Nickel superalloys in the aerospace industry

Import 05/08/2014Tato bakalářská práce pojednává o vysoce legovaných materiálech na bázi niklu tzv. superslitinách. Jejím cílem bylo popsat chemické složení, typ přítomných fází, zpevňující mechanizmy a procesy ovlivňující jejich životnost. V experimentální části se zabývá studiem superslitiny Inconel 625. U slitiny byla po naleptání kovu v základním stavu zkoumána struktura. Mikrostrukturní analýza byla provedena s využitím světelného mikroskopu.This bachelor's thesis discusses high-alloy materials for nickel-based superalloys called. Its aim was to describe the chemical composition, type of phases present, strengthening mechanisms and processes that affect their life. In the experimental part deals with the study of superalloy Inconel 625. The alloy was after etching metal in the ground state structure studied. Microstructural analysis was performed using a light microscope.636 - Katedra materiálového inženýrstvívelmi dobř

Implementation, Preservation and Improvement of the Quality Management System in a Selected Testing Laboratory According to ČSN EN ISO/IEC 17025: 2018 Standard

Tato diplomová práce se zabývá implementací normy ČSN EN ISO/IEC 17025:2018 na pracovišti 3D měření ve společnosti Hella Mohelnice. Hlavním záměrem bylo popsat změny nutné pro vytvoření vhodných podmínek, které vedly k úspěšnému zvládnutí akreditace. Práce je rozdělena do dvou částí. V první teoretické části je čtenářovi přiblížena norma ČSN EN ISO/IEC 17025:2018 a její struktura. Dále pak výhody její implementace a proces akreditace. Poté následuje kapitola s názvem management rizik, která analyzuje možná rizika s využitím různých metod a technik prevence rizik vedoucí k jejich eliminaci. Praktická část je zaměřená na popis pracoviště 3D měření a jeho přeměnu v závislosti na implementaci požadavků normy ČSN EN ISO/IEC 17025:2018. Mezi hlavní body tohoto oddílu patří řízení rizik týkající se nestrannosti, určení velikosti nejistoty měření v případě souřadnicového měřícího stroje, nastavení procesu zlepšování a celkové náklady na akreditaci dle normy ČSN EN ISO/IEC 17025:2018.This thesis deals with the implementation of ČSN EN ISO / IEC 17025:2018 in the workplace of 3D measurements in Hella Mohelnice company. The main intention was describing the changes for creating of the suitable conditions that lead to successful management of accreditation. The thesis is divided into two parts. The first theoretical part is introducing ČSN EN ISO / IEC 17025:2018 and its structure. Furthermore, the benefits of its implementation and the accreditation process. Other chapter describes risk management, which analyzes the possible risks using various methods and techniques of risk prevention leading to their elimination. The practical part is focused for the description of the 3D measurement workplace and its transformation depending on the implementation of the requirements of ČSN EN ISO/IEC 17025:2018. The main points of this section include risk management related to impartiality, determining the magnitude of SMS uncertainty, improvement process and total costs of accreditation according to ČSN EN ISO/IEC 17025:2018.639 - Katedra managementu kvalityvelmi dobř

Digital skills among youth: a dataset from a three-wave longitudinal survey in six European countries

This dataset provides longitudinal survey data from a European project, ySKILLS, which was focused on the role of digital skills in youths’ development. It contains data from 10,821 participants from Grades 6-10 (in Wave 1) in Estonia, Finland, Germany, Italy, Poland, and Portugal. The data was collected between Spring 2021 and Spring 2023, the participants were recruited through schools, where the data collection also took place, except for online data collections due to restrictions caused by COVID-19. The dataset is novel in its multidimensional approach to the construct of digital literacy. It provides insight into the development of digital skills in youth and the role of digital skills and internet usage in youths’ positive and negative online experiences and wellbeing. It also contains data that allows for the analysis of the role of digital skills in class networks. The data are beneficial for researchers interested in the examination of youths’ online skills, internet usage, online experiences, and wellbeing from a longitudinal perspective

Bioinformatics analysis of immune characteristics in tumors with alternative carcinogenesis pathways induced by human papillomaviruses

Abstract Background Human papillomaviruses (HPVs) induce a subset of head and neck squamous cell carcinomas (HNSCC) and anogenital cancers, particularly cervical cancer (CC). The major viral proteins that contribute to tumorigenesis are the E6 and E7 oncoproteins, whose expression is usually enhanced after the integration of viral DNA into the host genome. Recently, an alternative tumorigenesis pathway has been suggested in approximately half of HNSCC and CC cases associated with HPV infection. This pathway is characterized by extrachromosomal HPV persistence and increased expression of the viral E2, E4, and E5 genes. The E6, E7, E5, and E2 proteins have been shown to modify the expression of numerous cellular immune-related genes. The antitumor immune response is a critical factor in the prognosis of HPV-driven cancers, and its characterization may contribute to the prediction and personalization of the increasingly used cancer immunotherapy. Methods We analyzed the immune characteristics of HPV-dependent tumors and their association with carcinogenesis types. Transcriptomic HNSCC and CC datasets from The Cancer Genome Atlas were used for this analysis. Results Clustering with immune-related genes resulted in two clusters of HPV16-positive squamous cell carcinomas in both tumor types: cluster 1 had higher activation of immune responses, including stimulation of the antigen processing and presentation pathway, which was associated with higher immune cell infiltration and better overall survival, and cluster 2 was characterized by keratinization. In CC, the distribution of tumor samples into clusters 1 and 2 did not depend on the level of E2/E5 expression, but in HNSCC, most E2/E5-high tumors were localized in cluster 1 and E2/E5-low tumors in cluster 2. Further analysis did not reveal any association between the E2/E5 levels and the expression of immune-related genes. Conclusions Our results suggest that while the detection of immune responses associated with preserved expression of genes encoding components of antigen processing and presentation machinery in HPV-driven tumors may be markers of better prognosis and an important factor in therapy selection, the type of carcinogenesis does not seem to play a decisive role in the induction of antitumor immunity

CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade

Cluster of differentiation (CD) 80 is mainly expressed in immune cells but can also be found in several types of cancer cells. This molecule may either activate or inhibit immune reactions. Here, we determined the immunosuppressive role of CD80 in the tumor microenvironment by CRISPR/Cas9-mediated deactivation of the corresponding gene in the mouse oncogenic TC-1 cell line. The tumor cells with deactivated CD80 (TC-1/dCD80-1) were more immunogenic than parental cells and induced tumors that gained sensitivity to cytotoxic T-lymphocyte antigen 4 (CTLA-4) blockade, as compared with the TC-1 cells. In vivo depletion experiments showed that the deactivation of CD80 switched the pro-tumorigenic effect of macrophages observed in TC-1-induced tumors into an anti-tumorigenic effect in TC-1/dCD80-1 tumors and induced the pro-tumorigenic activity of CD4+ cells. Moreover, the frequency of lymphoid and myeloid cells and the CTLA-4 expression by T helper (Th)17 cells were increased in TC-1/dCD80-1- compared with that in the TC-1-induced tumors. CTLA-4 blockade downregulated the frequencies of most immune cell types and upregulated the frequency of M2 macrophages in the TC-1 tumors, while it increased the frequency of lymphoid cells in TC-1/dCD80-1-induced tumors. Furthermore, the anti-CTLA-4 therapy enhanced the frequency of CD8+ T cells as well as CD4+ T cells, especially for a Th1 subset. Regulatory T cells (Treg) formed the most abundant CD4+ T cell subset in untreated tumors. The anti-CTLA-4 treatment downregulated the frequency of Treg cells with limited immunosuppressive potential in the TC-1 tumors, whereas it enriched this type of Treg cells and decreased the Treg cells with high immunosuppressive potential in TC-1/dCD80-1-induced tumors. The immunosuppressive role of tumor-cell-expressed CD80 should be considered in research into biomarkers for the prediction of cancer patients’ sensitivity to immune checkpoint inhibitors and for the development of a tumor-cell-specific CD80 blockade

Experimental Combined Immunotherapy of Tumours with Major Histocompatibility Complex Class I Downregulation

Combined immunotherapy constitutes a novel, advanced strategy in cancer treatment. In this study, we investigated immunotherapy in the mouse TC-1/A9 model of human papillomavirus type 16 (HPV16)-associated tumors characterized by major histocompatibility complex class I (MHC-I) downregulation. We found that the induction of a significant anti-tumor response required a combination of DNA vaccination with the administration of an adjuvant, either the synthetic oligodeoxynucleotide ODN1826, carrying immunostimulatory CpG motifs, or α-galactosylceramide (α-GalCer). The most profound anti-tumor effect was achieved when these adjuvants were applied in a mix with a one-week delay relative to DNA immunization. Combined immunotherapy induced tumor infiltration with various subsets of immune cells contributing to tumor regression, of which cluster of differentiation (CD) 8+ T cells were the predominant subpopulation. In contrast, the numbers of tumor-associated macrophages (TAMs) were not markedly increased after immunotherapy but in vivo and in vitro results showed that they could be repolarized to an anti-tumor M1 phenotype. A blockade of T cell immunoglobulin and mucin-domain containing-3 (Tim-3) immune checkpoint had a negligible effect on anti-tumor immunity and TAMs repolarization. Our results demonstrate a benefit of combined immunotherapy comprising the activation of both adaptive and innate immunity in the treatment of tumors with reduced MHC-I expression

Aspartate-β-hydroxylase and hypoxia marker expression in head and neck carcinomas: implications for HPV-associated tumors

Abstract Background A proportion of head and neck carcinomas (HNSCCs) are induced by high-risk human papillomaviruses (HPVs) and are associated with better patient outcomes compared to patients with HNSCCs related to tobacco and alcohol abuse. In the microenvironment of solid tumors, including HNSCCs, oxygen levels are often reduced, and a hypoxic state is induced. This can lead to a poor treatment response and a worse patient prognosis. One of the hypoxia-responsive genes is aspartate-β-hydroxylase (ASPH), whose activity promotes the growth, invasiveness, and metastasis of many types of solid tumors. Methods In our study, HNSCC samples were analyzed for the expression of ASPH and selected endogenous hypoxia markers by real-time PCR and/or multiplex fluorescence immunohistochemistry. Results Except for the EPAS1 gene, which had higher mRNA expression in the HPV-negative group of HNSCC (p < 0.05), we found no other differences in the expression of the tested genes that were related to HPV status. On the contrary, a statistically significantly higher number of cells producing ASPH (p < 0.0001), HIF1A (p < 0.0001), GLUT1 (p < 0.0001), and MMP13 (p < 0.05) proteins were detected in the HPV-positive tumor group than in the HPV-negative sample group. All the evaluated markers, except for MMP9/13, were more abundant in the tumor parenchyma than in the tumor stroma. The Cox proportional hazard models showed that increased numbers of cells with GLUT1 and HIF1A protein expression were positive prognostic markers for overall and disease-specific survival in patients independent of HPV tumor status. Conclusion The study examined HNSCC samples and found that elevated ASPH and hypoxia marker proteins, typically associated with poor prognosis, may actually indicate active HPV infection, the strongest prognostic factor in HNSCC patients. In cases where HPV status is uncertain, increased expression of HIF1A and GLUT1 can serve as positive prognostic factors