Naturwissenschaften

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    Flowful work design
    (2025) Kloep, Leonie
    Modern work contexts present new kinds of changes and flexibilization, digitalization, and new dynamics confront people with novel challenges. These changes also alter opportunities to experience positive states at work, such as flow and team flow. Flow is defined as the state of being completely absorbed in an activity that is perceived as optimally demanding, and it is associated with positive effects on well-being and performance. Similar assumptions apply to team flow, which is defined as a shared experience of flow within a team during optimal team dynamics. Different work design models propose systematically considering the characteristics of a work task to further develop and redesign it towards specific goals. However, the overarching context is often overlooked. This dissertation aims to examine flow and team flow promoting forms of work design from a context-specific perspective. The goal is to identify factors that promote or hinder flow and team flow at work, and to investigate the effect of external contextual factors in challenging work environments. To this end, three examples of modern work contexts are examined: work in a start-up, industrial manufacturing work, and virtual teamwork. Study I employs qualitative interviews to investigate how flow and team flow are experienced during the early start-up stage, which is often characterized by high levels of autonomy and meaningfulness, yet also by uncertainty and lack of support. Some of the influencing factors and consequences discussed are known from previous research, while others appear specifically relevant to the challenges start-ups face. Overall, the importance of promoting flow and team flow in the context of start-ups becomes apparent, and the results provide some recommendations for work design. Study II focuses on manufacturing work, which can be considered a flow-aversive context due to monotony and boredom. The study examines how gamification, a strategy for designing work to promote flow, affects both flow and performance. The study suggests that gamification could be particularly effective at the beginning of work processes; however, flow can also arise in non-gamified manufacturing work via other mechanisms. Study III examines the context of international virtual teams and investigates team flow experiences, exploring the possibility of identifying them through communication parameters. Depending on the task type, the examined communication parameters are insufficient for identifying team flow. Nevertheless, the study makes an important contribution to the ongoing methodological debates in flow research concerning the development of interruption-free measurement approaches. While each of the studies conducted in this cumulative dissertation addresses different research questions, they all contribute to a better understanding of flow and team flow in the workplace. Furthermore, they enable the development of recommendations for work designs that promote flow and team flow. The central results of the three studies are integrated into a work design model. This model is developed as an extension of an Input-Process-Output model and is based on the Job Characteristics Model. The model systematizes the various factors influencing flow and team flow at work, as well as the consequences of these states, with an emphasis on the influence of the context. The relevance of the key contextual factors examined in the dissertation, such as playful approaches and intercultural perspectives in work design, is also addressed. Furthermore, methodological reflections on the dynamics and the measurement of flow and team flow are presented. Based on the three contexts studied, concrete work design practices and recommendations are formulated. Future research should consider additional work contexts relevant to the evolving challenges faced in today's working world and evaluate the effectiveness of specific interventions. The methodological questions raised regarding the operationalization and measurement of flow and team flow should be examined more closely in light of the results. Overall, this dissertation demonstrates that promoting flow and team flow may be possible in challenging and dynamic modern work contexts. However, this is context-dependent and should be planned in a reflective, evidence-based manner.
