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Scribes and Scribal Practice in Fifteenth-Century Iceland: A Study on the Evolution of Script and Language.
(University of Iceland, School of Humanities, Faculty of Icelandic and Comparative Cultural Studies, 2026-06-19) Pagani, Roberto Luigi; Haraldur Bernharðsson; Faculty of Icelandic and Comparative Cultural Studies (UI); Íslensku- og menningardeild (HÍ); School of Humanities (UI); Hugvísindasvið (HÍ)
This dissertation investigates Icelandic scribal and linguistic practices during the socalled “long” fifteenth century, roughly spanning from the late fourteenth century to the early sixteenth. The period has traditionally been regarded as one of stagnation in both language and script, yet such an assessment has rarely been tested through systematic analysis. The present study re-examines this assumption by tracing selected palaeographic and orthographic developments across a corpus of fifty scribal hands drawn from manuscripts dated between c. 1375 and c. 1525. Three palaeographic and seven linguistic features were selected on the basis of their frequency, diagnostic value, and chronological sensitivity. These include, among others, the distribution of forms of the letter “a”, of the tall “s” and of the “r” rotunda on the one hand, and on the other the fricativisation of unstressed wordfinal k, the diphthongisation of e before ng and that of é, the drop of intervocalic g before i/j, the u-epenthesis, and the orthographic representation of palatal consonants. Data were gathered through systematic random sampling of images of manuscript texts and converted into quantitative tables allowing comparison between conservative and innovative forms. The results demonstrate that the fifteenth century was not a static period but rather one characterised by gradual and uneven change. Certain features reveal clear chronological trajectories, while others display persistent coexistence of competing forms. When the individual profiles of scribal hands are compared, no coherent clusters emerge that could correspond to geographical or institutional affiliations, suggesting a highly individualised scribal practice which challenges the notion of “scribal schools” or “scribal milieu”. The combination of palaeographic and linguistic data thus provides a more nuanced picture of late-medieval Icelandic manuscript culture. Far from representing a period of decline, the “long” fifteenth century appears as a dynamic phase of transition, bridging the classical and early modern stages of Icelandic writing. Not least, the findings offer a basis for refining the dating of broadly-dated manuscripts and for reassessing the evolution of Icelandic orthography and script.
Verk
Extending the Limits of Monitorability
(2026) Xuereb, Jasmine; Achilleos, Antonios; Francalanza, Adrian; Department of Computer Science
One of the most fundamental and long-standing issues in computer science is making sure that a system behaves as intended. To address this challenge, systems may be verified dynamically using a lightweight monitoring technique called runtime verification. Even though runtime verification circumvents issues associated with traditional techniques, it is limited by the fact that observations are typically constrained to the current computation path of the system. This limitation is even more acute for correctness properties describing the system’s computational graph, known as branching-time properties. This thesis investigates whether runtime verification can be extended to meaningfully verify a wider range of branching-time properties. We depart from the classical setup where monitoring is limited to a single execution and investigate the enhanced observational capabilities when monitoring a system over multiple runs. To ensure generality in our results, we focus on branching-time properties expressed in the modal mu-calculus, a well-studied foundational logic used by state-of-the-art model checkers. As part of a comprehensive theory, the first part of this thesis focuses on deterministic systems and demonstrates that the proposed multi-run monitoring setup can systematically extend previously established monitorability limits for branching-time properties. The second part extends the multi-run framework and corresponding results to systems that may exhibit non-deterministic behaviour. To show that the proposed setup is implementable, the third part outlines the steps for a full automation, as well as proves bounds that capture the correspondence between the syntactic structure of a property and the number of system runs required to adequately verify it. We also validate our results by instantiating the proposed multi-run monitoring setup to verify actor-based concurrent systems, a widely used concurrency paradigm. Given that these systems are inherently non-deterministic, the fourth part presents a general study of a highly non-deterministic calculus, where we systematically explore how the defining characteristics of the actor model enable the recovery of a certain degree of determinism.
