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    A Closer Look into Mitochondrial Functional and Morphological Causes of Rett Syndrome

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    Rett syndrome is a neurodevelopmental disorder and one of the primary causes of cognitive impairment in females. Affected individuals typically exhibit normal development until 6-18 months of age, followed by stagnation and regression of acquired skills, such as speech and purposeful hand movements. In addition to cognitive impairments, patients with Rett syndrome may develop microencephaly, seizures, autism spectrum disorder-like features, and metabolic changes, all of which contribute to the complex pathology of the disorder. Recent evidence suggests that mitochondrial alterations play a crucial role in the pathophysiology of Rett syndrome, although the specific mechanisms by which mitochondria contribute to these symptoms remain unclear. The main hypothesis of this thesis is that mitochondrial alterations are a contributing feature in Rett syndrome. To explore this, we investigated mitochondrial abnormalities in the brains of MeCP2-deficient mice, focusing on mitochondrial functionality and morphology. P50 symptomatic male and pre-symptomatic female MeCP2-deficient mice were studied to examine mitochondrial alterations, and a therapeutic approach was applied aimed to increase the expression of mitochondrial catalase, a key scavenger of H2O2, to potentially counteract oxidative stress linked to mitochondrial alterations. Various technical approaches were employed, including biochemical assays to assess mitochondrial function, multiparametric correlative ratiometric 2-photon redox imaging for evaluating cellular redox status, and high-resolution fluorespirometry to measure mitochondrial respiratory efficiency. Additionally, mitochondrial morphology was assessed using electron microscopy to evaluate structural abnormalities in mitochondrial shape, size, and distribution. The findings reveal significant differences in mitochondrial density and functionality between the sexes, and across brain regions, with the cortex exhibiting the highest mitochondrial density and activity. This thesis also presents further evidence of mitochondrial alterations in MeCP2-deficient mice, including decreased citrate synthase activity, reduced oxygen consumption rates, and increased oxidative stress, supporting its contribution to the observed phenotypic features of Rett syndrome. Notably, increased mitochondrial catalase expression improved redox balance and partially restored mitochondrial functionality, highlighting its therapeutic potential in Rett syndrome. Future directions include additional investigations of mitochondrial alterations at different disease stages to better understand the sequence of changes in mitochondrial functionality, oxidative stress, and morphology, and to determine how these alterations influence one another over time. Moreover, the observed regional and sex-specific differences underscore the importance of tailored approaches, while supporting the potential of antioxidant strategies, such as increased mitochondrial catalase, in reducing the harmful effects of mitochondrial dysfunction in Rett syndrome.2025-08-2

    Sequence of Pathological Changes in Subtype III Multiple Sclerosis Lesions

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    Die Auslöser der Multiplen Sklerose (MS) sind bis heute nicht vollständig geklärt; die Pathogenese scheint heterogen und abhängig vom jeweiligen Subtyp zu sein. Ziel der vorliegenden Dissertation war es, die zeitliche Abfolge zwischen Entzündungsreaktionen und Oligodendrozytenveränderungen in Subtyp-III-Läsionen der MS detailliert zu untersuchen. Dabei sollte insbesondere geklärt werden, ob Oligodendrozytenschädigungen unabhängig von Entzündungsinfiltraten auftreten oder ob sie durch diese verursacht werden, sowie ob Veränderungen der Oligodendrozyten bereits in normal erscheinender weißer Substanz (NAWM) vor Beginn der Demyelinisierung nachweisbar sind. Hierzu wurden immunhistochemische Färbungen von 15 gut charakterisierten Subtyp-III-Fällen analysiert. Quantifiziert wurden Entzündungszellen (T-Zellen, B-Zellen, Plasmazellen, Makrophagen und Mikroglia), Oligodendrozyten (reife und Vorläuferzellen), apoptotische Oligodendrozyten sowie akute axonale Schäden in verschiedenen Stadien (periplaquäre weiße Substanz [PPWM], frühaktive entmarkende Läsionen [FA] und inaktive Läsionen [IA]). Es zeigte sich, dass sowohl Apoptosen der Oligodendrozyten als auch Entzündungsinfiltrate bereits in der PPWM auftraten, also in Arealen ohne Demyelinisierung. Im weiteren Verlauf nahmen insbesondere T-Zellen und Makrophagen deutlich zu. Axonale Schäden korrelierten überwiegend mit der Präsenz von Makrophagen. Zudem ließ sich ein klarer Zusammenhang zwischen Oligodendrozytenapoptosen und Entzündungszellen (CD3⁺-, CD8⁺-T-Zellen sowie KiM1P⁺- und MRP14⁺-Makrophagen) nachweisen. Auch die Anzahl reifer Oligodendrozyten war abhängig vom Ausmaß der Entzündung in der PPWM. Diese Ergebnisse sprechen dafür, dass im Subtyp III der MS kein primär degenerativer Mechanismus zugrunde liegt, sondern dass der Oligodendrozytenuntergang durch initiale Entzündungsprozesse ausgelöst wird. Damit wird die „Outside-in“-Hypothese gestützt, welche die Autoimmunität als ursächlichen Mechanismus der MS-Entstehung annimmt.The ultimate triggers of multiple sclerosis (MS) remain unknown, and its pathogenesis appears to be heterogeneous and dependent on the lesion subtype. In this dissertation, the temporal sequence between inflammatory responses and oligodendrocyte alterations was investigated in detail in subtype III MS lesions. The aim was to determine whether oligodendrocyte damage occurs independently of inflammatory infiltrates or is inflammation-driven, and whether oligodendrocyte alterations are already detectable in the normal-appearing white matter (NAWM) before demyelination begins. Immunohistochemical analyses were performed on 15 well-characterized subtype III cases. Quantification included inflammatory cells (T cells, B cells, plasma cells, macrophages, and microglia), oligodendrocytes (mature oligodendrocytes and precursor cells), acutely damaged axons, and apoptotic oligodendrocytes across different stages (periplaque white matter [PPWM], early active demyelinating lesions [FA], and inactive lesions [IA]). Results demonstrated that oligodendrocyte apoptosis and inflammatory infiltrates were already present in PPWM, i.e., in areas without demyelination, with subsequent lesion stages showing increased inflammation, particularly by T cells and macrophages. Axonal damage was largely correlated with macrophage presence. Importantly, oligodendrocyte apoptosis in PPWM was associated with inflammation, involving CD3⁺ and CD8⁺ T cells as well as KiM1P⁺ and MRP14⁺ macrophages. The number of mature oligodendrocytes was likewise dependent on the degree of inflammation in PPWM. These findings indicate that in subtype III MS, oligodendrocyte loss is not the result of a primary degenerative process but is driven by initial inflammation. This supports the “outside-in” theory, which posits autoimmunity as the initiating factor in MS pathogenesis.2025-11-0

