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Simultaneous confidence intervals dual to stepwise methods of multiple comparison
Moravec, Jan ; Komárek, Arnošt (advisor) ; Hlávka, Zdeněk (referee)
The central theme of this thesis is the construction of simultaneous confidence regions (SCR) corresponding to stepwise multiple comparison procedures (MCP). The first chapter is devoted to the theory of multiple comparisons, including the class of closed testing procedures which contains every MCP that strongly con- trols the familywise error rate. The second chapter is concerned with the gene- ral principle of construction of SCR corresponding to closed testing procedures. These general results are used in the third and the forth chapter for deriving the SCR corresponding to a subclass of closed testing procedures which are based on weighted Bonferroni tests. The SCR corresponding to the Holm, the Holm(W), the fixed-sequence and the fallback MCP are derived explicitly. The theoretical results are numerically illustrated on a bioequivalence study. In the fifth chapter we briefly discuss the SCR corresponding to the Hommel, the Hochberg and the step-down Dunnett MCP.
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Point processes on linear networks
Moravec, Jan ; Prokešová, Michaela (advisor) ; Pawlas, Zbyněk (referee)
The central theme of this thesis is the theory of point processes on linear net- works, in particular two kinds of the network K-function. The first part is devoted to the theory of stationary point processes in the plane, including the K-function and its estimator. The second part is concerned with the theory of point proces- ses on linear networks. There is defined the Okabe-Yamada network K -function and its estimator, the geometrically corrected network K-function, including its estimator, and there are explained their theoretical properties. In the third part we examine the ability of these two kinds of the network K-function to detect clustering or regularity in point processes on linear networks. There is explained the envelope test, the refined envelope test and the deviation tests. The software environment R with library spatstat is used for simulations.
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Echocardiographic assessment of heart function in laboratory rats and mice
Hrdlička, Jaroslav ; Papoušek, František (advisor) ; Moravec, Jan (referee)
- 5 - Abstract Experimental cardiology deals with the study of mechanisms related to development of cardiovascular disease, risk factors and possibilities of improving heart resistance to oxygen deficiency and increased workload. Observed mechanisms and context are proved in experiments using laboratory rats and mice where its effect on the heart function is detected. Many invasive and non-invasive methods are used for that. One of the basic non-invasive methods are echocardiography of nuclear magnetic resonance, which is both technically and methodically more challenging. Echocardiography allows to evaluate the heart function and geometry in laboratory rats and mice repeatedly and in physiological conditions and minimal influence to the animal. Using echocardiography allows observing changes and effect of studied mechanisms continuously. From the range of parameters used for echocardiographic measurement some have their origin in clinical praxis and empiric nature and other are introduced to cover specific needs in the experiment. Suitability of various echocardiographic parameters for evaluating heart function in laboratory rats and mice is given by accuracy reached for this small hears, need for approximation the heart and ventricles using simple shapes and for clear context of parameter values and its...
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Cholinergic regulation of ion transport in the large intestine
Hock, Miroslav ; Pácha, Jiří (advisor) ; Moravec, Jan (referee) ; Kolínská, Jiřina (referee)
anglicky Acetylcholine is one of the most important mediators of enteric nervous system involved in the regulation of ion transport in the large intestine. Although, recently, plenty of new evidences of various expression of ion transport proteins in distal and proximal colon was published, there still lacks an electrophysiological study comparing these parts of colon considering all that new findings. The aim of this study was thus to compare cholinergic regulation of ion transport in distal and proximal colon. We measured responses of distal and proximal colon in Ussing chambers by voltage-clamp method. The colonic epithelium was clamped to 0 mV and responses were recorded as changes of short-circuit current (SCC). Instead of acetylcholine we used its stable analogue carbachol. Data were processed and analyzed using a VBA code I wrote for this purpose for MS Excel 2007. We confirmed that carbachol acts directly on epithelial cells via muscarinic acetylcholine receptors in both, distal and proximal colon. These responses to carbachol were not influenced by inhibitors of Cl- channels situated in apical membrane (CFTRinh-172 and niflumic acid). Inhibition of basolateral influx of Cl- by serosal Ba2+ and furosemid reduced responses to carbachol in both, distal and proximal colon. Inhibitors of K+...
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The role of synaptic modulation in pain states.
