The availability of spatial light modulators as standard turnkey components and their ongoing development makes them attractive for a huge variety of optical measurement systems in industry and research. Here, we outline two examples of how optical measurements can benefit from spatial light modulators. Ultrasound testing has become an indispensable tool for industrial inspection. Contact-free measurements can be achieved by laser-induced ultrasound. One disadvantage is that due to the highly divergent sound field of the generated shear waves for a point-wise thermoelastic excitation, only a poor spatial selectivity can be achieved. This problem can be solved by creating an ultrasound focus by means of a ring-like laser intensity distribution, but standard fixed-form optical components used for their generation are always optimised to a fixed set of parameters. Here, we demonstrate, how a predefined intensity pattern as e.g. a ring can be created from an arbitrary input laser beam using a phase-retrieval algorithm to shape an ultrasound focus in the sample. By displaying different patterns on the spatial light modulator, the focus can be traversed in all three directions through the object allowing a fast and highly spatially resolving scanning of the sample. Optical measurements take often place under difficult conditions. They are affected by variations of the refractive index, caused e.g. by phase boundaries between two media of different optical density. This will result in an increased measurement uncertainty or, in the worst case, will cause the measurement to fail. To overcome these limitations, we propose the application of adaptive optics. Optical flow velocity measurements based on image correlation in water that are performed through optical distortions are discussed. We demonstrate how the measurement error induced by refractive index variations can be reduced if a spatial light modulator is used in the measurement setup to compensate for the wavefront distortions.

The signaling mechanisms involved in UVB-induced skin cancer are complex and although the scope of this work is inherently limited in focus, the findings may provide insight into how estrogen receptor signaling impacts cell growth, senescence, and apoptosis to protect keratinocytes. Additional signaling due to E2-activation of the estrogen receptor may provide back-up or redundant pathways in response to UVB.

No description available.

This dissertation presents the fabrication and analysis of in-fiber devices based on elliptical core D-shaped optical fiber. Devices created inside optical fibers are attractive for a variety of reasons including low loss, high efficiency, self-alignment, light weight, multiplexibility, and resistance to electromagnetic interference. This work details how D-fiber can be used as a platform for a variety of devices and describes the creation and performance of two of these devices: an in-fiber polymer waveguide and a surface relief fiber Bragg grating. In D-fiber the core is very close to the flat side of the ‘D’ shape. This proximity allows access to the fields in the fiber core by removal of the cladding above the core. The D-fiber we use also has an elliptical core, allowing for the creation of polarimetric devices. This work describes two different etch processes using hydrofluoric acid (HF) to remove the fiber cladding and core. For the creation of devices in the fiber core, the core is partially removed and replaced with another material possessing the required optical properties. For devices which interact with the evanescent field, cladding removal is terminated before acid breaches the core. Etching fibers prepares them for use in the creation of in-fiber devices. Materials are placed into the groove left when the core of a fiber is partially removed to form a hybrid waveguide in which light is guided by both the leftover core and the inserted material. These in-fiber polymer waveguides have insertion loss less than 2 dB and can potentially be the basis for a number of electro-optic devices or sensors. A polarimetric temperature sensor demonstrates the feasibility of the core replacement method. This work also describes the creation of a surface relief fiber Bragg gratings (SR-FBGs) in the cladding above the core of the fiber. Because it is etched into the surface topography of the fiber, a SR-FBG can operate at much higher temperatures than a standard FBG, up to at least 1100 degrees Celsius. The performance of a SR-FBG is demonstrated in temperature sensing at high temperatures, and as a strain sensor.

