Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with rising global incidence. Merkel cell polyomavirus (MCV) was discovered in 2008 in 80% of MCC samples and since then a causal link between MCV and the majority of MCC cases has been established. microRNAs (miRNA, miR) are a family of small non-coding RNAs which play a key role in post-transcriptional regulation of gene expression and are considered significant players in disease and development in many species. Whilst the focus of MCV research has thus far been on the oncogenic MCV early proteins, large tumour (LT) and small tumour (sT) antigens, there is a knowledge gap regarding MCV miRNA and its functional significance in MCV pathogenesis. Given the emerging importance of viral miRNAs in virus-host interaction and pathogenesis, the aim of this doctoral research project was to investigate alterations in host cell transcripts induced by MCV miRNA and determine any functional significance these might have on virus-host cell interaction. RNA sequencing (RNA-Seq) in the presence and absence of MCV miRNA uncovered a multitude of downregulated cellular transcripts. Gene ontology analysis revealed that MCV miRNA targets transcripts associated with multiple cellular processes, however, regulation of immune response was overrepresented in our datasets. Validation of RNA-Seq data using MCV miRNA mimics and a synthetic, fully replicative MCV genome (MCVSyn) confirmed RNA-Seq data at mRNA and protein expression level for several targets, including the cytokine stimulating gene, SP100, and the neutrophil stimulator chemokine, CXCL8. Moreover, dual luciferase assays revealed that SP100 and MAPK10 (a member of mitogen-activated protein kinases (MAPK) family which is involved in regulation of CXCL8 expression) are directly and specifically targeted and downregulated by MCV miRNA. The MCV miRNA-dependent dysregulation of CXCL8 secretion is associated with impaired neutrophil migration, suggesting that the virus miRNA may be implicated in evasion of the host immune response.

Background: Iron deficiency, anemia, and iron excess have been associated with altered hearing functions in children and adults. Animal studies suggest that iron deficiency during pregnancy negatively affect fetal auditory development. The relationship between maternal iron status and auditory functions in healthy term newborns has not been clearly elucidated among humans. The goal of this pilot study was to determine the relationship between markers of iron status during pregnancy and brainstem auditory function in healthy neonates. Methods: Pregnant women who gave birth at the Montfort Hospital were recruited to take part in this study (n=6). Within two weeks after birth, their newborn’s hearing function was assessed by wave amplitude, latency and inter-latency from the Auditory Brainstem Response (ABR) test. Markers of iron status, namely hemoglobin (Hb) and mean corpuscular volume (MCV), were collected retrospectively for the first and second trimester from the women’s medical chart. Results: Overall, no significant relationship was observed between maternal Hb and MCV concentrations and newborns auditory function. Although two significant Spearman correlations were observed (MCV and inter-latency I-V; r=0.87; p=0.005 and Hb and amplitude V; r=0.89; p=0.04), these findings may be due to chance because of multiple testing and the small sample size. Conclusion: Although iron is a key nutrient involved in the brain and auditory system development, we were not able to demonstrate a relationship between iron status during pregnancy and newborn hearing function. Prospective or intervention studies with a larger sample size and with more specific iron markers (ex. ferritin) are required to confirm these findings.

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The Master’s thesis deals with the precision of machine tools, especially with the three-axis vertical milling machine. It is structurally divided into a theoretical and practical part. While the theoretical part focuses on problems of geometric errors and measuring devices, the practical one is devoted to the machine tool being tested. In this case, the data processing and the proposed statistical analysis are essential, and at the end of the thesis another possible way of developing the data processing is outlined.

Sickle cell disease is a disabling chronic autosomal recessive blood disease characterized by abnormal hemoglobin, pain crises, and frequent emergency department visits. Adherence to hydroxyurea therapy has been shown to improve these patient outcomes. Guided by the theory of comfort, the purpose of this project was to determine if an educational intervention would increase adherence to hydroxyurea therapy in pediatric patients between 2 and 17 years of age recruited from an urban university hospital hematology clinic. The RE-AIM model was used to support the translation of evidence and the change process. An educational video produced by AFLAC was viewed by patients' parents 4 weeks after enrollment into this pretest/posttest design project. A total of 22 African-American parent participants completed the 8-item Morisky Medication Adherence Scale at baseline and again at 8 weeks to assess hydroxyurea adherence. The Short Test of Functional Health Literacy in Adults tool was used to assess parents' health learning needs; all parents met the adequate literacy level at baseline. Using t test statistics, no statistically significant differences were found pretest to posttest on the Morisky Medication Adherence Scale scores, mean corpuscular hemoglobin, and fetal hemoglobin percentages. Wilcoxon Signed Rank tests showed no significant differences in emergency room visits nor number of pain crisis. Although no significant changes emerged in short-term hematologic findings, emergency room visits, and pain crises, social change in the health care setting was promoted by confirming parents were able to understand education and a high level of hydroxyurea adherence was maintained; literature indicated that long-term adherence to hydroxyurea limits severe attacks.

Multi-combination vehicles (MCVs) in urban areas impact on productivity, safety, infrastructure, congestion and the environment. However, psychological effects of MCVs on other drivers may also influence the positioning of vehicles and congestion. A literature review revealed little information on the psychological effects of heavy vehicles on other road users. This research can be used to quantify some psychological impacts of MCVs. A testing program was undertaken on the Gateway Motorway to observe passenger car behaviour around MCVs in a lateral and longitudinal sense. Video footage was collected on a four lane divided urban motorway section which was level, straight and away from any off/on ramps. It experiences high traffic volumes with a one-way AADT of approximately 33,500. The route is currently designated for B-doubles, which is the most common MCV in urban areas. In a lateral sense, the research showed that passenger car behaviour changes around heavy vehicles (prime mover semi-trailer combination and B-doubles); however, there is no statistical difference in passenger car behaviour around semi-trailers and B-doubles. Longitudinally it was found that, even though passenger cars shy away from B-doubles more than semi-trailers, B-doubles are still more efficient in a spatial sense since they carry more freight. The outcomes of this research indicate that there is no further psychological impact on passenger cars, when travelling around B-doubles compared with semi-trailers. Where the results identified longitudinal behaviour changes, it was still concluded that B-doubles were more efficient at transporting freight when the passenger car equivalent (PCE) per tonne of freight was considered. Tracking ability testing was undertaken in a rural area to determine the lateral spatial requirements of three different MCVs. The rural testing was considered appropriate since parts of the urban network have similar characteristics to rural networks. A model was developed as a part of this project to process the data collected by Haldane (2002), but results could not be relied upon due to poor quality data.

The Master’s thesis deals with design of digital twins of machine tools and application of designed procedure on a case study – digital twin of the machine tool MCV 754 Quick. In the first part are described current roles of digital twins in the field of machine tools and also hardware and software options for creating them. Software and hardware tools by Siemens (Mechatronics Concept Designer and SIMIT) are used for the case study. The complex procedure of creating the digital twin is designed in the second part, starting with preparation of a model, ending with the virtual commissioning of the machine tool MCV 754 Quick. The procedure is described in detail, including preparation of 3D model of the machine tool, assignment of physical properties and joints, preparation of PLC, connection all the elements of the whole system: Sinumerik – SIMIT – Mechatronics Concept Designer and controlling the twin via CNC automation system. Output of the thesis is the virtually commissioned machine tool, capable of being controlled by Sinumerik 840D sl. This is the first step in development of the full-fledged digital twin of machine tool, which can be used for testing the functionality and capability of this new technology in industry.

No description available.