    Zusammenhänge zwischen psychischem Befinden, Krankheitsschwere, körperlicher Aktivität, Ruheherzfrequenz und Schlafdauer bei Koronarpatient*innen

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    Die Koronare Herzkrankheit (KHK) stellt in Deutschland einen bedeutenden Faktor für Todesfälle dar und verursacht hohe Gesundheitskosten. Neben den kardiologischen Aspekten ist auch die Berücksichtigung des psychischen Befindens und die Anpassung des Lebensstils in der Therapie von Bedeutung. Ein Ansatz, der dies berücksichtigt und die begrenzten Ressourcen der Allgemeinmediziner*innen entlasten könnte, ist der der „Blended Collaborative Care“ oder auch „Team basierten Behandlung“. Die Wirksamkeit dieser aus den USA stammenden Methode soll in Deutschland in der TEACH-Studie bei psychisch belasteten Patient*innen mit einer chronischen KHK geprüft werden. Neben der Lebensqualität werden Veränderungen im herzgesunden Lebensstil erfasst, insbesondere durch Fitnesstracker, die eine Woche lang Daten zur Aktivität, Herzfrequenz und Schlafdauer aufzeichnen. Um diese Werte für die Auswertung der Studie nutzen zu können, müssen die Messungen validiert werden. Dies ist Gegenstand dieser Arbeit und wurde mittels bivariaten Korrelationen zwischen den Fitnesstracker-Werten und Ergebnissen des International Physical Activity Questionnaire (IPAQ), beziehungswerte der in der Baseline gemessenen Ruheherzfrequenz, sowie durch Kreuzvalidation der Fitnesstracker-Werte durchgeführt. Außerdem wurden die Fitnesstracker-Werte auf Zusammenhänge mit der Krankheitsschwere der KHK und dem psychischen Befinden untersucht. Dies geschah bei den linear vermuteten Zusammenhängen der Aktivitäts-Variablen und der Ruheherzfrequenz nach einer bivariaten Vorauswahl mittels multivariater linearer Regressionsanalyse. Die U-förmig erwarteten Zusammenhänge der Schlafdauer mit dem psychischen Befinden und der Krankheitsschwere wurden durch Gruppenvergleiche mittels einfaktorieller Varianzanalyse untersucht. Die Analyse zeigte, dass die Fitnesstracker zuverlässig die Herzfrequenz und Schrittzahl messen, jedoch nicht die Schlafdauer. Es bestand eine erwartete inverse Korrelation zwischen der Krankheitsschwere und der körperlichen Aktivität. Das psychische Befinden korrelierte weniger stark, zeigte aber den erwarteten positiven Zusammenhang mit der körperlichen Aktivität. Einige Ergebnisse wiesen darauf hin, dass Bewegung im Freizeitbereich einen stärkeren Zusammenhang mit dem psychischen Befinden haben könnte als die gesamte Bewegung. Die Ruheherzfrequenz korrelierte mit der Krankheitsschwere weniger stark als erwartet. Dies war vermutlich einer Reihe von Confoundern, wie der Betablocker-Therapie, geschuldet. Mit dem psychischen Befinden zeigte die Ruheherzfrequenz keinen Zusammenhang. Ein Rückschluss von der Ruheherzfrequenz auf psychisches Befinden oder Krankheitsschwere ist daher diesen Ergebnissen zufolge, nicht möglich. Das Zusammenspiel von Ruheherzfrequenz und psychischem Befinden kann vermutlich besser bei der Betrachtung des Herzfrequenzverlaufs über den Tag, zusammen mit einem Tagebuch, beurteilt werden. Zwischen den Schlafdauer-Gruppen zeigten sich keine signifikanten Unterschiede bezüglich der Krankheitsschwere oder des psychischen Befindens. Die gemessene Schlafdauer war allerdings nicht zuverlässig validierbar, da ein Vergleichsmessung durch ein anderes Instrument fehlte. Interpretationen der Ergebnisse sind somit nicht fundiert möglich. Für die Auswertung der TEACH-Studie werden auf Basis dieser Ergebnisse die Betrachtung der Schrittzahl und der Ruheherzfrequenz empfohlen. Im medizinischen Alltag könnten Fitnesstracker insbesondere durch den Einsatz von Schrittzahl und Herzfrequenz eine Bereicherung darstellen. Weitere Studien könnten zusätzliche Erkenntnisse zum Herzfrequenzverlauf und zur Schlafdauer liefern und die Messmethodik möglicherweise verbessern.Coronary heart disease (CHD) is a significant cause of death in Germany and incurs high healthcare costs. In addition to the cardiological aspects, it is also important to consider mental well-being and lifestyle adjustments in therapy. One approach that takes this into account and could relieve the limited resources of general practitioners is ‘blended collaborative care’ or ‘team-based treatment’. The effectiveness of this method, which originated in the USA, is to be tested in Germany in the TEACH study on mentally distressed patients with chronic CHD. In addition to quality of life, changes in heart-healthy lifestyle are recorded, in particular by fitness trackers that record data on activity, heart rate and sleep duration over a week. In order to use these values for the evaluation of the study, the measurements must be validated. This is the subject of this thesis and was carried out using bivariate correlations between the fitness tracker values and the results of the International Physical Activity Questionnaire (IPAQ), values related to the resting heart rate measured at baseline, and cross-validation of the fitness tracker values. In addition, the fitness tracker values were examined for correlations with the severity of CHD and mental well-being. This was done for the linearly assumed correlations between the activity variables and resting heart rate after a bivariate preselection using multivariate linear regression analysis. The expected U-shaped correlations between sleep duration and mental well-being and disease severity were examined by group comparisons using one-factor analysis of variance. The analysis showed that the fitness trackers reliably measured heart rate and step count but not sleep duration. There was an expected inverse correlation between disease severity and physical activity. Mental well-being correlated less strongly but showed the expected positive correlation with physical activity. Some results indicated that leisure-time physical activity may have a stronger correlation with mental well-being than total physical activity. Resting heart rate correlated less strongly with disease severity than expected. This was probably due to several confounders, such as beta-blocker therapy. Resting heart rate showed no correlation with mental well-being. According to these results, it is therefore not possible to draw conclusions about mental well-being or disease severity from resting heart rate. The interaction between resting heart rate and mental well-being can probably be better assessed by observing the heart rate curve throughout the day, together with a diary. There were no significant differences between the sleep duration groups in terms of disease severity or mental well-being. However, the measured sleep duration could not be reliably validated, as there was no comparative measurement using another instrument. It is therefore not possible to make any well-founded interpretations of the results. Based on these results, the analysis of step count and resting heart rate is recommended for the evaluation of the TEACH study. In everyday medical practice, fitness trackers could be an asset, particularly using step count and heart rate. Further studies could provide additional insights into heart rate patterns and sleep duration and potentially improve the measurement methodology.2025-11-1

