Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2008-2009 / Suite aux traumatismes crâniens pénétrants, le cerveau devient graduellement hyperexcitable et génère des activités paroxystiques spontanées. Les mécanismes qui sous-tendent l’épileptogénèse demeurent cependant peu connus. La ligne directrice de nos travaux consiste en l'hypothèse que la diminution de l'activité corticale engendrée par la déafférentation déclenche des mécanismes homéostatiques agissant tant au niveau cellulaire qu’au niveau du réseau cortical, et qui mènent à une excitabilité neuronale accrue culminant en crises d’épilepsie. Nous avons testé cette hypothèse chez des chats adultes, lors de différents états de vigilance ou sous anesthésie, ayant subits une déafférentation partielle du gyrus suprasylvien. Nous avons évalué les effets de la déafférentation corticale aigue et chronique sur la survie des neurones et des cellules gliales et nous avons investigué comment la privation chronique d'afférences neuronales pourrait modifier les propriétés du réseau cortical et déclencher des crises d’épilepsie. Après la déafférentation du gyrus suprasylvien, les neurones situés dans les couches corticales profondes, en particulier les neurones inhibiteurs GABAérgiques, dégénèrent progressivement et parallèlement à une fréquence croissante des activités paroxystiques, notamment pendant le sommeil à ondes lentes. La privation chronique d'afférences neuronales et la perte de neurones activent les mécanismes homéostatiques de plasticité qui favorisent une plus grande connectivité neuronale, une efficacité plus élevée des connexions synaptiques excitatrices et des changements des propriétés neuronales intrinsèques. Ensemble, ces facteurs favorisent une excitation accrue du réseau cortical. L'activité corticale spontanée, mesurée par les taux moyens de décharge, augmente progressivement, en particulier pendant le sommeil à ondes lentes, caractérisé par des périodes silencieuses alternant avec des périodes actives. Ceci soutient, en outre, notre hypothèse concernant la participation des mécanismes de plasticité homéostatique. La dégénération des neurones des couches corticales profondes produit des changements importants dans la distribution laminaire de l'activité neuronale, qui est déplacée vers les couches plus superficielles, dans la partie déafferenté du gyrus. Ce changement dans la distribution de profils de profondeurs de décharges neuronales modifie également le déclenchement de l'activité corticale spontanée. Dans le cortex normal et dans la partie relativement intacte du gyrus suprasylvien, l'activité corticale est générée dans les couches corticales profondes. Pourtant, dans le cortex chroniquement déafferenté, l'oscillation lente et les activités ictales sont générées dans les couches superficielles et puis diffusent vers les couches plus profondes. Le traumatisme cortical induit également une importante gliose réactive et une altération de la fonction normale des cellules gliales, ce qui cause l’enlèvement dysfonctionnel du K+ extracellulaire et qui augmente l'excitabilité des neurones favorisant ainsi la génération d’activités paroxystiques. En conclusion, les mécanismes de plasticité homéostatique déclenchés par le niveau diminué d'activité dans le cortex déafferenté produisent une hyperexcitabilité corticale incontrôlable et génèrent finalement les crises d’épilepsie. Dans ces conditions, l’augmentation de l'activité corticale plutôt que la diminution avec des médicaments antiépileptiques pourrait être salutaire pour empêcher le développement de l'épileptogenèse post-traumatique. / After penetrating cortical wounds, the brain becomes gradually hyperexcitable and generates spontaneous paroxysmal activity, but the progressive mechanisms of epileptogenesis remain virtually unknown. The guiding line of our experiments was the hypothesis that the reduced cortical activity following deafferentation triggers homeostatic mechanisms acting at cellular and network levels, leading to an increased neuronal excitability and finally generating paroxysmal activities. We tested this hypothesis either in anesthetized adult cats, or during natural sleep and wake, using the model of partially deafferented suprasylvian gyrus to induce posttraumatic epileptogenesis. We evaluated the effects of acute and chronic cortical deafferentation on the survival of neurons and glial cells and how long-term input deprivation could shape up the properties of neuronal networks and the initiation of spontaneous cortical activity. Following cortical deafferentation of the suprasylvian gyrus, the deeply laying neurons, particularly the inhibitory GABAergic