Autosomal dominant polycystic disease (ADPKD) is the most common hereditary renal disease and is characterized by renal cyst growth and enlargement. Hypertension occurs early when renal function is normal and is characterized by decreased renal blood flow. Accordingly, the measurement of blood flow in the renal arteries can be a valuable tool in evaluating disease progression. In studies performed in conjunction with this work, blood flow was measured through the renal arteries using magnetic resonance imaging (MRI). In order to validate these in vivo measurements, a vascular phantom was created using polyvinyl alcohol (PVA) and also scanned using MRI under controlled steady flow conditions. Ranges of vessel diameters and flow velocities were used to simulate actual flow in a normal and diseased population of adults and children. With the vessel diameters studied in this experiment, minimization of field of view and an increase in spatial resolution is important in obtaining accurate data. However, a significant difference does not exist between the results when using the 160 or 200 mm FOV. An increase in the number of phase encodings provides improved results, although an increase in image acquisition time is observed. Velocity-encoding in all three orthogonal directions does not improve image data. This method of using MRI to measure flow through a vessel is shown to be both accurate and reproducible, and the protocol providing the most correct results is prescribed. Breath-hold phase-velocity encoded MRI proves to be an accurate and reproducible technique in capturing flow and has the potential to be used for the purpose of observing hemodynamic changes in the renal arteries with the progression of ADPKD.

Since the human inclination to estimate and trace natural diversity, usable species definitions as well as taxonomical systems are required. As a consequence, the first proposed classification schemes assigned the filamentous and parenchymatous taxa to the green algal order Chaetophorales sensu Wille. The introduction of ultrastructural and molecular methods provided novel insight into algal evolution and generated taxonomic revisions based on phylogenetic inference. However, until now, the number of molecular phylogenetic studies focusing on the Chaetophorales s.s. is surprisingly low. To enhance knowledge about phylogenetic relationships among taxa within the order, the nuclear?encoded SSU rDNA sequences from 30 strains covering all three chaetophoralean families have been investigated. All revealed monophyletic groupings were further screened for molecular non-homoplasious synapomorphies within the Viridiplantae. To address the question of the correspondence between morphological characters traditionally used for taxonomical delimitation of the Chaetophorales and the tree topology favored by molecular data, the list of morphological/ ultrastructural/ecological characters was elaborated and further analyzed. In addition, to obtain a close-up view into the evolution of Compensatory Base Changes (CBCs) of the second internal transcribed spacer (ITS2) which is currently often used to delimit putative biological species, 86 newly obtained/published sequences of ITS2 for five families of the order Ulvales were analyzed. Furthermore, a detailed comparative study of all ITS2 substitutions has been done. Subsequently all revealed CBCs and hemi- CBCs have been mapped upon the ITS2 phylogenetic tree topology. Finally, CBCs/hCBCs taxonomic inference in the Ulvales has been discussed.

