V této diplomové práci se zaměřujeme na vytvoření plně automatizovaného algoritmu pro předpovědi finančních řad, který se snaží využít kombinační proceduru na dvou úrovních mezi dvěma rodinami předpovědních modelů, Box-Jenkins a Exponenciální stavové modely, které jsou schopny modelovat jak homoskedastické tak heteroskedastické časové řady. Pro tento účel jsme navrhli selekční proceduru v prostředí MATLAB pro modely ARIMA. Výsledný kombinovaný model je pak aplikován několik finančních časových řad a jeho výkonost je diskutována.

SARS-CoV-2 började cirkulera i slutet av 2019 och ungefär tre månader senare klassades utbrottet som en pandemi. Idag, ungefär ett och ett halvt år efter virusutbrottet kämpar människor i hela världen fortfarande för att ta sig ur kriserna som pandemin orsakar. Trots stora forskningsinsatser är det ännu mycket som är ovisst kring virusets uppkomst. Olika teorier försöker bevisas men till dagens datum är det inte bekräftat var SARS-CoV-2 har sitt ursprung. Det verkar troligt att SARS-CoV-2 har en gemensam förfader med β-coronaviruset RaTG13. Det är sannolikt att fladdermus tillsammans med minst en mellanvärd har varit inblandad i uppkomsten av viruset. Viruset har gett upphov till flera varianter som spridit ut sig i världen. Globalt samarbete med övervakning av mutationer och varianter är viktigt för hur utvecklingen av pandemin ska fortgå. Med SARS-CoV-2 och Covid-19-pandemin som utgångspunkt analyseras möjligheter och utmaningar med undervisning i gymnasieskolan om aktuella stora händelser. / The outbreak of SARS-CoV-2 occurred at the end of 2019 and three months later, it was declared as a pandemic. Today, roughly one and a half years later, people across the world are still struggling to get out of the crises caused by the pandemic. Despite the huge efforts within science, much is still uncertain about the virus’ origin. Different theories are trying to be proven by scientists but to date, there is no confirmation from where the virus has its origin, nor whether one or several intermediate hosts have been involved. It seems likely that SARS- CoV-2 has a common ancestor with the bat β-coronavirus RaTG13. Therefore, it is probable that bats with at least one other intermediate host have been involved in the origin of the virus. Several variants have emerged and spread throughout the world. Global cooperation in regards of surveilling mutations and variants is of great importance regarding the development of the pandemic. Using SARS-CoV-2 and the Covid-19 pandemic as a focal point, there is an analysis showing opportunities and challenges when teaching big contemporary events.

The Master's thesis deals with the subject of life insurance as the tool for motivation and remuneration of employees. The theoretical part summarizes current knowledge of insurance, insurance market and life insurance. The practical part analyses the present circumstrances in the observed company and compares the particular offers of the capital life insurance of the chosen insurance companies. The practical part also includes the suggestion for the use of capital life insurance as the employee's amenities.

The subject of my thesis is to evaluate proposal to improve the marketing strategy of the hotel Joseph 1699 in Trebic after a year of the operation. It is important for the hotel Joseph 1699, to develop a proposal, how to improve the quality of marketing strategy to be competitive and viable on the market in Trebic and surroundings. In the theoretical section are explained the economic matters, which were used in the practical part. The practical part is focused on processing of marketing analyzes, and proposal how to change and improve marketing strategies. With these proposed changes would have the hotel Joseph 1699 to improve and strengthen its position in the market in Třebíč.

