One of the most powerful and important applications that the brain accomplishes is solving the sensory "cocktail party problem:" to adaptively suppress extraneous signals in an environment. Theoretical studies suggest that the solution to the problem involves an adaptive filter, which learns to remove the redundant noise. However, neural learning is also in its infancy and there are still many questions about the stability and application of synaptic learning rules for neural computation. In this thesis, the implementation of an adaptive filter in the brain of a weakly electric fish, A. Leptorhynchus, was studied. It was found to require a cerebellar architecture that could supply independent frequency channels of delayed feedback and multiple burst learning rules that could shape this feedback. This unifies two ideas about the function of the cerebellum that were previously separate: the cerebellum as an adaptive filter and as a generator of precise temporal inputs.

One of the most powerful and important applications that the brain accomplishes is solving the sensory "cocktail party problem:" to adaptively suppress extraneous signals in an environment. Theoretical studies suggest that the solution to the problem involves an adaptive filter, which learns to remove the redundant noise. However, neural learning is also in its infancy and there are still many questions about the stability and application of synaptic learning rules for neural computation. In this thesis, the implementation of an adaptive filter in the brain of a weakly electric fish, A. Leptorhynchus, was studied. It was found to require a cerebellar architecture that could supply independent frequency channels of delayed feedback and multiple burst learning rules that could shape this feedback. This unifies two ideas about the function of the cerebellum that were previously separate: the cerebellum as an adaptive filter and as a generator of precise temporal inputs.

The present thesis is an experimental study of some aspects of unsteady two dimensional boundary layers subject to adverse pressure gradient. An adverse pressure gradient usually leads to boundary layer separation or an instability which may result in transition to turbulence. Unsteady boundary layer separation is not yet fully understood and there is no specific criterion proposed in literature for its occurrence. The details of separation depend on the Reynolds number, the geometry of the body (streamlined or bluff) and the type of imposed unsteady motion (impulsive, oscillatory etc.). Similarly there are many unknowns with respect to instability and transition in unsteady boundary layers, especially those having a streamwise variation. For unsteady flows it is useful to break up the pressure gradient term in the unsteady boundary layer equation into two components:(Formula) is the velocity at the edge of the boundary layer. The first term of the right hand side of this equation may be called the temporal component (Πt) which signifies acceleration or deceleration in time of the free stream and the second term is the spatial component (Πx) which represents the spatial or convective acceleration of the free stream. Many of the studies on instability in unsteady flows found in literature are carried out in straight tubes or channels, where the Πx term is absent. However, in many cases, especially in biological systems both terms are present. An example is the unsteady flow over the moving body of a fish. To study the effects of Πt and Πx on unsteady separation and instability we have built an unsteady water tunnel where the two components can be systematically varied. The flow is created by a controlled motion of a piston. By a suitable combination of the geometry of the model and the piston motion, different types of separation bubbles may be generated. In our studies the piston motion follows a trapezoidal variation: constant acceleration from rest, followed by constant velocity and then deceleration to zero velocity. We have chosen two geometries. One is a bluff body and thus has a high value of Πx and other is a small angle diffuser with a divergence angle 6.2° and thus having a small value of Πx. Upstream and downstream of the diffuser are long lengths of constant cross section. We have performed experiments with the above mentioned geometries placed in the tunnel test section. Flow is visualized using the laser induced fluorescence technique by injecting a thin layer of fluorescein dye on the test wall. Numerical simulations have been done using the software FLUENT. Boundary layer parameters like boundary layer, displacement and momentum thicknesses are calculated from the simulations and used to analyze the experimental results. For the flow in the diffuser, quasi-steady stability analysis of the instantaneous velocity profiles gives a general idea of stability behavior of the flow. Two types of experiments have been done with the bluff body. One is the unsteady boundary layer separation and the formation of the initial vortex for a flow that is uniformly accelerated from rest. We have found some scalings for the formation time (tv) of the separation vortex. The second type of experiment was to study the vortex shedding from the separating shear layer after the boundary layer has fully separated. At high enough Reynolds number shear layer vortices are seen to shed from the separation bubble. The Strouhal number based on the momentum thickness and the velocity at the edge of the boundary layer just upstream of the separation point is found to vary between 0.004 and 0.008. This value is close to the Strouhal number value of 0.0068 found in laminar separation bubbles on a flat plate. The second part of the study concerns with the evolution of the flow in the small angle diffuser with a mild variation of the spatial component of the pressure gradient. From the experimental visualizations we have found that the ratio of Πx and Πt at the start of the deceleration phase of the piston motion is an important parameter that determines the type of instability. This value of Πx/Πt is controlled by controlling the piston deceleration: a large deceleration gives a low Πx/Πt value and a low deceleration gives a large Πx/Πt value. Three types of instabilities have been observed in our experiments. In Type I, the first vortex forms at the maximum pressure gradient point (MPGP) and which grows disproportionately with time. However, instability vortices are seen later at other locations around the MPGP. In type II an array of vortices over a certain length are observed; the vortices grow with time. In Type III, which we observe for low decelerations, we observe initial vortices only in the diffuser section in the deceleration phase of the piston motion. Type III instability is similar to the one observed in dynamic stall experiments. In all cases the instability is very localized - it occurs only over some length of the boundary layer. Transition to turbulence, which is also localized, is observed at higher Reynolds numbers. The non-dimensional time for vortex formation is not very different from that found in straight channel experiments. Quasi-steady linear stability analyses for the boundary layer at the MPGP both for the top and the bottom walls show that the flow is absolutely unstable for some cases. In summary, the thesis looks at in a unified way the separation and instability of unsteady boundary layers with reverse flow. It is hoped that the results will be useful in predicting and understanding onset of separation and instability in practically occurring unsteady flows.