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    Advances in femtosecond laser refractive eye surgery
    (2025) Freidank, Sebastian
    The advent of reliable short-pulsed lasers in the 1980s and 1990s made it possible to perform refractive laser surgery that offers correction without glasses. In laser-assisted in situ keratomileusis (LASIK), argon fluoride excimer laser ablation at 193 nm wavelength was employed to ablate central corneal stroma that had been exposed by cutting a flap using a mechanical microkeratome. Later, the mechanical keratome was replaced by a femtosecond (fs) laser that can produce a corneal dissection through applying a grid of near-IR laser pulses at  1030 nm with small energy at high repetition rate. This way, flaps with flat bed and side cut can be produced that enable precise repositioning of the flap after surgery. It enables to perform wave front-guided ablation for correction of higher-order aberrations besides myopia or hyperopia. In the 2010s, small incision lenticule extraction (SmILE) was introduced, in which a lenticule is dissected out of the central stroma using only fs laser pulses and removed through a small side cut. This technique requires only one laser and optical delivery system and involves less dissection of corneal nerves and biomechanical weakening of the cornea than LASIK. The thesis analyses the mechanisms of corneal dissection and explores novel dissection concepts for improving precision, efficacy and gentleness of refractive surgery both in LASIK and SmILE. Dissection relies on a sequence of laser-induced plasma formation, shock wave emission, and cavitation bubble dynamics. Pulse repetition rate, energy and spot separation influence the interaction of events from subsequent laser pulses and, thus, the cutting dynamics. The fundamentals of plasma formation and its dependence on laser pulse duration, wavelength, focusing angle and focus shape are described using generic equations for photo- and avalanche ionization, thermal ionization, and recombination. Laser-induced bubble formation and its interplay with shock wave emission is described using an extended Gilmore model of cavitation bubble dynamics. This analysis and previous experiments show that UVA sub-nanosecond laser pulses with stable temporal shape and a wavelength around 350 nm offer the potential of creating more precise cuts with more compact devices than conventional near-IR fs laser systems. Furthermore, the introduction of a helical phase plate can transform the Gaussian laser beam with elongated focus into a vortex beam with a ring shaped focus of similar length. Such focus shaping promises to improve the dissection efficacy in direction parallel to the corneal surface, which should reduce mechanical side effects and increase precision. The dynamics of corneal dissection by 330 fs, 1030 nm laser pulses was investigated using stroboscopic photography with sub-micrometer spatial resolution, high-speed photography with up to 50 million frames/s and videography at 1 kHz. The cavitation bubble size was determined from stroboscopic photographs through digital image evaluation. The morphology of the cuts was investigated histologically, and the quality of the cuts evaluated through scanning electron microscopy. It turned out that the plasma extends through several corneal lamellae and its rapid expansion leads to irregularly shaped lobular cavitation bubbles. Lobes from neighboring bubbles do not always meet, which leads to tissue bridges hindering flap lifting and lenticule extraction. The cutting process is largely an addition of individual disruption/cleavage effects, which depend mainly on pulse energy and spot separation. However, it has also a dynamic component resembling crack propagation during fracture in solids, which implicates a dependence on pulse repetition rate. The use of a vortex beam was explored for IR and UV wavelengths and found to improve dissection efficiency and quality. Scanning electron microscopy showed that the cuts are smoother than with a Gaussian beam. The force distribution during the plasma expansion from a ring focus facilitates tissue cleavage in the cutting direction parallel to the corneal surface and minimizes tissue bridges. Therefore, the volumetric energy density in the focal volume required for dissection is smaller with a vortex beam than with a Gaussian beam, which reduces plasma pressure and mechanical side effects. The smaller plasma energy density results also in less gas generation through free-electron-mediated molecular disintegration. This is advantageous because long-lived gas bubbles impair pupil tracking during clinical procedures and distort the corneal morphology during dissection of the upper lenticule cut in SmILE. Altogether, dissection using a vortex beam is more precise and gentler than with a Gaussian beam. Experiments with fs pulses at 343 nm wavelength and sub-ns pulses at 355 nm showed that the precision of corneal dissection could be further improved by reducing the laser wavelength. However, although the damage potential of the investigated UVA wavelengths lies four orders of magnitude below the peak value around 260 nm and although no corneal damage has been observed in previous animal experiments, the radiant exposure required for flap cutting lies above the permissible dose. The pulse duration dependence of laser pulse energy required for dissection with easy flap lifting was investigated for IR pulses between 480 fs and 8 ps duration and UV pulses between 1 ps and 400 ps duration. A strong pulse duration dependence is found even for the absorbed laser energy needed for flap cutting, which indicates that the efficiency of the cutting process drops. For durations L > 10 ps, stress and inertial confinement of energy deposition decrease, which reduces the plasma peak pressure and delays or even inhibits the formation of a shock front. For L < 3 ps, the reduced cutting energy is related to an increase of plasma energy density with decreasing pulse duration. These findings confirm the high suitability of pulse durations in the lower fs range down to about 150 fs, which are used in state-of the art clinical laser systems. The improvement of dissection through use of a vortex beam instead of a Gaussian beam is the finding of this thesis with greatest clinical relevance and potential for LASIK and SmILE. It has already been demonstrated that a helical phase plate can be easily implemented into the beam delivery system of existing clinical devices and is compatible with focus scanning. The next step is the conduction of a clinical study.