Actuellement, le développement d’un logiciel de taille industriel repose généralement surdes tests ou des preuves unitaires pour garantir rigoureusement ses exigences. En outre, il adéjà été montré que l’utilisation combinée du test et de la preuve unitaires est plus efficaceque l’utilisation d’une seule de ces deux techniques. Néanmoins, un ingénieur en vérificationhésite encore à utiliser ces deux techniques conjointement, faute d’une notion de couverturecommune au test et à la preuve. Définir une telle notion est l’objet de cette thèse.En effet, nous introduisons une nouvelle couverture, appelée « couverture label-mutant ».Elle permet de représenter les critères de couverture structurelle habituels du test, comme lacouverture des instructions, la couverture des branches ou la couverture MC/DC et de décidersi le critère choisi est satisfait en utilisant une technique de vérification formelle, qu’elle soitpar test, par preuve ou par une combinaison des deux. Elle permet également de représenterles critères de couverture fonctionnelle. Nous introduisons aussi dans cette thèse une méthodereposant sur des outils automatiques de test et de preuve pour réduire l’effort de vérificationtout en satisfaisant le critère de couverture choisi. Cette méthode est mise en oeuvre au seinde la plateforme d’analyse de code C (Frama-C), fournissant ainsi à un ingénieur un moyenopérationnel pour contrôler et réaliser la vérification qu’il souhaite. / Currently, industrial-strength software development usually relies on unit testing or unitproof in order to ensure high-level requirements. Combining these techniques has already beendemonstrated more effective than using one of them alone. The verification engineer is yetnot been to combine these techniques because of the lack of a common notion of coverage fortesting and proving. Defining such a notion is the main objective of this thesis.We introduce here a new notion of coverage, named « label-mutant coverage ». It subsumesmost existing structural coverage criteria for unit testing, including statement coverage,branch coverage or MC/DC coverage, while allowing to decide whether the chosen criterionis satisfied by relying on a formal verification technique, either testing or proving or both.It also subsumes functional coverage criteria. Furthermore, we also introduce a method thatmakes use of automatic tools for testing or proving in order to reduce the verification costwhile satisfying the chosen coverage criterion. This method is implemented inside Frama-C, aframework for verification of C code (Frama-C). This way, it offers to the engineer a way tocontrol and to perform the expected verifications.

Introduction: In South Africa, breast cancer has the highest prevalence with a life time risk of 1 in every 9 women being diagnosed annually. There are four sub-types of breast cancer and according to the stage of the cancer, various treatment regimens are prescribed. A major obstacle is that majority of cancers have developed multi-drug resistance and new treatment regimens need to be developed in order to obtain therapeutic efficacy. Cancer cells use aerobic glycolytic metabolism for energy generation and inhibition of this pathway increases sensitivity of the cells to anti-neoplasic treatments. 2-Deoxyglucose (2-DG) competes with and inhibits glucose uptake inhibiting the glycolytic pathway which can result in depolarisation of the mitochondrial membrane potential releasing cytochrome c. Two 2-Methoxyestradiol (2-ME) derivatives, ESE- 15-ol and ESE-16 have shown to be promising anti-cancer agents and combination therapy could allow the use of these compounds with a decreased side effect profile. The combination of these compounds with 2-DG was therefore investigated. Aim: To investigate combinations of two oestrone analogues and the glycolysis inhibitor 2- deoxyglucose for potential synergistic effects using a cell enumeration assay, mitochondrial membrane potential and cell cycle analysis, on breast cancer cells in an in vitro setting. Cell apoptosis, necrosis and autophagy pathways were assessed to indicate the mechanism of cytotoxicity. Methods: The breast cancer MCF-7 and non-tumorigenic MCF-12A cell line were used. Cells were exposed to ESE-15-ol, ESE-16 and 2-DG alone and in combination. Mechanistic studies were performed using the various research methodologies including the sulforhodamine B assay for cell enumeration, Annexin-V FITC and propidium iodide labeling for apoptosis/necrosis studies, PlasDIC and light microscopy for morphological analysis, propidium iodide staining for cell cycle progression, JC-1 for mitochondrial membrane potential studies, transmission electron microscopy and western blotting for the analysis of autophagy. Results: A GI50 of 34.1 nM was reported for MCF-7 cells after treatment with ESE-15-ol, 141 nM for ESE-16 and 1.3 mM 2-DG. The GI50 of ESE-15-ol treated MCF-12A cells was 141 nM, 140.1 nM for ESE-16 treated cells and 1.7 mM for 2-DG. ESE-16 had the greatest effect on cell viability in MCF-7 cells and a shift from an inhibitory effect to the initiation of cell death was evident after treatment of 100 nM of ESE-15-ol and ESE-16. 2-DG had a lower cytotoxic effect than the oestrone analogues. The MCF-12A cell line was less susceptible to the experimental compounds. The combination of the oestrone analogues with 2-DG elicited a greater effect on cell enumeration than each of the compounds alone with a less pronounced effect on the MCF- 12A cell line in comparison to the MCF-7 cells. The experimental compounds initiated apoptosis with ESE-16 eliciting a greater effect than ESE-15-ol. The combination of the oestrone analogues with 2-DG resulted in increased apoptosis in contrast to the compounds alone. ESE-16 alone and in combination with 2-DG lead to the most prominent morphological changes, with ESE-15-ol decreasing cell density slightly. The combination of ESE-15-ol with 2-DG decreased cell density with membrane blebbing apparent. The MCF-12A cell line was less susceptible to morphological changes after treatment of ESE-15-ol with 2-DG however ESE-16 and the combination with 2- DG resulted in similar attributes seen in MCF-7 treated cells. ESE-15-ol resulted in accumulation of cells in the G2 cell cycle phase which was further amplified after the combination of 2-DG. A sub-G1 accumulation was observed after treatment with ESE-16 with a shift to a G2 accumulation after the combined treatment of ESE-16 with 2-DG. After 48 hours, ESE-15-ol alone and in combination with 2-DG on MCF-7 cells resulted in depolarisation of the mitochondrial membrane. A slight decrease in the membrane potential was observed after treatment with ESE-16 and this was further increased after the combined treatment of ESE-16 with 2-DG. The MCF-12A were less susceptible after 24 hour treatment than 48 hour exposure of the experimental compounds. The presence of autophagic-like vacuoles were apparent in all treatment groups as well as the increased expression of LC3-II. Conclusion: The combined treatment of synthetic oestrone analogues with 2-DG displayed greater therapeutic efficacy than each of the compounds alone. As a result, the apoptotic and autophagic pathways were induced and a shift in cell cycle progression was observed. Mitochondrial involvement was apparent and the compounds significantly affected cell viability. This suggests that the combinations between the antimitotic oestrone analogues and glycolysis inhibitor 2-DG act synergistically to induce apoptosis and autophagy in MCF-7 breast cancer cells. / Dissertation (MSc)--University of Pretoria, 2017. / Pharmacology / MSc / Unrestricted

