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Generational differences in language use and language attitudes in a Lombard-speaking family
No full textSince the unification of Italy in 1861, an increasing number of Italians have been giving up their heritage languages in favour of Italian monolingualism. One of the languages concerned is Lombard, an endangered Gallo-Italic language spoken in the Italian region of Lombardy and the Swiss canton of Ticino. This thesis discusses language ideology and intergenerational language transmission in one bilingual Lombard family. Semi-structured interviews with five speakers of three generations provide insight into the influence of their Italian-centered family language policy on language use among the generations. The study compares each generation’s attitudes towards Lombard and explores the factors involved in their language choice in different contexts, taking into account each speaker’s social and linguistic background as well as the potential influence of language policy and planning strategies employed by authorities and activists. Most participants have a positive attitude towards Lombard and consider it essential to their community and identity, but some differences have been identified. It is also notable that Lombard is not used less by each subsequent generation. While the results of this study cannot be generalised to all Lombard-speaking families, they can provide insight into the dynamics of the language shift and the influence of micro-level behavioural patterns and attitudes of one generation on the next generation’s speech practices.:1 Introduction
2 The Lombard language
2.1 Vitality
2.2 Language history and the term dialetto
2.3 Language policy
2.4 Language planning
2.4.1 Corpus planning
2.4.2 Status planning
2.4.3 Acquisition planning
3 Methodology
3.1 Language attitude research
3.2 Semi-structured interviews
3.3 Selection of questions
3.4 Participants
4 Interview results
4.1 Intergenerational transmission
4.2 Language use
4.2.1 Associations and stigmatisation
4.2.2 Writing in Lombard
4.3 Language or dialetto
4.3.1 Diatopic variation
4.3.2 Abstand and ausbau
4.4 Emotional attachment
4.4.1 Lombard identity
4.4.2 Promotion and preservation
4.4.3 Language loss
4.5 Summary: Attitudes
5 Conclusio
Evaluation of a Point-of-Need Molecular Diagnostic Tool Coupled with Rapid DNA Extraction Methods for Visceral Leishmaniasis
No full textA rapid, cost-effective, and simple nucleic acid isolation technique coupled with a point-of-
need DNA amplification assay is a desirable goal for programmatic use. For diagnosis of Visceral
Leishmaniasis (VL), Recombinase Polymerase Amplification (RPA) rapid tests for the detection of
Leishmania DNA are versatile and have operational advantages over qPCR. To facilitate the delivery
of the RPA test at point-of-need for VL diagnosis, we compared two rapid DNA extraction methods,
SwiftDx (SX) and an in-house Boil and Spin (BS) method, coupled with RPA amplification, versus
more widely used methods for DNA extraction and amplification, namely Qiagen (Q) kits and qPCR,
respectively. A total of 50 confirmed VL patients and 50 controls, matched for age and gender, were
recruited from Mymensingh, Bangladesh, a region highly endemic for VL. Blood samples were
collected from each participant and DNA was extracted using Q, SX and BS methods. Following
DNA extraction, qPCR and RPA assays were performed to detect L. donovani in downstream analysis.