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    Unravel principles of pemphigus vulgaris pathogenesis
    (2025) Hartmann, Veronika
    Pemphigus vulgaris (PV) is an autoimmune disease affecting the mucosa and the skin. The autoantibodies which are produced in this disease, target desmoglein (Dsg) 3 and Dsg1. These two are adhesion molecules providing intercellular connection between epidermal, hair follicle and mucosal keratinocytes. Once the autoantibodies have bound to these structures, the keratinocytes separate from each other, leading to the formation of blisters in the skin and erosions in the mucosa. The exact molecular mechanism of the pathogenesis is not fully understood yet. This project has the aim to investigate and identify the clinically relevant communication code in the affected tissues. The human skin organ culture (HSOC) model for PV was used to uncover the early events in basal keratinocytes which were incubated with either the single chain variable fragment PX43 (directed against Dsg3/1) or the murine antibody AK23 (directed against Dsg3). The skin samples were prepared 5, 10, and 24 hours after injection for the quantification of split formation, proliferation, and the basal keratinocytes were isolated for bulk RNA-sequencing. Similarly, further analysis of the proteome was conducted 24 hours after injection and a qualitative staining for the binding of PX43 to Dsg3/1 was done. As another quality control, the distribution of Dsg3/1 in the human skin was visualized by immunofluorescence. As controls, human and murine immunoglobulin G were used, respectively. As it is evident from hematoxylin and eosin-stained sections, PX43 induced a split in the skin which was increasing with prolonged incubation time. However, AK23 was not able to induce split formation. Further analysis of the proliferation after incubation with PX43 and AK23 shows that the binding of them does not lead to a significant increase in proliferation at the site of basal and suprabasal keratinocytes. The analysis of the transcriptome used a multi-variate linear model including nuisance factors and reveals prominent upregulation of IFNγ and TNF𝜶 pathways in the basal keratinocytes. This coincides with the upregulation of NFkB and JAK-STAT-mediated circuits and increased keratinocyte detachment. In contrast, basal keratinocytes from AK23-injected HSOC models do not show significant differentially regulated genes. These two observations lead to the conclusion that the inflammatory response induced in the basal keratinocytes, does not originate from the binding of PX43 to Dsg3/1 but is a secondary response to the increasing cell detachment. Analysis of the proteome of basal keratinocytes after 24 hours confirmed the described transcriptomic results showing differentially regulated proteins and pathways of inflammation. All-together, the cell-wide and long-lasting changes on the transcriptomic and proteomic level originate from the loss of cell-cell adhesion and mechanical stress but are not caused by the binding of PX43 or AK23 to their targets.
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    Biophysical characterization and analysis of different mycobacterial WXG100 proteins to study possible inter-loci complex formation
    (2025) Kallenberg, Christina Jana Luise
    Tuberculosis has remained a global public health concern for the past 30 years. The causative agent Mycobacterium tuberculosis has developed several strategies to evade the host immune system and for intracellular survival. Extensive genomic and proteomic studies have revealed hundreds of genes involved in the bacterium’s resistance and survival. The first known secreted virulence factors, EsxA and EsxB, are the paragons of a group of heterologous proteins, termed the “WXG100 family”. M. tuberculosis has 23 WXG100 proteins (EsxA-EsxW), five of such protein pairs are found within a genomic cluster making up a type-VII-secretion system (ESX-1 to ESX-5). Mycobacterial WXG100 proteins appear to share a similar secondary structure and form complexes with neighboring co-expressed proteins. The question arises as to whether Esx proteins from different genomic loci, i.e. not within the same operon, can form complexes. If this were the case, even only for some, the recombination of individual complex partners could greatly increase the versatility of the bacterium in reacting to the numerous host defense mechanisms. In this work, ten different mycobacterial Esx proteins were recombinantly expressed and purified in order to evaluate the possibility of inter-loci complex formation and their structural properties. The results suggest that inter-loci complex formation between several Esx proteins is possible. Special focus was put on the complex formation between EsxB and EsxT, which was evaluated with chemical crosslinking studies and single-molecule FRET experiments. Kinetic evaluations suggest a rather low binding constant between EsxB and EsxT (mM range), compared to the high binding constant between the native partners EsxB and EsxA (nM range). The proteins EsxF and EsxE were found to be highly heat resistant, both in complex and monomeric form, with a high structural recovery of over 90 % after heating to 96 °C. In addition, evidence of homo-dimer or homo-oligomer formation was found for EsxF and EsxU, which has not been reported previously.
