and core structures of the dislocations in the ossicle for stiffness, strength, and toughness; 2) the 3D property compensation of dual-scale crystallographic coalignment for improved mechanical isotropy; and 3) mechanical benefits (improved mechanical isotropy and effective fragment jamming) and morphological benefits (minimal surface and highest surface area to volume ratio) for 50% relative density. / Doctor of Philosophy / Architected lattice materials, featured by their tailorable 3D multiscale architectures, achieve unique mechanical properties such as breaking the trade-off between strength and toughness, and mechanical isotropy reaching theoretical limit. In nature, as a result of evolutionary driving force, the biomineralized skeletons of the animals such as sea sponge, sea urchin, and starfish usually delicately control the architectural arrangements in different length scales and provide excellent templates for the design of architected lattices with desirable properties. Quantitative understanding of the 3D multiscale structures and mechanics of these natural biomineralized lattices allows the development of bio-inspired materials that are, for example, simultaneously stiff, strong, and tough. This dissertation establishes the quantitative structural-mechanical/functional relationships in multiscale of three biomineralized lattices with high mineral contents (~99 wt%) and a wide range of porosity (50~99 vol%) in Hexactinellid sponges with main emphasis on species (Euplectella aspergillum), sea urchin Heterocentrotus mammillatus, and starfish Protoreaster nodosus. They are selected for their representative multiscale structures, i.e., multiscale hierarchical structure, multiscale functionally graded structure, and dual-scale (i.e., atomic and microlattice scales) periodic structure, respectively. Study of these biomineralized lattices significantly improve our understanding of the biological strategies in structural arrangement and pave the way towards bio-inspired modeling to leverage the mechanical benefits.

Today, “zoomable” maps are a state-of-the-art way to explore the world, available to anyone with Internet access. However, the process of creating this visualization has been rather loosely investigated and documented. Nevertheless, with an increasing amount of available data, interactive maps have become a more integral approach to visualizing and exploring big datasets and user-generated data. OpenStreetMap and online platforms such as Twitter and Flickr offer application programming interfaces (APIs) with geographic information. They are well-known examples of this visualization challenge and are often used as examples. In addition, an increasing number of public administrations collect open data and publish their data sets, which makes the task of visualization even more relevant. This dissertation deals with the visualization of user-generated geodata as a multiscale map. The basics of today’s multiscale maps—their history, technologies, and possibilities—are explored and abstracted. This work introduces two new multiscale-focused visualization approaches for point data from volunteered geographic information (VGI) and location-based social media (LBSM). One contribution of this effort is a visualization methodology for spatially referenced information in the form of point geometries, using nominally scaled data from social media such as Twitter or Flickr. Typical for this data is a high number of social media posts in different categories—a post on social media corresponds to a point in a specific category. Due to the sheer quantity and similar characteristics, the posts appear generic rather than unique. This type of dataset can be explored using the new method of micro diagrams to visualize the dataset on multiple scales and resolutions. The data is aggregated into small grid cells, and the numerical proportion is shown with small diagrams, which can visually merge into heterogenous areas through colors depicting a specific category. The diagram sizes allow the user to estimate the overall number of aggregated points in a grid cell. A different visualization approach is proposed for more unique points, considered points of interest (POI), based on the selection method. The goal is to identify more locally relevant points from the data set, considered more important compared to other points in the neighborhood, which are then compared by numerical attribute. The method, derived from topographic isolation and called discrete isolation, is the distance from one point to the next with a higher attribute value. By using this measure, the most essential points can be easily selected by choosing a minimum distance and producing a homogenous spatial of the selected points within the chosen dataset. The two newly developed approaches are applied to multiscale mapping by constructing example workflows that produce multiscale maps. The publicly available multiscale mapping workflows OpenMapTiles and OpenStreetMap Carto, using OpenStreetMap data, are systematically explored and analyzed. The result is a general workflow for multiscale map production and a short overview of the toolchain software. In particular, the generalization approaches in the example projects are discussed and these are classified into cartographic theories on the basis of literature. The workflow is demonstrated by building a raster tile service for the micro diagrams and a vector tile service for the discrete isolation, able to be used with just a web browser. In conclusion, these new approaches for point data using VGI and LBSM allow better qualitative visualization of geodata. While analyzing vast global datasets is challenging, exploring and analyzing hidden data patterns is fruitful. Creating this degree of visualization and producing maps on multiple scales is a complicated task. The workflows and tools provided in this thesis will make map production on a worldwide scale easier.:1 Introduction 1 1.1 Motivation .................................................................................................. 