One of the most powerful and important applications that the brain accomplishes is solving the sensory "cocktail party problem:" to adaptively suppress extraneous signals in an environment. Theoretical studies suggest that the solution to the problem involves an adaptive filter, which learns to remove the redundant noise. However, neural learning is also in its infancy and there are still many questions about the stability and application of synaptic learning rules for neural computation. In this thesis, the implementation of an adaptive filter in the brain of a weakly electric fish, A. Leptorhynchus, was studied. It was found to require a cerebellar architecture that could supply independent frequency channels of delayed feedback and multiple burst learning rules that could shape this feedback. This unifies two ideas about the function of the cerebellum that were previously separate: the cerebellum as an adaptive filter and as a generator of precise temporal inputs.

This dissertation describes the advantages and feasibility of newly synthesized near-infrared (NIR) bis-heptamethine cyanine (BHmC) dyes for non-covalent labeling schemes. The NIR BHmCs were synthesized for biomolecule assay. The advantages of NIR BHmCs for biomolecule labeling and the instrumental advantages of the near-infrared region are also demonstrated. Chapter 1 introduces the theory and applications of dye chemistry. For bioanalysis, this chapter presents covalent and non-covalent labeling. The covalent labeling depends on the functionality of amino acids and the non-covalent labeling relies on the binding site of a protein. Due to the complicated binding process in non-covalent labeling, this chapter also discusses the binding equilibria in spectroscopic and chromatographic analyses. Chapter 2 and 3 evaluate the novel BHmCs for non-covalent labeling with human serum albumin (HSA) and report the influence of micro-environment on BHmCs. The interesting character of BHmCs in aqueous solutions is that the dyes exhibit non- or low-fluorescence compared to their monomer counterpart, RK780. It is due to their H-type closed clam-shell form in the solutions. The addition of HSA or organic solvents opens up the clam-shell form and enhances fluorescence. The binding equilibria are also examed. Chapter 4 provides a brief introduction that summaries the use of capillary electrophoresis (CE), and offers a detailed instrumentation that discusses the importance and advantage of a detector in NIR region for CE separation. Chapter 5 focuses on the use of NIR cyanine dyes with capillary electrcophoresis with near-infrared laser induce fluorescence (CE-NIR-LIF) detection. The NIR dyes with different functional groups show that RK780 is a suitable NIR dye for HSA labeling. The use of BHmCs with CE-NIR-LIF reduces signal noises that are commonly caused by the interaction between NIR cyanine dyes and negatively charged capillary wall. In addition, bovine carbonic anhydrase II (BCA II) is applied to study the influence of hydrophobicity on non-covalent labeling. Finally, chapter 6 presents the conformational dependency of BHmCs on the mobility in capillary and evaluates the further possibility of BHmCs for small molecule detection. Acridine orange (AO) is used as a sample and it breaks up the aggregate and enhances fluorescence. The inserted AO into BHmC changes the mobility in capillary, owing to the conformational changes by AO.

