Oral drug administration remains the most popular route of drug delivery. Absorption of the dissolved drug through the intestinal epithelial membrane is a prerequisite to systemic bioavailability and drug efficacy. In efforts to reduce the long lead times, attrition rates, and costs of drug discovery and development, computational models have been developed to predict the membrane permeability and absorption efficiency of a dosed drug. Many models utilize various molecular descriptors to correlate with in vitro permeability or human intestinal absorption data. It is widely accepted that the two most significant physicochemical properties that control a compound's passive transport process are its aqueous solubility and lipophilicity characteristics.This work will discuss the theoretical background of passive transport, a number of computational models developed to predict in vitro permeability, other models that predict human fraction of dose absorbed, and predicting absorption efficiency relative to a maximum dose. A newly developed prediction method is also presented, that reveals an interesting relationship between fraction absorbed and the melting point of the drug.

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For all organisms, segregation and proper intracellular localization of DNA are essential processes in ensuring faithful inheritance of genetic material. In prokaryotes, several different mechanisms have developed for efficiently moving chromosomal DNA to proper cellular locations prior to cell division, and the same holds true for bacterial plasmids. Low-copy-number plasmids and bacterial chromosomes encode active partition systems to ensure their inheritance within a bacterial cell population. One of the well-studied models of partition is that of the P1 plasmid in E. coli. The partition system encoded by the P1 plasmid is known as parABS - ParA is the partition ATPase, ParB is the partition site binding protein and parS is the partition site. The goal of this thesis was to investigate the nucleoprotein complexes essential in the P1 plasmid partition reaction. First, I examined how a single ParB dimer can bind its complicated arrangement of recognition motifs in parS to initiate the partition reaction. I then characterized a novel ParA interaction with the host nucleoid that is critical for proper P1 plasmid dynamics in vivo. Finally, I demonstrate how ParA can act as an adaptor between the nucleoid and the partition complex; effectively allowing the plasmid to use the nucleoid as a track for its intracellular movement and localization. My thesis work provides evidence towards a model that explains the P1 plasmid partition mechanism.

In this paper we propose an unsupervised voting-merging scheme that is capable of clustering data sets, and also of finding the number of clusters existing in them. The voting part of the algorithm allows us to combine several runs of clustering algorithms resulting in a common partition. This helps us to overcome instabilities of the clustering algorithms and to improve the ability to find structures in a data set. Moreover, we develop a strategy to understand, analyze and interpret these results. In the second part of the scheme, a merging procedure starts on the clusters resulting by voting, in order to find the number of clusters in the data set. / Series: Working Papers SFB "Adaptive Information Systems and Modelling in Economics and Management Science"

Honey bee population decline has been attributed to a variety of causes including infestation of hives with Varroa destructor mites. Fluvalinate has been extensively used in the United States to combat these mites for nearly 30 years, despite its high toxicity to honey bees. The objectives of the current research project were to investigate the extent of fluvalinate contamination in commercially available wax and to define exposure pathways from the contaminated wax and fluvalinate-impregnated strips to larval and adult honey bees. All of the commercial wax tested in the current study contained elevated fluvalinate concentrations, ranging from 170 to 1040 ng/g wet weight, indicating a need for regulation of the sources of wax being rendered for resale. Based on the negative logarithm of the partition coefficient between wax and pollen (-0.54) and the fact that all of the tested wax samples contained elevated concentrations of fluvalinate, it is evident that fluvalinate has the potential to actively transfer from the contaminated wax into bee hive matrices. This point was confirmed by adding fluvalinate-dosed wax, fluvalinate-impregnated strips, or a combination of the two to 10-frame hives. Larvae and adult bees from those hives were checked for fluvalinate exposure using gas chromatography-mass spectrometry analysis. Larvae had detectable concentrations of fluvalinate in all three treatments. Bioaccumulation in adult bees was significantly affected by the interaction between treatment type and application time. In other words, residues were comparable from hives that only had fluvalinate-dosed wax to those that were actively being treated with impregnated strips, strongly suggesting that transfer of fluvalinate from wax into adult bees was an important exposure route. In conclusion, exposure of fluvalinate from contaminated wax and treatment strips to larvae and adult honey bees is an important factor that needs to be considered when applying miticides and evaluating risk in honey bee hives.