Many diseases display a multitude of relevant factors that contribute to the persistence of the disease and difficulty treating it. The multifactorial characteristics of some diseases lead to the requirement of combination of treatments in order to restore health. The latter may necessitate the mixing of treatments, medications, and therapeutics to first halt the disease, then assist the human body in returning itself to a state of normality. For example, chronic wounds exhibit this multifactor characteristic in which there exist many factors that lead to the body’s inability to properly heal in a timely manner. This presents a further threat to the body, such as exposure to infection and long-term pain. In this example, it is important to look at the ultimate cause of a chronic wound, which may be due to presence of other diseases impairing the body’s ability to properly heal. This may include diabetes, initial antibiotic-resistant infection, autoimmune disorders, and poor vasculature. Furthermore, the mentioned causes for chronic wounds may have associations with one another in a single case of a chronic wound. Treating each interrelated cause with drug combinations may run the risk of adverse side effects or further complications due to mixing drugs in a systemic method. The goal of this study is to develop a point-specific, protein-based therapy that incorporates a single-protein molecule with multifunctional characteristics based on what we know about chronic wounds and infections, as a proof of concept of multifunctional proteins. Multifunctionality of a single therapeutic molecule is desirable because it may eliminate the unknowns of how differing individual chemical or protein therapies may interact when simply mixed. In addition, examples of peptides, such as antimicrobial peptides, are known to have synergy, and creating a single protein platform that consists of two synergistic peptides could be of value in the making of a protein with greater activity by guaranteeing that the synergistic peptides are local to one another. Furthermore, broad spectrum activity can be obtained by combining two differing peptides. This proof of concept was accomplished by targeting two proteinases that are upregulated in chronic wounds: Matrix Metalloproteinase-2 (MMP-2) and Neutrophil Elastase. Recombinant DNA techniques were used to create a fusion protein that incorporates an inhibitor of MMP-2, which is a β-Amyloid Precursor Protein-derived Inhibitory Peptide (APP-IP), and PMP-D2, an inhibitor of Neutrophil Elastase. PMP-D2 was joined to the N-terminus of an Elastin-like peptide, while the APP-IP was joined to the C-terminus of the same Elastin-like peptide. Elastin-like peptides (ELPs) are commonly used as a backbone for recombinant protein production as their distinct thermoresponsive characteristics provide adequate protein purification using an inverse transition cycling [3]. In addition, ELPs can serve as point-specific drug delivery platforms with a transition temperature (Tt) near that of normal body temperature causing low diffusivity [3]. Therefore, when ELPs are applied to a site at their Tt, they will aggregate, which provides diffusional limitations of the protein in the application site, and may decrease the reapplication rate needed for a therapeutic, as well as eliminate adverse side effects by retaining the protein to the specific application site. From this dual fusion, the final resulting protein is PMP-D2٠ELP٠APP-IP. This protein was tested for its inhibitory activity of both MMP-2 and Neutrophil Elastase. It was hypothesized that the fusion protein, PMP-D2٠ELP٠APP-IP, would inhibit MMP-2 just as effectively as APP-IP·ELP unaccompanied by PMP-D2, as well as effectively inhibit Neutrophil Elastase to the same degree as PMP-D2·ELP unaccompanied by APP-IP. Furthermore, an additional dually fused ELP fusion protein was currently made with two synergistic antimicrobial peptides fused to each end of the ELP. The two antimicrobial peptides used were human-derived LL37 and insect-derived Cecropin A. This novel fusion peptide contains synergistic increase in antibacterial activity in which preliminary data suggests.