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    Robotische, endoskopische und dynamische Megahertz-Optische Kohärenztomographie und deren Anwendungen in Klinik und Forschung
    (2025) Göb, Madita
    Die Optische Kohärenztomographie (OCT, engl. optical coherence tomography) hat sich als leistungsstarke Technik zur dreidimensionalen Visualisierung von Gewebestrukturen etabliert. Forschungsergebnisse zeigen das enorme Potenzial dieser Technologie zwischen gesundem und pathologischem Gewebe zu unterscheiden. Im Gegensatz zur Biopsie ist OCT nicht-invasiv und liefert sofortige diagnostische Ergebnisse. Dennoch stoßen handelsübliche OCT-Systeme aufgrund langsamer Scangeschwindigkeiten und kleiner Bildfelder im klinischen Alltag an ihre Grenzen. Die MHz-OCT, eine Weiterentwicklung mit Linienraten im Megahertz-Bereich, überwindet diese Einschränkungen und ermöglicht ultraschnelle 3D-Bildgebung in Echtzeit. Um die hohe Geschwindigkeit der MHz-OCT gezielt nutzbar zu machen, wurden im Rahmen dieser Arbeit drei neuartige Systeme entwickelt und ihre Anwendungen in spezifischen medizinischen und wissenschaftlichen Bereichen erforscht: 1. Robotische MHz-OCT: Eine robotergestützte Plattform wurde für die automatisierte Bildgebung großer Bereiche entwickelt. Mit zwei verschiedenen Robotersystemen wird eine präzise Abtastung ganzer Hautareale in vivo demonstriert sowie die Eignung als automatisiertes Hochdurchsatz-Messgerät für innovative ex vivo Forschungsansätze in der Dermatologie. 2. Endoskopische MHz-OCT: Ein 4D-Echtzeit-OCT-Endoskop wurde konzipiert, das die Lumen-Topografie abbildet und mikroskopische Einblicke in die Gewebemorphologie liefert. Kolorektale Bildgebungsexperimente an Körperspendern zeigen die mögliche Anwendung zur Früherkennung gastrointestinaler Läsionen und der Beurteilung tiefer Gewebeschichten. 3. Dynamische MHz-OCT: Zur Analyse physiologischer und metabolischer Prozesse wurde die MHz-OCT um ein Verfahren zur dynamischen Bildgebung erweitert. Diese Technologie bietet durch zusätzlichen funktionellen Kontrast detaillierte Einblicke in zelluläre Strukturen, ähnlich der Histologie, und deren Funktion. Die Methodik wird an ex vivo Gewebe demonstriert. Diese Ansätze zeigen das Potenzial der MHz-OCT, diagnostische Verfahren nicht nur zu ergänzen, sondern auch neue Anwendungsfelder in der medizinischen Bildgebung zu erschließen. Die vorliegende Arbeit beschreibt die Entwicklung, Validierung und Anwendung dieser Methoden sowie deren Beitrag zur Integration der MHz-OCT in die klinische Praxis.
