The endocrine heart synthesises and secretes two polypeptide hormones: the natriuretic peptides (NP) atrial natriuretic factor (ANF) and B-type natriuretic peptide (BNP). The biological actions of these hormones serve both acutely and chronically to reduce systemic blood pressure and hemodynamic load to the heart, thus contributing to the maintenance of cardiorenal homeostasis. Considerable effort has been focused on the elucidation of the mechanistic underlying ANF and BNP gene expression and secretion but much remains to be determined regarding specific molecular events involved in the cardiocyte secretory function. These hormones are produced by the atrial muscle cells (cardiocytes), which display a dual secretory/muscle phenotype. In contrast, ventricular cardiocytes display mainly a muscle phenotype. Comparatively little information is available regarding the genetic background for this important phenotypic difference with particular reference to the endocrine function of the heart. We postulated that comparison of gene expression profiles between atrial and ventricular muscles would help identify transcripts that underlie the phenotypic differences associated with the endocrine function of the heart as well as identify signaling pathways involved in its regulation. The cardiac atrial and ventricular transcriptomes were analyzed using oligonucleotide microarrays under normal or chronically induced aortocaval shunt volume-overload conditions. Transcriptional differences were validated by RT-PCR and transcripts of interest were knocked-down by RNAi. Comparison of gene expression profiles in the rat heart revealed a total of 1415 differentially expressed genes between normal atrial and ventricular tissues. Functional classification and pathway analysis identified numerous transcripts involved in mechanosensing, vesicle trafficking, hormone secretion, and G protein signaling. Volume-overloaded animals exhibited a progressive increase in cardiac mass over the four-week time course, an increase in expression of known hypertrophic genes, as well as the differential expression of 700 genes within the atria. Volume-overload specifically downregulated the accessory protein for heterotrimeric G protein signaling RASD1 in the atria. In vitro, knockdown of RASD1 in the atrial-derived HL-1 cells, significantly increased ANF secretion, demonstrating a previously unknown negative modulator role for RASD1. The data developed in this investigation provides insight into the expression profiles of genes particularly centered on the secretory function of the heart under normal and chronic hemodynamic overload conditions. Genome-wide expression profile analysis identified RASD1 as being differentially expressed between cardiac tissues as well as being modulated by chronic volume overload. RASD1 emerges as a tonic inhibitor of ANF secretion. The novel function identified herein for RASD1 in the atria is of considerable interest given the fact that secretory impairment of the cardiac natriuretic hormones can negatively impact cardiovascular homeostasis.

Background: Patent Foramen Ovale (PFO), a remnant of the foetal circulation, is emerging as a new cause of disease. It has been found to be associated with cryptogenic stroke in young adults, peripheral arterial embolism and neurological decompression sickness in divers. The detection of PFO remains a diagnostic challenge; transoesophageal echocardiogram being currently considered the ‘gold standard’. The development of a non-invasive technique is crucial for the identification of a venous-to-arterial shunt (v-aCS) which may permit paradoxical embolism. Little is known about the genetic basis of PFO and our limited knowledge is based on animal studies and gene mutations detected in patients with other cardiac septal defects. Methods: Study 1: PFO Detection and Evaluation: This study was designed to evaluate transcranial Doppler (TCD), transthoracic echocardiogram (TTE) and transoesophageal echocardiogram (TOE) with administration of contrast via arm and femoral veins. We then developed a standardized protocol for PFO detection and quantification using TCD. Study 2: PFO and Migraine: The PFO detection protocol developed from the first study formed the diagnostic technique to detect v-aCS in an adequately powered matched case control study to explore the association between PFO and migraine. Study 3: The Genetic basis of PFO: This study was designed to explore the genetic basis of a PFO using a candidate gene approach. Results: Study 1 - PFO Detection Study: When compared with TOE with femoral vein contrast injection as the ‘gold standard’, TCD with arm vein contrast was 100% sensitive and 97.4% specific for detecting a PFO. We defined a PFO positive (+ve) study on TCD as > 15 microbubbles entering the cerebral circulation, on TCD following arm vein injection and >16 microbubbles with a femoral contrast injection. A ‘major’ PFO+ve v-aCS was defined as >35 microbubbles with arm vein injection or >90 microbubbles with femoral vein injection. We then developed a new diagnostic pathway for PFO detection in clinical practice. Study 2 - PFO Migraine study: A significant difference in prevalence of v-aCS between migraine with aura M+A) and their matched controls was demonstrated with adjusted OR=3.72 (1.48-9.38) p=0.005 for a PFO+ve v-aCS, and a highly significant difference between M+A and controls for a ‘major’ PFO+ve v-aCS with adjusted OR = 6.38 (1.89 – 21.48) p = 0.003. There was significant association with APC resistance and migraine on thrombophilia screen. Study 3 - The PFO Genetics Study: This study detected mutations of GATA4 and NKX2-5 in both PFO+ve cases and PFO-ve controls. Two novel non synonymous mutations of GATA4, c.461T>A and c.994G>A were found only in PFO positive individuals and may be associated with a PFO. All the PFO+ve cases with a GATA4 gene mutation had a major PFO+ve v-aCSConclusion:TCD detects PFO with a sensitivity of 100% and specificity of 92.3% and is the most reliable non-invasive technique for PFO detection. When arm vein injections are used both cough and valsalva provocation is essential. There was a highly significant association between PFO+ve v- aCS and M+A, especially with a ‘major’ PFO+ve v-aCS. GATA 4 mutations though infrequent were found PFO+ve cases and all had major v-aCS.