Title: Methodic of selected judo techniques for younger school age children. Objectives: The aim of the thesis is to build visual material, which has the form of mental maps, selected technic in judo for beginner's athletes during the younger school age. Mental maps will be formed in conjunction with each other in a successful design, failed design, or in individual combinations. Techniques will be selected on the basis of the Testing Regulations of the Czech Judo Association. Methods: The collection of knowledge was carried out by a literature search, which deals with the topic of Juda and the chosen age category. Another reason for choosing the suitability of these techniques is the direct link to the judo test rule, which is given by Czech judo association. Keywords: judo, a younger school age, methods technique, mental maps, combination

Le modèle de concordance de la cosmologie, appelé ΛCDM, est un succès de la physique moderne, car il est capable de reproduire les principales observations cosmologiques avec une grande précision et très peu de paramètres libres. Cependant, il prédit l'existence de matière noire froide et d'énergie sombre sous la forme d'une constante cosmologique, qui n'ont pas encore été détectées directement. Par conséquent, il est important de considérer des modèles allant au-delà de ΛCDM et de les confronter aux observations, afin d'améliorer nos connaissances sur le secteur sombre de l'Univers. Le futur satellite Euclid, de l'Agence Spatiale Européenne, explorera un énorme volume de la structure à grande échelle de l'Univers en utilisant principalement le regroupement des galaxies et la distorsion de leurs images due aux lentilles gravitationnelles. Dans ce travail, nous caractérisons de façon quantitative les performances d'Euclid vis-à-vis des contraintes cosmologiques, à la fois pour le modèle de concordance, mais également pour des extensions phénoménologiques modifiant les deux composantes sombres de l'Univers. En particulier, nous accordons une attention particulière aux corrélations croisées entre les différentes sondes d'Euclid lors de leur combinaison et estimons de façon précise leur impact sur les résultats finaux. D'une part, nous montrons qu'Euclid fournira d'excellentes contraintes sur les modèles cosmologiques qui définitivement illuminera le secteur sombre. D'autre part, nous montrons que les corrélations croisées entre les sondes d'Euclid ne peuvent pas être négligées dans les analyses futures et, plus important encore, que l'ajout de ces corrélations améliore grandement les contraintes sur les paramètres cosmologiques. / The concordance model of cosmology, called ΛCDM, is a success, since it is able to reproduce the main cosmological observations with great accuracy and only few parameters. However, it predicts the existence of cold dark matter and dark energy in the form of a cosmological constant, which have not been directly detected yet. Therefore, it is important to consider models going beyond ΛCDM, and confront them against observations, in order to improve our knowledge on the dark sector of the Universe. The future Euclid satellite from the European Space Agency will probe a huge volume of the large-scale structure of the Universe using mainly the clustering of galaxies and the distortion of their images due to gravitational lensing. In this work, we quantitatively estimate the constraining power of the future Euclid data for the concordance model, as well as for some phenomenological extensions of it, modifying both dark components of the Universe. In particular, we pay special attention to the cross-correlations between the different Euclid probes when combining them, and assess their impact on the final results. On one hand, we show that Euclid will provide exquisite constraints on cosmological models that will definitely shed light on the dark sector. On the other hand, we show that cross-correlations between Euclid probes cannot be neglected in future analyses, and, more importantly, that the addition of these correlations largely improves the constraints on the cosmological parameters.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Study program: Pharmacy Author: Simona Novotná Supervisor: RNDr. Klára Konečná, Ph.D. Title of diploma thesis: Advanced antibacterial activity testing of candidate newly synthesized compounds Background: The aim of this thesis was to perform an extended study of the antibacterial activity of selected newly synthesized rhodanine derivatives. In this study, activity against clinical isolates of bacterial strains of the genus Staphylococcus and Enterococcus was evaluated. The main part of the work also includes the evaluation of the antibacterial activity of one selected substance in combination with commercially available antibiotics using the checkerboard method. Methods: Evaluation of the antibacterial activity of tested substances was performed using the broth microdilution method according to EUCAST guidelines (with minor modifications). The activity of these substances was evaluated against clinical isolates of bacteria of the genera Staphylococcus and Enterococcus and one Staphylococcus aureus MRSA reference strain (ATCC 43300, CCM 4750). For a selected compound with a demonstrably promising antistaphylococcal effect, the combined effect of this substance was tested with three...