    Analysis of the murine cardiac proteome and phosphoproteome using Tandem-Mass-Tag Mass Spectrometry (TMT-MS)

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    The heterozygous deletion of arginine 14 in phospholamban (PLN Arg14del) is a cause of arrhythmogenic cardiomyopathy. Patients present with a high rate of ventricular tachycardias and life-threatening malignant ventricular arrhythmias, with excess mortality starting from as early as 25 years old. In the present study, a mass spectrometry based workflow was established to detect early changes in the cardiac proteome and phosphoproteome of PLN Arg14del mice. Wild type and diseased mice were sacrificed at 12 weeks of age, at which time the PLN Arg14del mice are known to show a distinct phenotype with electrophysiological changes but no significant cardiac remodeling yet. The resulting data set provides the most in-depth proteome and phosphoproteome dataset of PLN Arg14del cardiomyocytes reported to date. PLN Arg14del mutant mice show reduced phosphorylation of phospholamban at serine 16 as well as threonine 17, supporting the idea of reduced affinity of the mutant isoform to PKA and CaMKII. Furthermore, phosphorylation of the muscle specific ankyrin isoform sAnk1 at serine 55 is decreased in PLN Arg14del mice, but the biological effect of this remains unclear. PLN Arg14del mutant mice also show reduced expression of the E3 ubiquitin-protein ligase Itch and the Sodium-Calcium exchanger NCX1. Itch regulates important signaling proteins from the Wnt/β-Catenin pathway as well as mTOR and NF-κB pathway and its involvement in the development of heart failure has already been described. The PLN Arg14del heterozygous cardiomyocytes also showed a reduction in mitochondrial, myofibrillary and dystrophin complex proteins compared to wild type cardiomyocytes, hinting at a reduced cardiac output at an early disease stage.2026-01-0

    Large-Scale Land Acquisitions in Developing Countries: Impacts on Welfare, Mental Health, and Social Conflict

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    Diese Dissertation untersucht umfassend die Wohlfahrtsfolgen großflächiger Landkäufe (eng. LSLAs). Mithilfe quantitativer und qualitativer Methoden, darunter modernste quasi-experimentelle und experimentelle Designs, werden die sozioökonomischen, psychischen und konfliktbezogenen Auswirkungen großflächiger Ölpalmplantagen und anderer landbasierter Investitionen isoliert und quantifiziert. Der erste Teil der Arbeit analysiert, wie LSLAs lokale Lebensgrundlagen beeinflussen. Anhand von Daten aus Liberia zeigt sich, dass Beschäftigung auf Ölpalmplantagen zwar zu moderaten Lohnsteigerungen führt, jedoch Ausgaben, Vermögen und Ernährungssicherheit nicht signifikant verbessert und Ungleichheit leicht erhöht wird. Ohne inklusivere Inves- titionsmodelle sind LSLAs daher kaum geeignet, eine breite ländliche Entwicklung zu fördern. In Indonesien, speziell Westkalimantan, ergibt die quasi-experimentelle Analyse neuerer Plantagen ähnliche Ergebnisse: Der Übergang von traditioneller Landwirtschaft zu Lohnarbeit und kleinbäuerlichem Ölpalmanbau zeigt keine oder negative wirtschaftliche Effekte für ländliche Haushalte. Das steht im Kontrast zu indonesischen Regionen, die in früheren Phasen der Ölpalmexpansion beteiligt waren. In Gegenüberstellung mit den hohen Umweltkosten durch Entwaldung stellen die nicht vorhandenen bis negativen ökonomischen Auswirkungen die Darstellung von LSLAs als Motoren ländlichen Wachstums infrage. Über materielle Aspekte hinaus beleuchtet die Arbeit auch Auswirkungen der Palmölexpansion auf die psychische Gesundheit. Ein Lab-in-the-Field-Experiment in Westkalimantan zeigt, dass LSLAs und Abholzung die psychische Gesundheit indigener Gemeinschaften deutlich verschlechtern. Entscheidend ist dabei die spirituell-kulturelle Entwurzelung, während Diskriminierung oder wirtschaftliche Nachteile den Effekt nicht erklären können. Dies unterstreicht die tiefgreifenden immateriellen Folgen von Landnutzungsveränderungen. Der zweite Teil widmet sich den sozialen Folgen von LSLAs, insbesondere Konflikten. Aufbauend auf dem Konzept der relativen Deprivation wird ein theoretischer Rahmen entwickelt, die Literatur synthetisiert und Fallstudien vorgestellt. Die Analyse zeigt, dass insbesondere intransparent ablaufende Investitionen Unzufriedenheit erzeugen können, die sich zu gewaltsamen Auseinandersetzungen zuspitzt. Die Arbeit schließt mit politischen Empfehlungen, die inklusive Beteiligung, Transparenz und Beschwerdemechanismen als wichtige Mittel zur Konfliktvermeidung hervorheben. Abschließend ergänzt eine neuartige quantitative Studie die qualitativen Erkenntnisse durch räumliche und gestaffelte Difference-in-Differences-Methoden. Die Studie deckt auf, dass LSLAs die lokale Konflikthäufigkeit in Subsahara-Afrika nahezu verdreifachen, getragen von Unruhen und Protesten. Konfliktrisiken sind bei Investoren aus einkommensschwachen Ländern sowie bei mehrjährigen Kulturpflanzen besonders hoch. Diese Ergebnisse belegen das Konfliktpotenzial von LSLAs und betonen die Bedeutung von Investorenverhalten und Projektgestaltung für lokale Auswirkungen. Insgesamt unterstreichen die Kapitel die Notwendigkeit eines vorsichtigen und inklusiven Vorgehens bei Landinvestitionen, der sichtbare und verborgene Kosten berücksichtigt.This dissertation offers a comprehensive examination of the welfare implications of large-scale land acquisitions (LSLAs). By applying both quantitative and qualitative methods, including advanced quasi-experimental and experimental designs, it seeks to isolate and quantify the socio-economic, mental health and conflict impacts of large-scale oil palm expansion and other land-based investments. The first chapters examine how LSLAs affect local livelihoods. Drawing on empirical evidence from Liberia, the analysis begins with an evaluation of two oil palm plantations. Although employment on these plantations leads to modest wage increases, it does not significantly improve household expenditure, asset ownership, or food security, and instead marginally exacerbates inequality. This suggests that, without more inclusive investment models, LSLAs are unlikely to foster broad-based rural development. Turning to Indonesia, the analysis continues with a quasi-experimental assessment of newer oil palm developments in West Kalimantan. Unlike earlier phases of plantation expansion in the country, these newer investments lead to no change or even a decline in welfare outcomes for rural households. A shift from traditional agriculture to wage labor and smallholder oil palm production has not yielded economic improvements. Juxtaposed with the high environmental costs resulting from deforestation, the non-existent to negative economic outcomes challenges the narrative of LSLAs as engines of rural growth. Beyond material well-being, the research also explores mental health impacts. A lab-in-the-field experiment in West Kalimantan reveals that LSLAs and accompanying deforestation significantly deteriorate the mental health of indigenous communities. Crucially, this effect is primarily driven by spiritual-cultural displacement rather than more commonly cited mechanisms such as discrimination or economic disadvantage. These findings highlight the deeply rooted, non-material consequences of land transformations. The second part of the dissertation shifts to the broader social consequences of LSLAs, particularly their role in generating conflict. Based on the concept of relative deprivation the paper develops a conceptual framework, synthesizes the literature and presents case study evidence. This analysis finds that deprivation, especially when linked to opaque investment processes, can fuel grievances that escalate into violent mobilization. The paper concludes with policy recommendations highlighting the importance of inclusive consultations, transparent procedures, and accessible grievance mechanisms in mitigating tensions. Finally, these qualitative findings are complemented by a novel quantitative study that investigates the causal relationship between LSLAs and social conflict across sub-Saharan Africa using a spatial design and staggered Difference-in-Differences methods. The study reveals that LSLAs almost triple local conflict incidence, driven by riots and protests. Conflict risk is heightened for investments from low-income countries and for projects involving perennial crops. These findings not only provide robust evidence of the conflict potential associated with LSLAs but also underscore the importance of investor behavior and project design in shaping local outcomes. Overall, the chapters highlight the need for a more cautious and inclusive approach to land investment that accounts for both visible and hidden costs.2025-10-0