Sphingosine 1-phosphate (S1P) receptor (S1PR) modulators have a complex mechanism of action, which are among the most efficient therapeutic options in multiple sclerosis (MS) and represent a promising approach for other immune-mediated diseases. The S1P signaling pathway involves the activation of five extracellular S1PR subtypes (S1PR1–S1PR5) that are ubiquitous and have a wide range of effects. Besides the immunomodulatory beneficial outcome in MS, S1P signaling regulates the cardiovascular function via S1PR1–S1PR3 subtypes, which reside on cardiac myocytes, endothelial, and vascular smooth muscle cells. In our review, we describe the mechanisms and clinical effects of S1PR modulators on the cardiovascular system. In the past, mostly short-term effects of S1PR modulators on the cardiovascular system have been studied, while data on long-term effects still need to be investigated. Immediate effects detected after treatment initiation are due to parasympathetic overactivation. In contrast, long-term effects may arise from a shift of the autonomic regulation toward sympathetic predominance along with S1PR1 downregulation. A mild increase in blood pressure has been reported in long-term studies, as well as decreased baroreflex sensitivity. In most studies, sustained hypertension was found to represent a significant adverse event related to treatment. The shift in the autonomic control and blood pressure values could not be just a consequence of disease progression but also related to S1PR modulation. Reduced cardiac autonomic activation and decreased heart rate variability during the long-term treatment with S1PR modulators may increase the risk for subsequent cardiac events. For second-generation S1PR modulators, this observation has to be confirmed in further studies with longer follow-ups. The periodic surveillance of cardiovascular function and detection of any cardiac autonomic dysfunction can help predict cardiac outcomes not only after the first dose but also throughout treatment.

Importance: Immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is important, especially in people with multiple sclerosis (pwMS) on immunosuppressive therapies. Objective: This study aims to determine whether adjuvanted protein-based vaccine NVX-CoV2373 is able to induce an immune response to SARS-CoV-2 in pwMS with inadequate responses to prior triple mRNA/viral vector vaccination. Design, setting, and participants: We conducted a single-center, prospective longitudinal cohort study at the MS Center in Dresden, Germany. In total, 65 participants were included in the study in accordance with the following eligibility criteria: age > 18 years, immunomodulatory treatment, and insufficient T-cellular and humoral response to prior vaccination with at least two doses of SARS-CoV-2 mRNA (BNT162b2, mRNA-1273) or viral vector vaccines (AZD1222, Ad26.COV2.S). Interventions: Intramuscular vaccination with two doses of NVX-CoV2373 at baseline and 3 weeks of follow-up. Main outcomes and measures: The development of SARS-CoV-2-specific antibodies and T-cell responses was evaluated. Results: For the final analysis, data from 47 patients on stable treatment with sphingosine-1-phosphate receptor (S1PR) modulators and 17 on ocrelizumab were available. The tolerability of the NVX-CoV2373 vaccination was overall good and comparable to the one reported for the general population. After the second NVX-CoV2373 vaccination, 59% of S1PR-modulated patients developed antispike IgG antibodies above the predefined cutoff of 200 binding antibody units (BAU)/ml (mean, 1,204.37 [95% CI, 693.15, 2,092.65] BAU/ml), whereas no clinically significant T-cell response was found. In the subgroup of the patients on ocrelizumab treatment, 23.5% developed antispike IgG > 200 BAU/ml (mean, 116.3 [95% CI, 47.04, 287.51] BAU/ml) and 53% showed positive spike-specific T-cellular responses (IFN-gamma release to antigen 1: mean, 0.2 [95% CI, 0.11, 0.31] IU/ml; antigen 2: mean, 0.24 [95% CI, 0.14, 0.37]) after the second vaccination. Conclusions: Vaccination with two doses of NVX-CoV2373 was able to elicit a SARS-CoV-2-specific immune response in pwMS lacking adequate immune responses to previous mRNA/viral vector vaccination. For patients receiving S1PR modulators, an increase in anti-SARS-CoV-2 IgG antibodies was detected after NVX-CoV2373 vaccination, whereas in ocrelizumab-treated patients, the increase of antiviral T-cell responses was more pronounced. Our data may impact clinical decision-making by influencing the preference for NVX-CoV2373 vaccination in pwMS receiving treatment with S1PR modulation or anti-CD20 treatment.