3 1.2 Visualization of crowdsourced geodata on multiple scales ............ 5 1.2.1 Research objective 1: Visualization of point collections ......... 6 1.2.2 Research objective 2: Visualization of points of interest ......... 7 1.2.3 Research objective 3: Production of multiscale maps ............. 7 1.3 Reader’s guide ......................................................................................... 9 1.3.1 Structure ........................................................................................... 9 1.3.2 Related Publications ....................................................................... 9 1.3.3 Formatting and layout ................................................................. 10 1.3.4 Online examples ........................................................................... 10 2 Foundations of crowdsourced mapping on multiple scales 11 2.1 Types and properties of crowdsourced data .................................. 11 2.2 Currents trends in cartography ......................................................... 11 2.3 Definitions .............................................................................................. 12 2.3.1 VGI .................................................................................................. 12 2.3.2 LBSM .............................................................................................. 13 2.3.3 Space, place, and location......................................................... 13 2.4 Visualization approaches for crowdsourced geodata ................... 14 2.4.1 Review of publications and visualization approaches ........... 14 2.4.2 Conclusions from the review ...................................................... 15 2.4.3 Challenges mapping crowdsourced data ................................ 17 2.5 Technologies for serving multiscale maps ...................................... 17 2.5.1 Research about multiscale maps .............................................. 17 2.5.2 Web Mercator projection ............................................................ 18 2.5.3 Tiles and zoom levels .................................................................. 19 2.5.4 Raster tiles ..................................................................................... 21 2.5.5 Vector tiles .................................................................................... 23 2.5.6 Tiling as a principle ..................................................................... 25 3 Point collection visualization with categorized attributes 26 3.1 Target users and possible tasks ....................................................... 26 3.2 Example data ......................................................................................... 27 3.3 Visualization approaches .................................................................... 28 3.3.1 Common techniques .................................................................... 28 3.3.2 The micro diagram approach .................................................... 30 3.4 The micro diagram and its parameters ............................................ 33 3.4.1 Aggregating points into a regular structure ............................ 33 3.4.2 Visualizing the number of data points ...................................... 35 3.4.3 Grid and micro diagrams ............................................................ 36 3.4.4 Visualizing numerical proportions with diagrams .................. 37 3.4.5 Influence of color and color brightness ................................... 38 3.4.6 Interaction options with micro diagrams .................................. 39 3.5 Application and user-based evaluation ............................................ 39 3.5.1 Micro diagrams in a multiscale environment ........................... 39 3.5.2 The micro diagram user study ................................................... 41 3.5.3 Point collection visualization discussion .................................. 47 4 Selection of POIs for visualization 50 4.1 Approaches for point selection .......................................................... 50 4.2 Methods for point selection ................................................................ 51 4.2.1 Label grid approach .................................................................... 52 4.2.2 Functional importance approach .............................................. 53 4.2.3 Discrete isolation approach ....................................................... 54 4.3 Functional evaluation of selection methods .................................... 56 4.3.1 Runtime comparison .................................................................... 56 4.3.2 Use cases for discrete isolation ................................................ 57 4.4 Discussion of the selection approaches .......................................... 61 4.4.1 A critical view of the use cases ................................................. 61 4.4.2 Comparing the approaches ........................................................ 62 4.4.3 Conclusion ..................................................................................... 