<p>This thesis deals with energetic oxygen ions (i.e. single-charged atomic oxygen ions, O+) at altitudes higher than 5 Earth radii (RE) and at latitudes above 75 (toward 90) degrees invariant latitude (deg ILAT) in the dayside polar magnetosphere observed by Cluster. The instrument used in this study is CIS (Cluster Ion Spectrometry experiment) / CODIF (a time-of-flight ion COmposition and DIstribution Function analyser), which covers an energy range from »10 eV up to 38 keV. Cluster detected O+ with energies more than 1 keV (hereafter termed “keV O+”), indicating that energization and/or acceleration process(es) take place in the dayside high-altitude (inside magnetopause) and high-latitude region. These O+ are outflowing (precisely, upward-going along the geomagnetic field lines), and these outflowing keV O+ show a heated (or energized) signature in the velocity distribution as well.</p><p>First, outflowing O+ are observed at the poleward cusp and/or the mantle formed a partial shell-like configuration seen in the velocity distribution. Second, the latitudinal distribution of outflowing O+ (most of them have energies less than 1 keV statistically) observed below 7 RE is consistent with velocity filter effect by the polar convection, while the latitudinal distribution of outflowing keV O+ observed above 7 RE cannot be explained by velocity filter effect only, i.e. this indicates that additional energization and/or acceleration takes place at higher altitudes in the dayside polar region. Thirdly, a tendency to observe outflowing keV O+ for during different geomagnetic conditions is studied. The keV O+ above 9 RE is more often for K p¸5 rather than for K p•3. However the energy of O+ is not dependent on ASY /SYM indices.</p><p>Finally, the dependence on the solar wind conditions is also studied. The energization and/or acceleration of outflowing O+ is controlled by both solar wind moments (except solar wind electric field) and strong southward interplanetary magnetic field (IMF) at the time scale of tens of minutes at only higher altitudes. Further examination shows that solar wind dependence is different at three regions: one is the poleward cusp, another is the low-altitude polar cap, and finally the high-altitude polar cap, combining all the results. There is (a) new energization and/or acceleration process(es) at the high-altitude polar cap. On the other hand, flux enhancement of O+ observed above 5 RE is also controlled by solar wind moments (e.g. solar wind electric field) and strong southward IMF, however the ionospheric changes play a more important role on the flux enhancement of O+.</p>

This thesis deals with energetic oxygen ions (i.e. single-charged atomic oxygen ions, O+) at altitudes higher than 5 Earth radii (RE) and at latitudes above 75 (toward 90) degrees invariant latitude (deg ILAT) in the dayside polar magnetosphere observed by Cluster. The instrument used in this study is CIS (Cluster Ion Spectrometry experiment) / CODIF (a time-of-flight ion COmposition and DIstribution Function analyser), which covers an energy range from »10 eV up to 38 keV. Cluster detected O+ with energies more than 1 keV (hereafter termed “keV O+”), indicating that energization and/or acceleration process(es) take place in the dayside high-altitude (inside magnetopause) and high-latitude region. These O+ are outflowing (precisely, upward-going along the geomagnetic field lines), and these outflowing keV O+ show a heated (or energized) signature in the velocity distribution as well. First, outflowing O+ are observed at the poleward cusp and/or the mantle formed a partial shell-like configuration seen in the velocity distribution. Second, the latitudinal distribution of outflowing O+ (most of them have energies less than 1 keV statistically) observed below 7 RE is consistent with velocity filter effect by the polar convection, while the latitudinal distribution of outflowing keV O+ observed above 7 RE cannot be explained by velocity filter effect only, i.e. this indicates that additional energization and/or acceleration takes place at higher altitudes in the dayside polar region. Thirdly, a tendency to observe outflowing keV O+ for during different geomagnetic conditions is studied. The keV O+ above 9 RE is more often for K p¸5 rather than for K p•3. However the energy of O+ is not dependent on ASY /SYM indices. Finally, the dependence on the solar wind conditions is also studied. The energization and/or acceleration of outflowing O+ is controlled by both solar wind moments (except solar wind electric field) and strong southward interplanetary magnetic field (IMF) at the time scale of tens of minutes at only higher altitudes. Further examination shows that solar wind dependence is different at three regions: one is the poleward cusp, another is the low-altitude polar cap, and finally the high-altitude polar cap, combining all the results. There is (a) new energization and/or acceleration process(es) at the high-altitude polar cap. On the other hand, flux enhancement of O+ observed above 5 RE is also controlled by solar wind moments (e.g. solar wind electric field) and strong southward IMF, however the ionospheric changes play a more important role on the flux enhancement of O+.

