O propósito deste trabalho tem sido a utilização das técnicas de Desenho Óptico para o desenvolvimento de sistemas ópticos altamente otimizados. Após a confeccção destes sistemas ópticos torna-se necessário avaliar o desempenho do sistema construído, para isto tem sido utilizado uma das técnicas mais modernas para avaliação de qualidade da imagem óptica, a função de transferência óptica FTO, mais especificamente a função de transferência de modulação FTM. FTM representa o módulo da função complexa FTO e está associada à medida direta e quantitativa da qualidade de imagem, descrevendo a estrutura da imagem como uma função da freqüência espacial. Estas duas técnicas são as ferramentas fundamentais para os desenhistas ópticos. Instrumentos oftálmicos como o microscópio cirúrgico, sistema óptico para adaptação de uma câmera CCD e a lâmpada de fenda são desenvolvidos e analisados por estas técnicas neste trabalho. / The purpose of this work has been the use of design optical techniques to development of highly optimized optical systems. After the fabrication of these systems, it is necessary to evaluate the performance of building systems. A modern technique used to evaluate the quality of optical image is the optical transfer function OTF, more exactly the modulation transfer function MTF. MTF is the modulus of the complex function OTF. MTF is associated the direct and quantitative measure of the image quality and it describes the image structure as a function of spatial frequency. This bides techniques are the tools of optical designers. Ophthalmic instruments like surgery microscope, optical system of CCD camera adaptation and slit lamps are developed and analyzed for this techniques in this work.

The human eye is a complex optical system comprised of many components. The crystalline lens, an optical component with a gradient index (GRIN), is perhaps the least understood as it is situated inside the eye and as a result is difficult to characterize. Its complex nonlinear structure is not easily measured and consequently not easily modeled. Presently several models of the GRIN structure exist describing the average performance of crystalline lenses. These models, however, do not accurately describe the performance of crystalline lenses on an individual basis and a more accurate individual eye model based on anatomical parameters is needed. This thesis proposes an anatomically correct, individually customizable crystalline lens model. This is an important tool and is needed both for research on the optical properties of human eyes and to diagnose and plan the treatment of optically based visual problems, such as refractive surgery planning. The lens model consisted of an interior GRIN with a constant refractive index core. The anterior and posterior surface was described by conic sections. To realize this eye model, the optical and biometric properties of mammalian lenses were measured and the correlation relationships between these measurements were used to simplify the model down to one fitting parameter which controls the shape of the GRIN. Using this data, an anatomically correct individualizable model of the lens was successfully realized with varying parameters unique to each lens. Using this customizable lens model, customizable human eye models based on measurements of the entire human eye can be realized.

We present a fluid-membrane lens with two piezoelectric actuators that offer versatile, circular symmetric lens surface shaping. A wavefront-measurement-based control system ensures robustness against creeping and hysteresis effects of the piezoelectric actuators. We apply the adaptive lens to correct synthetic aberrations induced by a deformable mirror. The results suggest that the lens is able to correct spherical aberrations with standard Zernike coefficients between 0 μm and 1 μm, while operating at refractive powers up to about 4m-1. We apply the adaptive lens in a custom-built confocal microscope to allow simultaneous axial scanning and spherical aberration tuning. The confocal microscope is extended by an additional phase measurement system to include the control algorithm. To verify our approach, we use the maximum intensity and the axial FWHM of the overall confocal point spread function as figures of merit. We further discuss the ability of the adaptive lens to correct specimen-induced aberrations in a confocal microscope.

The aim of this master's thesis is to explore and study dynamic aberration correction options in electron-beam lithography systems. For the calculations, the thesis uses the optical column of the BS600 electron-beam writer. The thesis focuses on corrections of the third order field curvature, astigmatism, and distortion aberrations of the currently used magnetic deflection system and a newly designed electrostatic deflection system. The parameters of the two deflection and correction systems were compared.

This work is focussed on different unwanted effects that damage a digitally acquired image. An image acquired using a digital camera can suffer from a series of defects. First, the noise is concerned. It occures due to discretisation. Next, there are the defects including vignetting, radial image distortion, chromatic aberration. In my thesis I also worked on backlight image compensation and panorama creation from an image sequence. For backlight images we need to increase the brightness in the dark parts of the image, so that the details became more visible. At panorama creation we are careful about brightness evenness in partial images, which is usually not conserved and consequently we try to find a suitable boundary-line to connect images and smooth it. The fundamental part of my work was writing the algorithms that are able to compensate these defects at least partly. For this aim I took use of the Matlab environment.

