Environmental pollution has become a global concern as consequence of industrializa-tion and urbanization. The ongoing subsurface contamination by dense non-aqueous phase liquids (DNAPLs) bears tremendous hazardous potential for humans and ecosys-tems including aquifer systems. Intended or accidental spill events have led to a vast number of registered sites affected by DNAPL type chemicals. Despite the existence of novel techniques for their exploration, characterization and remediation, economical constraints often limit efforts for risk prevention or reduction, so that information and data to characterize highly complex DNAPL contamination scenarios are often insuffi-cient and compensated by natural attenuation of groundwater-dissolved contaminant plumes. Especially, knowledge on the DNAPL source zone geometry (SZG) and source zone formation are critically required yet very scarce. Against the previously stated background, this cumulative doctoral dissertation critically examined the processes of DNAPL source zone formation at laboratory scale. A comprehensive literature review identified current limitations and open research questions in the latter research field, revealing evidence for the relevance of SZG for plume response at different scales. Giv-en only a limited number of published studies related to DNAPL source zone formation, two simplified experimental setups mimicking source zone formation in an initially fully water-saturated aquifer were developed and intensively tested. The performance of aqueous and non-wetting phase dyes was evaluated for DNAPL release into three non-consolidated porous media using reflective optical imaging in combination with a cus-tom-made image processing and analysis (IPA) framework. The latter suite allowed for the generation of physically plausible DNAPL saturation distributions with determinable level of uncertainty. Then, a limited number of DNAPL release experiments were per-formed under controlled ambient as well as with boundary and initial conditions to generate robust observation data, while further adopting the IPA framework. The latter data was introduced into a numerical multiphase flow model. While most system pa-rameters could be directly determined, the parameters defining the capillary pressure-saturation and relative permeability-saturation retention curves were inversely deline-ated through a classical Monte Carlo analysis. Overall, the successfully calibrated nu-merical setup mimicking the transient DNAPL source zone formation allowed to quanti-fy uncertainties related to the experiment, IPA framework and model setup configura-tion. In addition, a number of new research questions pointing towards future im-provements of laboratory-scale methodologies to understand DNAPL contamination were derived. Especially in light of numerous existing contaminated sites with unclear history and even more vague future, given by potential impacts through climate change and anthropogenic activity, an increasing need for sophisticated strategies to better un-derstand DNAPL contamination and to reduce hazard potential is expected.:Statement I List of publications II Abstract VI Acknowledgements and funding information IX List of figures XIII List of tables XIV Abbreviations and symbols used in the main text XV 1 Introduction and background 1-1 1.1 Motivation of this thesis 1-1 1.2 Incorporation of this thesis in research projects 1-4 1.3 Definition of objectives and workflow strategy of this thesis 1-5 1.4 Formal structure of this thesis 1-11 2 Existing knowledge on DNAPL contamination 2-1 3 Fundamentals of DNAPL migration in porous media 3-1 3.1 Basic concepts for multiphase flow in porous media 3-1 3.2 Capillary pressure-saturation correlation 3-3 3.3 Relative permeability-saturation correlation 3-5 3.4 Balance equations for laminar fluid phase flow in porous media 3-7 4 Core research complex A : Development of a framework for the semi-automatized generation of DNAPL saturation distribution observation data 4-1 5 Core research complex B : Experimental and model-based simulation of DNAPL source zone formation 5-1 6 Summary and conclusions 6-1 6.1 Summary of perceptions for each main section of this thesis 6-1 6.2 New research questions with regard to DNAPL source zone formation at the laboratory scale 6-5 6.3 General recommendations for future works related to DNAPL contamination 6-8 References Ref-1 Appendix I : ENGELMANN ET AL. (2019a) App I-1 Published journal article App I-1 Appendix II : ENGELMANN ET AL. (2019b) App II-1 Published journal article App II-1 Electronic Supplementary Material 1 : Unprocessed raw TIFF format images used for IPA frame-work evaluation App II-26 Electronic Supplementary Material 2 : Sensitivities for color model change and binary conversion algorithms App II-36 Electronic Supplementary Material 3 :Relevance of spatially non-uniform illumination correction and background exclusion App II-76 Appendix III : ENGELMANN ET AL. (2021) App III-1 Published journal article App III-1 Electronic Supplementary Material 1 : Unprocessed raw TIFF format images for IPA framework ap-plication App III-30 Electronic Supplementary Material 2 : Processed images with all intermediate steps of IPA frame-work application App III-58 Electronic Supplementary Material 3 : IPA fitness App III-86 Electronic Supplementary Material 4 : Partial objective functions App III-87 Electronic Supplementary Material 5 : Model verification App III-93

