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Memristor with optically tunable dynamics
Item type: Dataset
Christoph, Weilenmann; Kevin, Portner; Till, Zellweger; et al. (2022)
Characterization of immune escape mechanisms in colorectal cancer organoids.
Item type: Doctoral Thesis
Lewków, Bohdan (2025)
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, despite the development of novel immunotherapies. The efficacy of these therapies is frequently limited due to the low antigenicity of CRC, which is largely attributable to its genomic stability and low mutational burden. Many CRC tumours also exhibit immunosuppressive traits that enable progression despite an intact and functional immune system. Furthermore, disseminating metastatic tumour cells can evade immune elimination even in the absence of an immunosuppressive tumour microenvironment. This dissertation investigates novel immune evasive mechanisms in CRC that contribute to immune evasion and metastatic progression.
The human immune system comprises two major components: the innate immune system, responsible for rapid, non-specific responses, and the adaptive immune system, mediating targeted long-term protection. In this research, I utilized colorectal cancer organoid co-cultures, a three-dimensional tissue culture system, to model interactions between CRC and selected
populations of immune cells, enabling the study of immune-evasive events during metastatic dissemination.
In the first part of this work, I demonstrate that a small fraction of patient-derived CRC organoids evades direct killing by natural killer (NK) cells, the cytotoxic effectors of the innate immune system. NK cells preferentially eliminated CRC organoids over healthy control organoids, confirming their selective activation. A subpopulation of evading CRC organoids was characterized, and mediators of evasion were identified through transcriptomic analysis and CRISPRa screening. These mediators were experimentally validated using loss-of-function models and pharmacological inhibition, confirming their role in resistance to NK cell-mediated cytotoxicity. The primary mechanism of evasion was linked to MUC1-expressing cells displaying a loss of stemness, where MUC1 activation promoted STAT3-mediated expression of antiapoptotic genes, thereby protecting these cells from NK cell-induced apoptosis.
The second part of the thesis focuses on immune-evasive mechanisms of CRC in CD4⁺ T cell mediated responses. I show that CRC cells express MHC class II machinery, a feature typically restricted to professional antigen-presenting cells. This expression was recapitulated in vitro in both human and mouse organoids. Using an antigen-specific presentation system, I demonstrate that mouse CRC organoids are capable of processing and presenting endogenous antigens via MHC-II and activating effector Th1 CD4⁺ T cells. However, these organoids failed to activate naïve CD4⁺ T cells due to the absence of co-stimulatory signals. The functional relevance of MHC-II expression was further verified in vivo, where MHC-II-expressing and -deficient organoids were co-injected via the mesenteric vein. While metastasis size did not differ, MHC-II-deficient
organoids produced significantly fewer metastatic lesions, suggesting that tumour-specific MHC-II expression can confer resistance to immune elimination during early metastatic events.
Collectively, this dissertation provides novel insights into strategies employed by colorectal cancer cells to evade recognition by both innate and adaptive immune systems. The mechanisms described here highlight potential avenues for the development of new therapeutic interventions for CRC patients.
Monitoring Short-Term Glacier Mass Balance Variations
Item type: Monograph
Cremona, Aaron (2025)
Glaciers worldwide are melting at unprecedented rates, driven by ever-increasing climate change. Glacier melting affects society and economy on several fronts, impacting natural hazards, water supply and hydropower production, tourism, and sea level rise. Aiming to understand and quantify these impacts has driven substantial developments related to glacier mass balance monitoring, relying on direct measurements, remote sensing observations, and mathematical models. Despite significant advancements in the field, monitoring short-term mass balance variations, i.e. at the daily to weekly scale, is hindered by the lack of observational data and thus only sparsely explored.
Direct observation of core-shell structure and water uptake of individual submicron urban aerosol particles
Item type: Journal Article
Man, Ruiqi; Zhu, Yishu; Wu, Zhijun; et al. (2026)
Determining the particle chemical morphology is crucial for unraveling reactive uptake in atmospheric multiphase and heterogeneous chemistry. However, it remains challenging due to the complexity and inhomogeneity of aerosol particles. Using a scanning transmission X-ray microscopy (STXM) coupled with near-edge X-ray absorption fine structure (NEXAFS) spectroscopy and an environmental cell, we imaged and quantified the chemical morphology and hygroscopic behavior of individual submicron urban aerosol particles. Results show that internally mixed particles composed of organic carbon and inorganic matter (OCIn) dominated the particle population (73.1±7.4 %). At 86 % relative humidity, 41.6 % of the particles took up water, with OCIn particles constituting 76.8 % of these hygroscopic particles. Most particles exhibited a core-shell structure under both dry and humid conditions, with an inorganic core and an organic shell. Our findings provide direct observational evidence of the core-shell structure and water uptake behavior of typical urban aerosols, which underscore the importance of incorporating the core-shell structure into models for predicting the reactive uptake coefficient of heterogeneous reactions.
Electrified Fish Guidance and Intake Racks for Safe Downstream Fish Passage at Water Intakes
Item type: Monograph
Moldenhauer-Roth, Anita (2025)
The ecological sustainability of hydropower production is increasingly scrutinized due to its adverse effects on aquatic ecosystems, particularly the disruption of up- and down stream fish migration, hydropeaking and sediment continuity. Run-of-river hydropower plants (HPPs), along with associated infrastructure such as dams and weirs and intakes of diversion power plants, obstruct natural fish movement, resulting in delays, physical injuries, or mortality during turbine or spillway passage. This doctoral research addresses the need for cost effective, scalable, and operationally feasible fish protection measures at HPPs, with a focus on electrified racks.