    The influence of purchasing and consumption motives as well as lifestyle factors on the willingness to buy innovative foods with health and sustainability benefits

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    Lebensmittelinnovationen spielen eine zentrale Rolle, um gesellschaftlichen Anforde rungen und globalen Herausforderungen wie dem Klimawandel und der Ressourcenver knappung zu begegnen. Dabei prägen insbesondere die Megatrends Gesundheit, Nachhal tigkeit und Convenience die Innovationspotenziale. Während die Lebensmittelindustrie diese Potenziale bereits mit zahlreichen Produktneuheiten bedient, bleibt die Innovationskraft in der landwirtschaftlichen Primärproduktion begrenzt. Die agronomische Anreicherung bietet einen innovativen Ansatz, um die Verbrau cherbedürfnisse nach Gesundheit und Nachhaltigkeit miteinander zu vereinen. Durch die gezielte Nährstoffanreicherung von Obst und Gemüse trägt die agronomische Anreicherung zur Verbesserung des ernährungsphysiologischen Wertes, aber auch zur Ressourcenscho nung bei. Darüber hinaus bieten agronomisch angereicherte Lebensmittel vielfältige Weiter verarbeitungspotenziale hin zu einem convenienten Produktangebot. Trotz dieser Potenziale gibt es nur wenige Studien zur Verbraucherakzeptanz agro nomisch angereicherter Lebensmittel in Industrieländern wie Deutschland. Diese spielt je doch eine zentrale Rolle bei der erfolgreichen Einführung im deutschen Handel. Hohe Inves titionskosten, Verbraucherunsicherheiten sowie eine hohe Marktscheiterquote erfordern ge zielte Strategien zur Konsumentenaufklärung und Akzeptanzsteigerung. Dabei erschweren eine hohe Food Neophobia und ein ausgeprägtes Attitude-Behavior-Gap die Marktdurch dringung in Deutschland. Klassische Marketinginstrumente wie Produktnutzen, Promotion, Preis und Platzierung reichen nicht aus, um Verbraucher von neuen agronomisch angerei cherten Produkten zu überzeugen. Stattdessen ist ein tiefgehendes Verständnis des Ent scheidungsprozesses erforderlich, das sowohl soziodemografische als auch psychologische und emotionale Faktoren berücksichtigt. Allerdings sind die Wechselwirkungen von Lebens stilen, Kaufmotiven und emotionalen Faktoren auf die Kaufbereitschaft innovativer, agrono misch angereicherter Lebensmittel mit gesundheitlichem und nachhaltigem Mehrwert noch nicht ausreichend erforscht. Eine zielgruppengerechte Ansprache, die über demografische Kriterien hinausgeht und individuelle Lebensstile sowie emotionale Beweggründe mit einbe zieht, ist jedoch entscheidend für den Erfolg innovativer Produkte. Ziel dieser Dissertation ist es daher, die Akzeptanz und Kaufwahrscheinlichkeit inno vativer Lebensmittel mit gesundheitlichen und nachhaltigen Mehrwerten in Deutschland ganzheitlich zu analysieren. Dabei stehen die Identifikation relevanter Kauf- und Konsummo tive unter Berücksichtigung interner und externer Einflussfaktoren sowie die Ermittlung po tenzieller Zielgruppen im Fokus. Die Forschungsmethodik dieser Dissertation basiert auf ei ner integrativen Forschungsstrategie, die quantitative Verbraucherforschung mit Fallbeispie len kombiniert. Die quantitative Forschung ermöglicht eine systematische und objektive Ana lyse von Daten großer Stichproben, die repräsentativ für die deutsche Bevölkerung sind. Dabei werden validierte Skalen wie der Food Choice Questionnaire (FCQ), die Food Neo phobia Scale (FNS) und die Positive and Negative Affect Schedule (PANAS) verwendet, um psychologische und emotionale Aspekte zu messen. Die Arbeit mit Fallbeispielen ermöglicht es darüber hinaus, praxisnahe Erkenntnisse über Konsumentscheidungen und Verhaltens muster zu gewinnen. Damit ermöglicht die Methodenkombination sowohl generalisierbare als auch kontextspezifische Erkenntnisse. Die Ergebnisse dieser Studie zeigen, dass drei Kauf- und Konsummotive als grundle gende Hygienefaktoren für agronomische Innovationen bezeichnet werden können: Ge schmack, Sicherheit und Natürlichkeit. Sie sollten bei jeder Produktentwicklung berücksich tigt werden, um eine breite Basis an Verbrauchern zu adressieren. Sie sind als grundlegende V Eigenschaften zu verstehen. Ihr Fehlen oder ihre negative Ausprägung führen zu Unzufrie denheit und Ablehnung des Produktes. Ihre positive Ausprägung wird hingegen als selbst verständlich erachtet. Im Gegensatz zu den Hygienefaktoren, die nahezu universell gelten, sind Motivationsfaktoren mit der Persönlichkeit, den individuellen Bedürfnissen und Werten einer Person verknüpft. Als differenzierende und clusternde Einflussgrößen ermöglichen sie es, spezifische Kaufanreize zu setzen, indem sie ein Produkt klar vom Wettbewerbsangebot differenzieren. Dies erweist sich als besonders relevant im Kontext agronomisch angerei cherter Lebensmittel, die im Handel mit etablierten Alternativangeboten konkurrieren. Denn obgleich soziodemografische Variablen einen ersten Anhaltspunkt für die Zielgruppendefini tion liefern, erweist sich diese Perspektive als relativ grob und stößt angesichts der Komple xität individueller Bedürfnisse und Werte zunehmend an ihre Grenzen. Hier zeigen Motivati onsfaktoren aber auch Stimmungen und Food Neophobia ihre Potenziale. Zu den relevanten und clusternden Motivationsfaktoren agronomisch angereicherter Innovationen zählen Ge sundheit, Nachhaltigkeit, Convenience und Genuss/Luxus. Um diese Zielgruppen entspre chend ihrer Motivationsfaktoren effektiv anzusprechen, müssen Produkte und Kommunikati onsstrategien gezielt auf deren jeweilige Bedürfnisse abgestimmt werden. Die größten Marktpotenziale bieten dabei die Motivationsfaktoren Gesundheit und Convenience. Ent sprechend sollte die Kernbotschaft ausgerichtet sein, um die Komplexität für den Verbrau cher zu reduzieren und ein klares Verständnis der Produktvorteile zu gewährleisten. Das Produktportfolio kann sich, dem Convenience-Bedürfnis entsprechend, von unverarbeitetem frischem Obst und Gemüse über verschiedene vorgeschnittene Varianten in Portionsgrößen bis hin zu verzehrfertigen Produkten erstrecken. Gleichzeitig zeigte die Analyse der Motivati onsfaktoren unter Berücksichtigung von Stimmungen und Food Neophobia die zentrale Rolle von Marken als Faktor der Akzeptanzsteigerung. Sie genießen ein hohes Grundvertrauen, das insbesondere in Deutschland essenziell für die Akzeptanz innovativer, agronomisch an gereicherter Lebensmittel ist. Die ganzheitliche Betrachtung der vielfältigen Einflussfaktoren auf die Kaufbereit schaft innovativer Lebensmittel leistet einen wichtigen Beitrag zur erfolgreichen Einführung agronomisch angereicherter