An innate desire of many vision researchers IS to unravel the mystery of human visual perception Such an endeavor, even ~f it were not wholly successful, is expected to yield byproducts of considerable significance to industrial applications Based on the current understanding of the neurophysiological and computational processes in the human bran, it is believed that visual perception can be decomposed into distinct modules, of which feature / contour extraction and recognition / classification of the features corresponding to the objects play an important role. A remarkable characteristic of human visual expertise is its invariance to rotation shift, and scaling of objects in a scene Researchers concur on the relevance of imitating as many properties as we have knowledge of, of the human vision system, in order to devise simple solutions to the problems in computational vision. The inference IS that this can be more efficiently achieved by invoking neural architectures with specific characteristics (similar to those of the modules in the human brain), and conforming to rules of an appropriate mathematical baas As a first step towards the development of such a framework, we make explicit (1) the nature of the images to be analyzed, (11) the features to be extracted, (111) the relationship among features, contours, and shape, and (iv) the exact nature of the problems To this end, we formulate explicitly the problems considered in this thesis as follows Problem 1 Given an Image localize and extract the boundary (contours) of the object of Interest in lt Problem 2 Recognize the shape of the object characterized by that contour employing a suitable coder-recognizer such that ~t IS unaffected by rotation scaling and translation of the objects Problem 3 Gwen a stereo-pair of Images (1) extract the salient contours from the Images, (ii)establish correspondence between the points in them and (111) estimate the depth associated with the points We present a few algorithm as practical solutions to the above problems. The main contributions of the thesis are: • A new algorithm for extraction of contours from images: and • A novel method for invariantly coding shapes as pulses to facilitate their recognition. The first contribution refers to a new active contour model, which is a neural network designed to extract the nearest salient contour in a given image by deforming itself to match the boundary of the object. The novelty of the model consists in the exploitation of the principles of spatial isomorphism and self organization in order to create flexible contours characterizing shapes in images. It turns out that the theoretical basis for the proposed model can be traced to the extensive literature on: • Gestalt perception in which the principles of psycho-physical isomorphism plays a role; and • Early processing in the human visual system derived from neuro-anatomical and neuro-physiological properties. The initially chosen contour is made to undergo deformation by a locally co-operative, globally competitive scheme, in order to enable it to cling to the nearest salient contour in the test image. We illustrate the utility and versatility of the model by applying to the problems of boundary extraction, stereo vision, and bio-medical image analysis (including digital libraries). The second contribution of the thesis is relevant to the design and development of a machine vision system in which the required contours are first to be extracted from a given set of images. Then follows the stage of recognizing the shape of the object characterized by that contour. It should, however, be noted that the latter problem is to be resolved in such a way that the system is unaffected by translation, relation, and scaling of images of objects under consideration. To this end, we develop some novel schemes: • A pulse-coding scheme for an invariant representation of shapes; and • A neural architecture for recognizing the encoded shapes. The first (pulse-encoding) scheme is motivated by the versatility of the human visual system, and utilizes the properties of complex logarithmic mapping (CLM) which transforms rotation and scaling (in its domain) to shifts (in its range). In order to handle this shift, the encoder converts the CLM output to a sequence of pulses These pulses are then fed to a novel multi-layered neural recognizer which (1) invokes template matching with a distinctly implemented architecture, and (11) achieves robustness (to noise and shape deformation) by virtue of its overlapping strategy for code classification The proposed encoder-recognizer system (a) is hardware implementable by a high-speed electronic switching circuit, and (b) can add new patterns on-line to the existing ones Examples are given to illustrate the proposed schemes. The them is organized as follows: Chapter 2 deals with the problem of extraction of salient contours from a given gray level image, using a neural network-based active contour model It explains the need for the use of active contour models, along with a brief survey of the existing models, followed by two possible psycho-physiological theories to support the proposed model After presenting the essential characteristics of the model, the advantages and applications of the proposed approach are demonstrated by some experimental results. Chapter 3 is concerned with the problem of coding shapes and recognizing them To this end, we describe a pulse coder for generating pulses invariant to rotation, scaling and shift The code thus generated IS then fed to a recognizer which classifies shapes based on the pulse code fed to it The recognizer can also add new shapes to its 'knowledge-base' on-line. The recognizer's properties are then discussed, thereby bringing out its advantages with respect to various related architectures found in the literature. Experimental results are then presented to Illustrate some prominent characteristics of the approach. Chapter 4 concludes the thesis, summarizing the overall contribution of the thesis, and describing possible future directions