Verk
The non-antibacterial mechanism of action of azithromycin and other macrolides in respiratory epithelium
(University of Iceland, School of Health Sciences, Faculty of Medicine, 2026-06) Asbjarnarson , Arni; Þórarinn Guðjónsson; Faculty of Medicine (UI); Læknadeild (HÍ); School of Health Sciences (UI); Heilbrigðisvísindasvið (HÍ)
Epithelial barrier failure is a common denominator in multiple acute and chronic respiratory diseases. The respiratory epithelial barrier presents the first line of defence against infectious agents and other particulate matter; continuous exposure of epithelial cells results in molecular and phenotypic changes that evoke conditions such as inflammation, fibrosis, and epithelial-to-mesenchymal transition (EMT). Macrolide antibiotics are known for their off-label use in treatments of chronic respiratory diseases (CRD), primarily due to their anti-inflammatory and immunomodulatory effects. Azithromycin (AZM), in particular, has been recognized for its use in decreasing the frequency of CRD exacerbations. Our research group has previously shown that AZM maintains bronchial epithelial integrity in air-liquid interface (ALI) cell culture conditions. However, the mechanisms underlying this effect are not completely known. The aim of this thesis is to understand the non-antibiotic mechanism of action of macrolides, particularly AZM, in modulation of barrier integrity and metabolism of bronchial epithelial cells. In paper I, the effects of different macrolides (AZM, clarithromycin, erythromycin, roxithromycin and solithromycin) on gene expression and epithelial integrity in ALI culture were compared. AZM treatment, when compared to other macrolides, drastically enhanced barrier integrity, induced phospholipid retention and vesicle build-up. Analysis of gene sequencing data sets revealed AZM treatment distinctly enriched several gene sets, most notably increasing the expression of genes related to keratinocyte differentiation, establishment of skin barrier and downregulation of EMT pathways. The focus of Paper II was the potential role of AZM in EMT. AZM inhibited TGF-β1-induced upregulation of SNAI1, N-cadherin and vimentin, key features of EMT. Furthermore, AZM reduced the expression of caveolin-1 that has previously been linked to EMT. The data presented in Paper II report a potential mechanism by which AZM inhibits EMT via depletion of caveolin-1 and cholesterol from the cell membrane through their transport to a perinuclear location. The aim of Paper III was to expand on and compare the effects of the same macrolide antibiotics as those examined in Paper I, but with a focus on oxidative phosphorylation and mitochondrial function. Macrolide treatment indirectly decreased mitochondrial respiration and lowered protein levels of electron transport chain proteins. However, only AZM treatment caused an increase in reactive oxygen species at 72 hours post treatment along with a downstream increase in lipid peroxidation. The antioxidant pathway of KEAP1/NRF2 was activated and gene expression data from longer treatments (14 and 21 days) in ALI culture revealed that AZM initiated mitochondrial dynamic and protective pathways through mitohormesis. In Paper IV, AZM was compared to a nonantibacterial derivative of AZM (EP395) to determine whether the effects of AZM are distinct from its antimicrobial activity. It was shown that EP395 retained the barrier integrity enhancing capabilities of AZM along with positive enrichment of the same gene sets found to be uniquely affected by AZM treatment, indicating that these effects are distinct from the antibacterial activity. Papers V and VI focused on ventilatorinduced lung injury (VILI) in a rodent model where it was investigated whether macrolides ameliorate the negative effects caused by mechanical ventilation. It was shown that barrier failure correlated with increased expression of the pro-inflammatory cytokine IL-6 and higher tidal volumes. Furthermore, increased oxidative stress and phenotypic changes in mitochondria were observed. Finally, we reported that AZM and EP317, another derivative of AZM with reduced antibacterial activity, ameliorated pulmonary oedema, enhanced barrier integrity, and attenuated inflammatory responses caused by ventilation. Collectively, I have shown that AZM has greater effects on bronchial epithelial barrier integrity than other macrolides, that it inhibits EMT and fortifies mitochondrial resilience. I propose possible mechanistic pathways involved in the beneficial effects of AZM treatment, while recognising that additional research is needed to fully uncover AZM’s involvement in the discussed pathways.