No significant differences in sensitivity of the RPA assay were observed between DNA extraction
methods, 94.00% (95% CI: 83.45–98.75%), 90% (95% CI: 78.19–96.67%), and 88% (95% CI: 75.69–95.47%)
when using Q, SX, and BS, respectively. Similarly, using qPCR, no significant differences in sensitivity
were obtained when using Q or SX for DNA extraction, 94.00% (95% CI: 83.45–98.75%) and 92.00%
(80.77–97.78%), respectively. It is encouraging that RPA and qPCR showed excellent agreement
(k: 0.919–0.980) when different extraction methods were used and that the DNA impurities using
BS had no inhibitory effect on the RPA assay. Furthermore, significantly higher DNA yields were
obtained using SX and BS versus Q; however, a significantly higher parasite load was detected using
qPCR when DNA was extracted using Q versus SX. Considering the cost, execution time, feasibility,
and performance of RPA assay, rapid extraction methods such as the Boil and Spin technique appear
to have the potential for implementation in resource-limited endemic settings. Further clinical
research is warranted prior to broader application
Tumor-Tissue Interfaces: Instructive Triggers of Phenotype Switching in Breast Cancer
No full textTumor-tissue interfaces represent critical regulators of breast cancer progression, demonstrating that extracellular matrix (ECM) heterogeneity directs cancer cell behavior. The results of this thesis reveal that MDA-MB-231 breast cancer cells experience strong, highly localized contractile forces while transmigrating across collagen I-based biomimetic tumor-tissue interfaces. This mechanical stress induces deformation of the cell body and nucleus, DNA damage, and misregulation of mechanotransductive pathways, ultimately triggering a coordinated switch toward a more invasive and aggressive phenotype. Analysis of migration as well as proliferation heterogeneity confirmed that the phenotype switch is population-wide and not due to selective enrichment of pre-existing aggressive subpopulations. Importantly, this interface-induced response is not limited to MDA-MB-231 cells but is also observed across multiple triple-negative breast cancer (TNBC) cell lines, suggesting that ECM topology functions as a common regulator of cell state transitions. The sharp decrease in fibrillar collagen density at tumor-tissue interfaces provides a spatial cue that promotes persistent phenotypic and transcriptional reprogramming, including cell cycle regulation, chromatin remodeling, and activation of DNA repair pathways, which together enhance invasive potential.:Bibliography I
Table of contents II
1. Introduction 1
1.1 Breast Cancer and Breast Cancer Metastasis
1.1.1 Breast Cancer Subtypes
1.1.2 Breast Cancer Metastasis
1.2 Clonal Heterogeneity and Cancer Cell Plasticity
1.3 Tumor Microenvironment
1.3.1 The Extracellular Matrix in the Tumor Microenvironment
1.3.2 Tumor-Tissue Interfaces
1.3.3 Mimicking Tumor Microenvironments in vitro
1.4 Mechanotransduction 12
1.4.1 Force Transmission from the Extracellular Matrix into the Cell’s Interior
1.4.2 Nuclear Mechanotransduction
2. Aims of the study
3. Publications
3.1 Publication I
3.2 Publication II
3.3 Publication III
4. Summary
5. References
6. Supplement
Zusammenfassung
Curriculum Vitae
List of Publications
Oral Presentations
Danksagung
Declaration of Generative AI
Selbstständigkeitserklärung
Nachweis über Anteile der Co-Autor*innenTumor-Gewebe-Grenzflächen sind wichtige Regulatoren der Brustkrebsprogression und zeigen, dass die Heterogenität der extrazellulären Matrix das Verhalten von Krebszellen steuert. Die Ergebnisse dieser Arbeit zeigen, dass MDA-MB-231-Brustkrebszellen starken, hochgradig lokalisierten kontraktilen Kräften ausgesetzt sind, während sie über biomimetische Tumor-Gewebe-Grenzflächen auf Kollagen I-Basis migrieren. Diese mechanische Belastung führt zu einer Verformung des Zellkerns, zu DNA-Schäden und zu einer Fehlregulation der mechanotransduktiven Signalwege, was letztlich einen koordinierten Wechsel zu einem invasiveren und aggressiveren Phänotyp auslöst. Die Analyse der Migration, sowie der Proliferationsheterogenität bestätigte, dass der Phänotypwechsel populationsweit auftritt und nicht auf eine selektive Anreicherung bereits vorhandener aggressiver Subpopulationen zurückzuführen ist. Wichtig ist, dass diese durch die Grenzfläche induzierte Reaktion nicht auf MDA-MB-231-Zellen beschränkt ist, sondern auch bei mehreren triple-negativen Brustkrebszelllinien beobachtet wird, was darauf hindeutet, dass die EZM-Topologie als allgemeiner Regulator von Zellzustandsübergängen fungiert. Die starke Abnahme der Kollagendichte an den Grenzflächen zwischen Tumor und gesundem Gewebe liefert ein topologisches Signal, das eine anhaltende phänotypische und transkriptionelle Umprogrammierung fördert, einschließlich der Regulation des Zellzyklus, der Chromatin-Umgestaltung und der Aktivierung von DNA-Reparaturwegen, die zusammen das invasive Potenzial erhöhen.:Bibliography I
Table of contents II
1. Introduction 1
1.1 Breast Cancer and Breast Cancer Metastasis
1.1.1 Breast Cancer Subtypes
1.1.2 Breast Cancer Metastasis
1.2 Clonal Heterogeneity and Cancer Cell Plasticity
1.3 Tumor Microenvironment
1.3.1 The Extracellular Matrix in the Tumor Microenvironment
1.3.2 Tumor-Tissue Interfaces
1.3.3 Mimicking Tumor Microenvironments in vitro