Huntington’s Disease (HD) ist eine neurodegenerative Erkrankung, die sich durch motorische, kognitive sowie psychiatrische Beeinträchtigungen auszeichnet. Die Verlängerung eines Polyglutamin (polyQ)-Abschnittes im Protein Huntingtin (Htt) über 37 Qs hinaus bedingt die Aggregation des mutierten Proteins (mHtt) und dessen Ablagerung in neuronalen Einschlüssen. Als potenzieller Modulator der polyQ-abhängigen mHtt Aggregation und Toxizität wurde der Q-reiche Transkriptionstransaktivator SS18L1 in silico identifiziert. Rekombinantes Volllängen-SS18L1 sowie die beiden verkürzten Fragmente SS18L1_NM und SS18L1_C weisen in wässriger Lösung einen hohen Anteil an Random-Coil-Strukturen auf und bilden Oligomere. Alle SS18L1-Proteine verzögern dosisabhängig die spontane Aggregation eines Htt Exon 1 Fragmentes mit 49 Glutaminen (Ex1Q49). Dabei wird die Entstehung SDS-stabiler Ex1Q49 Aggregate durch die Stabilisierung von Ex1Q49 Mono- und Oligomeren gebremst. In HEK293 Zellen verringern rekombinante SS18L1-Proteine sowohl die Anzahl der SDS-unlöslichen Ex1Q49-Aggregate als auch die mHtt-vermittelte Zytotoxizität. Auch hierbei scheint eine Stabilisierung früher Aggregatspezies, wahrscheinlich durch die Interaktion der SS18L1-Proteine mit dem jeweiligen mHtt Fragment, eine wesentliche Rolle zu spielen. Entsprechende Interaktionen konnten mittels LUMIER-Studien und konfokaler Mikroskopie nachgewiesen werden. Humanes, exogenes SS18L1 unterdrückt die polyQ-bedingte Aggregation in einem C. elegans-Modell für HD und in transgenen R6/2 HD-Mäusen sind die Mengen an endogenem SS18L1 im Vergleich zu Wildtyp-Mäusen verändert. Beides weist darauf hin, dass SS18L1 auch in vivo von Relevanz sein könnte. Dafür spricht zudem, dass murines SS18L1 in Gehirnen von R6/2-Mäusen mit neuronalen mHtt-Aggregaten co-lokalisiert. Die Ergebnisse dieser Arbeit könnten einen Ausgangspunkt für die Entwicklung neuer Therapieansätze und die weitere Erforschung der HD Pathologie darstellen. / Huntington’s Disease (HD) is a neurodegenerative disease, which is characterised by motor, cognitive and psychiatric disturbances. The abnormal extension of an N-terminal polyQ tract in the protein huntingtin (Htt) results in aggregation of the mutant protein (mHtt) and the deposition of neuronal inclusions. The Q-rich transcriptional transactivator SS18L1 was identified in silico as a potential modulator of polyQ-mediated mHtt aggregation and toxicity. Recombinant full-length SS18L1 and the truncated fragments SS18L1_NM and SS18L1_C have a high random-coil content and form oligomeric structures in aqueous solutions. In addition, all three proteins delay the spontaneous aggregation of an Htt exon 1 fragment with a stretch of 49 glutamines (Ex1Q49). The formation of SDS-resistant Ex1Q49 aggregates is postponed in a concentration-dependent manner as monomers and oligomers, appearing early in the amyloid formation cascade, are stabilised. In mammalian cells recombinant SS18L1 proteins reduce both the number of SDS-stable Ex1Q49 aggregates and mHtt-induced cytotoxicity. These effects are likely due to the stabilisation of early aggregation intermediates, which could result from interactions of the SS18L1 proteins with the respective mutant Htt exon 1 fragment. Such interactions have been demonstrated employing a LUMIER assay and confocal microscopy. Exogenous human SS18L1 suppresses polyQ-mediated aggregation in a C. elegans model of HD and levels of endogenous SS18L1 are altered in transgenic R6/2 HD mice compared to wild type mice. As a consequence, SS18L1 might be of relevance in vivo. This is also supported by the finding that murine SS18L1 interacts with mHtt inclusions in R6/2 mice. The results of this study could provide a basis for the development of a therapeutical strategy or for the further elucidation of HD pathology.