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

Carriers of apparently balanced chromosomal aberrations (BCA) are usually phenotypically normal. However, it has been estimated that up to 27% of these BCA may be associated with an abnormal phenotype, most often caused by cryptic imbalances at the breakpoints, gene disruption by the breakpoint or via the position effect. In contrast to conventional karyotyping, molecular cytogenetic techniques enable more detailed BCA characterization and better correlation between genotype and phenotype of the patient. The aim of this thesis was to evaluate the presence of copy number variants (CNVs) at breakpoints or elsewhere in the genome in patients with abnormal phenotype who carry de novo or inherited BCA. 54 BCA were investigated using array CGH (20 de novo cases, 27 inherited and 7 cases of unknown origin) including 32 reciprocal translocations, 6 robertsonian translocations, 12 inversions and 4 complex chromosomal rearrangements. If possible, the parents were also examined to ascertain the inheritance of the relevant CNVs. In order to specify microarray findings or exclude gene disruption, FISH was used in selected patients. Among the patients included, in 31,5% (17/54) at least one (in 8 patients more than one) significant CNV was detected. Four cases carried cryptic imbalances only at the breakpoints,...

In space exploration optical imaging is one of the key measurements conducted, with a vast majority of missions heavily relying on optical data acquisition to examine alien worlds. One such endeavor is ESA’s F-class mission Comet Interceptor, a multi-element spacecraft expected to be launched in 2028. It consists of a primary platform and two sub-spacecraft, one of which carrying the Optical Periscopic Imager for Comets (OPIC). An accurate prediction of the generated imagery is of undeniable importance as mission planning and instrument design strongly depend on the real-world output quality of the camera system. In the case of OPIC, the collected image data will be used to reconstruct three dimensional models of targeted celestial bodies. Furthermore, the sub-spacecraft faces a risk of high velocity dust impacts, leading to a limited number of data samples to be broadcasted back to the primary spacecraft before collision. Testing image prioritization algorithms and reconstruction methods prior to mission start requires accurate computer-generated images. Camera sensors and lens systems are subjected to various optical distortions and aberrations that degrade the final image. Popular render engines model those effects to a certain degree only and as a result produce content that is looking too perfect. While more sophisticated software products exist, they often come with compatibility limitations and other drawbacks. This report discusses the most important optical aberrations, as well as their relevance for optical instruments in space applications with a particular focus on the Comet Interceptor mission. The main part of this work is however the implementation of a dedicated software tool that simulates a variety of optical aberrations complementing the basic camera model of the Blender render engine. While its functionality is mostly demonstrated for OPIC, the software is designed with a broad range of usage scenarios in mind.

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Indiana University-Purdue University Indianapolis (IUPUI) / Introduction: Multiphoton fluorescence excitation microscopy (MPM) is an invaluable tool for studying processes in tissue in live animals by enabling biologists to view tissues up to hundreds of microns in depth. Unfortunately, imaging depth in MPM is limited to less than a millimeter in tissue due to spherical aberration, light scattering, and light absorption. Spherical aberration is caused by refractive index mismatch between the objective immersion medium and sample. Refractive index heterogeneities within the sample cause light scattering. We investigate the effects of refractive index mismatch on imaging depth in MPM. Methods: The effects of spherical aberration on signal attenuation and resolution degradation with depth are characterized with minimal light absorption and scattering using sub-resolution microspheres mounted in test sample of agarose with varied refractive index. The effects of light scattering on signal attenuation and resolution degradation with depth are characterized using sub-resolution microspheres in kidney tissue samples mounted in optical clearing media to alter the refractive index heterogeneities within the tissue. Results: The studies demonstrate that signal levels and axial resolution both rapidly decline with depth into refractive index mismatched samples. Interestingly, studies of optical clearing with a water immersion objective show that reducing scattering increases reach even when it increases refractive index mismatch degrading axial resolution. Scattering, in the absence of spherical aberration, does not degrade axial resolution. The largest improvements in imaging depth are obtained when both scattering and refractive index mismatch are reduced. Conclusions: Spherical aberration, caused by refractive index mismatch between the immersion media and sample, and scattering, caused by refractive index heterogeneity within the sample, both cause signal to rapidly attenuate with depth in MPM. Scattering, however, seems to be the predominant cause of signal attenuation with depth in kidney tissue. Kenneth W. Dunn, Ph.D., Chair