Spatially-resolved measurements of flame temperature have been demonstrated with diode lasers for the first time. The technique is based on the use of blue diode lasers to perform laser-induced fluorescence on indium atoms seeded to the flame. Temperature measurements have been carried out in laminar flames both by the two-line atomic fluorescence technique, and also by a novel line-shape thermometry method that requires the use of only a single diode laser. The first part of this work involved the development of blue extended cavity diode lasers with favourable tuning properties. Two custom-designed extended cavity diode lasers (ECDL) have been built, emitting at wavelengths of around 410 nm and 451 nm respectively. These devices are capable of mode-hop free tuning over ranges greater than 90 GHz. The performance of these devices exceeds that of commercially available systems and a patent application has been filed. High resolution fluorescence spectroscopy has been performed on both the 52P1/2→62S1/2 and 52P3/2→62S1/2 transitions of indium atoms seeded at trace quantities into atmospheric pressure flames. In both cases, the spectra obtained show excellent agreement with a theoretical fit based on the individual hyperfine components of the transition. The two ECDLs have been used to build a sensor for the measurement of temperature in combustion systems. It is much simpler, more compact, less expensive, and more versatile than any previously existing device. The two lasers were used sequentially to probe indium atoms seeded to the flame. The ratio of the resulting fluorescence signals is related to the relative populations in the two sub-levels of the spin-orbit split ground state of indium, and thus to the temperature. Temperature measurements have been successfully performed in a laminar flame and the data thus obtained do not need to be corrected by any ‘calibration constant’. This novel thermometry technique offers a robust alternative to traditional methods involving bulky high power lasers. A further development has been made by demonstrating a fluorescence line-shape thermometry technique requiring only a single diode laser excitation source. Progress has been made towards the goal of rapid temperature measurements appropriate to the study of turbulent flames. This involved the development of a simple technique for actively locking the wavelength of the blue diode laser to a resonance line of the tellurium molecule. A high-speed thermometry system would work by rapidly switching between the two locked laser beams using an optical modulator.

One of the most powerful and important applications that the brain accomplishes is solving the sensory "cocktail party problem:" to adaptively suppress extraneous signals in an environment. Theoretical studies suggest that the solution to the problem involves an adaptive filter, which learns to remove the redundant noise. However, neural learning is also in its infancy and there are still many questions about the stability and application of synaptic learning rules for neural computation. In this thesis, the implementation of an adaptive filter in the brain of a weakly electric fish, A. Leptorhynchus, was studied. It was found to require a cerebellar architecture that could supply independent frequency channels of delayed feedback and multiple burst learning rules that could shape this feedback. This unifies two ideas about the function of the cerebellum that were previously separate: the cerebellum as an adaptive filter and as a generator of precise temporal inputs.

Ce travail s'intéresse à la compréhension du comportement des flammes non-prémélangées issues d'un jet de méthane assisté par un coflow d'air dilué avec du CO2, ou d'autres gaz chimiquement inertes pour discriminer les différents phénomènes impliqués dans la dilution. Les phénomènes transitionnels, décrochage et extinction, quantifiés par des limites de stabilité, sont analysés à l'aide de grandeurs physiques représentatives. Le domaine de stabilité de flamme est limité par des surfaces 3D dans le domaine physique ( Qdiluant/Qair (taux de dilution), Uair (vitesse d'air), UCH4 (vitesse de méthane)), révélant un effet compétitif entre l'aérodynamique et la dilution. Des cartographies génériques de décrochage et d'extinction communes à tous ces diluants sont proposées. Des grandeurs liées à la stabilisation sont toutes soumises à des lois d'évolution auto-simlilaires. Il en ressort que la vitesse de propagation de flamme est l'élément clé du mécanisme de stabilisation lors de la dilution. / This work focuses on the understanding of the behaviours of non-premixed methane flame inside an air coflow diluted by carbon dyoxide (CO2) or by other chemically inert diluents in order to discriminate different phenomena involved in dilution. Transitional phenomena (liftoff and extinction) quantified trough the stability limits, are analyzed trough representative physical quantities. The flame stability domain is limited by 3D-surfaces (liftoff and extinction) in the physical domain (Qdiluant/Qair (dilution level), Uair (air velocity), UCH4 (methane velocity)) revealing a competitive effect between aerodynamics and dilution. Generic diagrams of flame liftoff and extinction are proposed for all the diluents. Physical quantities related to flame stabilization process are all submitted to, regardless of diluent, self-similar laws. This is explained by flame burning velocity which is considered as the key element in the flame stabilization mechanism with air-side dilution.

No description available.

