No description available.

The subject of this thesis was to compare injuries. First comparison accidents took place within the area of SK - NACE, their sources, and their causes in the Slovak Republic in the years 2012 - 2015. In the next step compared accidents within the area CZ - NACE, their sources, and causes in the Czech Republic in years 2011 - 2015. The last took place juxtaposition between the Slovak and Czech Republic.

Tesis para optar al grado de Mag?ster en Literatura / Partiendo de las aproximaciones cr?ticas que examinan el fen?meno literario en di?logo fecundo con sus condiciones de producci?n y consideran que las obras se inscriben ?a veces integr?ndose, a veces resistiendo? en el ?mbito cultural y social que las sostiene, este trabajo se propone explorar la obra cuent?stica de Antonio Sk?rmeta en el contexto de su producci?n inicial. Lo que interesa ac? es revisar la po?tica original y el gesto narrativo de un autor que escoge el cuento como un g?nero eficaz, provechoso y esencialmente comunicativo para producir, seg?n sus propios t?rminos, ?un momento intenso de humanidad?. Lejos de pensar en la literatura como un reflejo inmediato de la sociedad, la propuesta de esta investigaci?n apunta a conectar la obra de Sk?rmeta con aquella concepci?n del mundo que la encauza. Esto supone considerar la escritura como un trabajo transformativo plagado de referencias que, siguiendo a No? Jitrik, se adhiere a cierto ?instrumental ideol?gico que no por internalizado (modas, selectividad de temas o im?genes, etc.) es menos resultado de una previa existencia cultural?. Para Jitrik el acto de escritura ocurrir? siempre desde la ideolog?a. Y desde ella, entonces, tendr? lugar la elecci?n de las t?cnicas aptas para que el trabajo se realice adecuadamente. Los cuentos de Sk?rmeta, en ese sentido, hacen suya la visi?n del mundo propia de una juventud que respira y protagoniza una ?poca de tanto entusiasmo y apertura como incertidumbre hist?rica. En efecto, 1967 no s?lo fue el a?o del debut en la narrativa de este escritor chileno nacido en 1940, sino tambi?n un momento clim?tico en el desarrollo cultural de Occidente, marcado por las invocaciones de una juventud en emergencia. Durante la alborotada d?cada del sesenta, por decirlo as?, confluyeron las aguas de una riqu?sima corriente de sensibilidades que se manifestaron en lo que Susan Sontag designar?a entonces como una ?voracidad de entusiasmos?. Los cuentos que aqu? estudiaremos (en el tercer cap?tulo de esta investigaci?n) se alojan en la atm?sfera plena de estos cambios en la metr?poli, en la regi?n latinoamericana y en nuestro pa?s, lo que entre otras cosas implica una ruptura formal y de contenidos con la producci?n literaria inmediatamente previa, la de la generaci?n del cincuenta, marcada en gran medida por la sensibilidad de postguerra y el pesimismo que le sobrevino como una cortina de acero. Y en Chile y en nuestra literatura, adem?s, por la ruptura frente al anquilosado criollismo de los a?os treinta y cuarenta, vigente todav?a en las letras locales. Tal como apunta el cr?tico Jos? Promis, los autores del cincuenta fueron ?testigos del resquebrajamiento del espacio social en que estaban insertos?. Con marcado talante individualista, los j?venes escritores de aquellos a?os dieron cuenta de la angustia vital que los aquejaba a trav?s de im?genes apocal?pticas, de un mundo cerrado y sin salida, ?frente al cual la ?nica respuesta posible, o quiz?s la m?s f?cil de asumir, era el escepticismo?. En este contexto, tal vez la pieza clave de la ?poca haya sido el libro de cuentos La dif?cil juventud, de Claudio Giaconi, que a partir de los inquietantes versos de Nicanor Parra citados en el ep?grafe (?Me preguntaron que de d?nde ven?a/ Contest? que s?, que no ten?a planes determinados/ Contest? que no, que de ah? en adelante?) fij? las coordenadas de lo que Antonio Avaria denominar?a acertadamente ?la anatom?a de la abulia?. Pero si el temple an?mico imperante en estos cuentistas fue el del hast?o, la atm?sfera de la d?cada siguiente ?la que nos interesa revisar en este trabajo? ser? la opuesta y corresponder?, como ya dijimos, al horizonte hist?rico de buena parte del mundo occidental. El arrojo y la vitalidad, as? como el ?nimo comunitario, la incorporaci?n de la cultura popular y del habla de la calle, el ?nfasis en la cotidianeidad y la disposici?n al goce, marcar?n la ruta de los narradores del sesenta. Especialmente de los veintea?eros, como el propio Antonio Sk?rmeta y sus cong?neres de la llamada nov?sima generaci?n o generaci?n del postboom. M?s all? de las etiquetas, sin embargo, la mirada de estas obras no estar? puesta en el individuo pesaroso ni en su atormentada existencia, sino m?s bien en los movimientos de hombres y mujeres que nacen, viven, leen, comen, bailan, fornican, viajan y tambi?n mueren. Seres que se configuran como una pluralidad. Si Giaconi parafraseaba la idea de Tolstoi, cuestion?ndola, cuando dec?a que era necesario describir bien el alma de la propia aldea para ser universal, es posible admitir que la tendencia de la d?cada siguiente ser? regresar al cuerpo colectivo de esa misma aldea, a su atm?sfera extasiada que movilizar? tanto al individuo como a la sociedad en su conjunto, para ser todav?a m?s universales.

