Aberrationen in der DNA-Kopienzahl sind häufige genetische Veränderungen bei malignen Lymphomerkrankungen. Zugewinne sowie Deletionen stellen dabei Mechanismen zur Onkogen-Aktivierung sowie Tumorsuppressorgen-Inaktivierung dar und tragen somit zur Pathogenese der Erkrankung bei. Array-CGH und SNP-Array sind Messplattformen, die die genomweite Bestimmung von Kopienzahlaberrationen in einem Experiment ermöglichen. Die bei der Analyse entstehenden Datensätze sind komplex und erfordern automatische Methoden zur Unterstützung der Analyse und Interpretation der Messergebnisse. In dieser Promotionsarbeit wurden Methoden entwickelt, welche die Analyse von Array-CGH- und SNP-Array-Messungen ermöglichen. Diese Methoden wurden für die Auswertung umfangreicher Datensätze von malignen Non-Hodgkin-Lymphomen verwendet. Dabei wurden Lymphome der Entitäten Burkitt-Lymphom, diffus großzelliges B-Zell-Lymphom, Mantelzelllymphom, primäres ZNS-Lymphom und peripheres T-Zell-Lymphom – nicht anderweitig spezifiziert – analysiert. Für die untersuchten Lymphom-Entitäten konnten hierbei zahlreiche neue rekurrente Kopienzahlaberrationen sowie uniparentale Disomien gezeigt werden, die neue Einblicke in die Pathogenese der jeweiligen Erkrankungen erlauben. Darüber hinaus erfolgte ein Vergleich beider Messplattformen anhand eines Datensatzes mit gepaarten Array-CGH- und SNP-Array-Daten. Für die eingesetzten Plattformen (2800k-BAC-Array vs. Affymetrix 250k-Sty-SNP-Array) konnte eine circa zwölffach höhere effektive Auflösung der SNP-Array-Plattform gezeigt werden. Die wesentlichen Ergebnisse dieser Arbeit sind in sieben Publikationen eingeflossen.:Inhaltsverzeichnis Abkürzungsverzeichnis Tabellenverzeichnis Abbildungsverzeichnis 1. Einführung 1.1 Biologischer Hintergrund 1.1.1 Aberrationen der DNA-Kopienzahl und Tumorentstehung 1.1.2 Lymphome 1.2 Motivation und Rationale für die Arbeit 1.3 Array-CGH Analyse 1.4 SNP-Array-Analyse 1.5 Vergleich von Array-CGH und SNP-Array-Analyse 1.6 Assoziationen von DNA-Kopienzahlaberrationen mit RNA-Expression, Lymphomentität sowie klinischen und phänotypischen Faktoren 2.Publikationen 2.1 Publikation 1: “Development and implementation of an analysis tool for array-based comparative genomic hybridization” Methods Inf Med. 2007;46(5):608-13 2.2 Publikation 2: “Recurrent loss of the Y chromosome and homozygous deletions within the pseudoautosomal region 1: association with male predominance in mantle cell lymphoma” Haematologica. 2008 Jun;93(6):949-50 2.3 Publikation 3: “GeneChip analyses point to novel pathogenetic mechanisms in mantle cell lymphoma” Br J Haematol. 2009 Feb;144(3):317-31 2.4 Publikation 4: “Chromosomal imbalances and partial uniparental disomies in primary central nervous system lymphoma.” Leukemia. 2009 Oct;23(10):1875-84 2.5 Publikation 5: “High resolution SNP array genomic profiling of peripheral T cell lymphomas, not otherwise specified, identifies a subgroup with chromosomal aberrations affecting the REL locus” Br J Haematol. 2010 Feb;148(3):402-12 2.6 Publikation 6: “Detection of genomic aberrations in molecularly defined Burkitt\''s lymphoma by array-based, high resolution, single nucleotide polymorphism analysis” Haematologica. 2010 Dec;95(12):2047-55 2.7 Publikation 7: “Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma” Blood. 2012 Feb 23;119(8):1882-7 2.8 Kennzeichnung des Eigenanteils für alle eingeschlossenen Publikationen 3. Diskussion und Ausblick 4. Zusammenfassung 5. Referenzen 6. Eigene Publikationen 7. Erklärung 8. Danksagung 9. Curriculum vitae