Cardiotrophin-1 ist ein Zytokin der Familie Interleukin-6-Familie, zu der auch IL-11, CNTF, OSM und LIF gehören. Diese Substanzen wirken über die gemeinsame Rezeptoruntereinheit gp130. CT-1 induziert die Hypertrophie von Kardiomyozyten und inhibiert die Apoptose kardialer und Zellen. In verschiedenen Tiermodellen der Herzinsuffizienz konnte eine gesteigerte myokardiale CT-1 Expression beobachtet werden. Kardiomyopathien sind wiederum kardiale Erkrankungen, die mit einer Hypertrophie und Apoptose einhergehen und zu einer Herzinsuffizienz führen können. Man geht davon aus, dass 25-50 Prozent der familiär sind. Hierbei handelt es sich um eine monogenetische Erkrankung, die überwiegend autosomal-dominant vererbt werden. Daneben konnten aber auch modifizierende Polymorphismen in neurohumoralen Faktoren identifiziert werden. Basierend auf diesen Ergebnissen war das Ziel dieser Arbeit die Analyse der möglichen Beteiligung genetischer Varianten der kodierenden sowie der regulatorischen Region an der Pathogenese der Hypertrophen bzw. Dilatativen Kardiomyopathie. Zusätzlich sollte die mRNA-Expression von CT-1 in Myokardbiopsien von Patienten mit Herzinsuffizienz quantifiziert werden. Hierfür musste zunächst die Sequenzen der 5´-flankierenden Region identifiziert und bezüglich ihrer regulatorischen Eigenschaften analysiert werden. Es konnten 1,1 kb der 5´-flankierenden Region sequenziert werden. Die anschließende Luciferase-Reportergen-Analyse wies regulatorische Aktivitäten für den gesamten Bereich nach. Diese Region enthält zahlreiche cis-aktive DANN-Sequenzen aber keine TATA-Box. Für die Mutationssuche wurden 64 Patienten mit DCM, 53 Patienten mit HCM sowie 100 Kontrollpersonen mittels PCR-SSCP-Analyse untersucht. Es konnte eine kodierende Variante A92T bei jeweils einem DCM- bzw. HCM-Patienten identifiziert werden. Diese Substitution liegt in einem Bereich, der zwischen verschiedenen Spezies (Ratte, Maus, Mensch) konserviert ist. Diese Mutation könnte eine Veränderung der Sekundärstruktur bewirken und liegt in einem möglichen funktionellen Bereich. Die Promotorregion wies eine Basenpaarsubstitution bei -130 (G/T) sowie eine Deletion der Basen CTTT zwischen -992 und -995 auf. Der Polymorphismus an Position -130 fand sich tendenziell häufiger bei Patienten mit Dilatativer Kardiomyopathie. Die CTTT-Deletion konnte nur bei einer Patientin mit HCM nachgewiesen werden. Für die Quantifizierung der CT-1 mRNA wurden rechtsventrikuläre Endomyokardbiopsien von 6 Patienten mit eingeschränkter LVEF (CHI), 5 Patienten nach Herztransplantation (TX) sowie 3 Kontrollpatienten (KO) eingesetzt. Es konnte ein relativer Anstieg der CT-1 Expression um 82% bei den Patienten mit eingeschränkter LVEF festgestellt werden. Interessanterweise besteht eine enge Korrelation zur Schwere der eingeschränkten Herzfunktion sowie zur Zunahme der Hypertrophie. / Cardiotrophin-1 is a cytokine, which belongs to the interleukin-6 family, which includes IL-11, CNTF, OSM and LIF. These factors act via the receptor subunit gp130. CT-1 induces the hypertrophy of cardiomyocytes and inhibits the apoptosis of cardiac cells. Studies in animal models of congestive heart failure showed an enhanced expression of CT-1 in the myocardium. Cardiomyopathies are cardiac diesorders, which are charakterized by hypertrophy and apoptosis and which can terminate with congestive heart failure. About 25-50 percent of all cases are familial. It is a monogenetic mendelian disorder with an autosomal-dominant inheritance in most cases. Beside this, modifying polymorphisms in neurohunoral factors could be identified. Based on these facts, the aim of this study was to identify genetic variants within the coding and regulatory region of the CT-1 gene, which could influence the pathogenesis of hypertrophic or dilated cardiomyopathy. Additionally, the mRNA-expression of CT-1 in myocardial biopsies of heart failure patients should be quantified. First, it was necessary to sequence the 5´-untranslated region and to analyse its regulatory function. We could sequence 1.1 kb of the 5´-UTR. The luciferase reportergene assay showed a significant promoter activity for the whole region. The region contains various cis-active DNA sequences but no TATA-box.The TRANSFAC-analysis identified different binding sites for transcription factors but no TATA-box. The genetic material of 64 DCM and 53 HCM patients and 100 controls was screened for mutaions by using a PCR-based SSCP-analysis. A coding variant A92T could be identified for a patient with DCM and for an HCM patient. This mutation lies within a region which is conserved between different species (rat, mouse, human). This variant could disturb the secondary structure and lies in a probable functional region. Within the promoter we could identify a basepair substitution at position -130 (G/T) and a 4-basepair deletion between -992 and -995 (CTTTdel). The polymorphism at -130 showed a tendency for a higher occurrence in DCM patients. One HCM patient was heterozygous for the CTTT-deletion. To quantify the CT-1 mRNA we used endomyocardial biopsies of 6 patients with reduced LVEF (CHI), 5 patients after heart transplantation (TX) and 3 controls (KO). We performed a semiquantitative analysis by using HPLC and an external standard (PDH mRNA). We found an increased expression of CT-1 by 82% for patients with heart failure. Interestingly, we saw a tight correlation with to the reduction in LV function and to the degree of hypertrophy.