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Gradient mapping of functions of several variables
Jechumtál Skálová, Alena ; Zelený, Miroslav (advisor)
Title: Gradient mapping of functions of several variables Author: Alena Skálová Department: Department of Mathematical Analysis Supervisor: doc. RNDr. Miroslav Zelený, Ph.D., Department of Mathematical Analysis Abstract: In the thesis we prove that the following statement holds true. For each d ≥ 2, for each open bounded set U ⊂ Rd and for each set F ⊂ Rd of the Borel class Fσ there exists an everywhere differentiable function u: Rd → R such that ∇u(x) ∈ U for all x ∈ Rd , ∇u(x) ∈ U for all x ∈ F, ∇u(x) ∈ ∂U for λd-almost all x ∈ Rd \ F.
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Somatic and Germline Molecular Analysis and Morphological Aspects of Unusual Variants of Malignant Melanomas and Uncommon Melanocytic Neoplasms
Donati, Michele ; Skálová, Alena (advisor) ; Baldi, Alfonso (referee) ; Paolino, Giovanni (referee)
Somatic and germline molecular analysis and morphological aspects of unusual variants of malignant melanomas and uncommon melanocytic neoplasms Abstract Background: The histopathological diagnosis of melanocytic tumors represented one of the greatest challenges of pathology. In the last years, the concept of melanoma as a single entity have been questioned. In fact, several subgroups of melanocytic neoplasms have been recognized on the bases of their clinical and histological presentation. The microscopic assessment of these lesions is based upon the detection of a constellation of morphological features, some of which lack interobserver reproducibility. In recent years, thanks to the development of molecular biology, a significant step forward has been made in the diagnosis of melanocytic neoplasms. Considering clinicopathological and genetic data some authors have suggested a stepwise model of evolution of melanocytic neoplasm to melanoma from a conventional nevus. Moreover, in the era of precision medicine, several efforts are being made to identify molecular biomarkers to predict prognosis. These biomarkers can be detected also in germline status of the patients to identify predisposing factors to tumor development. Aims: Primary aim of our projects is to perform of molecular analysis on morphologically...
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Boland, McGuckian and Groarke: nature and the self in three contemporary Irish women poets
Skálová, Alena ; Wallace, Clare (advisor) ; Quinn, Justin (referee)
This thesis comprises historical and critical introduction to contemporary women's poetry in Ireland and close reading of three poets of its two latest generations, Eavan Boland, Medbh McGuckian and Vona Groarke. It focuses on her perception of nature and attitude to the relationship between the human self and natural processes and objects. The contextual background to my reading emphasizes the feminist critique of the traditional false images of the woman's self in Irish poetry and politics, and suggests new opportunities of the most recent female poetic voices. The culturally rooted simplifying or even harmful connection between femininity and the fertile land or Catholic ideals of virginity has provoked a lot of indignation among contemporary women poets, and caused abundant literary attempts of its re-negotiation. The authentic poetic representation of the woman's sexual and spiritual connection to the land and nature along with women's subjective use of nature imagery belongs to crucial points of this re-negotiation. It is pursued extensively in all of the poetesses discussed in this paper. My close reading considers the political objectives of the poems and notices different modes of their artistic response to the relevant cultural questions. Nevertheless, it emphasizes also the independence...
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Correlation of morphologic and moleculargenetic features of selected tumors
Šíma, Radek ; Skálová, Alena (advisor) ; Boudová, Ludmila (referee) ; Ehrmann, Jiří (referee)
We present a series of 16 salivary gland tumors with histomorphological and immunohistochemical features reminiscent of secretory carcinoma of the breast. This is a hitherto undescribed and distinctive salivary gland neoplasm, with features resembling both salivary acinic cell carcinoma and low grade cystadenocarcinoma, as well as displaying strong similarities to breast secretory carcinoma. Microscopically, the tumors have a lobulated growth pattern and are composed of microcystic and glandular spaces with abundant eosinophilic homogenous or bubbly secretory material positive for PAS, mucicarmine, MUC1, MUC4 and mammaglobin. The neoplasms also show strong vimentin, S-100 protein, and STAT5a positivity. For this tumor we propose a designation mammary analogue secretory carcinoma of salivary glands (MASC). The 16 patients comprised 9 men and 7 women, with a mean age of 46 years (range 21-75). Thirteen cases occurred in the parotid gland, and one each in the minor salivary glands of the buccal mucosa, upper lip, and palate. The mean size of the tumors was 2.1 cm (range 0.7 to 5.5 cm). The duration of symptoms was recorded in 11 cases and ranged from 2 months to 30 years. Clinical follow-up was available in 13 cases, and ranged...
