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"The cancer cell proteome and its changes after anti-cancer drug treatment".
Tylečková, Jiřina ; Kovářová, Hana (advisor) ; Strnad, Miroslav (referee) ; Petrák, Jiří (referee)
Cancers represent a group of unprecedented heterogeneous diseases and currently available anti-cancer therapies provide highly variable efficacy with unsatisfactory cure rates. A wide range of proteomic technologies are being used in quest for newer approaches which could significantly contribute to the discovery and development of selective and specific cancer biomarkers for monitoring the disease state and anti-cancer therapy success. Taking into consideration the above aspects, this research was undertaken to study cancer cell proteomes and their changes after anti-cancer treatment with specific focus on: (a) response to conventional anthracycline/anthracenedione drugs with respect to their different clinical efficacy and (b) identification of novel targets for therapy in cancer cells resistant to biological drugs such as inhibitors of (b1) cyclin-dependent kinases and (b2) Aurora kinases. This study identified several interesting key aspects related to the effects of daunorubicin, doxorubicin and mitoxantrone. With the main focus on early time intervals when the influence of apoptosis is minimised, changes common for all three drugs belonging mainly to metabolic and cellular processes were observed. More importantly, significant changes in proteins involved in the generation of precursor...
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Mechanisms of replicative, drug- and oncogene-induced cellular senescence
Košař, Martin ; Bartek, Jiří (advisor) ; Strnad, Miroslav (referee) ; Mistrík, Martin (referee)
Cells continuously experience various forms of exogenous and endogenous stress stimuli. Cellular senescence, a state of permanent cell-cycle arrest, is a physiological response that prevents proliferation of damaged cells. It is an important tumor suppressive mechanism, because evading senescence in pre-malignant tumors leads to cancer progression. However, in the long term, senescence can also contribute to tissue aging. Our understanding of the causes and consequences of senescence can provide important insights into processes such as cancer development and aging and may help us design new therapeutic approaches. In the first part of my thesis, we investigated a relationship between two known tumor suppressor pathways, the DNA Damage Response (DDR) and the Alternative Reading Frame (ARF), in response to oncogenic insults. By using several mouse models, human clinical samples and cell culture models we showed, that ARF activation occurs at a later stage of tumor progression than activation of the DDR. Moreover, ARF activation requires a higher level (threshold) of oncogenic stress than DDR. Therefore, we proposed, that ARF represents a delayed and complementary barrier to tumor progression. Senescence-associated heterochromatin foci (SAHF) formation, representing pronounced changes in chromatin,...
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The Study of Effectiveness of the Use of Machines in the Selected Operation
Strnad, Miroslav ; Sládek, Radim (referee) ; Jurová, Marie (advisor)
Master thesis is focused on the study of effectiveness of selected machines in the company through indicators of Overall Equipment Effectiveness. The aim is to increase productivity of machinery by monitoring machine run. Analyses are performed on selected machines which are found out downtimes reducing machine run. Methods and tools of lean manufacturing are used for determine downtimes as a core part. Specifically, the implementation of the first phase of TPM – “Total Productive Maintenance” which is used in manufacturing, for determine current status of machines. Maintenance of machinery is also referred in the master thesis as important part of Overall Equipment Effectiveness. Individual factors of OEE are identified as a result of these analyses which are directly affected to productivity of machines. The output of these analyses is to design countermeasures against each downtime and system design of monitoring tools including technical and economical evaluation. Machine monitoring with automatic data collection based on calculated data is suitable option for the company.
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Manufacturing possibilities of sparking plug body
Strnad, Miroslav ; Kopřiva, Miloslav (referee) ; Podaný, Kamil (advisor)
Difficulties of manufacturing sparking plug body are analyzed in this thesis, which aims to select the most appropriate option. Body is circular section of steel 1.1191 (12 050), with a hole in the middle and upper part of this body is ended with hexagonal shape. The series is estimated at 1 000 000 units per year. For the production of sparking plug body are selected options from the machining and forming technologies. Specifically, turning and milling, casting, forging, a method using superplastic material and cold extrusion. Selected technologies will be reviewed based on cost to produce one piece, time requirements of manufacture of the unit, material usability and overall feasibility. According to these parameters forming is chosen as the best option.
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The Repechy Guest-House
Strnad, Miroslav ; Keith, Petr (referee) ; Vojtová, Lea (advisor) ; Kalousek, Lubor (advisor)
Bachelor’s thesis is based on a studio project created in the summer term of the third year of the undergraduate studies. The task was the renewal and the extension of the farmhouse for an accommodation facility and other services. The farmhouse is situated in a small village Repechy near the town of Prostejov and is complemented by two other unused buildings. In the second half of the 20th century, rectangular shaped farmhouse with a yard was roofed, interior walls were partially demolished and interior space was used for keeping the cattle. It had a big impact for the current condition of the object. Aggressive environment and high humidity, for which structures were not designed, significantly accelerate the degradation process. Later, the cattle was moved away and the original farmhouse is deteriorating until these days. Currently, the object and its surroundings are in a bad condition. Most of the constructions are damaged and it is not possible to use them anymore. Northern tract is the only part worth protection. There are preserved precious historical chambranles and other plastic decoration. Surroundings is overgrown with wild vegetation. The aim was to preserve and bring out valuable parts of the original object and find them appropriate use under specified conditions. The proposal deals with the removal of three sides of a rectangular farmhouse and preserving the northern tract in the form of a torso. Extension is based on the original farmhouse. Extends the original built up area boundary to use existing structure and creates the first volume, which symbolizes the traditional static form. Rotated duplicate of the first volume then characterized a modern and dynamic attitude in architecture. The final design of an extension is created by synthesis of both volumes as an evidence of the coexistence of a traditional and a modern form. Designed extension has one floor, locally basement and second floor. The extension is also characterized by the use
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