This thesis exploits so called “Optical Eigenmodes” (OEi) in the focal plane of an optical system. The concept of OEi is introduced and the OEi operator approach is outlined, for which quadratic measures of the light field are expressed as real eigenvalues of an Hermitian operator. As an example, the latter is employed to locally minimise the width of a focal spot. The limitations of implementing these spots with state of the art spatial beam shaping technique are explored and a selected spot with a by 40 % decreased core width is used to confocally scan an in focus pair of holes, delivering a two-point resolution enhanced by a factor of 1.3. As a second application, OEi are utilised for fullfield imaging. Therefore they are projected onto an object and for each mode a complex coupling coefficient describing the light-sample interaction is determined. The superposition of the OEi weighted with these coefficients delivers an image of the object. Compared to a point-by-point scan of the sample with the same number of probes, i.e. scanning points, the OEi image features higher spatial resolution and localisation of object features, rendering OEi imaging a compressive imaging modality. With respect to a raster scan a compression by a factor four is achieved. Compared to ghost imaging as another fullfield imaging method, 2-3 orders of magnitude less probes are required to obtain similar images. The application of OEi for imaging in transmission as well as for fluorescence and (surface enhanced) Raman spectroscopy is demonstrated. Finally, the applicability of the OEi concept for the coherent control of nanostructures is shown. For this, OEi are generated with respect to elements on a nanostructure, such as nanoantennas or nanopads. The OEi can be superimposed in order to generate an illumination of choice, for example to address one or multiple nanoelements with a defined intensity. It is shown that, compared to addressing such elements just with a focussed beam, the OEi concept reduces illumination crosstalk in addressing individual nanoelements by up to 70 %. Furthermore, a fullfield aberration correction is inherent to experimentally determined OEi, hence enabling addressing of nanoelements through turbid media.

L'objectif de cette thèse est de fabriquer différents dispositifs optiques basés sur la structuration des cristaux liquides. Nous avons tout d'abord présenté différentes méthodes pour aligner les molécules de cristaux liquides et détaillé celles que nous avons utilisées au cours de ce travail. L'alignement et certaines propriétés physiques des cristaux liquides ont permis de fabriquer des dispositifs optiques. Ces dispositifs se divisent généralement en trois catégories : les filtres optiques, les modulateurs spatiaux et les guides d'ondes optiques. Ils sont présents dans divers secteurs et particulièrement dans le domaine des télécommunications. La structure des cristaux liquides cholestériques a une biréfringence périodique qui donne lieu à une réflexion sélective de la polarisation circulaire de la lumière. Nous avons tiré profit de cette propriété en fabricant un miroir de Bragg commutable. Ce miroir nous a permis de fabriquer un filtre de Fabry-Pérot commutable et accordable. Un réseau de polymère a été utilisé pour stabiliser le cristal liquide cholestérique, afin d'apporter résistance mécanique et durabilité aux champs électriques. Les cristaux liquides ferroélectriques présentent des propriétés électro-optiques efficaces, en particulier un temps de réponse élevé. Cette propriété a été exploitée pour fabriquer des obturateurs optiques pour lunettes 3D actives basées sur des cristaux liquides ferroélectriques. Malgré un temps de réponse élevé, les cristaux liquides ferroélectriques présentent certains défauts structurels. Nous avons proposé une nouvelle technique pour pallier ces défauts. Enfin, nous avons fabriqué des guides d'ondes gravés dans le polymère à cristaux liquides. Nous avons fabriqué ce polymère à cristaux liquides de manière à obtenir deux phases de cristal liquide différentes : isotrope et anisotrope, sur le même substrat. Le substrat a ensuite été gravé afin de créer un séparateur de polarisation séparant le mode TE et TM dans les deux branches du guide.

No description available.