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Correlation of Immunohistochemistry and Molecular Biologic Methods in The Diagnosis of Tumors
Michal, Michael ; Skálová, Alena (advisor) ; Rychlý, Boris (referee) ; Zambo, Iva (referee)
This thesis is a collection of commentaries on altogether 13 first-authored and 20 co- authored publications where morphology, immunohistochemistry (IHC) and molecular genetic methods were used to provide novel clues for arriving at an accurate diagnosis of tumors, as well as to propose novel approaches and refinement of classification of certain tumors. The presented manuscripts are the result of the postgraduate studies of MUDr. Michael Michal at the Charles University in Prague, Faculty of Medicine in Pilsen in the period between 2015-2018. The author focused the main part of his research, particularly his first-authored manuscripts, on soft tissue tumors but also largely participated in research activities focusing on other body systems. Over the course of his studies, four main areas of interests within the topic of soft tissue pathology emerged. The first is oriented on soft tissue tumors of presumed (but unconfirmed) fibroblastic lineage. First two publications regard two related low-grade sarcomas called Myxoinflammatory fibroblastic sarcoma (MIFS) and Pleomorphic hyalinizing angiectatic tumor (PHAT). In the first manuscript, a high-grade variant of the former is described. The latter publication is focused on the morphological and IHC similarities between both MIFS and PHAT. The third and...
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The value of endoscopy of the salivary glands in the prevention of chronic disease
Hostička, Lubor ; Skálová, Alena (advisor) ; Slípka, Jaroslav (referee) ; Mazánek, Jiří (referee)
The author of this work deals with the problems of the sialolithiasis. He summarizes current knowledge of the etiology of the disease, diagnostic and therapeutic procedures. There are described conventional therapeutic approaches, but the main part is dedicated to current practices which are used after the introduction of new technology-sialoendoscopy. The endoscopic technique is described in this work, the evaluation of its benefits, but also its limits. The author's efforts for conservative approach to the issue sialolithiasis, the exact localization of the sialith and extraction with preservation of the salivary gland is based on publications in the scientific literature. He documents this procedure with the resultes of his own research. There is evaluated using sialoendoscopy in treatment of the sialolithiasis in cases where the sialolith is located in hilum of the submandibular gland. This localization was in the past often an indication for extirpation of the submandibular gland. The author statistically rates files of extirpated submandibular glands in the author's workplace in two five-years periods. The first period is in the time when the sialoendoscopy is not used for examination and treatment of the sialolithiasis yet. In the second period the sialoendoscopy is available, there is also...
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Molecular genetic characteristics of salivary gland tumors in differential diagnosis and prognosis prediction
Hauer, Lukáš ; Skálová, Alena (advisor) ; Laco, Jan (referee) ; Mazánek, Jiří (referee)
Molecular genetic characteristics of salivary gland tumors in differential diagnosis and prognosis prediction Abstract: In the presented manuscript the author summarizes the current knowledge on molecular biomarkers of salivary gland cancer, focusing on tumor-type specific fusion oncogenes and their use as diagnostic, prognostic and therapeutic biomarkers. In detail, the author deals with adenoid cystic carcinoma (AdCC), the second most common salivary gland cancer. New facts of its biological behavior as well as new fusion oncogenes probably responsible for its carcinogenesis were described in the last few years. A retrospective case series evaluating 27 patients suffering from AdCC, who were treated at the University Hospital in Pilsen in the last 30 years (1986- 2016), is presented in this study. The following characteristics were observed: age, gender, tumor location, clinical stage at diagnosis, presence of regional and distant metastases, tumor grade, duration of follow-up, treatment and outcomes. Detection of the 1p36 deletion and the t(6;9)(q22-23;p23-24) chromosomal translocation resulting in the MYB-NFIB gene fusion were performed. The incidence of AdCC in minor salivary glands, submandibular gland, parotid gland and sublingual gland was 41 %, 26 %, 22 % and 11% respectively. The following staging...