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    One miR to rule them all
    (2025) Naujack, Alison-Michelle
    Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 30% of the global population. With rising numbers it presents a risk for global health and health care systems. The development of MASLD and the more severe stage, metabolic dysfunction-associated steatohepatitis (MASH), is driven not only by comorbidities like obesity and type 2 diabetes, but also by hypothyroidism. Independent of the systemic thyroid hormone levels, dysregulation of hepatic thyroid hormone signaling plays an important role in MASLD pathogenesis, with the only approved medication for MASH treatment, resmetirom, being a thyroid hormone receptor beta (THRB) agonist. While the effect of thyroid hormone signaling dysregulation on the hepatic metabolism has been investigated thoroughly there is little information on whether epigenetic regulations contribute to this dysregulation in MASLD. Therefore, the aim of this thesis was the investigation of epigenetic regulations on hepatic thyroid hormone signaling in MASLD. Since the expression of THRB negatively correlates with the disease progression marker MASLD activity score (MAS) and since miRNAs have inhibiting effects on their target genes, miRNAs that potentially bind to THRB were identified. The expression of miRNAs and mRNAs potentially involved in the regulation of thyroid hormone action in the liver was measured in human and mouse liver tissue using qPCR. Verification of increased expression of potential THRB targeting miRNAs was performed in a cohort of obese individuals (BMI > 30 kg/m 2) which was divided into a non-MASH group (n = 41, MAS ≤ 3) and MASH group (n = 27, MAS ≥ 4), as well as in multiple mouse models mimicking different stages of MASLD. Binding of miRNA to target mRNAs was verified using luciferase reporter assays, as well as RNA-interacting protein immunoprecipitation-sequencing. Furthermore, cell culture models were metabolically stimulated to induce a MASLD-like state in the cells and investigate the effect on the expression of thyroid hormone metabolism genes. Additionally, DNA methylation was measured at THRB and miRNA genes, to further investigate involvement of additional epigenetic regulators. Unfortunately, no suitable THRB antibody was available to verify the results of mRNA measurements on the protein level. To address this, plasmids were designed to identify tags, that when added to THRB do not interfere with thyroid hormone signaling. miR-34a-5p was identified to be increased in MASLD and was predicted to bind not only THRB but also the thyroid hormone receptor alpha, the thyroid hormone activating enzyme DIO1 as well as the thyroid hormone transporters SLC10A1 and SCL16A2. The binding to THRB and DIO1 was verified and induced overexpression of miR-34a-5p reduced the levels of THRB regulated genes after stimulation with thyroid hormones. Cell culture experiments further showed induction of miR-34a-5p by stimulation with fatty acids. Interestingly, the results of the overexpression of miR-34a-5p on potential target genes could also be induced by stimulation with fructose and insulin without miR-34a- 5p involvement. Repression of thyroid hormone signaling through miR-34a-5p, reducing the expression of THRB as well as DIO1 which reduces the amount of available active thyroid hormone further, is exacerbated by increased DNA methylation in the THRB gene, which negatively correlates with THRB expression. Finally, treatment of high-fat diet fed mice with metformin reduced the expression level of miR-34a-5p. This reduced dysregulation of the miRNA could potentially recover THRB expression and signaling and might also be of use to patients unresponsive to resmetirom due to low THRB levels.