64 5 Creating multiscale maps 65 5.1 Examples of multiscale map production .......................................... 65 5.1.1 OpenStreetMap Infrastructure ................................................... 66 5.1.2 OpenStreetMap Carto ................................................................. 67 5.1.3 OpenMapTiles ............................................................................... 73 5.2 Methods of multiscale map production ............................................ 80 5.2.1 OpenStreetMap tools ................................................................... 80 5.2.2 Geoprocessing .............................................................................. 80 5.2.3 Database ........................................................................................ 80 5.2.4 Creating tiles ................................................................................. 82 5.2.5 Caching .......................................................................................... 82 5.2.6 Styling tiles .................................................................................... 82 5.2.7 Viewing tiles ................................................................................... 83 5.2.8 The stackless approach to tile creation ................................... 83 5.3 Example workflows for creating multiscale maps ........................... 84 5.3.1 Raster tiles: OGC services and micro diagrams .................... 84 5.3.2 Vector tiles: Slippy map and vector tiles ................................. 87 5.4 Discussion of approaches and workflows ....................................... 90 5.4.1 Map production as a rendering pipeline .................................. 90 5.4.2 Comparison of OpenStreetMap Carto and OpenMapTiles .. 92 5.4.3 Discussion of the implementations ........................................... 93 5.4.4 Generalization in map production workflows .......................... 95 5.4.5 Conclusions ................................................................................. 101 6 Discussion 103 6.1 Development for web mapping ........................................................ 103 6.1.1 The role of standards in map production .............................. 103 6.1.2 Technological development ..................................................... 103 6.2 New data, new mapping techniques? ............................................. 104 7 Conclusion 106 7.1 Visualization of point collections ..................................................... 106 7.2 Visualization of points of interest ................................................... 107 7.3 Production of multiscale maps ........................................................ 107 7.4 Synthesis of the research questions .............................................. 108 7.5 Contributions ....................................................................................... 109 7.6 Limitations ............................................................................................ 110 7.7 Outlook ................................................................................................. 111 8 References 113 9 Appendix 130 9.1 Zoom levels and Scale ...................................................................... 130 9.3 Full information about selected UGC papers ................................ 131 9.4 Timeline of mapping technologies .................................................. 133 9.5 Timeline of map providers ................................................................ 133 9.6 Code snippets from own map production workflows .................. 134 9.6.1 Vector tiles workflow ................................................................. 134 9.6.2 Raster tiles workflow.................................................................. 137 / Heute sind zoombare Karten Alltag für jeden Internetznutzer. Die Erstellung interaktiv zoombarer Karten ist allerdings wenig erforscht, was einen deutlichen Gegensatz zu ihrer aktuellen Bedeutung und Nutzungshäufigkeit darstellt. Die Forschung in diesem Bereich ist also umso notwendiger. Steigende Datenmengen und größere Regionen, die von Karten abgedeckt werden sollen, unterstreichen den Forschungsbedarf umso mehr. Beispiele für stetig wachsende Datenmengen sind Geodatenquellen wie OpenStreetMap aber auch freie amtliche Geodatensätze (OpenData), aber auch die zunehmende Zahl georeferenzierter Inhalte auf Internetplatformen wie Twitter oder Flickr zu nennen. Das Thema dieser Arbeit ist die Visualisierung eben dieser nutzergenerierten Geodaten mittels zoombarer Karten. Dafür wird die Entwicklung der zugrundeliegenden Technologien über die letzten zwei Jahr-zehnte und die damit verbundene Möglichkeiten vorgestellt. Weitere Beiträge sind zwei neue Visualisierungsmethoden, die sich besonders für die Darstellung von Punktdaten aus raumbezogenen nutzergenerierten Daten und georeferenzierte Daten aus Sozialen Netzwerken eignen. Ein Beitrag dieser Arbeit ist eine neue Visualisierungsmethode für raumbezogene Informationen in Form von Punktgeometrien mit nominal skalierten Daten aus Sozialen Medien, wie beispielsweise Twitter oder Flickr. Typisch für diese Daten ist eine hohe Anzahl von Beiträgen mit unterschiedlichen Kategorien. Wobei die Beiträge, bedingt durch ihre schiere Menge und ähnlicher Ei-genschaften, eher generisch als einzigartig sind. Ein Beitrag in den So-zia len Medien entspricht dabei einem Punkt mit einer bestimmten Katego-rie. Ein solcher Datensatz kann mit der neuen Methode der „micro diagrams“ in verschiedenen Maßstäben und Auflösungen visualisiert und