Overall topic of presented thesis is development of methods of measurement of low impedances below 10 Ohm in a frequency range up to 1 MHz. The thesis comprises of three main parts. First part of thesis describes design of unique and simple calculable standards of resistance that are used for calibration of the bridge and as the reference standards for the calibrations. Next part of theses is focused on design of digital sampling bridge in various topologies suitable for measurement of various types of impedance standards up to frequency of 1 MHz. The thesis describes the HW components, data processing and corrections scheme allowing the designed bridge to reach expanded uncertainties (k=2) below 0.005% and 250 µrad at 1 MHz. One of the key points of the proposed corrections scheme is unique automatic linearity calibration method requiring minimal operator's effort. The theses also describes integration of Spice model of the bridge the bridge SW that allowed validation of functionality of the bridge and also analysis of uncertainty contributions related to interferences between the bridge components. The last part of the thesis shows selection of measurements of known impedances and international comparisons that proofs performance of the bridge.

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Práce je věnována modelování mikrovlnných rezonátorů z metamateriálů (materiálů se záporným indexem lomu). V úvodu je rozebráno, co metamateriály jsou, jak se vytvářejí a které jejich vlastnosti jsou podstatné při návrhu rezonátorů. Následuje návrh planárního rezonátoru z metamateriálů. Pro tento účel byly naprogramovány funkce počítající rozměry jednotlivých součástí struktury. Simulace navržené struktury probíhala v programu Zeland IE3D. Simulované struktury byly optimalizovány s ohledem na požadované kmitočty rezonance. První rezonátor sestával z jedné elementární buňky, druhý ze dvou buněk, naladěných na rozdílné kmitočty. Rezonátory byly vyrobeny a experimentálně byly ověřeny jejich vlastnosti.

In this masters's thesis is closely studied questins of current (power) side channel. It deals with attack upon this type of side channels and methods, which can this channel analyse. Also two methods of measurements, which make possible successfully attack, are presented here. Below the work describes progress, which was used for analyse current side channel of chip PIC16F84A. This chip, which was plugged in the circuit in agreement with diagram introduced here, processes step by step variety of programs implementing always other operation, which matches concrete used instruction. In corresponding chapters are introduced resulting values and graphs, which was obtained by measurement.

This thesis deals with the high speed transient modelling in the electrical networks. The introduction of this work discusses mathematical models of the individual devices used in the system and focuses on the line representation. It also contains a more detailed description of Bergeron and frequency dependent line model. The objective of this thesis is to design a network model using ATP-EMTP simulation program. In this model, the switching overvoltage caused by shunt reactor switching and lightning overvoltage are simulated. The thesis thoroughly describes the settings of the components used in the model of analysed network and in conclusion evaluates obtained simulation results in a relation to the insulation coordination.

Despite decades of research of normal pressure hydrocephalus (NPH), a clear pathophysiological mechanism of the disease is sill unknown. This results in the absence of a unambiguous diagnostic biomarker. Moreover, NPH in contrast to similar neurodegenerative diseases is curable by insertion of a ventrikulo-peritoneal shunt. Now the diagnostics is based on invasive functional testing, on the contrary, imaging methods play only a supporting role. This work is processed with an effort to find a sufficiently sensitive and specific biomarker of MRI imaging using advanced analytical methods. For this reason, the structural volumetry and the phase contrast method were tested. The individual partial results of both of these modalities have already been described in the literature, but the conclusions were controversial. The main contribution of this work is the range of tested parameters and their to date untested advanced analysis - accurate automatic segmentation in volumetric study and machine learning algorithms in phase contrast study. In a volumetric study, we segmented a total of 26 structures in 74 patients (29 with diagnosed NPH, 45 without NPH). In the case of preoperative examination, we demonstrated statistically significant differences in the size of the left hippocampus, corpus callosum, left...

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Crocodiles are ectothermic, intermittent breathing reptiles with low metabolic rates. Additionally, they are diving animals that can stay submerged for long periods, which poses special demands on their cardiovascular system. The crocodilian heart is four-chambered with completely separated ventricles, making it unique among other reptiles. It has special anatomical structures that give it the capability to shunt blood away from the lungs, which results in mixing of deoxygenated and oxygenated blood. The purpose of this study was to morphologically describe the heart and review its functions and the significance of its circulatory patterns. Dissection of two crocodilian hearts was performed for morphological characterization of the heart, including the special features that contribute to the shunting: the left aorta, the foramen of Panizza and the cog-teeth-like valves. Obstruction of the pulmonary outflow tract by the cog-teeth-like valves decreases pulmonary blood flow and generates an increased right ventricular pressure, diverting venous blood into the ‘extra’ left aorta and the systemic circulation. Thus, during shunting conditions, venous blood from the left aorta and arterial blood from the right aorta is mixed. The functional significance of this shunting pattern has been extensively discussed and several hypotheses have been proposed. A recent study showed that the absence of the right-to-left shunt does not affect the diving physiology of crocodiles negatively, but it did result in cardiac hypertrophy, indicating that the shunt might have a significance for the circulation and physiology of extant crocodiles.