Lebensmittel. Die Unterscheidung zwischen Hygiene- und Moti vationsfaktoren liefert den Unternehmen wertvolle Implikationen für die Produktentwicklung, strategische Markenführung und zielgruppenorientierte Kommunikation. Für die Wissen schaft ergeben sich auf Basis der Ergebnisse vielfältige weitergehende Forschungspotenzia le wie die Arbeit mit PLS-Modellen oder Reaktionszeitmessungen. Aber auch neue For schungsfelder wie die Weiterverarbeitung agronomisch angereicherter Lebensmittel bieten vielfältige Forschungspotenziale.Food innovations play a central role in addressing social demands and global chal lenges such as climate change and the scarcity of resources. In particular, the megatrends of health, sustainability, and convenience are shaping the potential for innovation. While the food industry is already exploiting this potential through numerous new products, innovation in primary agricultural production remains limited. Agronomic enrichment offers an innovative approach to combining consumer needs for health and sustainability. By enriching fruits and vegetables with nutrients, agronomic enrichment contributes not only to improving the nutritional value but also to diverse opportu nities for further processing, facilitating the development of a convenient product range. Despite this potential, only a few studies have examined consumer acceptance of agronomically enriched foods in industrialized countries such as Germany. However, con sumer acceptance plays a crucial role in the successful market introduction within the Ger man retail sector. High investment costs, consumer uncertainties, and a high market failure rate require targeted strategies to educate consumers and increase acceptance. A high level of food neophobia and a pronounced attitude-behavior gap complicate market penetration in Germany. Traditional marketing tools such as product benefits, promotion, price, and place ment are insufficient to convince consumers of agronomically enriched products. Instead, a comprehensive understanding of the decision-making process is required, taking into ac count socio-demographic as well as psychological and emotional factors. However, the inter actions of lifestyles, purchase motives, and emotional influences on the willingness to buy agronomically enriched foods with added health and sustainability benefits have not yet been sufficiently investigated. A target group-specific approach that extends beyond purely demo graphic criteria and incorporates individual lifestyles and emotional motivations is therefore essential for the successful market introduction of innovative products. The aim of this dissertation is thus to comprehensively analyze the acceptance and purchase likelihood of innovative foods with added health and sustainable benefits in Ger many. The focus lies on identifying relevant purchase and consumption motives while con sidering internal and external influencing factors, as well as defining potential target groups. The research methodology is based on an integrative research strategy that combines quan titative consumer research with case studies. Quantitative research enables a systematic and objective analysis of data from large, nearly representative samples of the German population. Validated scales such as the Food Choice Questionnaire (FCQ), the Food Neo phobia Scale (FNS), and the Positive and Negative Affect Schedule (PANAS) are used to measure psychological and emotional aspects. Case studies further provide practical insights into consumption decisions and behavioral patterns. The combination of these methods fa cilitates both generalizable and context-specific findings. The results of this study indicate that three purchasing and consumption serve as fundamental hygiene factors for agronomic innovations: taste, safety, and naturalness. These factors should be considered in every product development process to appeal to a broad consumer base. They represent essential product attributes whose absence or nega tive perception leads to dissatisfaction and product rejection, while their presence is taken for granted. Unlike hygiene factors, which apply universally, motivational factors are linked to an individual´s personality, needs, and values. As differentiating and segmenting influences, they enable the target creation of purchase incentives by clearly distinguishing a product III from competitors. This is particularly relevant in the case of agronomically enriched foods, which compete with well-established alternatives in the retail sector. While socio demographic variables provide an initial point of reference for target group definition, this perspective proves relatively imprecise given the complexity of individual needs and values. Here, motivational factors, moods, and food neophobia reveal their potential. The key moti vational factors influencing the acceptance of agronomically enriched innovations include health, sustainability, convenience, and enjoyment/luxury. In order to effectively address these target groups according to their motivational factors, products and communication strategies must be tailored to their specific needs. Among these, health and convenience offer the greatest market potential. Consequently, core messaging should be aligned accord ingly to reduce complexity and ensure a clear understanding of product benefits. In line with the demand for convenience, product portfolios can range from unprocessed fresh fruit and vegetables to pre-cut portions and ready-to-eat products. Additionally, the analysis of motiva tional factors, considering moods and food neophobia, underscores the crucial role of brands as an acceptance-enhancing element. Brands enjoy a high level of fundamental trust, which is particularly relevant for the acceptance of innovative agronomically enriched foods in Ger many. A holistic examination of the diverse factors influencing consumer willingness to pur chase innovative foods provides valuable insights for the successful market introduction of agronomically enriched foods. The distinction between hygiene and motivation factors offers companies important implications for product development, strategic brand management, and target group- oriented communication. Based on these findings, further research oppor tunities emerge, such as the application of PLS models or reaction time measurements. Ad ditionally, new research fields, such as the processing of agronomically enriched foods, pre sent further promising avenues for exploration.2025-10-0