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    The role of sleep on enhancing the efficacy of psychotherapy
    (2025-10-13) Ehsanifard, Mojgan
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    The reactive pyruvate metabolite dimethylglyoxal in experimental disease models and the role of Ilvbl in its generation in the brain
    (2025) Costalunga, Riccardo
    Reactive glucose metabolites are involved in neurological complications of diabetes by the generation of advanced glycated end products (AGEs), which are formed by the interaction between α-dicarbonyls and proteins. AGEs induce oxidative stress, inflammation and tissue damage and have been associated with neuropathy, nephropathy and retinopathy. So far, only the α-dicarbonyls 3-deoxyglucosone, glyoxal and methylglyoxal have been recognized as reactive glucose metabolites and associated with complications in diabetes. Only recently, the α-dicarbonyl dimethylglyoxal (DMG) has been categorized as mammal cellular pyruvate metabolite, and its levels were higher in the plasma of type-1 diabetic mice and in the serum of patients with diabetes. In this thesis, I investigated the α-dicarbonyl DMG in mouse models under pathological conditions and its metabolic pathway in mammals using liquid chromatography coupled to tandem mass spectrometry (LC-MS2). Here, plasma DMG concentrations were upregulated in mouse experimental models of type-1 and type-2 diabetes. In contrast, high-fat diet did not influence the serum levels of DMG, suggesting that diabetic conditions – but not obesity itself – are associated with plasma DMG upregulation and accumulation. Moreover, DMG levels were enormously augmented in the ipsilateral side of a mouse model of hyperglycemic stroke compared to sham control. Interestingly, DMG levels were also higher in the contralateral hemisphere of the brain of mice with stroke compared to sham controls, showing that the contralateral hemisphere is also affected by ischemic stroke. Furthermore, the current study confirmed that DMG is a post-glycolytic product in mammals and its levels are increased under hypoxic conditions in vitro. Then, I investigated the role of the gene ilvB acetolactate synthase-like (Ilvbl), the mammal orthologue gene of acetolactate synthase that generates DMG from pyruvate in bacteria, yeast and plants. Importantly, Ilvbl knockout reduced DMG levels in the brain of mice with type-1 diabetes or hyperglycemic stroke, showing that Ilvbl has conserved its role in DMG generation in mammals. Moreover, DMG interacted with lysine, generating the glycated amino acid Nε-3-hydroxy-2-butanonelysine (HBL), confirming that DMG is a reactive compound and can glycate proteins generating AGEs. Thus, DMG induced oxidative stress and neuroinflammation in mouse hippocampal neuronal (HT-22) cells, probably based on protein glycation. In conclusion, this study characterizes the α-dicarbonyl DMG in experimental models under pathological conditions, showing that DMG could play a significant role in diabetic complications and ischemic stroke complications. DMG is the only α-dicarbonyl generated after glycolysis, and the current discovery could explain why cells consuming lactate – such as neurons – are not protected by dicarbonyl stress. Importantly, this study shows that ILVBL plays a significant role in the DMG generation from pyruvate in the brain of acute or chronic hyperglycemic mice. Further investigation on DMG and the attenuation of its concentrations may lead to improvement in diabetic and ischemic stroke complications.
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    High-content screen for cardiovascular modulators in zebrafish (Danio rerio)
    (2024) Vedder, Viviana Luisa
    Over the past two decades, cardiovascular diseases (CVDs) have remained the leading cause of death worldwide. Among these diseases, congenital heart disease is the most common type of human birth defect, affecting 1 in 100 live-born infants. It is crucial to identify new therapeutic targets and treatments for CVDs. Zebrafish are a suitable model for this task, as they can provide new insights into CVDs. Further, their small size and translucency make them an ideal model for high-content drug screenings. In this study, a phenotype-based high-content screening approach in zebrafish was established to identify cardiovascular modulators. Utilizing the ‘Acquifer Imaging Machine‘, 1,280 compounds of the Prestwick Chemical Library were screened for angiogenesis and heartbeat phenotypes. The previously established type III receptor tyrosine kinase inhibitor sunitinib malate, which inhibits angiogenesis in zebrafish, was used as a positive control. Additionally, the competitive 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) inhibitor atorvastatin, which was previously shown to cause severe heart phenotypes in zebrafish, served as a positive control for heart rate (HR) and heart morphology. HR was selected as a screening phenotype under the assumption that morphological and functional changes in the heart during development would result in altered HR. In search of angiogenesis modulators, blood vessel diameters of treated fish were measured for 320 of the 1,280 tested compounds. Application of different filters for known toxicities, previously published results and unknown targets, led to