analysiert werden. Dazu werden die Daten in kleine Gitterzellen aggregiert. Die Menge und Verteilung der über die Kategorien aggregierten Punkte wird durch kleine Diagramme dargestellt, wobei die Farben die verschiedenen Kategorien visualisieren. Durch die geringere Größe der einzelnen Diagramme verschmelzen die kleinen Diagramme visuell, je nach der Verteilung der Farben für die Kategorien. Bei genauerem Hinsehen ist die Schätzung der Menge der aggregierten Punkte über die Größe der Diagramme die Menge und die Verteilung über die Kategorien möglich. Für einzigartigere Punkte, die als Points of Interest (POI) angesehen werden, wird ein anderer Visualisierungsansatz vorgeschlagen, der auf einer Auswahlmethode basiert. Ziel ist es dabei lokal relevantere Punkte aus dem Datensatz zu identifizieren, die im Vergleich zu anderen Punkten in der Nachbarschaft des Punktes verglichen nach einem numerischen Attribut wichtiger sind. Die Methode ist von dem geographischen Prinzip der Dominanz von Bergen abgeleitet und wird „discrete isolation“ genannt. Es handelt sich dabei um die Distanz von einem Punkt zum nächsten mit einem höheren Attributwert. Durch die Verwendung dieses Maßes können lokal bedeutende Punkte leicht ausgewählt werden, indem ein minimaler Abstand gewählt und so räumlich gleichmäßig verteilte Punkte aus dem Datensatz ausgewählt werden. Die beiden neu vorgestellten Methoden werden in den Kontext der zoombaren Karten gestellt, indem exemplarische Arbeitsabläufe erstellt werden, die als Er-gebnis eine zoombare Karte liefern. Dazu werden die frei verfügbaren Beispiele zur Herstellung von weltweiten zoombaren Karten mit nutzergenerierten Geo-daten von OpenStreetMap, anhand der Kartenprojekte OpenMapTiles und O-penStreetMap Carto analysiert und in Arbeitsschritte gegliedert. Das Ergebnis ist ein wiederverwendbarer Arbeitsablauf zur Herstellung zoombarer Karten, ergänzt durch eine Auswahl von passender Software für die einzelnen Arbeits-schritte. Dabei wird insbesondere auf die Generalisierungsansätze in den Beispielprojekten eingegangen und diese anhand von Literatur in die kartographische Theorie eingeordnet. Zur Demonstration des Workflows wird je ein Raster Tiles Dienst für die „micro diagrams“ und ein Vektor Tiles Dienst für die „discrete isolation“ erstellt. Beide Dienste lassen sich mit einem aktuellen Webbrowser nutzen. Zusammenfassend ermöglichen diese neuen Visualisierungsansätze für Punkt-daten aus VGI und LBSM eine bessere qualitative Visualisierung der neuen Geodaten. Die Analyse riesiger globaler Datensätze ist immer noch eine Herausforderung, aber die Erforschung und Analyse verborgener Muster in den Daten ist lohnend. Die Erstellung solcher Visualisierungen und die Produktion von Karten in verschiedenen Maßstäben ist eine komplexe Aufgabe. Die in dieser Arbeit vorgestellten Arbeitsabläufe und Werkzeuge erleichtern die Erstellung von Karten in globalem Maßstab.:1 Introduction 1 1.1 Motivation .................................................................................................. 3 1.2 Visualization of crowdsourced geodata on multiple scales ............ 5 1.2.1 Research objective 1: Visualization of point collections ......... 6 1.2.2 Research objective 2: Visualization of points of interest ......... 7 1.2.3 Research objective 3: Production of multiscale maps ............. 7 1.3 Reader’s guide ......................................................................................... 9 1.3.1 Structure ........................................................................................... 9 1.3.2 Related Publications ....................................................................... 9 1.3.3 Formatting and layout ................................................................. 10 1.3.4 Online examples ........................................................................... 10 2 Foundations of crowdsourced mapping on multiple scales 11 2.1 Types and properties of crowdsourced data .................................. 11 2.2 Currents trends in cartography ......................................................... 11 2.3 Definitions .............................................................................................. 12 2.3.1 VGI .................................................................................................. 12 2.3.2 LBSM .............................................................................................. 13 2.3.3 Space, place, and location......................................................... 13 2.4 Visualization approaches for crowdsourced geodata ................... 14 2.4.1 Review of publications and visualization approaches ........... 14 2.4.2 Conclusions from the review ...................................................... 15 2.4.3 Challenges mapping crowdsourced data ................................ 17 2.5 Technologies for serving multiscale maps ...................................... 17 2.5.1 Research about multiscale maps .............................................. 17 2.5.2 Web Mercator projection ............................................................ 18 2.5.3 Tiles and zoom levels .................................................................. 19 2.5.4 Raster tiles ..................................................................................... 21 2.5.5 Vector tiles .................................................................................... 23 2.5.6 Tiling as a principle ..................................................................... 25 3 Point collection visualization with categorized attributes 26 3.1 Target users and possible tasks ....................................................... 