La maladie de Parkinson (MP) est une maladie neurodégénérative caractérisée par une perte dopaminergique (DA) de la voie nigro-striée. Cette dégénérescence des neurones DA, induit un déséquilibre entre les transmissions dopaminergique, GABAergique et glutamatergique au sein des ganglions de la base qui se traduit par des troubles de l'excitabilité neuronale aboutissant à l'apparition des symptômes moteurs et non-moteurs. Nous avons étudié l'effet de la modulation des canaux SK et Kv4 par des toxines issues de venins d'animaux. Pour ce faire, nous avons utilisé deux modèles lésionnels à la 6-hydroxydopamine (6-OHDA): une lésion bilatérale partielle du striatum mimant la phase précoce de la MP pour tester les déficits cognitifs et émotionnels, et une lésion unilatérale totale au niveau de la substance noire mimant la rigidité et la bradykinésie en phase tardive pour tester les déficits moteurs. Nos résultats montrent que le blocage des canaux SK par l'apamine (injection systémique, 0.1-0.3 mg/kg) améliore partiellement et transitoirement les déficits moteurs dans le test du cylindre et la rotation induite par l'apomorphine dans le modèle tardif de la MP. L'AmmTX3 (injection intrastriatale, 0.2-0.4 g), réduit les déficits moteurs et restaure des comportements cognitifs déficitaires (mémoire sociale et spatiale à court terme) et émotionnels (anxiété), après une dégénérescence DA bilatérale et partielle. L'ensemble de ces données suggère que l'inhibition pharmacologique de l'activité des canaux SK par l'apamine et Kv4 par l'AmmTX3, pourrait représenter une voie thérapeutique innovatrice quant au traitement des déficits moteurs, cognitifs et émotionnels de la MP. / Parkinson's disease (PD) is a neurodegenerative disease associated to a loss of dopaminergic nigrostriatal pathway that innervates the basal ganglia (GB). The DA neuron degeneration in PD induces imbalance between dopaminergic transmission, GABAergic and glutamatergic resulting in impaired neuronal excitability leading to the onset of motor and non-motor symptoms. Potassium channels, Kv4 and SK, are extensively involved in the phenomenon of neuronal excitability. We addressed the question of whether further blockade of SK or Kv4 activity could restore normal GB function in vivo. In this aim, we used a neurotoxin, 6-hydroxydopamine (6-OHDA) to produce two lesional models of Parkinson's disease in rats that mimics the cognitive and emotional deficits of the early phase of PD (partial and bilateral striatal lesions) and the motor deficits observed in the late phase of the disease (total unilateral nigral lesion). Apamin from bee venom (systemic injection, 0.1-0.3 mg/kg) and AmmTX3 from scorpion venom (intrastriatal injection, 0.2-0.4 g) were chosen to block SK and Kv4 channels respectively.In a first study, apamin treatment partially reduced motor deficits in the cylinder test and the rotation induced by apomorphine. In the second study, the AmmTX3 also decreased parkinsonian motor deficits. This late toxin restored cognitive behaviors (short-term social and spatial memory) and emotion (anxiety).Taken together, these results underlie the importance of SK channels as modulators of neuronal excitability of Kv4 channels as players of the homeostatic responses, and more importantly, provide potential targets for adjunctive therapies for Parkinson's disease.