    Analysis of small RNA-based regulatory effects on heterosis and genome-wide association study of flowering time in Brassica napus L.

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    Brassica napus L., commonly known as oilseed rape, is an allotetraploid that originated ~7500 years ago by natural hybridization between two diploid progenitors, Brassica rapa and Brassica oleracea. Oilseed rape is extensively cultivated providing edible oil for humans, protein-rich feed for animals, and renewable biofuels for industry. As the third largest source of vegetable oil, the yield of oilseed rape directly affects global agricultural production and food supply. Heterosis has been exploited by hybrid breeding as an important method to increase yield and yield stability, while flowering time is a key trait that affects the growth cycle, adaptability and final yield of oilseed rape. Studying the molecular mechanism of these traits will not only help to optimize breeding strategies and improve crop productivity but is also important for coping with climate change and expanding the cultivation area of oilseed rape. Heterosis is a phenomenon in which the F1 hybrid is superior to its parental inbred lines. Despite the fact that the root system, as the basis of plant growth and development, plays a crucial role in nutrient uptake, water utilization and stress tolerance, little research has been conducted on heterosis for root traits in oilseed rape. High-precision root growth rate measurements of a panel of 24 oilseed rape hybrids by a non-invasive phenotyping platform revealed remarkably high variation of mid-parent heterosis (MPH) for root growth rate ranging from -28% to 196%. Recent studies have suggested the contribution of small RNAs (sRNAs) to heterosis. Taking advantage of the high trait variation for root growth, its quantitative relationship with sRNAs expression and their regulation of genes was investigated by integrating small RNA, transcriptome, degradome and DNA methylation data. To increase statistical power, we divided 24 hybrids into 4 groups with distinct heterotic responses. sRNA expression and transcriptome analysis revealed that the number of sRNAs and genes with non-additive expression patterns increases with heterotic response. The degradome sequencing analysis confirmed targets degraded by non-additively sRNAs through post-transcriptional gene silencing (PTGS), and showed that the proportion of non-additively expressed genes that are regulated by non-additively expressed sRNAs increases with the root growth heterotic response. This regulation affects plant growth and stress/defense response genes, which have been described to contribute to heterosis formation. Additionally, 24-nt sRNAs can mediate transcriptional gene silencing (TGS) through the RNA-directed DNA methylation (RdDM) pathway. CHH methylation at loci with down-regulated 24-nt sRNA decreased in the F1 hybrid compared to the mid-parent value in the extreme high heterosis group. Non-additively expressed 24-nt sRNAs were located in genic and flanking regions of seven non-additively expressed genes. Three out of these seven genes are related to root growth. Overall, the integration of omics data illustrates that sRNA-based regulatory interactions via PTGS and TGS are quantitatively associated with root growth heterosis in oilseed rape. The timing of flowering in oilseed rape is a pivotal phenological trait that profoundly influences reproductive success, yield potential and adaptation to changing environmental conditions. Therefore, identifying genes that advance or delay flowering time will have important practical implications for sustainable agriculture under different climatic conditions, which is increasingly important in the face of global climate change. To identify quantitative trait loci (QTL) associated with flowering time, 780 accessions were used for a Genome-Wide Association Study (GWAS). Genotyping was performed using the Brassica 60K Illumina Infinium™ SNP genotyping array, and flowering time data were collected from multiple environments and locations. GWAS for flowering time was performed using five different GAPIT models: GLM, BLINK, FarmCPU, MLMM and MLM. A total of 12 quantitative trait nucleotides (QTNs) associated with flowering time were identified. Two QTNs located on chromosomes A02 and C06 were consistently identified by all models and up to 6.89% of the phenotypic variance explained (PVE). Considering flanking genomic regions of 200kb of QTNs identified the well-characterized flowering time gene of oilseed rape, BnaFT.A02, confirming the reliability of the study. Based on comparing with homologous known flowering genes in Arabidopsis thaliana, we proposed 22 promising candidate genes for flowering time in oilseed rape, involved in the regulation of photoperiodism, circadian clock and gibberellin response. In summary, this thesis reveals an important role of sRNAs in the establishment of heterosis for root growth and successfully identified QTLs related to flowering time in oilseed rape. These findings enhance our understanding of heterosis and flowering time and lay a foundation for improving the yield and yield stability of oilseed rape.2025-10-2

    Outcomes after circumcision in children - factors influencing parental satisfaction