>Magister Scientiae - MSc / The new 64-dish radio telescope array MeerKAT will be absorbed into the international Square Kilometre Array (SKA) in late 2020s. These two telescope arrays will produce three-dimensional maps of the integrated intensity of the 21cm emission from neutral hydrogen in galaxies, out to redshifts of 1:5 and 3 respectively. These maps contain a signature of the growth of large-scale structure in the Universe. This signature can be uncovered via redshift space distortions of the two-point correlation function, or power spectrum, of the 21cm brightness temperature uctuations. The growth rate governs the amplitude of the anisotropic signal from redshift-space distortions. It is a powerful probe of gravity and its measurement has the potential to test whether general relativity holds. We use models of the 21cm intensity and its power spectrum, starting from a simple linear model of redshift-space distortions and then extending to nonlinear models. With these models, we make Fisher forecast predictions of the precision with which MeerKAT and the SKA can measure the growth rate

Plasmonics is an important branch of nanophotonics and is the study of the interaction of electromagnetic fields with the free electrons in a metal at metallic/dielectric interfaces or in small metallic nanostructures. The electric component of an exciting electromagnetic field can induce collective electron oscillations known as surface plasmons. Such oscillations lead to the localization of the fields that can be at sub-wavelength scale and to its significant enhancement relative to the excitation fields. These two characteristics of localization and enhancement are the main components that allow for the guiding and manipulation of light beyond the diffraction limit. This thesis focuses on developing plasmonic devices for near and far-field applications. In the first part of the thesis, we demonstrate the detection of single point mutation in peptides from multicomponent mixtures for early breast cancer detection using selfsimilar chain (SCC) plasmonic devices that show high field enhancement and localization. In the second part of this work, we investigate the anomalous reflection of light for TM polarization for normal and oblique incidence in the visible regime. We propose gradient phase gap surface plasmon (GSP) metasurfaces that exhibit high conversion efficiency (up to ∼97% of total reflected light) to the anomalous reflection angle for blue, green and red wavelengths at normal and oblique incidence. In the third part of the thesis, we present a theoretical approach to narrow the plasmon linewidth and enhance the near-field intensity at a plasmonic dimer gap (hot spot) through coupling the electric localized surface plasmon (LSP) resonance of a silver hemispherical dimer with the resonant modes of a Fabry-Perot (FP) cavity. In the fourth part of this work, we demonstrate numerically bright color pixels that are highly polarized and broadly tuned using periodic arrays of metal nanosphere dimers on a glass substrate. In the fifth and final part of the thesis, we propose numerically an approach to narrow the plasmon linewidth and enhance the magnetic near field intensity at a magnetic hot spot in a hybridized metal-insulator-metal (MIM) structure. The computational method used throughout the thesis is the finite-difference time-domain method (FDTD).

Taking inspiration from a variety of creatures found in nature, this thesis demonstrates a new class of materials designed for light capture and guidance. Through the facile method of waveguide self-inscription developed herein, the arrangement of these self-generated light channels can be influenced to produce complex architectures. Inspired by the arrangement of ommatidia found in arthropodal eyes, this was first demonstrated through the fabrication of a radial arrangement of waveguides. This resulted in a thin, polymer film which demonstrated a continuous, panoramic field of view (FOV) able to successfully control the light of a light emitting diode (LED). Moving to more complex architecture, waveguides self-generated in a conical geometry were fabricated. More closely reminiscent of the geometry seen in arthropodal eyes, this waveguide architecture demonstrated a seamless omnidirectional FOV and enhanced imaging capabilities in conjunction with a CMOS camera chip. Lastly, using the method of waveguide self-inscription with an electroactive hydrogel precursor, remote controllable light guiding architectures, as inspired by deep sea creatures, are designed and fabricated. The application of an electric field, in conjunction with the stimuli-responsive waveguides, allows for precise control of the waveguide structures and therefore control over the waveguided light. / Thesis / Doctor of Philosophy (PhD)

Array comparative genomic hybridization (aCGH) is a technique for identifying duplications and deletions of DNA at specific locations across a genome. Potential objectives of aCGH analysis are the identification of (1) altered regions for a given subject, (2) altered regions across a set of individuals, and (3) clinically relevant clusters of hybridizations. aCGH analysis can be particularly useful when it identifies previously unknown clusters with clinical relevance. This project focuses on the assessment of existing aCGH clustering methodologies. Three methodologies are considered: hierarchical clustering, weighted clustering of called aCGH data, and clustering based on probabilistic recurrent regions of alteration within subsets of individuals. Assessment is conducted first through the analysis of aCGH data obtained from patients with ovarian cancer and then through simulations. Performance assessment for the data analysis is based on cluster assignment correlation with clinical outcomes (e.g., survival). For each method, 1,000 simulations are summarized with Cohen's kappa coefficient, interpreted as the proportion of correct cluster assignments beyond random chance. Both the data analysis and the simulation results suggest that hierarchical clustering tends to find more clinically relevant clusters when compared to the other methods. Additionally, these clusters are composed of more patients who belong in the clusters to which they are assigned.