La musique peut être monophonique – une seule note est jouée à chaque instant – ou polyphonique – plusieurs notes sont jouées simultanément, formant des harmonies. Comprendre la musique polyphonique peut être très complexe. L'objectif de cette thèse en informatique musicale est de simplifier l'analyse de partitions polyphoniques en les décomposant en voix monophoniques ou en streams (ensembles cohérents de notes). Ces deux approches n'ayant jamais été confrontées, mes premiers travaux consistent à comparer trois algorithmes de séparation en voix et trois algorithmes de séparation en streams. Je propose pour cela des méthodes d'évaluation équitables pour ces deux approches. Les tests réalisés sur un corpus de musique classique et de musique pop ont mis en avant les qualités de l'algorithme de séparation en voix de Chew et Wu. La première étape de cet algorithme, qui segmente la partition en "contigs" avec un nombre de voix constant, est particulièrement robuste. La suite des travaux de cette thèse porte sur la seconde étape de l'algorithme de Chew et Wu, qui définit l'ordre de connexions des contigs et la manière de les connecter. J'améliore ces connexions en utilisant des paramètres musicaux comme la différence des moyennes des hauteurs des notes entre contigs voisins. La thèse se conclut en évaluant conjointement la séparation en voix et la recherche de motifs pour l'analyse musicale de fugues / Music can be either monophonic (a single note sounds at each time) or polyphonic (several notes sound simultaneously, building harmonies). Understanding polyphonic music can be very complex. The goal of this thesis in computer music is to ease the analysis of polyphonic scores by splitting them in either monophonic voices or streams (coherent sets of notes). Research in this thesis first consists in comparing three voices separation algorithms and three streams separation algorithms. I propose an evaluation method to fairly compare these two approaches. This study shows the qualities of the Chew and Wu algorithm. The first step of this algorithm, which segments the score into “contigs” having a constant number of voices, is particularly robust. Further work of this thesis focuses on the second stage of the Chew and Wu algorithm that defines what contigs to connect and how to connect them. I improve these connections by using musical parameters such as the average pitch difference between neighbor contigs. The thesis concludes by evaluating simultaneously voice separation and pattern matching for the music analysis of fugues

MOTIVATION Mindfulness is the active pursuit of focused attention, and through practice has been shown to benefit psychological and physical well-being. While mindfulness is not a new idea, it has only tangentially been linked to Interior Design such as through performative objects (Niedderer, 2007 and 2014) which promote personal reflection before enacting a choice. If mindfulness is the active pursuit of mental presence, then Attention Restoration Theory (ART) is a passive route by which environmental cues imbue a resurgence in attention capacity (Kaplan, 2001). ART studies exemplified successful restoration through scenes of nature, and unsuccessfully in outdoor urban scenes (Berto, 2005) while interior environments went unexamined. Encouraging mindfulness and ART through interior design is worth exploring as it converges from the studies of Niedderer, Kaplan, and Berto. PROBLEM How can mindfulness be supported by, or achieved through interior design, and what design principle(s) align with the practice of mindfulness? How can interior spaces and artifacts facilitate ART to passively or unconsciously support mindfulness in a residence? METHODS Evaluations of mindfulness and ART case studies as related to design, and environmental interpretation will inform associative aspects to understand and employ relevant design elements. RESULTS People prefer different spaces in which to experience mindfulness where the variety of colors, sound levels, lighting, privacy, smells, and textures affect them to be attuned. Based on an site interview, the designer is informed on specific interaction styles, design attributes, and solutions to pursue. Questions prompting personal reflection will lead to a personalized design which was determined to be an important psychological tool to achieving mindfulness. The use of warm and cool colors were found to be more intriguing than achromatic settings. Placing design artifacts in the space which encouraged or even required interaction from the client were found to encourage their mental presence in the moment as well. Views to outdoor, natural scenery from the space or at a minimum objects that represent nature add to the presence of mind and attention restoration. The designer educates the client on the impact of pertinent design principles such as light, color, scale, balance, texture, and harmony to obtain design by-in. REFLECTIONS/CONCLUSIONS Creating a mental and physical connection for the client to the space is essential to achieving mindfulness through interior design. Mindfulness and Attention Restoration Theory augment each other from different psychological and physiological positions when the client is actively and passively engaged with their surroundings; linking the two through interior environments is key. A designed residential space that reflects the inhabitant’s interactive tendencies, prompts exploration, requires choice, and arouses intrigue will promote mindfulness, and attention restoration. Incorporating textured surfaces, natural materials, interactive objects, and purposeful views are important design goals. 1. Niedderer, K. (2007). Designing Mindful Interaction: The Category of Performative Object. Design Issues, 23(1), 3-17. DOI: 10.1162/desi.2007.23.1.3 2. Niedderer, K. (2014). “Mediating Mindful Social Interactions Through Design.” The Wiley Blackwell Handbook of Mindfulness. Ie, A. (Ed.). Chichester, UK: John Wiley & Sons. 345-366. DOI: 10.1002/9781118294895 3. Kaplan, S. (2001). Meditation, Restoration, and the Management of Mental Fatigue. Environment and Behavior, 33(4), 480-506. DOI: 10.1177/00139160121973106 4. Berto, R. (2005). Exposure to restorative environments helps restore attentional capacity. Journal of Environmental Psychology, 25(3), 249-259.