ones, degenerate progressively in parallel with an increased propensity to paroxysmal activity, mainly during slow-wave sleep. The chronic input deprivation and the death of neurons activate homeostatic plasticity mechanisms, which promote a gradual increased neuronal connectivity, higher efficacy of excitatory synaptic connections and changes in intrinsic cellular properties favoring increased excitation. The spontaneous cortical activity quantified by means of firing rate augments also progressively, particularly during slow-wave sleep, characterized by periods of silent states alternating with periods of active states, which supports furthermore our hypothesis regarding the involvement of homeostatic plasticity mechanisms. The degeneration of neurons in the deep cortical layers generates important changes in the laminar distribution of neuronal activity, which is shifted from the deeper layers to the more superficial ones, in the partially deafferented part of the gyrus. This change in the depth profile distribution of firing rates modifies also the initiation of spontaneous cortical activity which, in normal cortex, and in the relatively intact part of the deafferented gyrus, is initiated in the deep cortical layers. Conversely, in late stages of the undercut, both the cortical slow oscillation and the ictal activity are initiated in the more superficial layers and then spread to the deeper ones. Cortical trauma induces also an important reactive gliosis associated with an impaired function of glial cells, responsible for a dysfunctional K+ clearance in the injured cortex, which additionally increases the excitability of neurons, promoting the generation of paroxysmal activity. We conclude, that the homeostatic plasticity mechanisms triggered by the decreased level of activity in the deafferented cortex, generate an uncontrollable cortical hyperexcitability, finally leading to seizures. If this statement is true, augmenting cortical activity rapidly after cortical trauma rather than decreasing it with antiepileptic medication, could prove beneficial in preventing the development of posttraumatic epileptogenesis.

A key component of natural photosynthesis are the antenna chromophores (chlorophylls and carotenoids) that capture solar energy and direct it towards the reaction centers of photosystems I and II. Highlighted by highly-ordered crystal structures and synthetic tunability via crystal engineering, metal–organic frameworks (MOFs) have the potential to mimic the natural photosynthetic systems in terms of the efficiency and directionality of energy transfer. Owing to their larger surface areas, MOFs have large absorption cross sections, which amplifies the rate of photon collection. Furthermore, MOFs can be constructed using analogues of chlorophyll and carotenoids that can participate in long-range energy transfer. Herein, we aimed to design photoactive MOFs that can execute one of the critical steps involved in photosynthesis - photon collection and subsequent energy transfer. The influence of spatial arrangement of chromophores on the efficiency and directionality of excitation energy transfer (EET) was investigated in a series of mixed-ligand pyrene- and porphyrin-based MOFs. Due to the significant overlap between the emission spectrum of 1,3,6,8-tetrakis(p-benzoic acid)pyrene (TBAPy) and the absorption spectrum of meso-tetrakis(4-carboxyphenyl)porphyrin (TCPP), the co-assembly of these two ligands in a MOF should enable facile energy transfer. Bearing this in mind, three TBAPy-based MOFs with markedly different network topologies (ROD-7, NU-901, and NU-1000) were chosen and a small number of TCPP units were incorporated in their backbone. To gain insight into the photophysical properties of mixed-ligand MOFs, we conducted time-resolved and steady-state fluorescence measurements on them. Stern-Volmer analysis was performed on the fluorescence lifetime data of mixed-ligand MOFs to determine the quenching constants. The quenching constant values for ROD-7, NU-901, NU-1000, and TBAPy solution were found to be 15.03 ± 0.82 M-1, 10.25 ± 0.99 M-1, 8.16 ± 0.41 M-1, and 3.35 ± 0.30 respectively. In addition, the ratio of the fluorescence intensities of TCPP and TBAPy was used to calculate the EET efficiencies in each of the three MOFs. EET efficiencies were in the following order: ROD-7 > NU-901 > NU-1000 > TBAPy-solution. Based on the trends observed for quenching constants and EET efficiencies, two conclusions were drawn: (1) the ligand-to-ligand energy transfer mechanism in MOFs outperforms the diffusion-controlled mechanism in solution phase, (2) energy transfer in MOFs is influenced