1.4 Mechanotransduction 12
1.4.1 Force Transmission from the Extracellular Matrix into the Cell’s Interior
1.4.2 Nuclear Mechanotransduction
2. Aims of the study
3. Publications
3.1 Publication I
3.2 Publication II
3.3 Publication III
4. Summary
5. References
6. Supplement
Zusammenfassung
Curriculum Vitae
List of Publications
Oral Presentations
Danksagung
Declaration of Generative AI
Selbstständigkeitserklärung
Nachweis über Anteile der Co-Autor*inne
Enhancing ecosystem services through collaborative grass removal and fire exclusion in the Eastern Ghats
No full textHuman activities in mesic savanna ecosystems have resulted in plant communities that are heavily dominated by fire-tolerant grass species, are less diverse, and offer fewer ecosystem services such as palatable plant biomass. Experimental studies manipulating fire and grass presence have mostly been conducted in ecosystems invaded by exotic grass species. However, these experiments are also relevant to ecosystems that have become dominated by native grass species due to changes in human activities. Our study compared three different management treatments in the Eastern Ghats of India, where mesic savanna ecosystems are highly dominated by the unpalatable native Cymbopogon grasses, specifically: (1) control (both Cymbopogon grasses and fire are present), (2) fire exclusion, and (3) manual removal of Cymbopogon grasses and fire exclusion. We found that both grass removal and fire exclusion were necessary to significantly increase palatable herbaceous plant biomass and species diversity, and that species diversity responses were only significant at larger spatial grains of investigation. High site-to-site variation in the grass removal and fire exclusion treatment prevented us from detecting significant differences in species composition across treatments, even though particular palatable grass species benefited from the treatment. Our study is in line with research from other mesic savanna systems showing that fire management alone is not sufficient to transition ecosystems to a desired or historical state. We demonstrate how normally costly management practices, such as manual removal of dominant grasses, can be reasonably achieved through collaboration between scientists, community governed village institutions, and government and nongovernment agencies in socioecological systems
Gravity waves generated by the Hunga Tonga–Hunga Ha'apai volcanic eruption and their global propagation in the mesosphere/lower thermosphere observed by meteor radars and modeled with the High-Altitude general Mechanistic Circulation Model
No full textThe Hunga Tonga–Hunga Ha′apai volcano erupted on 15 January 2022, launching Lamb waves and gravity waves into the atmosphere. In this study, we present results using 13 globally distributed meteor radars and identify the volcanogenic gravity waves in the mesospheric/lower thermospheric winds. Leveraging the High-Altitude Mechanistic general Circulation Model (HIAMCM), we compare the global propagation of these gravity waves. We observed an eastward-propagating gravity wave packet with an observed phase speed of 240 ± 5.7 m s−1 and a westward-propagating gravity wave with an observed phase speed of 166.5 ± 6.4 m s−1. We identified these waves in HIAMCM and obtained very good agreement of the observed phase speeds of 239.5 ± 4.3 and 162.2 ± 6.1 m s−1 for the eastward the westward waves, respectively. Considering that HIAMCM perturbations in the mesosphere/lower thermosphere were the result of the secondary waves generated by the dissipation of the primary gravity waves from the volcanic eruption, this affirms the importance of higher-order wave generation. Furthermore, based on meteor radar observations of the gravity wave propagation around the globe, we estimate the eruption time to be within 6 min of the nominal value of 15 January 2022 04:15 UTC, and we localized the volcanic eruption to be within 78 km relative to the World Geodetic System 84 coordinates of the volcano, confirming our estimates to be realistic
Die neuzeitlichen Handschriften der Nullgruppe (Ms 01-0300): Beschrieben von Detlef Döring
No full textDer Katalog neuzeitlicher Handschriften erschließt ca. zwei Drittel der Manuskripte des 16. bis 20. Jahrhunderts, die sich im Besitz der Leipziger Universitätsbibliothek befinden. Die inhaltlichen Schwerpunkte der Sammlung liegen bei Texten zur Wissenschafts- und Bildungsgeschichte und zur Stadt- und Landeshistorie (vor allem des mittel- und ostdeutschen Raumes). Es handelt sich im überwiegenden Maße um Briefsammlungen (oft Nachlässe), Vorlesungsnachschriften, Kollektaneen zu bestimmten Themen, Chroniken und Werkmanuskripte. Quantitativ überwiegen Handschriften der Frühen Neuzeit. Ein erheblicher Teil dieser Materialien ist von der bisherigen Forschung kaum oder überhaupt nicht berücksichtigt worden. Der Katalog enthält ein Personen- und Ortsregister
Integration of the Butina algorithm and ensemble learning strategies for the advancement of a pharmacophore ligand-based model: an in silico investigation of apelin agonists
No full textIntroduction: 3D pharmacophore models describe the ligand’s chemical interactions in their bioactive conformation. They offer a simple but sophisticated approach to decipher the chemically encoded ligand information, making them a valuable tool in drug design.