<p>The two major contributing populations to the outflow tract of the heart are the secondary heart field and the cardiac neural crest. These two populations are responsible for providing the myocardium that supports the outflow tract valves, the smooth muscle that surrounds these valves and the outflow vessels themselves, and the septum that divides the primitive, single outflow tract into an aorta and pulmonary trunk. Because the morphogenesis of this region is so complex, its development is regulated by many different signaling pathways. One of these pathways is the Sonic hedgehog pathway. This thesis tests the hypothesis that Sonic hedgehog induces secondary heart field proliferation, which is necessary for normal outflow tract development. To address this hypothesis, I took advantage of small chemical antagonists and agonists to determine how too little or too much hedgehog signaling would affect the secondary heart field, both in in vitro explants and in vivo. I have determined that Sonic hedgehog signaling maintains proliferation in a subset of secondary heart field cells. This proliferation is essential for generating enough myocardium and smooth muscle and also for the cardiac neural crest to septate the outflow tract into two equal-sized vessels. Up-regulating hedgehog signaling induces proliferation, which is quickly down-regulated, showing that the embryo exhibits a great deal of plasticity. Together, these studies have shown that Sonic hedgehog promotes proliferation in a subset of the secondary heart field and that the level of proliferation must be tightly regulated in order to form a normal outflow tract.</p> / Dissertation

Based on data from the Fermi Gamma-ray Space Telescope, we have discovered two gigantic gamma-ray emitting bubble structures in our Milky Way (known as the Fermi bubbles), extending \(\sim 50\) degrees above and below the Galactic center with a width of \(\sim 40\) degrees in longitude. The gamma-ray emission associated with these bubbles has a significantly harder spectrum \((dN/dE \sim E^{-2})\) than the inverse Compton emission from known cosmic ray electrons in the Galactic disk, or the gamma-rays produced by decay of pions from proton-ISM collisions. There is no significant difference in the spectrum or gamma-ray luminosity between the north and south bubbles. The bubbles are spatially correlated with the hard-spectrum microwave excess known as the WMAP haze; we also found features in the ROSAT soft X-ray maps at \(1.5 - 2 keV\) which line up with the edges of the bubbles. The Fermi bubbles are most likely created by some large episode of energy injection in the Galactic center, such as past accretion events onto the central massive black hole, or a nuclear starburst in the last \(\sim 10 Myr\). Study of the origin and evolution of the bubbles also has the potential to improve our understanding of recent energetic events in the inner Galaxy and the high-latitude cosmic ray population. Furthermore, we have recently identified a gamma-ray cocoon feature within the southern bubble, with a jet-like feature along the cocoon's axis of symmetry, and another directly opposite the Galactic center in the north. If confirmed, these jets are the first resolved gamma-ray jets ever seen. / Astronomy

In vivo, biomechanical stress plays an important role in tissue physiology and pathology, affecting cell and tissue behavior. Even though conventional outflow tissues in the eye are constantly exposed to dynamic changes in intraocular pressure (IOP), the effects of such biomechanical stressors on outflow tissue function have not been analyzed. In particular, changes in IOP with each heartbeat have been measured in human eyes approximating 2.7 mmHg/sec. The purpose of this dissertation is to determine the effect(s) of ocular pulse on conventional outflow tissue regulation and the effect that contractility plays in this mechanical stress-mediated response. The central hypothesis directing this research is that cyclic intraocular pulsations (i.e. ocular pulse) play a significant role in conventional outflow facility.In order to address our hypothesis we studied the effect of biomechanical stressors on conventional outflow physiology using three different strategies: (1) by comparing conventional outflow endothelial cells to blood and lymphatic capillary endothelia, we gained a better understanding of the effects of biomechanical stress on conventional outflow tissue physiology, (2) by modifying the anterior segment perfusion model, we were able to measure the effect of ocular pulse on conventional outflow facility, and (3) by exposing trabecular meshwork cell monolayers to cyclic biomechanical pressure oscillations in the presence of compounds known to affect trabecular meshwork contractility, we were able to analyze the effect of rho-kinase-mediated contractility on the ocular pulse-associated response.Perfused human and porcine anterior segments showed a significant ocular pulse-mediated decrease in outflow facility; in addition, perfused trabecular meshwork monolayers showed an increase in intra-chamber pressure when exposed to cyclic pressure oscillations. This effect was blocked by Y27632 inhibition of rho-kinase-mediated contraction.In conclusion, the work shown in this dissertation demonstrates for the first time that trabecular outflow tissues are capable of responding to a physiologically-relevant cyclic biomechanical stress. This response can be observed as an increase in outflow resistance that translates to lower baselines in outflow facility of anterior segments and lower hydraulic conductivity of trabecular meshwork monolayers. In addition, we concluded that the observed ocular pulse-mediated response of trabecular meshwork cells is regulated by rho-kinase-induced contractility.