the identification of 11 promising hit compounds. Three of these compounds, namely desonide, oxibendazole, and azlocillin sodium salt, directly targeted angiogenesis by significantly reducing the diameter of intersegmental vessels. The remaining nine compounds affected the diameter of the dorsal aorta and/or dorsal vein. Of the 134 compounds significantly altering HR, 21 compounds repeatedly induced significant HR alterations in two different transgenic zebrafish lines. In this study, two main target clusters were identified for HR modulators: the histaminergic receptor H1 (HRH1) and the glucocorticoid receptor (NR3C1). While HRH1 is commonly associated with allergic reactions, it has also been linked to CVDs. All antagonistic hit compounds targeting HRH1 caused significant bradycardia with moderate to severe dose-dependent teratogenicity. In situ hybridization for various hrh probes revealed that hrh1 was the only detectable hrh in the heart at 3 days post fertilization (dpf), indicating its involvement in heart development. Additionally, the heart analysis tool pyHeart4Fish showed chamber-specific effects of HRH1 antagonists. Collectively, the data suggests that hrh1 plays a role in heart contractility and heart size. However, further investigation on the mechanism of action is necessary to comprehend how Hrh1 is involved in cardiogenesis and what long-term effects HRH1 antagonists can have on the developing embryo to determine drug safety for pregnant women. NR3C1 is a ligand-activated transcription factor known to be involved in inflammation, metabolism, and stress response. In this study involving zebrafish larvae, a group of six NR3C1 agonists was found to significantly increase HR at 48 hours post fertilization. While previous research had identified nr3c1's involvement in heart development in zebrafish, its role in arrhythmias remained unclear. Here, expression of nr3c1 was detected in the larval heart at 5 dpf using in situ hybridization. Further analysis using pyHeart4Fish revealed that NR3C1 agonists induced chamber-specific phenotypes, including atrioventricular block. A homology model of zebrafish Nr3c1 was also developed, which suggested that the agonists known to bind in humans may also bind in zebrafish. These findings support the use of zebrafish as a screening model for cardiovascular phenotypes and highlight the potential role of nr3c1 in CVDs.
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    Single cell sequencing in development and disease
    (2025-05-20) Balachandran, Saranya
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    850 nm Fourier domain mode-locked laser for ophthalmic optical coherence tomography imaging
    (2025) Klufts, Marie
    Non-invasive imaging techniques have become essential in medical diagnostics over the past few decades. Among these, Optical Coherence Tomography (OCT) offers micrometer resolution with millimeter-scale depth penetration, making it particularly valuable in ophthalmology. OCT captures backscattered light to generate 3D volumes. For eye imaging, wavelengths around 850 nm are ideal due to minimal absorption by the vitreous and high scattering in the upper retinal layers. Imaging speed is also critical, as faster speeds reduce motion artifacts. Swept-source OCT, using wavelength-tunable lasers, enables high-speed imaging. Fourier Domain Mode-Locked (FDML) lasers providing megahertz-level scan rates are ideal for this purpose. This thesis explores the development and application of FDML lasers for ophthalmic imaging. Unlike other tunable lasers, FDML lasers have a unique design that stores a full sweep in their fiber cavity for hundreds of round trips, avoiding rebuilding of lasing from spontaneous emission after tuning to new wavelengths offering high phase stability and long coherence length necessary for high quality OCT images. A new megahertz FDML laser at 850 nm would merge the unique advantages of this wavelength with the proven benefits of FDML lasers allowing for a low latency, dynamic view of the retina, opening new doors for real-time diagnostics. The first part delves into the challenges of developing an FDML laser around 850 nm, addressing issues like polarization mode dispersion, chromatic dispersion, and low gain/loss ratios. These factors contribute to the complexity of managing short wavelength OCT lasers, which explain their scarcity to date. The second part presents in-vivo ophthalmic OCT imaging results, with comparisons to other imaging techniques. The newly designed FDML laser demonstrates strong performance for OCT imaging, achieving an axial resolution below 10 µm, sensitivity above 84 dB, and a ranging depth of 1.4 cm. Also, its high phase stability, with a time jitter of 25 ps over 1,000 sweeps, makes it suitable for phaseresolved techniques. Retinal images were captured at 414,000 axial scans per second using a master-slave based calibration technique, at 828 kHz with bidirectional sweeping, and at 1.7 MHz using optical buffering with a single-k-calibration technique. While increased scattering at 850 nm limits choroidal imaging, most retinal layers of interest are clearly visible. This FDML laser highlights the advantages of short-wavelength, high-speed imaging and paves the way for new applications.

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