Short ORF-encoded peptides (SEPs) are increasingly being identified as functional elements in various cellular processes. The current computational methods and experimental molecular biochemistry allow us to discover putative SEPs or micropeptides from proteogenomic datasets and experimentally validate them. Here, we identified a micropeptide produced from a putative long noncoding RNA (lncRNA) 1810058I24Rik which is downregulated in both human and murine myeloid cells exposed to lipopolysaccharide (LPS), as well as other TLR ligands and inflammatory cytokines. Analysis of lncRNA 1810058I24Rik subcellular localization revealed this transcript is localized in the cytosol, prompting us to evaluate its coding potential. In vitro translation with 35S-labeled methionine resulted in translation of a 47 amino acid micropeptide. Microscopy and subcellular fractionation studies in macrophages demonstrated endogenous expression of this peptide on the mitochondrion. We thus named this gene ‘Mitochondrial micropeptide-47 (Mm47)’. Functional studies using siRNA and Cripsr-cas9-mediated deletion in primary cells, showed that the transcriptional response downstream of TLR4 was not affected by Mm47 loss of function. In contrast, both the Crispr-cas9- and siRNA-targeted BMDM cells were compromised for Nlrp3 inflammasome responses. However, the primary macrophages derived from the Mm47 knockout mice do not require Mm47 for Nlrp3 activation, likely due to basal downregulation of a negative regulator microRNA of Nlrp3 called Mir-223. Notably, the Mm47-deficient mice are susceptible to influenza virus infection and succumb despite comparable antiviral and inflammatory response to wildtype mice. We hypothesize that the Mm47 deficiency may affect the antiviral resilience of mice due to secondary mitochondria dependent immunometabolic defect or failure of recovery from immune pathology, which warrants further investigation. This study therefore identifies a novel mitochondrial micropeptide Mm47 that is required for activation of the Nlrp3 inflammasome in cells and resistance to influenza virus infection. Broadly, this work highlights the presence of translatable ORFs is annotated noncoding RNA transcripts and underscores their importance in innate immunity and virus infection.

Due to the continuously decreasing feature sizes and the increasing complexity of integrated circuits, commercial off-the-shelf (COTS) hardware is becoming less and less reliable. However, dedicated reliable hardware is expensive and usually slower than commodity hardware. Thus, economic pressure will most likely result in the usage of unreliable COTS hardware in safety-critical systems. The usage of unreliable, COTS hardware in safety-critical systems results in the need for software-implemented solutions for handling execution errors caused by this unreliable hardware. In this thesis, we provide techniques for detecting hardware errors that disturb the execution of a program. The detection provided facilitates handling of these errors, for example, by retry or graceful degradation. We realize the error detection by transforming unsafe programs that are not guaranteed to detect execution errors into safe programs that detect execution errors with a high probability. Therefore, we use arithmetic AN-, ANB-, ANBD-, and ANBDmem-codes. These codes detect errors that modify data during storage or transport and errors that disturb computations as well. Furthermore, the error detection provided is independent of the hardware used. We present the following novel encoding approaches: - Software Encoded Processing (SEP) that transforms an unsafe binary into a safe execution at runtime by applying an ANB-code, and - Compiler Encoded Processing (CEP) that applies encoding at compile time and provides different levels of safety by using different arithmetic codes. In contrast to existing encoding solutions, SEP and CEP allow to encode applications whose data and control flow is not completely predictable at compile time. For encoding, SEP and CEP use our set of encoded operations also presented in this thesis. To the best of our knowledge, we are the first ones that present the encoding of a complete RISC instruction set including boolean and bitwise logical operations, casts, unaligned loads and stores, shifts and arithmetic operations. Our evaluations show that encoding with SEP and CEP significantly reduces the amount of erroneous output caused by hardware errors. Furthermore, our evaluations show that, in contrast to replication-based approaches for detecting errors, arithmetic encoding facilitates the detection of permanent hardware errors. This increased reliability does not come for free. However, unexpectedly the runtime costs for the different arithmetic codes supported by CEP compared to redundancy increase only linearly, while the gained safety increases exponentially.

The fast development of DNA-encoded chemical libraries (DECL) in the past 10 years has received great attention from pharmaceutical industries. It applies the selection approach for small molecular drug discovery. Because of the limited choices of DNA-compatible chemical reactions, most DNA-encoded chemical libraries have a narrow structural diversity and low synthetic yield. There is also a poor correlation between the ranking of compounds resulted from analyzing the sequencing data and the affinity measured through biochemical assays. By combining DECL with dynamical chemical library, the resulting DNA-encoded dynamic library (EDCCL) explores the thermodynamic equilibrium of reversible reactions as well as the advantages of DNA encoded compounds for manipulation/detection, thus leads to enhanced signal-to-noise ratio of the selection process and higher library quality. However, the library dynamics are caused by the weak interactions between the DNA strands, which also result in relatively low affinity of the bidentate interaction, as compared to a stable DNA duplex. To take advantage of both stably assembled dual-pharmacophore libraries and EDCCLs, we extended the concept of EDCCLs to heat-induced EDCCLs (hi-EDCCLs), in which the heat-induced recombination process of stable DNA duplexes and affinity capture are carried out separately. To replace the extremely laborious and repetitive manual process, a fully automated device will facilitate the use of DECL in drug discovery. Herein we describe a novel lab-on-a-chip platform for high throughput drug discovery with hi-EDCCL. A microfluidic system with integrated actuation was designed which is able to provide a continuous sample circulation by reducing the volume to a minimum. It consists of a cooled and a heated chamber for constant circulation. The system is capable to generate stable temperatures above 75 °C in the heated chamber to melt the double strands of the DNA and less than 15 °C in the cooled chamber, to reanneal the shuffled library. In the binding chamber (the cooled chamber) specific retaining structures are integrated. These hold back beads functionalized with the target protein, while the chamber is continuously flushed with library molecules. Afterwards the whole system can be flushed with buffer to wash out unspecific bound molecules. Finally the protein-loaded beads with attached molecules can be eluted for further investigation