In dieser Dissertation beschäftigen wir uns mit angepassten Zusammenhängen und ihren (horizontalen) Dirac-Operatoren auf strikt pseudokonvexen CR-Mannigfaltigkeiten. Einen Zusammenhang nennen wir dann angepasst, wenn er die relevanten Daten parallelisiert. Wir beschreiben den Raum der angepassten Zusammenhänge, indem wir ihre Torsionstensoren studieren, von denen gewisse Teile durch die Geometrie der Mannigfaltigkeit festgelegt sind, während andere frei wählbar sind. Als Anwendung betrachten wir die Eigenschaften der Dirac-Operatoren, die zu diesen Zusammenhängen gehören. Weiter betrachten wir horizontale Dirac-Operatoren, die nur in Richtung des horizontalen Bündels H ableiten. Diese Operatoren sind besser an die Sub-Riemannsche Struktur einer CR-Mannigfaltigkeit angepasst als die vollen Dirac-Operatoren. Wir diskutieren, wann diese Operatoren formal selbstadjungiert sind und beweisen eine Weitzenböck-Typ-Formel. Wir konzentrieren uns dann auf den horizontalen Dirac-Operator zum Tanaka-Webster-Zusammenhang. Dieser ändert sich konform kovariant, wenn wir die Kontaktform konform ändern. Für diesen Operator betrachten wir weiterhin zwei Beispiele: Wir betrachten S^1-Bündel über Kähler-Mannigfaltigkeiten, insbesondere berechnen wir für Sphären einen Teil des Spektrums. Außerdem betrachten wir kompakte Quotienten der Heisenberggruppe und berechnen hier in den Dimensionen 3 und 5 das volle Spektrum. Die horizontalen Dirac-Operatoren sind nicht mehr elliptisch, sondern „elliptisch in Richtung von H“. Mithilfe des Heisenbergkalküls stellen wir fest, dass die horizontalen Dirac-Operatoren nicht hypoelliptisch sind. Im Fall des Tanaka-Webster-Zusammenhangs lässt sich aber zeigen, dass der zugehörige Operator auf gewissen Teilen des Spinorbündels hypoelliptisch ist. Dies genügt, um zu beweisen, dass er (nun auf dem gesamten Spinorbündel) ein reines Punktspektrum hat und die Eigenräume, bis auf den Kern, endlich-dimensional sind und aus glatten Eigenspinoren bestehen. / In the present thesis, we study adapted connections and their (horizontal) Dirac operators on strictly pseudoconvex CR manifolds. An adapted connection is one that parallelises the relevant data. We describe the space of adapted connections through their torsion tensors, certain parts of which are determined by the geometry of the manifold, while others may be freely chosen. As an application, we study the properties of the Dirac operators induced by these connections. We further consider horizontal Dirac operators, which only derive in the direction of the horizontal bundle H. These operators are more adapted to the essentially sub-Riemannian structure of a CR manifold than the full Dirac operators. We discuss the question of their self-adjointness and prove a Weitzenböck type formula for these operators. Focusing on the horizontal Dirac operator associated with the Tanaka-Webster connection, we show that this operator changes in a covariant way if we change the contact form conformally. Moreover, for this operator we discuss two examples: On S^1-bundles over Kähler manifolds, we can compute part of the spectrum and for compact quotients of the Heisenberg group, we determine the whole spectrum in dimensions three and five. The horizontal Dirac operators are not elliptic, but rather "elliptic in some directions". We review the Heisenberg Calculus for such operators and find that in general, the horizontal Dirac operators are not hypoelliptic. However, in the case of the Tanaka-Webster connection, the associated horizontal Dirac operator is hypoelliptic on certain parts of the spinor bundle and this is enough to prove that its spectrum consists only of eigenvalues and except for the kernel, the corresponding eigenspaces are finite-dimensional spaces of smooth sections.