Während die güteorientierte Bewirtschaftung von Stauräumen in der Vergangenheit hauptsächlich bei der langfristigen Bewirtschaftung eine Rolle spielte, gewinnt sie in jüngerer Zeit immer mehr auch bei der kurzfristigen Abflusssteuerung als Vorentlastung und während der Hochwasserereignisse an Bedeutung. Dabei soll vor allem die Entlastung aus Horizonten mit geringerer Wasserqualität ermöglicht werden. Der vorliegende Beitrag beschäftigt sich mit den diesbezüglichen Möglichkeiten bei Nutzung vorhandener Entnahmeeinrichtungen und den Anforderungen an bauliche Ergänzungen. Es werden Grundsätze für die Planung, die Berechnung, den Betrieb und die Überwachung aus hydraulischer Sicht besprochen.

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. Elevated intraocular pressure (IOP), resulting from increased aqueous humor outflow resistance, is a major risk factor for the development and progression of POAG. Outflow resistance in the trabecular outflow pathway is mainly (50-75%) generated in the juxtacanalicular connective tissue (JCT), and partially (25-50%) in the portion distal to the inner wall of Schlemm’s canal. The details of how aqueous humor flows through these tissues and how resistance in these tissues is regulated are not fully understood in normal and POAG eyes. Aqueous humor outflow was shown to be “segmental”, with discontinuous active regions of aqueous humor filtration along the trabecular outflow pathway that can be labeled with perfused fluorescent tracers and measured as effective filtration area (EFA). In this study, we investigated the relationship between changes in EFA along the trabecular outflow pathway and outflow facility/IOP under two experimental conditions. The first experiment was designed to increase outflow facility by using netarsudil, a recently approved Rho kinase inhibitor class glaucoma medication, in normal human donor eyes. The second experiment was designed to increase IOP with topical steroid treatment for 5 weeks in mice. The purpose of this study is to verify whether EFA can be modulated by netarsudil or steroid treatment and to demonstrate the morphological changes that may be responsible for the changes of EFA. We analyzed EFA along the trabecular outflow pathway and found that elevated/reduced EFA correlated with increased outflow facility/IOP. Guided by EFA, we performed detailed morphological comparison between the active and inactive portions of aqueous humor filtration tissue to evaluate possible structural changes involved in EFA regulation. We found that increased EFA was associated with a loosened JCT structure and dilated episclearal veins, while decreased EFA was associated with a compacted JCT structure, increased deposition of curly collagen and/or fibrillary structure in the trabecular meshwork, and increased basement membrane continuity. Our data suggest that the netarsudil/steroid-induced morphological changes in the trabecular outflow pathway can result in either an increase or decrease in EFA, which in turn contributes to the regulation of outflow facility/IOP. / 2020-10-24T00:00:00Z

[pt] A vocação natural do Brasil para a hidroeletricidade fez com que o Sistema Interligado Nacional - SIN fosse desenvolvido com forte predominância de geração de origem hidroelétrica. Entretanto, ao se optar por uma base hidroelétrica há de se lidar com as significativas incertezas associadas às afluências futuras aos rios e, por extensão, a todas as bacias hidrográficas do país. Logo, a estrutura de produção de energia hidroelétrica do Brasil foi concebida de forma a minimizar os riscos associados ao comportamento aleatório das afluências. Para contemplar a estocasticidade das afluências no Planejamento da Operação do SIN, o Operador Nacional do Sistema Elétrico - ONS utiliza uma cadeia de modelos dentre os quais estão contidos o modelo de previsões de vazões determinísticas para o curto prazo, e os modelos de geração de cenários de afluências. Estes modelos fornecem insumos para que os modelos de otimização possam estabelecer as Estratégias e Políticas de Operação para o médio e curto prazo, considerando a volatilidade das afluências. Esta dissertação descreve os processos de séries temporais empregados no modelo de previsões determinísticas para o curto prazo e nos modelos de geração de cenários de afluências para o médio e curto prazo. Além disso, é apresentado um estudo de casos do Planejamento da Operação do SIN que avalia o acoplamento feito entre os modelos de otimização de médio e curto prazo através dos cenários hidrológicos de médio e curto prazo. Com esta análise, é possível verificar como o acoplamento entre os modelos de otimização pode impactar as Estratégias e Políticas de Operação para o médio e curto prazo. / [en] The natural vocation of Brazil for the hydroelectricity made the National Interconnected Electric System – NIS to be developed with strong predominance of hydroelectric origin creation. However, choosing for a hydroelectricity base you have to deal with significant uncertainness associated to the rivers inflows and all hydrographical basins of the country. Therefore, the production structure of Brazilian hydroelectric energy was created to minimize the risks associated to the random behavior of inflows. To contemplate the inflows stochasticity in the operation planning of NIS, the National Operator of the Electrical System - ONS uses a chain of models that contains a model of inflows forecasting for the short term, and a model to generate scenarios of inflows. These models provide inputs for the optimizations model can establish the strategies and policies for the operation of medium and short term, contemplating the volatility of inputs. This dissertation describes the time series processes used in the model of inflows forecasting for the short term and in the models to generate scenarios of inflows for the medium and short term. Moreover, this paper presents a study of cases of Operation Planning of the NIS that analyze the coupling made between the models for optimization of medium and short term through the hydrological scenarios for medium and short term. By this analysis, is possible realize how the coupling between the models of optimization can impact the strategies and policies for the operation of medium and short term.