Récemment, la chimie des phosphoramidites s’est montrée efficace et polyvalente en tant que plateforme pour accéder à des poly(phosphodiester)s à séquence définies abiotiques. Grâce à cette stratégie, les monomères peuvent être placés dans la chaîne à des positions choisies, ouvrant la voie à de nombreuses possibilités pour la préparation de macromolécules fonctionnelles. Ici, la méthode phosphoramidite a été explorée pour la synthèse de polymères dits numériques, qui contiennent des séquences de monomères encodées binairement. Des polymères dont les longueurs de chaînes et les séquences numériques sont contrôlées ont été préparés en utilisant une stratégie phosphoramidite classique impliquant des groupements protecteurs diméthoxytrityles, ou bien un procédé photocontrôlé faisant intervenir des groupements nitrophénylpropyloxycarbonyles clivables à la lumière. En outre, plusieurs stratégies pour modifier l’information contenue dans les chaînes latérales ont été étudiées dans cette thèse. Une modification binaire post-polymérisation à travers deux cycloadditions alcyne-azoture catalysées par le cuivre(I) consécutives a été examinée pour optimiser les chaînes latérales des poly(phosphodiester)s à séquences définies. De plus, la libération photocontrôlée de différents motifs éthers ortho-nitrobenzyliques latéraux a été étudiée. Ces fonctions ont permis la conception d’oligo(phosphodiester)s numériques dont les séquences d’information peuvent être effacées ou révélées grâce à la lumière. / Phosphoramidite chemistry has recently been evidenced to be an efficient and versatile platform to access sequence-defined abiotic poly(phosphodiester)s. Using this strategy, monomers can be placed at defined positions positions in a chain, thus opening up wide possibilities for the preparation of functional macromolecules.Here, the phosphoramidite platform was explored to synthesize so-called digital polymers, which contain monomer-coded binary sequences. Polymers with controlled chain lengths and digital sequences were prepared using either a standard phosphoramidite strategy involving dimethoxytrityl protective groups or a photo-controlled process involving light-cleavable nitrophenylpropyloxycarbonyl protective groups. Additionally, several strategies to modify the side chain information were investigated in this thesis. A binary post-polymerization modification by means of sequential copper(I)-catalyzed alkyne-azide cycloadditions was investigated for tuning the side chain functionality of sequence-defined poly(phosphodiester)s. Moreover, the photo-controlled release of several ortho-nitrobenzylic ether side chain motifs was studied. These moieties allowed the design of digital oligo(phosphodiester)s whose sequence information can be erased or revealed with light as a trigger.

The geometrical structure of a tree can consist of thousands, even millions, of branches, twigs and leaves in complex arrangements. The structure contains a lot of useful information and can be used for example to assess a tree's health or calculate parameters such as total wood volume or branch size distribution. Because of the complexity, capturing the structure of an entire tree used to be nearly impossible, but the increased availability and quality of particularly digital cameras and Light Detection and Ranging (LIDAR) instruments is making it increasingly possible. A set of digital images of a tree, or a point cloud of a tree from a LIDAR scan, contains a lot of data, but the information about the tree structure has to be extracted from this data through analysis. This work presents a method of reconstructing 3D models of trees from point clouds. The model is constructed from cylindrical segments which are added one by one. Bayesian inference is used to determine how to optimize the parameters of model segment candidates and whether or not to accept them as part of the model. A Hough transform for finding cylinders in point clouds is presented, and used as a heuristic to guide the proposals of model segment candidates. Previous related works have mainly focused on high density point clouds of sparse trees, whereas the objective of this work was to analyze low resolution point clouds of dense almond trees. The method is evaluated on artificial and real datasets and works rather well on high quality data, but performs poorly on low resolution data with gaps and occlusions.