Verk
BDPA radicals for DNP-NMR and a new method for RNA spin-labeling
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Physical Sciences, 2026-06-16) Ahmad, Iram; Snorri Þór Sigurðsson; Faculty of Physical Sciences (UI); Raunvísindadeild (HÍ); School of Engineering and Natural Sciences (UI); Verkfræði- og náttúruvísindasvið (HÍ)
Dynamic nuclear polarization (DNP) is a powerful approach for overcoming the low sensitivity of nuclear magnetic resonance (NMR) spectroscopy and has extensive applications in the study of both materials and biological systems. Electron paramagnetic resonance (EPR) and fluorescence spectroscopy are highly important complementary techniques and are particularly valuable for studying nucleic acid structure and dynamics. The broader application of these methods, however, depends on the availability of suitable polarizing agents and site-specific spectroscopic probes, respectively. This thesis focuses on the development of 1,3 bisdiphenylene-2-phenylallyl (BDPA)-based polarizing agents for DNP-NMR and a facile spin labeling strategy for nucleic acids. The first part describes the development of tailored BDPA derivatives for high-field DNPNMR. The synthesis of the key precursor, tetrabromo BDPA, was first optimized. A tetraazide-BDPA building block was subsequently prepared, enabling conjugation to a variety of alkynes via copper-catalyzed azide-alkyne cycloaddition. Using this strategy, four BDPA derivatives with varied polarity, size, and steric shielding were prepared. Of these, a BDPA-dendrimer derivative exhibited enhanced persistence and superior DNP performance, achieving the highest liquid-state DNP enhancement reported to date in viscous solutions. The second part describes a noncovalent RNA spin labeling strategy based on helical stacking of small RNA hairpins, containing the rigid spin label Çm, on RNA duplexes. Complementary overhangs promoted efficient hairpin-duplex stacking, monitored by EPR spectroscopy. In addition, collaborative projects involving incorporation of rigid and semirigid spin labels and fluorophores in nucleic acids to study their structure, dynamics and interactions with proteins using EPR and fluorescence spectroscopies, are recounted.
Verk
Development of AsymPol- and bTurea-Derived Bis-Nitroxides for DNP-Enhanced NMR in Biological Systems
(University of Iceland, School of Engineering and Natural Sciences, Faculty of Physical Sciences, 2026-06-16) Wilson, Ancy Trisha; Snorri Þór Sigurðsson; Faculty of Physical Sciences (UI); Raunvísindadeild (HÍ); School of Engineering and Natural Sciences (UI); Verkfræði- og náttúruvísindasvið (HÍ)
Dynamic nuclear polarization (DNP)-enhanced solid-state nuclear magnetic resonance (NMR) spectroscopy has emerged as a powerful technique to unravel complex biomolecular structures at atomistic resolution. DNP serves to overcome the inherent insensitivity of NMR by the polarization transfer from unpaired electrons to nuclei of interest under microwave irradiation. The sensitivity gain conferred by DNP enables the detection of biomolecules at their physiological concentration. Nitroxide biradicals have shown to be excellent polarizing agents at 9.4 T and 14.1 T, prompting our interest in utilizing them to investigate complex systems via DNP-NMR. However, their broader applicability is limited by several factors, including synthetic challenges, lack of specificity, poor aqueous solubility, and rapid reduction in a reducing environment. This thesis describes the development of synthetic strategies for nitroxide-based biradicals to address these limitations. Firstly, a series of AsymPol-derivatives, including an isothiocyanate, a tetrazine, a maleimide, a cholesterolbased tripod, and an azide, was synthesized to enable targeting of diverse systems ranging from biomolecules to materials. These radicals enabled targeted DNP, which allows selective enhancement of signals from specific sites. Secondly, bTurea-derived bcTCOOKs and bcTmols were developed as readily accessible and water-soluble derivatives to address synthetic limitations associated with highly performing bis-nitroxide biradicals. Among these, bcTCOOK-M2 was the highest yielding and exhibited particularly high DNP sensitivity. Finally, a synthetic strategy was established for highly water-soluble, reductionresistant nitroxide radicals (43 and 44) for in-cell DNP applications. Their stability in the presence of ascorbic acid was evaluated and compared with known radicals; however, they did not exhibit sufficient stability under reductive conditions.

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