Adámek, Pavel ; Paleček, Jiří (advisor) ; Moravec, Jan (referee)
Everybody has experienced pain. Pain by definition is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. In the peripheral tissues acute painful stimuli activate specialized endings of afferent neurons called nociceptors. The information about tissue damage is then transmitted to the cell bodies of these dorsal root ganglion neurons by unmyelinated or thinly myelinated axons (C and A fibers, respectively). The central branches of these neurons form synapses with superficial dorsal horn neurons in the spinal cord. The information is conveyed at the synaptic connections by neurotransmitters such as glutamate and many others neuromodulators. Important is the subsequent activation of projection neurons that transmit the information to supraspinal brain areas. Activity of excitatory and inhibitory interneurons, glial cells and descending pathways from the CNS are also important for the modulation of nociceptive information at the spinal cord level. After peripheral tissue damage and in other pathological states, increased sensitivity to peripheral stimuli may develop. As results of this change innocuous stimuli are perceived as painful (alodynia) and increased pain is perceived after noxious stimuli (hyperalgesia). The underlying mechanisms of these changes may be...
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Ionotropic glutamate receptors and excitotoxicity
Skřenková, Kristýna ; Vyklický, Ladislav (advisor) ; Moravec, Jan (referee)
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and its excitatory role is mediated trough activation of glutamatergic ionotropic receptors which are responsible for synaptic transmission and play an important role in learning and memory formation. However, excessive exposure to glutamate can result in excitotoxicity which may lead to cell death. The following text is focused on one group of glutamate receptors - NMDA receptors. The study of the receptors is in the centre of current neurobiology research because there is a series of experimental and clinical evidences that they directly participate in the development of serious diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and may cause neuronal damage in trauma, hypoxia and embolia. The aim of this bachelor thesis is to give a brief overview of current knowledge about the structure and function of NMDA receptors and mechanisms of their activation which leads to excitotoxicity and related neuroprotection.
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Neurosteroid modulation of ligand-gated ion-channel activity
Krausová, Barbora ; Vyklický, Ladislav (advisor) ; Moravec, Jan (referee)
The term neurosteroids refers to steroids that are synthetized in the nervous tissue from cholesterol or steroidal precursors from peripheral sources. These compounds affect the neuronal excitability by modulating the function of some ligand-gated ion channels. NMDA (N methyl D aspartate) receptors are glutamate gated ion channels involved in excitatory synaptic transmission, synaptic plasticity and excitotoxicity. GABAA ( aminobutyric acid type A) receptors mediate most of the inhibitory synaptic transmission in the mammalian brain and are targeted by many clinically important drugs. Function of NMDA and GABAA receptors can by affected by neurosteroids, both positively and negatively. The aim of this work is to summarize the current knowledge about the neurosteroid effects on the function of GABAA a NMDA receptors and suggest the physiological role and the potential therapeutic use of the neurosteroids as a regulator of some functions of the central nervous system.
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Biomedical models of Huntington disease
Žižková, Martina ; Motlík, Jan (advisor) ; Moravec, Jan (referee)
Huntington's diease is a dominant inherited neurodegenerative disorder that is caused by an expansion of a CAG repeats within a huntingtin gene. Mutant protein causes a neuron degeneration in a brain of HD pacients which leads to a motor abnormalities and personality decay. This disease is very malign because of its late onset. An equal therapy does not exist yet, but a lot of research teams focus on designig a suitable medical treatment. It is necessary to create animal models of Huntington disease which can be used for testing the therapies. In my work I aim to summarize the animal models of HD which are used in research. A rodent model is the most common due to its low price and easy breeding. However, more important are human related large animals like sheep, pigs or non-human primates. The principal criterion of animal model is its method of creation. We can divide the models into two categories, genetic and non-genetic. The memebers of the first one are able to reproduce better expression of human Huntington disease. Generation of animal models of HD leads to better comprehension the principles of HD, and developing an equal therapy for HD pacients.
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Vlastnosti a regulace objemově-závislých aniontových kanálů u astrocytů.
Harantová, Lenka ; Moravec, Jan (referee) ; Anděrová, Miroslava (advisor)
Animal cells need to preserve constant volume in the face of osmolarity perturbations to function properly. To regain their original volume after hyposmotically induced swelling, most cell types extrude intracellular electrolytes and organic osmolytes accompanied by osmotically driven water. This process is termed regulatory volume decrease and is ensured by various ion channels and transporters. Recently, much attention has been focused on the ubiquitous volume-regulated anion channels activated by cell swelling. VRACs are moderately outwardly rectifying with intermediary conductance, permeable to inorganic anions and organic osmolytes and sensitive to broad-spectrum anion channels blockers. Functional properties of VRACs in astrocytes are particularly interesting, because many brain pathologies, such as ischemia, traumatic brain injury or hyponatremia, are associated with marked astrocytic swelling and VRACs could thus constitute a possible target for therapy of cerebral edema. Furthermore, VRACs are thought to play a role in cell cycle progression, cell migration, apoptosis and intercellular communication. Despite intensive research, VRACs molecular identity and mechanism of their activation and regulation are still unclear. This work summarizes known facts about VRACs, accentuating their...
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