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Many chronic diseases manifest themselves in prolonged inflammation and often ignored dysregulated lipid metabolism, both also associated with inhalation of certain nanomaterials. Limited knowledge of involved molecular events and their causal connections prevents reliable prediction of outcomes by efficient testing strategies. To unravel how acute nanomaterial exposure leads to chronic conditions, we employed advanced microscopy and omics in vitro , in vivo and in silico . For selected metal-oxide nanomaterials, we show that epithelial cells survive the exposure by excreting internalized nanomaterials and passivating them on the surface, employing elevated lipid synthesis. Macrophages, on the contrary, attack the defending epithelium but die degrading passivized complexes, releasing nanomaterial, which is reuptaken by epithelial cells. Constant proinflammatory signalling recruits new phagocytes that feed the vicious cycle of events resulting in a long-lasting response to a single exposure. The discovered mechanism predicts the nanomaterial-associated in vivo chronic outcomes based on simple in vitro measurements and potentially enlightens other chronic diseases. Graphical abstract

We are daily exposed to a multitude of health hazardous airborne particulate matter with notable deposition in the fragile alveolar region of our lungs. Hence, there is a great need for identification and prediction of material-associated diseases, currently hindered due to the lack of in-depth understanding of causal relationships, in particular between acute exposures and chronic symptoms. By applying advanced microscopies and omics to in vitro and in vivo systems, together with in silico molecular modelling, we have here determined that the long-lasting response to a single exposure can originate from the interplay between the newly discovered nanomaterial quarantining and nanomaterial cycling between different lung cell types. This new insight finally allows us to predict the spectrum of lung inflammation associated with materials of interest using only in vitro measurements and in silico modelling potentially relating outcomes to material properties for large number of materials thus boosting safe-by-design-based material development. Because of its profound implications for animal-free predictive toxicology, our work paves the way to a more efficient and hazard-free introduction of numerous new advanced materials into our lives.

International audience; On a daily basis, people are exposed to a multitude of health-hazardous airborne particulate matter with notable deposition in the fragile alveolar region of the lungs. Hence, there is a great need for identification and prediction of material-associated diseases, currently hindered due to the lack of in-depth understanding of causal relationships, in particular between acute exposures and chronic symptoms. By applying advanced microscopies and omics to in vitro and in vivo systems, together with in silico molecular modeling, it is determined herein that the long-lasting response to a single exposure can originate from the interplay between the newly discovered nanomaterial quarantining and nanomaterial cycling between different lung cell types. This new insight finally allows prediction of the spectrum of lung inflammation associated with materials of interest using only in vitro measurements and in silico modeling, potentially relating outcomes to material properties for a large number of materials, and thus boosting safe-by-design-based material development. Because of its profound implications for animal-free predictive toxicology, this work paves the way to a more efficient and hazard-free introduction of numerous new advanced materials into our lives.

Helium Ion Microscopy (HIM) has not been thoroughly exploited for biological studies addressing relevant questions that range from the cellular to the subcellular level. One of the benefits of HIM compared to other high-resolution imaging techniques is definitely the large depth of focus, sub-nm resolution, nm surface sensitivity, and especially that no sample coating is needed that can change the nanostructure morphology on the surface. The prerequisite to getting the most from the technique is thus the appropriate sample preparation. Besides, to get the most from understanding the addressed biological question, a successful correlative microscopy approach is necessary. This is best shown in our recently published study (H Kokot, Advanced Materials, 2020), where we have addressed one of the most critical issues in toxicology, that is the poor understanding of chronic inflammation initiation in lung tissue caused by inhaled nanoparticles, with the correlative microscopy approach using advanced multimodal optical microscopy and HIM. HIM nicely revealed the TiO2 nanotube organization and passivation on the cell surface and confirmed lipid and protein binding to the TiO2 surface (Figure below), identified as well by in silico simulations. In brief, HIM is an extremely powerful technique for the surface, and in the case of porous samples also in-depth morphology characterization on an nm scale. In combination with complementary imaging techniques and proper sample preparation, many relevant biological questions can be addressed and solved. Still, there are many limitations and challenges in cell preparation and imaging using helium ions, such as imaging of internal structures, definitely pursuing discussions and new developments in the future.

Kvaliteten informacijski sistem je eden izmed temeljev vsake organizacije. Diplomsko delo z naslovom Prenova modula informacijskega sistema za vodenje disciplinskih kazni pri Nogometni zvezi Slovenije je smernica načrtovanju ostalih modulov informacijskega sistema NZS. Quality information system is one of the cornerstones of any organization. Reengineering of module for managing disciplinary measures at Slovenian Football Association is a guideline planning other modules of the information system of Slovenian FA.

Naloga se ukvarja z varnostjo v informacijskih sistemih. Informacijski sistemi zaradi izjemnega tehnološkega razvoja postajajo vse bolj kompleksni. Zakonodaja s tega področja se zato neprestano spreminja in dopolnjuje. V nalogi sem poskušal ugotoviti, kaj je potrebno, da informacijski sistemi delujejo varno in zanesljivo. Šele takrat se lahko začnejo povezovati med seboj. To pa je za prihodnjo konkurenčno sposobnost gospodarstva zelo pomembno. The subject of this dissertation is safety in information systems. The information systems are becoming increasingly more complex due to the extremely rapid technological development. Legislation governing this field is therefore being constantly amended and upgraded . In this dissertation I try to find out what is necessary for safe and reliable functioning of the information systems. Such functioning is the prerequisite for their interconnection. And this is very important for the competitive capacity of the economy in the future.

Presentations given at the 11th annual conference of the Undergraduate Linguistics Association of Britain, hosted online 16-18 April 2021 by the University of Aberdeen.