Massively parallel arrays of single walled carbon nanotubes (SWNT) have attracted significant research interests because of their ability to (i) average out inhomogeneities of individual SWNTs, (ii) provide larger on currents, and (iii) reduce noise to provide higher cutoff frequency for radio frequency applications. However, the array contains both metallic and semiconducting SWNTs and the presence of metallic nanotube in an aligned array negatively affects the device properties. Therefore, it is essential to selectively remove metallic nanotubes to obtain better transistor properties. It was recently found that although such a selective removal can be effective for a low density array, it does not work in a high density array and lead to a correlated breakdown of the entire array giving rise to a nanofissure pattern. In order to obtain a deeper understanding of such a correlated SWNT breakdown, we studied the breakdown power in the successive electrical breakdown of both low ( < 2 /um) and high density ( > 10 /um) SWNT arrays. We show that the breakdown voltage in successive electrical breakdown increases for low density array while it decreases for high density arrays. The estimated power required for the breakdown remains constant for low density arrays while it decreases for high density arrays in successive electrical breakdowns. We also show that, while a simple model of parallel resistor network can explain the breakdown of low density array, it cannot explain the behavior for the high density array implying that the correlation between the closely spaced parallel nanotubes plays a big role in the successive breakdowns of the high density SWNTs.

Phased-array antennas are commonplace in the radiofrequency portion of the electromagnetic spectrum. Exploitation of phasing effects between multiple antennas facilitates a wide range of applications, including synthetic-aperture radar, beam forming, and beam scanning. For the first time, the phased addition of multiple dipole antennas is demonstrated in the infrared, at a wavelength of 10.6 micrometers. Coplanar strip lines are used to interconnect the antennas, preserving the phase of the individual contributions. Several different proof-of-concept experiments are performed, using planar antennas fabricated with direct-write electron-beam lithography. Infrared-frequency currents from two dipole antennas are summed together at a common feedpoint and dissipated in a bolometric load. Angular pattern measurements show that the direction of maximum gain depends on the phase difference between the antennas. As more antennas are added together in phase, beam narrowing is observed in the angular response. Another experiment uses a two-dipole array to directly measure the magnitude of the mutual coherence function, at the plane of the antennas, of a spatially incoherent narrowband source. Measurements are also made of the broadside antenna response comparing air-side and substrate-side situations for a dipole antenna fabricated on a hemispherical immersion lens. In all cases, the measured behavior is confirmed by electromagnetic analysis.

No / In this study, a planar 4×4 phased array including modified E-shaped radiation elements is designed and fabricated to be incorporated in a Relay Station (RS) for realizing the communication with the super-ordinate Base Station. The proposed array provides 12.4% bandwidth at the 3.5GHz frequency band and gain of 21.2dB. Moreover a beamforming module is designed and simulated, aimed to be connected to the proposed array and realizing beamforming applications. This module provides 650 MHz bandwidth around 3.5GHz frequency band and is used for proper power division and controlling the amplitude/phase of the excitation currents.

An array of electronically-switched circular patch antennas is designed for breast tissue imaging for the purposes of cancer screening. Each array element is connected to a dedicated heterodyne radio, which performs amplification and downconversion to a single, low intermediate frequency for improved signal recovery. Data acquisition is accomplished with a VNA-based architecture. Details of the design are provided and are accompanied by simulated and experimental data. A receiver sensitivity of at least -120 dBm is expected, and an imaging sensor switching dynamic range between ON and OFF states of at least 127 dB is demonstrated based on experimental measurements. / Thesis / Master of Applied Science (MASc)

<p> A highly parallel computing system capable of computing transcendental functions, matrix operations and iterative calculations has been devised and a typical cell has been implemented. The system consists of an array of cells, a control unit, a PDP-11 computer and an interface unit. The array uses modified SOLOMON type of communication between cells. Each cell consists of 15 words and arithmetic hardware. Arithmetic and logic operations, on words or bytes, may be performed serially between pairs of these words. Division and floating-point arithmetic are under software control. Parallel algorithms have been developed. A set of instructions and mnemonics permits a practical use of the system. The possibility of using the array as an associative-memory processor is also considered. The system has been tested by using the software package prepared. Although only one cell has actually been constructed a complete array has been simulated on a PDP-11 computer.</p> / Thesis / Master of Engineering (MEngr)