Thresholding is a commonly used technique in image segmentation because of its fast and easy application. For this reason threshold selection is an important issue. There are two general approaches to threshold selection. One approach is based on the histogram of the image while the other is based on the gray scale information located in the local small areas. The histogram of an image contains some statistical data of the grayscale or color ingredients. In this thesis, an adaptive logical thresholding method is proposed for the binarization of blueprint images first. The new method exploits the geometric features of blueprint images. This is implemented by utilizing a robust windows operation, which is based on the assumption that the objects have &quote;C&quote; shape in a small area. We make use of multiple window sizes in the windows operation. This not only reduces computation time but also separates effectively thin lines from wide lines. Our method can automatically determine the threshold of images. Experiments show that our method is effective for blueprint images and achieves good results over a wide range of images. Second, the fuzzy set theory, along with probability partition and maximum entropy theory, is explored to compute the threshold based on the histogram of the image. Fuzzy set theory has been widely used in many fields where the ambiguous phenomena exist since it was proposed by Zadeh in 1965. And many thresholding methods have also been developed by using this theory. The concept we are using here is called fuzzy partition. Fuzzy partition means that a histogram is parted into several groups by some fuzzy sets which represent the fuzzy membership of each group because our method is based on histogram of the image . Probability partition is associated with fuzzy partition. The probability distribution of each group is derived from the fuzzy partition. Entropy which originates from thermodynamic theory is introduced into communications theory as a commonly used criteria to measure the information transmitted through a channel. It is adopted by image processing as a measurement of the information contained in the processed images. Thus it is applied in our method as a criterion for selecting the optimal fuzzy sets which partition the histogram. To find the threshold, the histogram of the image is partitioned by fuzzy sets which satisfy a certain entropy restriction. The search for the best possible fuzzy sets becomes an important issue. There is no efficient method for the searching procedure. Therefore, expansion to multiple level thresholding with fuzzy partition becomes extremely time consuming or even impossible. In this thesis, the relationship between a probability partition (PP) and a fuzzy C-partition (FP) is studied. This relationship and the entropy approach are used to derive a thresholding technique to select the optimal fuzzy C-partition. The measure of the selection quality is the entropy function defined by the PP and FP. A necessary condition of the entropy function arriving at a maximum is derived. Based on this condition, an efficient search procedure for two-level thresholding is derived, which makes the search so efficient that extension to multilevel thresholding becomes possible. A novel fuzzy membership function is proposed in three-level thresholding which produces a better result because a new relationship among the fuzzy membership functions is presented. This new relationship gives more flexibility in the search for the optimal fuzzy sets, although it also increases the complication in the search for the fuzzy sets in multi-level thresholding. This complication is solved by a new method called the &quote;Onion-Peeling&quote; method. Because the relationship between the fuzzy membership functions is so complicated it is impossible to obtain the membership functions all at once. The search procedure is decomposed into several layers of three-level partitions except for the last layer which may be a two-level one. So the big problem is simplified to three-level partitions such that we can obtain the two outmost membership functions without worrying too much about the complicated intersections among the membership functions. The method is further revised for images with a dominant area of background or an object which affects the appearance of the histogram of the image. The histogram is the basis of our method as well as of many other methods. A &quote;bad&quote; shape of the histogram will result in a bad thresholded image. A quadtree scheme is adopted to decompose the image into homogeneous areas and heterogeneous areas. And a multi-resolution thresholding method based on quadtree and fuzzy partition is then devised to deal with these images. Extension of fuzzy partition methods to color images is also examined. An adaptive thresholding method for color images based on fuzzy partition is proposed which can determine the number of thresholding levels automatically. This thesis concludes that the &quote;C&quote; shape assumption and varying sizes of windows for windows operation contribute to a better segmentation of the blueprint images. The efficient search procedure for the optimal fuzzy sets in the fuzzy-2 partition of the histogram of the image accelerates the process so much that it enables the extension of it to multilevel thresholding. In three-level fuzzy partition the new relationship presentation among the three fuzzy membership functions makes more sense than the conventional assumption and, as a result, performs better. A novel method, the &quote;Onion-Peeling&quote; method, is devised for dealing with the complexity at the intersection among the multiple membership functions in the multilevel fuzzy partition. It decomposes the multilevel partition into the fuzzy-3 partitions and the fuzzy-2 partitions by transposing the partition space in the histogram. Thus it is efficient in multilevel thresholding. A multi-resolution method which applies the quadtree scheme to distinguish the heterogeneous areas from the homogeneous areas is designed for the images with large homogeneous areas which usually distorts the histogram of the image. The new histogram based on only the heterogeneous area is adopted for partition and outperforms the old one. While validity checks filter out the fragmented points which are only a small portion of the whole image. Thus it gives good thresholded images for human face images.

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