Die Gewichte eines Portfolios liegen meist als als Kombination des Produkts der Präzisionsmatrix und des Erwartungswertvektors vor. In der Praxis müssen diese Parameter geschätzt werden, allerdings ist die Beschreibung der damit verbundenen Schätzunsicherheit über eine Verteilung dieses Produktes eine Herausforderung. In dieser Arbeit wird demonstriert, dass ein geeignetes bayesianisches Modell nicht nur zu einer leicht zugänglichen Posteriori-Verteilung führt, sondern auch zu leicht interpretierbaren Beschreibungen des Portfoliorisikos, wie beispielsweise einer Ausfallwahrscheinlichkeit des gesamten Portfolios zu jedem Zeitpunkt. Dazu werden die Parameter mit ihren konjugierten Prioris ausgestatet. Mit Hilfe bekannter Ergebnisse aus der Theorie multivariater Verteilungen ist es möglich, eine stochastische Darstellung für relevante Ausdrücke wie den Portfoliogewichten oder des effizienten Randes zu geben. Diese Darstellungen ermöglichen nicht nur die Bestimmung von Bayes-Schätzern der Parameter, sondern sind auch noch rechentechnisch hoch effizient, da Zufallszahlen nur aus bekannten und leicht zugänglichen Verteilungen gezogen werden. Insbesondere aber werden Markov-Chain-Monte-Carlo Methoden nicht benötigt. Angewendet wird diese Methodik an einem mehrperiodigen Portfoliomodell für eine exponentielle Nutzenfunktion, am Tangentialportfolio, zur Schätzung des effizienten Randes, des globalen Minimum-Varianz-Portfolios wie auch am gesamten Mittelwert-Varianz Ansatzes. Für alle behandelten Portfoliomodelle werden für wichtige Größen stochastische Darstellungen oder Bayes-Schätzer gefunden. Die Praktikabilität und Flexibilität wie auch bestimmte Eigenschaften werden in Anwendungen mit realen Datensätzen oder Simulationen illustriert. / Usually, the weights of portfolio assets are expressed as a comination of the product of the precision matrix and the mean vector. These parameters have to be estimated in practical applications. But it is a challenge to describe the associated estimation risk of this product. It is demonstrated in this thesis, that a suitable Bayesian approach does not only lead to an easily accessible posteriori distribution, but also leads to easily interpretable risk measures. This also includes for example the default probability of the portfolio at all relevant points in time. To approach this task, the parameters are endowed with their conjugate priors. Using results from the theory of multivariate distributions, stochastic representations for the portfolio parameter are derived, for example for the portfolio weights or the efficient frontier. These representations not only allow to derive Bayes estimates of these parameters, but are computationally highly efficient since all th necessary random variables are drawn from well known and easily accessible distributions. Most importantly, Markov-Chain-Monte-Carlo methods are not necessary. These methods are applied to a multi-period portfolio for an exponential utility function, to the tangent portfolio, to estimate the efficient frontier and also to a general mean-variance approach. Stochastic representations and Bayes estimates are derived for all relevant parameters. The practicability and flexibility as well as specific properties are demonstrated using either real data or simulations.

No description available.