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    Osteoporose ist eine Erkrankung des Knochenstoffwechsels, bei der es gehäuft zu Frakturen und damit einer Einschränkung der Lebensqualität kommen kann. In der Diagnostik werden vor allem die Knochendichtemessung mittels DXA und diverse Laborparameter verwendet. Vitamin K mit seinen Unterformen gehört aktuell noch nicht standardmäßig dazu, soll aber den Knochenstoffwechsel positiv beeinflussen. In der hier vorgestellten explorativen Studie wurde die Vitamin K2-Versorgung und Diagnostik bei Osteoporosepatienten des Endokrinologikums Göttingen untersucht. Dabei wurde die von amedes MVZ wagnerstibbe in diesem Rahmen neu etablierte LC-MS/MS-Messung verwendet. Es sollte analysiert werden, wie der Vitamin K2-Status des Kollektivs ist und ob die Messung von Vitamin K2 und seinen dazugehörigen relevanten Parametern eine sinnvolle Ergänzung in der Diagnostik der Osteoporose sein kann. Es handelt sich um eine retrospektive Studie, bei der sich das Patientenkollektiv aus 100 Osteoporosepatienten zusammensetzt, wovon sechs Patientinnen bei erniedrigtem Vitamin K2-Status im Verlauf substituiert wurden. Es zeigte sich ein Gesamtkollektiv mit 84% vorrangig postmenopausalen Frauen und 16% Männern, jedoch im Vergleich zu anderen Studien einer großen Altersspannweite. 45% der Patienten nahm regelmäßig eine Osteoporose-spezifische Therapie ein. 60% der Studienteilnehmer gaben anamnestisch Frakturen in der Vorgeschichte an. Die Auswertungen der Knochendichtemessungen mittels DXA ergaben, dass die Männer des Kollektivs tendenziell schlechtere Messwerte in den peripheren Knochen (Femur) aufwiesen, wohingegen die Frauen eine im Vergleich schlechtere Knochensubstanz der Wirbelsäule hatten. Wir konnten zeigen, dass unter spezifischer Osteoporose-Therapie wie Bisphosphonaten und Denosumab niedrigere und Teriparatid-Therapie höhere Osteocalcin-Werte im Gruppenvergleich messbar waren. Es stellte sich heraus, dass bereits zum ersten Messtermin die meisten Patienten des Kollektivs hohe Vitamin K2-MK7-Spiegel (1,9±4,4 μg/l, Normbereich: 0,1 – 0,82 μg/l), jedoch auch erhöhte Messwerte für das uncarboxylierte Osteocalcin (3,2±2,24 μg/l, Normbereich 0,6 – 3,34 μg/l) aufwiesen, welches ein indirekter Marker für den Vitamin K2-Status ist. Unter Vitamin K2-Substitution (bei n=6) zeigte sich ein Anstieg der Vitamin K2 MK7-Serumspiegel (von 1,0±0,8 μg/l auf 5,0±3,7 μg/l) sowie ein nicht signifikantes Absinken der ucOC-Werte (von 5,0±2,74 μg/l auf 4,3±2,14 μg/l). Ein signifikanter Zusammenhang der Höhe des Vitamin K1 und Vitamin K2-MK4 (p=0,038), sowie der Osteocalcin-Werte untereinander (p=<0,001) und von carboxyliertem Osteocalcin und der alkalischen Knochenphosphatase (p=<0,001) konnte dargestellt werden. In unserem Gesamtkollektiv zeigte sich ein schwach signifikanter Zusammenhang von erhöhtem Vitamin K2-MK7-Serumspiegel (p=0,04) bei höherem BMI und ein mit zunehmendem Lebensalter erniedrigter Vitamin K1-Spiegel (p=0,012). Signifikante Korrelationen der Vitamin K2-relevanten Parameter mit dem Vitamin D-Status, der Knochendichte und der Frakturrate zeigten sich nicht. Die Messung von Vitamin K1, Vitamin K2-MK7 und, wenn keine Osteoporose-spezifische Medikation eingenommen wird, auch den Osteocalcin-Formen, scheint eine sinnvolle Ergänzung in der Osteoporose-Diagnostik zu sein. Die Vitamin K2-Versorgung im Gesamtkollektiv war im Normbereich, aber grenzwertig niedrig. Bei Patienten mit erhöhtem uncarboxylierten Osteocalcin als Zeichen eines Vitamin K2-Mangels scheint eine Supplementierung von Vitamin K2 mit einer Dosierung von 100 μg täglich für eine signifikante Verbesserung des Vitamin K-Status in unserem Kollektiv nicht ausreichend und eine höhere Dosierung könnte sinnvoll sein. Grade bei älteren Patienten sollte auf einen ausreichenden Vitamin K-Status geachtet und bei günstigem Nebenwirkungsprofil substituiert werden. Ob dies auch positive Effekte auf die Knochendichte und Frakturrate hat, ist in der Literatur umstritten und sollte in weiteren Studien untersucht werden.Osteoporosis is a disease of bone metabolism that can lead to frequent fractures and thus a reduced quality of life. Diagnosis primarily involves bone density measurement using DXA and various laboratory parameters. Vitamin K and its subforms are not yet standard practice, but are believed to have a positive effect on bone metabolism. The exploratory study presented here investigated vitamin K2 supply and diagnostics in osteoporosis patients at the Endocrinology Center in Göttingen. The LC-MS/MS measurement newly established by amedes MVZ wagnerstibbe was used for this purpose. The aim was to analyze the vitamin K2 status of the collective and whether the measurement of vitamin K2 and its associated relevant parameters could be a useful addition to the diagnosis of osteoporosis. This is a retrospective study in which the patient group consists of 100 osteoporosis patients, six of whom were substituted with vitamin K2 during the course of the study due to low vitamin K2 status. The overall group consisted of 84% primarily postmenopausal women and 16% men, but compared to other studies, the age range was wide. Forty-five percent of patients regularly took osteoporosis-specific therapy. Sixty percent of study participants reported a history of fractures. The evaluations of bone density measurements using DXA showed that the men in the cohort tended to have poorer measurements in the peripheral bones (femur), whereas the women had comparatively poorer bone substance in the spine. We were able to show that specific osteoporosis therapy such as bisphosphonates and denosumab resulted in lower osteocalcin levels, while teriparatide therapy resulted in higher levels when comparing the groups. It turned out that at the first measurement date, most patients in the collective already had high vitamin K2-MK7 levels (1.9±4.4 μg/l, normal range: 0.1–0.82 μg/l), but also elevated levels of uncarboxylated osteocalcin (3.2±2.24 μg/l, normal range 0.6–3.34 μg/l), which is an indirect marker for vitamin K2 status. Vitamin K2 supplementation (in n=6), there was an increase in vitamin K2 MK7 serum levels (from 1.0±0.8 μg/l to 5.0±3.7 μg/l) and a non-significant decrease in ucOC values (from 5.0±2.74 μg/l to 4.3±2.14 μg/l). A significant correlation was found between vitamin K1 and vitamin K2 MK4 levels (p=0.038), as well as between osteocalcin levels (p=<0.001) and between carboxylated osteocalcin and alkaline bone phosphatase (p=<0.001). In our overall cohort, there was a weakly significant correlation between elevated vitamin K2-MK7 serum levels (p=0.04) and higher BMI, and a decrease in vitamin K1 levels with increasing age (p=0.012). No significant correlations were found between vitamin K2-related parameters and vitamin D status, bone density, or fracture rate. Measuring vitamin K1, vitamin K2-MK7, and, if no osteoporosis-specific medication is being taken, osteocalcin forms, appears to be a useful addition to osteoporosis diagnostics. Vitamin K2 levels in the overall cohort were within the normal range but borderline low. In patients with elevated uncarboxylated osteocalcin as a sign of vitamin K2 deficiency, supplementation with 100 μg of vitamin K2 daily does not appear to be sufficient for a significant improvement in vitamin K status in our cohort, and a higher dosage may be advisable. Particularly in older patients, attention should be paid to ensuring adequate vitamin K status and supplementation should be considered if the side effect profile is favorable. Whether this also has positive effects on bone density and fracture rate is controversial in the literature and should be investigated in further studies.2025-12-1

