Novel entities may pose risks to humans and the environment. The small particle size and relatively large surface area of micro- and nanoparticles (MNPs) make them capable of adsorbing other novel... Show moreNovel entities may pose risks to humans and the environment. The small particle size and relatively large surface area of micro- and nanoparticles (MNPs) make them capable of adsorbing other novel entities, leading to the formation of aggregated contamination. In this dissertation, we utilized advanced computational methods, such as molecular simulation, data mining, machine learning, and quantitative structure-activity relationship modeling. These methods were used to investigate the mechanisms of interaction between MNPs and other novel entities, the joint toxic action of MNPs and other novel entities, the factors affecting their joint toxicity to ecological species, as well as to quantitatively predict the interaction forces between MNPs and other novel entities, and the toxicity of their mixtures. The results indicate that understanding the mechanisms of interactions between novel entities and their modes of joint toxic action can provide an important theoretical basis for establishing effective risk assessment procedures to mitigate the effects of novel entities on ecosystems and human health. Furthermore, this dissertation provides important technical support and a practical basis for the quantitative prediction of the environmental behavior and toxicological effects of novel entities and their mixtures by applying various advanced in silico methods individually or in combination. Show less
Metagenomics enables the detection of all the genetic material of organisms present in a sample, making it a pathogen-agnostic approach for detecting common and rare or novel pathogens that are not... Show moreMetagenomics enables the detection of all the genetic material of organisms present in a sample, making it a pathogen-agnostic approach for detecting common and rare or novel pathogens that are not included in conventional testing. Beforehand, a clinician does not need to have a hypothesis of what pathogen is expected, unlike traditional polymerase chain reaction (PCR) testing.This thesis is focusing on diagnostic yield, clinical findings, and enhancing technical opportunities in viral metagenomics. The identification, typing, and quantification of viruses by means of viral metagenomics as a diagnostic tool are evaluated. Technical aspects are appraised for improved sensitivity and specificity of the wet and dry (bioinformatic) lab components of viral metagenomics. The use of a metagenomic protocol for virus discovery directly in a patient sample is assessed, and the best methods and approaches for performing genetic analysis of the SARS-CoV-2 virus are investigated.Viral metagenomic testing results in the identification of more viruses, therefore it is a valuable addition to current diagnostic test protocols. Additionally, it is a useful test for virus discovery and monitoring during infectious disease outbreaks caused by novel viruses. Show less
The research described in this thesis focuses on the responses of lung epithelial cells lining the airways and alveoli. In the study, the effects of viruses that cause lung infections on these... Show moreThe research described in this thesis focuses on the responses of lung epithelial cells lining the airways and alveoli. In the study, the effects of viruses that cause lung infections on these epithelial cells were mapped in detail. Combinations with exposure to cigarette smoke were also included. To do this, epithelial cells obtained from lung tissue were cultured in the lab and exposed to rhinovirus, a common cold virus, and to SARS-CoV-2, which causes COVID-19. Exposure of the epithelial cells to these viruses induces very specific reactions in the airway epithelium. These can be further affected by cigarette smoke. The results of our research have taught us more about the processes specifically involved in the different responses of the epithelium, and how external factors such as cigarette smoke influence these responses. For example, we now better understand how cigarette smoke leads to a higher infection rate of rhinovirus, and it has become clear that the response of the airway epithelium to SARS-CoV-2 differs from the response to other coronaviruses. Our findings are therefore important for a better understanding of the role of viral infections in patients with chronic obstructive pulmonary disease (COPD), and for understanding what makes SARS-CoV-2 a unique virus. Show less