Methods: Our research summarized the key studies for applying 3D pharmacophore models in virtual screening for 6,944 compounds of APJ receptor agonists. Recent advances in clustering algorithms and ensemble methods have enabled classical pharmacophore modeling to evolve into more flexible and knowledge-driven techniques. Butina clustering categorizes molecules based on their structural similarity (indicated by the Tanimoto coefficient) to create a structurally diverse training dataset. The learning method combines various individual pharmacophore models into a set of pharmacophore models for pharmacophore space optimization in virtual screening.
Results: This approach was evaluated on Apelin datasets and afforded good screening performance, as proven by Receiver Operating Characteristic (AUC score of 0.994 ± 0.007), enrichment factor of (EF1% of 50.07 ± 0.211), Güner-Henry score of 0.956 ± 0.015, and F-measure of 0.911 ± 0.031.
Discussion: Although one of the high-scoring models achieved statistically superior results in each dataset (AUC of 0.82; an EF1% of 19.466; GH of 0.131 and F1-score of 0.071), the ensemble learning method including voting and stacking method balanced the shortcomings of each model and passed with close performance measures
A novel experimental model of Cryptococcus neoformans-related immune reconstitution inflammatory syndrome (IRIS) provides insights into pathogenesis
No full textAntiretroviral therapy (ART) has yielded major advances in fighting the HIV pandemic
by restoring protective immunity. However, a significant proportion of HIV patients coinfected
with the opportunistic fungal pathogen Cryptococcus neoformans paradoxically
develops a life-threatening immune reconstitution inflammatory syndrome (IRIS) during
antiretroviral therapy. Despite several clinical studies, the underlying pathomechanisms
are poorly understood. Here, we present the first mouse model of cryptococcal
IRIS that allows for a detailed analysis of disease development. Lymphocyte-deficient
RAG-1−/− mice are infected with C. neoformans and 4 weeks later adoptively transferred
with purified CD4+ T cells. Reconstitution of CD4+ T cells is sufficient to induce a severe
inflammatory disease similar to clinical IRIS in C. neoformans-infected RAG-1−/− mice of
different genetic backgrounds and immunological phenotypes (i.e. C57BL/6 and BALB/c).
Multiorgan inflammation is accompanied by a systemic release of distinct proinflammatory
cytokines, i.e. IFN-γ, IL-6, and TNF-α. IRIS development is characterized by infectiondependent
activation of donor CD4+ T cells, which are the source of IFN-γ. Interestingly,
IFN-γ-mediated effects are not required for disease induction. Taken together, this novel
mouse model of cryptococcal IRIS provides a useful tool to verify potential mechanisms
of pathogenesis, revealing targets for diagnosis and therapeutic interventions
Percutaneous Left Atrial Appendage Occlusion: Current Evidence and Future Directions
No full textOver the past two decades, percutaneous left atrial appendage occlusion (LAAO) has
proven to be a viable alternative to oral anticoagulation (OAC) for stroke prevention in patients with
atrial fibrillation (AF), in particular in those patients who are at increased risk for stroke and bleeding
complications. This systematic review provides a comprehensive evaluation of anatomical features,
patient selection, procedural planning and execution, complications, medical treatment following the
procedure, and contemporary outcome data
Steady-state versus chemotherapy-based hematopoietic cell mobilization after anti-CD38-based induction therapy in newly diagnosed multiple myeloma
No full textThe incorporation of anti-CD38 monoclonal antibodies (mAb) in induction regimens of newly diagnosed transplant-eligible multiple myeloma (MM) patients has been established as a new standard. However, the optimal strategy of stem cell mobilization in this context is not yet clear