The mammalian suprachiasmatic nuclei (SCN) are located in the ventral part of the hypothalamus and orchestrate circadian rhythms in physiology and behaviour. The ~20.000 neurones of the murine SCN express key molecular clock components including the Cryptochrome (Cry1/2) and Period (Per1/2/3) genes and their protein products CRY1/2 and PER1/2/3. Using different mouse models, this work demonstrates that with disrupted expression of CRY in the after-hours (Afh/Afh) mouse, cells of the ventral part of the SCN (vSCN) have a propensity to desynchronise. They receive increased GABAergic inputs and are less excitable during the projected night but not during the day compared to congenic wildtype (+/+). The linkage between CRY protein expression and the reduced excitability at night is supported by recordings from SCN cells of Cry2 deficient mice (Cry2-/-), which exhibit similar electrophysiological behaviour. Luminometrical recordings of single cell Per2 expression confirms the involvement of GABAergic signalling in both, maintaining a coherent rhythm in synchronised SCN cells from +/+ controls and the propensity of Afh/Afh SCN cells to desynchronise. A mechanism by which neuronal excitability is regulated in mammals, is the modulation of activity of small-conductance Ca2+-activated K+ (SK) channels. Western blot analysis demonstrates the expression of SK2 and SK3 channel protein in SCN neurones. Functionally, we show with whole cell electrophysiology, calcium imaging and luminometry how SK channels regulate the levels of intracellular calcium ([Ca2+]i) from day to night. In the more hyperpolarised SCN network of the Afh/Afh genotype at night, SK channel activity is altered and contributes to the lower single cell excitability. Vasoactive intestinal polypeptide (VIP) and its cognate receptor, VPAC2, are synthesised by SCN neurones and this intercellular signal facilitates coordination of suprachiasmatic neuronal activity. How the loss of VPAC2 receptor signalling affects the electrophysiology of SCN neurones and their response to excitatory inputs is unclear. Here we made patch clamp recordings of SCN neurones in brain slices prepared from animals that do not express VPAC2 receptors (Vipr2-/- mice) as well as non-transgenic animals (Vipr2+/+ mice). While Vipr2+/+ SCN neurones exhibit coordinated day-night variation in their electrical state, Vipr2-/- neurones do not and instead manifest a range of states during both day and night. We find that Vipr2+/+ neurones vary the membrane threshold potential at which they start to fire actions potentials from day to night, while Vipr2-/- neurones lack this variation. This is due to Vipr2-/- neurones lacking a voltage-gated sodium current. Subsequently we determine that this aberrant temporal control of neuronal state and excitability alters appropriate neuronal responses to a neurochemical mimic of the light-input pathway to the SCN. Conclusively, these results highlight the critical role intercellular signalling plays in the activity of individual neuronal state and their response to neural input as well as ensemble activity and function of the suprachiasmatic neural network.

The small- and intermediate-conductance Ca2+ activated K + (SK/IK) channels play a fundamental role in the regulation of neurons in the central nervous system. In animal models, SK/IK channel positive modulators have been shown to be effective in reducing the symptoms of neurological diseases such as ataxia. Ataxia is a lethal neurological rare disease characterized by lack of balance and incoordination of muscle movements, often as a result of cerebellar or spinocerebellar neurodegeneration. SK/IK channel modulators have been developed over the past few decades. Currently available modulators are often weak in potency. Lack of knowledge about the binding site for the compounds is the main reason hindering the development of more potent and effective therapeutics targeting SK channels. Dr. Zhang and his colleagues recently discovered the binding pocket for these positive modulators of SK/IK channels. This pocket is located at the interface between the channel and calmodulin. Dr. Zhang and his colleagues performed screening of a large number of compounds in silico, to find those fitting into the binding pocket. I performed electrophysiological recordings to evaluate the efficacy and the potency of these modulators on SK2 channels. We discovered a correlation between the total binding energy values calculated from the structures and the potencies determined from electrophysiological recording.

Atomic force microscopy (AFM) can be used to acquire high-resolution topographical images of surfaces, but has the additional capability of detecting the local nanometer scale mechanical properties. For these reasons, it becomes a standard research tool in the surface science recently. In this paper, we used AFM to measure the several properties of two different human hepatocellular carcinoma cell lines, Hep G2 ( known as well differentiated and more highly carcinomatous hepatoma cell lines ) and SK-HEP-1 ( known as poorly differentiated and more lightly carcinomatous hepatoma cell lines ) cells fixed on the glass substrate, which including the surface morphology and the relationship between the cantilever deflections and loading forces ( force curve ). Considered the heterogeneous characteristics of the cell surface, the preferred experimental method is to make pixel-by-pixel force curves in a designated area ( force map ) , both adhesion forces and elasticity associated with different locations on the cell surfaces will be obtained. Finally, we use Hertzian model to calculate Young's modulus of Hep G2 and SK-HEP-1 respectively. Based on these results, we can understand the surface properties of two human hepatocarcinoma cell lines with different differentiated stage. The results showed the difference of the morphology, height, cell migration, degree of cell aggregation, roughness, elasticity, adhesive force of two cells. SK-HEP-1 cell has the wide distance of the folds, better cell migration, homogeneous properties of elasticity. It can be assumed that the SK-HEP-1 cells have a dense network structure of actin filaments under the cell membrane like branches (branched networks); Hep G2 cell has the narrow distance of the folds, poor cell migration, heterogeneous properties of elasticity. It can be assumed that the Hep G2 cells have the individual actin filaments and cross-linked network structure of actin filaments under the cell membrane. The above results can be speculated that the elastic properties of the membrane surface will be influenced of actin filaments.