The main objective of this thesis is the comparison of the position of the healthcare personnel on the labor market and migration in selected countries - Czech Republic, Germany, France and the United Kingdom. In the theoretical introduction it describes concepts such as brain drain, remittances, emigration and others subjects associated with the migration of the workforce. It analyzes the differences in labor market of healthcare personnel in selected countries and the activities of doctors for change of working conditions. The practical part presents and analyzes data from publicly available statistical sources (OECD, Eurostat, IHIS CR etc.) regarding the number of healthcare personnel, the number of migrating doctors and nurses and their destination countries, salary and wage conditions of health professionals. Expenses on health and quality of the health care are compared between selected countries. Finally, recommendations for Czech Republic, that could help prevent excessive drain of medical personnel abroad, are given - an increase in wages and health expenditures, increasing the number of medical personnel and reduction of administrative burdens.

Background: The right ventricular outflow tract (RVOT) is known to be the origin of potentially dangerous ventricular tachycardias (VT). Arrhythmias can occur in what are otherwise assume to be structurally normal hearts as well as in arrhythmia syndromes like Brugada syndrome, catecholaminergic polymorphic VT and arrhythmogenic right ventricular dysplasia. In adults with surgically corrected tetralogy of Fallot (ToF), VT often originates in the RVOT. Methods: To investigate potential arrhythmia substrates in the structurally normal heart, the RVOT of adult rats was investigated and compared to the right ventricle (RV). In the human, the right atrium (RA), RV and the RVOT were examined in patients free of electrical and structural disease at the time of clinically indicated surgery on the left heart. The same tissue samples were collected from adults with surgically corrected ToF at the time of pulmonary valve replacement. Real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to explore changes on the mRNA level. Antibody based techniques (immunohistochemistry and Western blot) and mass spectrometry were used to identify changes on the protein level. In the rat RVOT, fine microelectrodes were employed to investigate electrophysiological characteristics. Results: A reduction in the Na+ channel Nav1.5 was found in the structurally normal RVOT in the rat and human. In the rat, RVOT-nodal like myocytes were identified. Unlike ventricular myocytes, the myocytes did not express the gap junction channel Cx43 and the K+ channel Kir2.1, but they did express the pacemaker Ca2+ channel Cav3.2 and the transcription factor Tbx3. Ectopic pacemaker and nodal-like action potentials with phase 4 depolarization were recorded from the region of the pulmonary valve. In the RA of ToF patients, SERCA2A was found to be downregulated (mRNA and protein) as seen in heart failure and atrial fibrillation. Further widespread remodelling was found in the RA, the RV and RVOT identifying multiple changes as seen in heart failure with downregulation of K+ channels and β-receptors and an increase in inflammatory markers and extracellular matrix molecules. Multiple molecules involved in the mitochondrial respiration chain were found to be downregulated in the RVOT of ToF patients. Conclusion: This is the first study that demonstrates reduction in Nav1.5 in the RVOT of structurally normal human hearts. The changes found in the rat RVOT could explain why arrhythmias originate in the RVOT. The widespread remodelling in ToF, especially in the ECM, could form a substrate for reentry arrhythmias. Mitochondrial dysfunction could point towards potential treatment targets for heart failure in this patient group.