26 3.2 Example data ......................................................................................... 27 3.3 Visualization approaches .................................................................... 28 3.3.1 Common techniques .................................................................... 28 3.3.2 The micro diagram approach .................................................... 30 3.4 The micro diagram and its parameters ............................................ 33 3.4.1 Aggregating points into a regular structure ............................ 33 3.4.2 Visualizing the number of data points ...................................... 35 3.4.3 Grid and micro diagrams ............................................................ 36 3.4.4 Visualizing numerical proportions with diagrams .................. 37 3.4.5 Influence of color and color brightness ................................... 38 3.4.6 Interaction options with micro diagrams .................................. 39 3.5 Application and user-based evaluation ............................................ 39 3.5.1 Micro diagrams in a multiscale environment ........................... 39 3.5.2 The micro diagram user study ................................................... 41 3.5.3 Point collection visualization discussion .................................. 47 4 Selection of POIs for visualization 50 4.1 Approaches for point selection .......................................................... 50 4.2 Methods for point selection ................................................................ 51 4.2.1 Label grid approach .................................................................... 52 4.2.2 Functional importance approach .............................................. 53 4.2.3 Discrete isolation approach ....................................................... 54 4.3 Functional evaluation of selection methods .................................... 56 4.3.1 Runtime comparison .................................................................... 56 4.3.2 Use cases for discrete isolation ................................................ 57 4.4 Discussion of the selection approaches .......................................... 61 4.4.1 A critical view of the use cases ................................................. 61 4.4.2 Comparing the approaches ........................................................ 62 4.4.3 Conclusion ..................................................................................... 64 5 Creating multiscale maps 65 5.1 Examples of multiscale map production .......................................... 65 5.1.1 OpenStreetMap Infrastructure ................................................... 66 5.1.2 OpenStreetMap Carto ................................................................. 67 5.1.3 OpenMapTiles ............................................................................... 73 5.2 Methods of multiscale map production ............................................ 80 5.2.1 OpenStreetMap tools ................................................................... 80 5.2.2 Geoprocessing .............................................................................. 80 5.2.3 Database ........................................................................................ 80 5.2.4 Creating tiles ................................................................................. 82 5.2.5 Caching .......................................................................................... 82 5.2.6 Styling tiles .................................................................................... 82 5.2.7 Viewing tiles ................................................................................... 83 5.2.8 The stackless approach to tile creation ................................... 83 5.3 Example workflows for creating multiscale maps ........................... 84 5.3.1 Raster tiles: OGC services and micro diagrams .................... 84 5.3.2 Vector tiles: Slippy map and vector tiles ................................. 87 5.4 Discussion of approaches and workflows ....................................... 90 5.4.1 Map production as a rendering pipeline .................................. 90 5.4.2 Comparison of OpenStreetMap Carto and OpenMapTiles .. 92 5.4.3 Discussion of the implementations ........................................... 93 5.4.4 Generalization in map production workflows .......................... 95 5.4.5 Conclusions ................................................................................. 101 6 Discussion 103 6.1 Development for web mapping ........................................................ 103 6.1.1 The role of standards in map production .............................. 103 6.1.2 Technological development ..................................................... 103 6.2 New data, new mapping techniques? ............................................. 104 7 Conclusion 106 7.1 Visualization of point collections ..................................................... 106 7.2 Visualization of points of interest ................................................... 107 7.3 Production of multiscale maps ........................................................ 107 7.4 Synthesis of the research questions .............................................. 108 7.5 Contributions ....................................................................................... 109 7.6 Limitations ............................................................................................ 110 7.7 Outlook ................................................................................................. 111 8 References 113 9 Appendix 130 9.1 Zoom levels and Scale ...................................................................... 130 9.3 Full information about selected UGC papers ................................ 131 9.4 Timeline of mapping technologies .................................................. 133 9.5 Timeline of map providers ................................................................ 133 9.6 Code snippets from own map production workflows .................. 134 9.6.1 Vector tiles workflow ................................................................. 134 9.6.2 Raster tiles workflow.................................................................. 137