Αντικείμενο της παρούσας εργασία είναι ο υπολογισμός και η ταξινόμηση, με βάση το σύστημα, BIRADS της πυκνότητας του μαστού από εικόνες μαστογραφίας. Στα πλαίσια της προσπάθειας αυτής αναπτύχθηκε ολοκληρωμένο υπολογιστικό σύστημα σε γραφικό περιβάλλον ως λογισμικό πακέτο, σε γλώσσα Visual C++ .NET . Το υπολογιστικό αυτό σύστημα δέχεται σαν είσοδο εικόνες μαστογραφίας σε οποιοδήποτε από τα δημοφιλή bitmap format εικόνων όπως jpeg και tiff καθώς και DICOM αρχεία. Η λειτουργία του μπορεί να χωριστεί σε τρία στάδια: το στάδιο της προεπεξεργασίας, το στάδιο απομόνωσης της περιοχής του μαστού και το στάδιο καθορισμού της πυκνότητας του μαστού. Στο πρώτο στάδιο παρέχονται μια σειρά από στοιχειώδη εργαλεία επεξεργασίας εικόνας όπως εργαλεία περιστροφής, αποκοπής και αλλαγής αντίθεσης . Επιπρόσθετα παρέχεται η δυνατότητα Ανισοτροπικού Φιλτραρίσματος της εικόνας. Στο δεύτερο στάδιο γίνεται η απομόνωση της περιοχής του μαστού είτε απευθείας από τον χρήστη είτε αυτόματα με χρήση των ιδιοτήτων του μονογονικού (monogenic) σήματος για την αφαίρεση του παρασκηνίου (background) καθώς και κυματιδίων Gabor για τον διαχωρισμού του θωρακικού μυός. Στο τρίτο στάδιο παρέχεται η δυνατότητα ταξινόμησης της πυκνότητας του μαστού από τον χρήστη με τον καθορισμό κατάλληλου κατωφλίου των επιπέδων γκρίζου της εικόνας αλλά και η δυνατότητα αυτόματης ταξινόμησης της πυκνότητας του μαστού κατά BIRADS με χρήση Δομικών Στοιχείων Υφής (textons) και της τεχνικής pLSA. Όλες οι παραπάνω λειτουργίες παρέχονται μέσω μίας κατά το δυνατόν φιλικότερης προς τον χρήστη διεπαφής. / The present thesis aims at the classification of breast tissue according to BIRADS system based on texture features. To this end an integrated software system was developed in visual C ++. The system takes as inputs pictures in most of the popular bitmap formats like .jpeg and .till as well as DICOM. The functionality of the system is provided by three modules: (a) pre-processing module, (b) breast segmentation module and (c) the breast tissue density classification module. In the pre-processing module a set tools for image manipulation (rotation, crop, gray level adjustment) are available which are accompanied by the ability to perform anisotropic filtering to the input image. In the second module, the user has the ability to interactively define the actual borders of the breast or ask the system to perform it automatically. Automatic segmentation is a two step procedure; in the first step breast tissue is separated from its background by using the characteristics of monogenic signals, while in the second step the pectoral muscle region is subtracted using Gabor wavelets. In the density classification module the user can either ask for a calculation of breast density based on user-defined grey level threshold or perform an automatic BIRADS-based classification using texture characteristics in conjunction with Probabilistic Latent Semantic Analysis (pLSA) algorithm. Special emphasis was given to the development of a functional and user-friendly interface.

Title: The subnuclear localisation of Notch responsive genes. Candidate Name: Matthew Jones Notch signalling is a highly conserved cell-cell communication pathway with critical roles in metazoan development and mutations in Notch pathway components are implicated in many types of cancer. Notch is an excellent and well-studied model of biological signalling and gene regulation, with a single intracellular messenger, one receptor and two ligands in Drosophila. However, despite the limited number of chemical players involved, a striking number of different outcomes arise. Molecular studies have shown that Notch activates different targets in different cell types and it is well known that Notch is important for maintaining a stem cell fate in some situations and driving differentiation in others. Thus some of the factors affecting the regulation of Notch target genes are yet to be discovered. Previous studies in various organisms have found that the location of a gene within the nucleus is important for its regulation and genome reorganisation can occur following gene activation or during development. Therefore this project aimed to label individual Notch responsive loci and determine their subnuclear localisation. In order to tag loci of interest a CRISPR/Cas9 genome-editing method was established that enabled the insertion of locus tags at Notch targets, namely the well-characterized Enhancer of split locus and also dpn and Hey, two transcription factors involved in neural cell fate decisions. The ParB/Int system is a recently developed locus tagging system and is not well characterised in Drosophila. It has a number of advantages over the traditional LacO/LacI-GFP locus tagging system as it does not rely on binding site repeats for signal amplification and can label two loci simultaneously in different colours. This thesis characterised the ParB/Int system in the Drosophila salivary gland and larval L3 neuroblast. Using 3D image segmentation hundreds of nuclei were reconstructed and a volume based normalisation method was applied to determine the subnuclear localisation of several Notch targets with and without genetic manipulations of the Notch pathway.