No description available.

Kürzlich wurde mithilfe von Ribo-seq Experimenten die Translation hunderter Mikroproteine in menschlichen Herzen entdeckt. Diese blieben zuvor aufgrund ihrer geringen Größe (< 100 Aminosäuren) unentdeckt, und ihre physiologische Rolle ist noch weitgehend unbekannt. Ziel dieser Promotionsarbeit ist es, potentielle Funktionen dieser neuartigen Mikroproteine zu entschlüsseln. Dabei sollen insbesondere die Aufklärung ihrer evolutionären Konservierungssignatur, subzellulären Lokalisierung und ihres Proteininteraktoms helfen. Die Konservierungsanalyse ergab, dass fast 90% der Mikroproteine nur in Primaten konserviert ist. Weiterhin konnte ich die Produktion von Mikroproteine in vitro und in vivo nachweisen, die subzelluläre Lokalisierung von 92 Mikroproteinen definieren, und Interaktionspartner für 60 Mikroproteine identifizieren. Dutzende dieser Mikroproteine lokalisieren in Mitochondrien. Dazu gehörte ein im Herzen angereichertes Mikroprotein, das aufgrund der Interaktions- und Lokalisationsdaten einen neuartigen Modulator der mitochondrialen Proteintranslation darstellen könnte. Der Interaktom-Screen zeigte außerdem, dass evolutionär junge Mikroproteine ähnliche Interaktionsfähigkeiten wie konservierte Kandidaten haben. Schließlich wurden kurze Sequenzmotive identifiziert, die Mikroprotein-Protein-Wechselwirkungen vermitteln, wodurch junge Mikroproteine mit zellulären Prozessen – wie z.B. Endozytose und Spleißen – in Verbindung gebracht werden konnten. Zusammenfassend wurde die Produktion vieler kleiner Proteine im menschlichen Herzen bestätigt, von denen die meisten lediglich in Primaten konserviert sind. Zusätzlich verknüpften umfangreiche Lokalisierungs- und Interaktionsdaten mehrere Mikroproteine mit Prozessen wie Spleißen, Endozytose und mitochondrialer Translation. Weitere Untersuchungen dieses zuvor verborgenen Teils des Herzproteoms werden zu einem besseren Verständnis von evolutionär jungen Proteinen und kardiologischen Prozessen beitragen. / Recently, the active translation of hundreds of previously unknown microproteins was detected using ribosome profiling on tissues of human hearts. They had remained undetected due to their small size (< 100 amino acids), and their physiological roles are still largely unknown. This dissertation aims to investigate these novel microproteins and validate their translation by independent methods. Particularly, elucidating their conservation signature, subcellular localization, and protein interactome shall aid in deciphering their potential biological role. Conservation analysis revealed that sequence conservation of almost 90% of microproteins was restricted to primates. I next confirmed microprotein production in vitro and in vivo by in vitro translation assays and mass spectrometry-based approaches, defined the subcellular localization of 92 microproteins, and identified significant interaction partners for 60 candidates. Dozens of these microproteins localized to the mitochondrion. These included a novel cardiac-enriched microprotein that may present a novel modulator of mitochondrial protein translation based on its interaction profile and subcellular localization. The interactome screen further revealed that evolutionarily young microproteins have similar interaction capacities to conserved candidates. Finally, it allowed identifying short linear motifs that may mediate microprotein-protein interactions and implicated several young microproteins in distinct cellular processes such as endocytosis and splicing. I conclude that many novel small proteins are produced in the human heart, most of which exhibit poor sequence conservation. I provide a substantial resource of microprotein localization and interaction data that links several to cellular processes such as splicing, endocytosis, and mitochondrial translation. Further investigation into this hidden part of the cardiac proteome will contribute to our understanding of recently evolved proteins and heart biology.