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Correlation of Molecular-Genetic and Morphological Markers of Rare Salivary Gland Tumors
Šteiner, Petr ; Skálová, Alena (advisor) ; Laco, Jan (referee) ; Šíma, Radek (referee)
Thesis deals with relationship between histomorphological and molecular-genetic findings of selected salivary gland tumors. Author, as a molecular-cytogeneticist mainly focused on detection of tumor-specific translocations of the salivary gland tumors which can serve as differential diagnostic markers. The thesis is composed as a commented files of authors own publications, and it is divided into four parts. First part deepens the knowledge of salivary adenoid cystic carcinoma. It was proved, that t(6;9)(q22-23;p23-24) resulting in fusion of transcription factors MYB-NFIB, or more rarely t(8;9) resulting in MYBL1-NFIB fusion represent robust differential diagnostic marker of adenoid cystic carcinoma. Further it was proved, that the 1p36 deletion can serve as an unfavorable prognostic indicator of adenoid cystic carcinoma, as the patients with 1p36 deletion had significantly lower survival. Second part summarizes new developments about mammary analogue secretory carcinoma (MASC), which was described by our group as a new salivary tumor entity characterized by translocation t(12;15)(p13;q25) resulting in ETV6-NTRK3 fusion. Another novel observation is a discovery of ETV6-RET fusion in a subset of MASC cases. Further, the first two MASCs of nasal mucosa origin have been described. Third part consists...
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HPV Asociované karcinómy hlavy a krku: morfologická, klinická a molekulovo biologická korelácia
Švajdler, Marián ; Skálová, Alena (advisor) ; Vošmik, Milan (referee) ; Rychlý, Boris (referee)
This doctor thesis comprises two studies. (i) A retrospective study was performed on 22 patients who presented with cystic head and neck squamous cell carcinoma (SCC) metastases. The purpose of the study was to find out whether histomorphology, p16 protein expression, HPV and EBVstatus could be useful in predicting the localization of the primary tumor. The primary site was identified in 20 of 22 patients and included the oropharynx in 14 patients (63.6%), the nasopharynx in 3 patients (13.6%), the lungs in 2 cases (9%), and the skin of the auricle in one case (4.5%). No primary was found in two patients (9%). Sixteen of 17 cases (94.1%) originating in Waldayer's ring, and both cases with an unknown primary showed morphology of non-keratinizing SCC or non-keratinizing SCC with maturation. All tumors with oropharyngeal primary and both cases with unknown primary showed diffuse p16 staining and presence of HPV DNA. All three cystic metastases of nasopharyngeal carcinoma (NPCa) were EBV-positive and p16/HPV negative. In contrast, cutaneous and pulmonary metastases showed morphology of a well differentiated keratinizing SCC and poorly differentiated keratinizing SCC, respectively, and were HPV/EBV-negative. We confirmed that cystic SCC lymph node metastases of the head and neck region are strongly...
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Histological Quantification of MicrovesselsStereology of Vasa Vasorum and Brain Microvessels
Tomášek, Petr ; Tonar, Zbyněk (advisor) ; Skálová, Alena (referee) ; Kachlík, David (referee)
Considering the current knowledge on histology of microvessels suggested that quantification of the tissue microvessels itself should be accompanied by a description of the surrounding tissue components supplied by these microvessels. However, the microscopic anatomy of this tissue context can vary considerably on the scale of large-sized organs, such as the aorta of large mammals or the human brain. Given that the present knowledge on the variability of densities, spatial arrangement, and orientation of microvessels is usually limited to macroscopically small areas of these large organs, we consider mapping of the microvessels on a large macroscopic scale to be a matter of great importance. This became the unifying element of this thesis. The main findings based on six studies presented in the thesis were as follows: Finding #1: The density and the penetration depth of the vasa vasorum has a considerable segmental variability in the porcine aorta. The density of the vasa vasorum was greatest in thoracic aortic segments, as was the depth of penetration into the tunica media, which exceeded previously published findings. The vasa vasorum density declined with age, but the relative depth of their penetration did not. The individual segments of the porcine aorta were not interchangeable for being used...
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