    A real effective version of the Freĭman-Scourfield Theorem

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    We study the solvability of a Diophantine equation with mixed real exponents for sufficiently large natural numbers. The connection to a condition on the sum over the reciprocals of the exponents was first shown by Freĭman and Scourfield and recently made effective by Brüdern and Wooley. We prove an effective statement for the case of real exponents, which involves flooring in the equation. To this end, we apply the theory of the Hardy-Littlewood circle method adapted to Diophantine inequalities. In the fourth chapter, we show a mean value estimate utilising diminishing ranges and prove a novel Weyl-type estimate for exponential sums with a non-integer exponent. The calculations on the arcs in the fifth chapter lead to conditions that are translated into the effective result in the last chapter.2025-11-1

    Diagnostics of comprehensive simulations of the chromosphere

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    The solar chromosphere is a highly dynamic and complex region of the solar atmosphere. It plays an important role in the formation of many of the observed solar features, such as, prominences, spicules, and flares. In addition, the chromosphere provides the mass for the solar wind. The chromosphere can be seen in many aspects as a region of transitions. The plasma, which is mostly neutral in the photosphere, becomes partly ionized in the chromosphere. The temperature starts to increase to values that are higher than in the photosphere. The gas density decreases approximately exponentially. Filling almost the entire space in the chromosphere, the magnetic field becomes dynamically important. Many approximations that are valid in the photosphere such as local thermodynamic equilibrium break down in the chromosphere. The change in physical conditions within a relatively small height difference (typically 1–3 Mm) leads to a highly corrugated region. Interpreting observations of the chromosphere is thus challenging. Therefore, the chromosphere is probably the least understood part of the solar atmosphere. Nowadays the chromosphere can be observed at high spatial and spectral resolution either from the ground with for example the Swedish-Solar-Telescope, from space for example with the Interface-Region-Imaging-Spectrograph, or from stratospheric balloons with for example the SUNRISE observatory. Interpreting the observations is difficult due to the complex nonequilibrium (NE) and nonlocal formation of chromospheric spectral lines. Numerical simulations of the solar atmosphere can be a valuable tool to tackle this difficulty. Within the last two decades, it became possible to include a comprehensive set of physics in such models to treat the chromosphere with an unprecedented degree of realism. Until recently, Bifrost was the only simulation code that was capable of simulating the chromosphere. While present models of the chromosphere can produce features that are very similar in structure and appearance to those seen in observations, there are still discrepancies. For example, the line widths of simulated chromospheric spectral lines are typically too narrow and their intensities are too faint compared with observations. In this work, a simulation of the chromosphere is used that was computed with the “Max Planck Institute for Solar System Research/University of Chicago Radiation Magneto-hydrodynamics (MURaM)” code. MURaM is an radiaton-MHD (rMHD) code and was recently upgraded to treat the physics of the chromosphere under non-LTE (NLTE) and NE conditions. The new version is named chromospheric extension of MURaM (MURaM-ChE). An important step in validating a numerical model of the solar chromosphere is the forward modeling of spectral lines. To this end, important chromo- spheric spectral lines from the simulation have been synthesized and were compared with observations. In the first project, a simulation of an enhanced network (EN) region was used. Under the approximation of 1.5D radiative transfer (RT), the Mg ii h&k lines from this simulation have been synthesized. It was found that the line width is significantly increased compared to previous models. This is attributed to the magnitude of velocity variations along the line-of-sight (LOS), which is larger in the MURaM-ChE simulation compared to a similar simulation computed with the previously used Bifrost code. The spatially averaged spectra from the MURaM-ChE simulation compare well in terms of line width to the observations, but the peak intensities of the Mg ii h&k lines appear a bit too strong. The higher peak intensity in the simulation is partly due to a higher magnetic flux density in the simulation than in the observation but also due to the 1.5D RT approximation, which is known to overestimate the peak intensities. In the second project, the effects of full 3D RT on the Mg ii h&k spectra have been studied as well as correlations between spectral line properties and the underlying atmosphere in the same simulation as in the first project. 3D RT is computationally more expensive than 1.5D RT. The synthesis of a spectral line in a single snapshot from the simulation can be as expensive as the rMHD simulation itself. The computations presented in this project confirmed, however, that 3D RT effects play an important role in the synthesis of the Mg ii h&k lines and must be taken into account. In particular, the differences between 3D and 1.5D RT are larger in MURaM-ChE than in the Bifrost model. Additionally, it was found that correlations between spectral line properties and the underlying atmosphere are valid, which were found by similar studies with the Bifrost model. The scatter in these correlations is, however, larger in the more dynamic MURaM-ChE simulation. A general finding of the studies on the Mg ii h&k lines is that in the MURaM-ChE model, a reasonably good match of the line profiles with the observations can be achieved at a relatively moderate spatial resolution of the simulation of 23.46 km (horizontal) and 20 km (vertical). In the third project, the Ca ii 854.2 nm spectral line has been synthesized. This line forms in the lower to middle chromosphere and is widely used for magnetic field measurements in the chromosphere. The line itself has an asymmetric shape whose origin is under debate in the literature. On the one hand, the dynamic motions of the chromosphere might lead to the asymmetry, on the other hand, it could be due to isotopic splitting as there are six stable isotopes of calcium in the solar atmosphere. The width of this line could not be reproduced in previous models, which typically resulted in too-narrow line profiles. It was found that both the velocities and the isotopic splitting contribute significantly to the observed asymmetric line shape. The spatially averaged line profile of Ca ii 854.2 nm computed from the MURaM-ChE simulation shows a relatively close match with an observed line profile both in line width and asymmetry when the effect of isotopic splitting is taken into account. The close match of the line width is, similar to the findings for the Mg ii h&k lines, a result of the dynamic motions in the MURaM-ChE simulation. This work contributes to the scientific literature in that it presents the first forward modeled spectra of the new chromospheric extension of MURaM. The improved match with observations helps to interpret complex chromospheric spectral lines. Additionally, the here presented findings demonstrate the need to properly model the large velocities in the solar chromosphere, to account for horizontal RT effects in strong lines with considerable scattering, as well as to take the isotopic splitting into account for elements for which multiple isotopes are present in the solar atmosphere.2025-11-2

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