<p>Long-acting injectables (LAI) offer many practical benefits for patients in improving drug adherence to therapies for chronic diseases. LAI, administered either subcutaneously (SC) or intramuscularly (IM), can improve drug bioavailability, and reduce frequency of administration as well as regimen complexity. SC also has additional benefits over IM injections as being safer, less painful, and able to be administered at home. However, development and translation of these products into the clinic is often limited because of physiological complexity at injection site, such that absorption rate mechanisms are not well understood. Common predictive and correlative methods used in oral formulations, such as <em>in vitro-in vivo </em>correlations, are not well suited for SC physiology and are only capable of measuring a few parameters at a time, meaning relationships between parameters cannot be discriminately measured.</p> <p><br></p> <p>This project seeks to address this gap in knowledge by using computation to bridge the gap between suboptimal preclinical testing methods and human pharmacokinetic data. A Multiscale framework was developed by integrating a first-principles Multiphysics model of the SC space to experimental plasma concentration profiles using simulated absorption rates. First, our lab’s previous framework for lymphatic absorption of monoclonal antibodies (mAbs) was converted into small molecule absorption into the capillaries. Drug and formulation critical quality attributes (CQA) were determined for a solution injection of methotrexate, and a nanocrystal formulation of medroxyprogesterone acetate (MPA, Depo-SubQ Provera). Two dissolution models were incorporated to compare the difference between using average particle size (Noyes-Whitney) and particle size distributions (Population Balance Model, PBM) as CQA for nanocrystal LAI specifically. Absorption rates were validated using compartmental pharmacokinetic models, and sensitivity analyses were conducted to determine model parametric sensitivity. Overall, the modeling framework was able to determine the importance of and discriminate the effect of parameters on SC absorption rates. </p>

Many experiments demonstrate that the effects of hydrogen solutes decrease macroscopic fracture stresses and strains in ductile materials. Hydrogen-related failures have occurred in nearly all industries involving hydrogen-producing environments. The financial losses incurred from those failures reaches millions if not billions of dollars annually. With the ever-urgent needs for alternative energy sources, there is a strong push for a hydrogen economy from government and private sectors. Safe storage and transportation of hydrogen increases the momentum for studying hydrogen-related failures, especially in ductile materials. To quantify ductile material damage with the effects of hydrogen embrittlement, it is necessary to add hydrogen effects into the void nucleation, void growth, and void coalescence equations. In this research, hydrogen-enhanced void nucleation is our focus, with hydrogen-enhanced void growth and void coalescence t be studied in the future. Molecular Dynamic (MD) and Monte Carlo (MC) simulations with Embedded Atom Method (EAM) potentials were performed to study how hydrogen affects dislocation nucleation, dislocation structure formation and nanovoid nucleation at nickel grain boundaries. The results were inserted into the continuum void nucleation model by Horstemeyer and Gokhale, and the relationships between stress triaxiality-driven void nucleation, grain boundary hydrogen concentrations and local grain geometries were extracted. MD and MC simulations with EAM potentials were also performed to study how hydrogen interstitials affect the dislocation nucleation, dislocation structure formation and subsequent anovoid nucleation of single crystal nickel in different hydrogen-charging conditions. Evolutions of dislocation structures of nickel single crystal with different hydrogen concentrations were compared. The effects of nanovoid nucleation stress and strain at different hydrogen concentrations were quantified. The results were also inserted into the Horstemeyer and Gokhale model and the relationship between stress triaxiality-driven void nucleation and hydrogen concentration caused by stress gradient, which showed similar trends as the grain boundary studies. From nanoscale studies and existing experimental observations, a continuum void nucleation model with hydrogen effects was proposed and used in a continuum damage model based upon Bammann and coworkers. The damage model was implemented into user material code in FEA code ABAQUS. Finite element analyses were performed and the results were compared to the experimental data by Kwon and Asaro.

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