<p>  </p> <p>Understanding the mechanical properties of peripheral nerves is essential for chronically implanted device design. The work in this thesis aimed to understand the relationship between local deformation responses to global strain changes in peripheral nerves. A custom-built mechanical testing rig and sample holder enabled an improved cyclical uniaxial tensile testing environment on rabbit sciatic nerves (N=5). A speckle was placed on the surface of the nerve and recorded with a microscope camera to track local deformations. The development of a semi-automated digital image processing algorithm systematically measured local speckle dimension and nerve diameter changes. Combined with the measured force response, local and global strain values constructed a stress-strain relationship and corresponding elastic modulus. Preliminary exploration of models such as Fung and 2-Term Mooney-Rivlin confirmed the hyperelastic nature of the nerve. The results of strain analysis show that, on average, local strain levels were approximately five times smaller than globally measured strains; however, the relationship was dependent on global strain magnitude. Elastic modulus values corresponding to ~9% global strains were 2.070 ± 1.020 MPa globally and 10.15 ± 4 MPa locally. Elastic modulus values corresponding to ~6% global strains were 0.173 ± 0.091 MPa globally and 1.030 ± 0.532 MPa locally.   </p>

[pt] A Construção Civil é uma das indústrias que mais geram resíduos sólidos no mundo. Os agregados reciclados (RCD), como opção aos agregados obtidos por exploração de jazidas, derivam de materiais reprocessados que foram anteriormente utilizados na construção e demolição. Como o reaproveitamento de RCD vem crescendo em âmbito mundial, mas a qualidade e a padronização do material ainda são um impedimento à utilização em maiores escalas, faz-se necessário uma investigação das propriedades deste material. No presente estudo a microtomografia computadorizada (microCT) foi utilizada a fim de gerar imagens bidimensionais e tridimensionais para observar a estrutura porosa do material e, através de uma rotina computacional, as imagens obtidas foram avaliadas de forma qualitativa e quantitativa. Inicialmente, a rotina de processamento das imagens aconteceu para que fossem reduzidos os efeitos de ruídos provenientes da obtenção das imagens no microtomógrafo, além de uma padronização dos histogramas de todas as camadas. As imagens das amostras foram segmentadas e quantificadas para que a porosidade (poros e canais porosos) pudesse ser identificada e analisada. De forma complementar foram utilizadas também as técnicas de microscopia óptica e a microscopia eletrônica de varredura para análise da porosidade. Os resultados de volume, razões de aspecto e esfericidade dos poros dos concretos com e sem agregados reciclados foram analisados e comparados com as suas respectivas resistências à compressão. Os resultados mostraram, como esperado, uma porosidade maior nos corpos de prova com adição de RCD. Com uma diferença de quase 50 por cento no volume da porosidade, é importante destacar que a resistência à compressão de ambas as amostras foi satisfatória e dentro de uma faixa próxima de valores (31,4MPa para o concreto de referência e 25,73 MPa para o concreto com adição de RCD). Este resultado pode ser explicado pela necessidade de se eliminar os objetos menores de 1 voxel, o que pode ter causado uma alteração nos valores dos volumes encontrados, ou seja, eliminou-se mais poros menores de 1voxel nos CP s de referência. / [en] Civil Construction is one of the industries that generate the most solid waste in the world. Recycled aggregates (RCD), as an option to aggregates obtained by mining deposits, derive from reprocessed materials that were previously used in construction and demolition. As the reuse of RCD has been growing worldwide, but the quality and standardization of the material are still an impediment to its use on larger scales, it is necessary to investigate the properties of this material. In the present study, computerized microtomography (microCT) was used in order to generate two-dimensional and three-dimensional images to observe the porous structure of the material and, through a computational routine, the images obtained were evaluated qualitatively and quantitatively. Initially, the image processing routine was carried out to reduce the noise effects resulting from the acquisition of the images in the microtomograph, in addition to a standardization of the histograms of all layers. The images of the samples were segmented and quantified so that the porosity (pores and porous channels) could be identified and analyzed. In a complementary way, optical microscopy and scanning electron microscopy techniques were also used for porosity analysis. The results of volume, aspect ratios and pore sphericity of concretes with and without recycled aggregates were analyzed and compared with their respective compressive strengths. The results showed, as expected, a higher porosity in the specimens with the addition of RCD. With a difference of almost 50 percent in the porosity volume, it is important to highlight that the compressive strength of both samples was satisfactory and within a range close to values (31.4MPa for the reference concrete and 25.73 MPa for the concrete with the addition of RCD). This result can be explained by the need to eliminate objects smaller than 1 voxel, which may have caused a change in the values of the volumes found, that is, more pores smaller than 1 voxel were eliminated in the reference CPs.

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