by their structural parameters and spectral overlap integrals. The enhanced EET efficiency in ROD-7 is attributed to shorter interchromophoric distance, larger orientation factor, and larger spectral overlap integral. Directionality of energy transfer in these MOFs was assessed by calculating excitonic couplings between neighboring TBAPy linkers using the atomic transition charges approach. Rate constants of EET (kEET) along different directions were determined from the excitonic couplings. Based on the kEET values, ROD-7 is expected to demonstrate highly anisotropic EET along the stacking direction. In order to explore the mechanistic aspects of EET in porphyrin-based MOFs, we studied the energy transfer characteristics of PCN-223, a zirconium-based MOF containing TCPP ligands. After performing structural characterization, the photophysical properties of PCN-223 and free TCPP were investigated using steady state and time-resolved spectroscopy. pH-dependent fluorescence quenching experiments were performed on both the MOF and ligand. Stern-Volmer analysis of quenching data revealed that the quenching rate constants for PCN-223 and TCPP were 8.06 ± 1011 M-1s-1 and 2.71 ± 1010 M-1s-1 respectively. The quenching rate constant for PCN-223 is, therefore, an order of magnitude larger than that for TCPP. Additionally, PCN-223 demonstrated a substantially higher extent of quenching (q = 93%) as compared to free TCPP solution (q = 51%), at similar concentrations of quencher. The higher extent of quenching in MOF is attributed to energy transfer from neutral TCPP linkers to N-protonated TCPP linkers. Using the Förster energy transfer model, the rate constant of EET in PCN-223 was calculated. The magnitude of rate constant was in good agreement with the kEET values reported for other porphyrin-based MOFs. Nanosecond transient absorption measurements on PCN-223 revealed the presence of a long-lived triplet state (extending beyond 200 μs) that exhibits the characteristic features of a TCPP-based triplet state. The lifetime of MOF is shorter than that of free ligand, which may be attributed to triplet-triplet energy transfer in the MOF. Lastly, femtosecond transient absorption spectroscopy was employed to study the ultrafast photophysical processes taking place in TCPP and PCN-223. Kinetic analysis of the femtosecond transient absorption data of TCPP and PCN-223 showed the presence of three distinct time components that correspond to: (a) solvent-induced vibrational reorganization of excitation energy, (b) vibrational cooling, and (c) fluorescence. Materials that allow control over the directionality of energy transfer are highly desirable. Core-shell nanocomposites have recently emerged as promising candidates for achieving long-distance, directional energy transfer. For our project, we aim to employ UiO-67-on-PCN‐222 composites as model systems to explore the possibility of achieving directional energy transfer in MOF-based core-shell structures. The core–shell composites were synthesized by following a previously published procedure. Appropriate amounts of Ruthenium(II) tris(5,5′-dicarboxy-2,2′-bipyridine), RuDCBPY, were doped in the shell layer to produce a series of Ru-UiO-67-on-PCN‐222 composites with varying RuDCBPY loadings (CS-1, CS-2, and CS-3). The RuDCBPY-doped core–shell composites were characterized by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) imaging, Nitrogen adsorption-desorption isotherms, and diffuse reflectance spectroscopy. Efforts are currently underway to quantify RuDCBPY loadings in CS-1, CS-2, and CS-3. After completing structural characterization, the photophysical properties of CS-1, CS-2, and CS-3 will be investigated with the help of time-resolved and steady-state fluorescence spectroscopy. / Doctor of Philosophy / The pigment−protein complexes in natural photosynthetic units (also known as light harvesting antennas) efficiently capture solar energy and transfer this energy to reaction centers that carry out water splitting reactions. The collective chromophoric behavior of antennas can be replicated by metal-organic frameworks (MOFs). MOFs are crystalline, self-assembled materials composed of metal clusters connected by organic molecules. In this dissertation, we study the factors that govern the energy transfer and light harvesting capabilities of MOFs. In chapter 2, we examined the role of 3D structure of MOFs in energy transfer. In chapter 3, we investigated the influence of pH and temperature on the photophysical properties of MOFs. In chapter 4, we explored the possibility of energy transfer in novel MOF-on-MOF composites. This work is intended to pave the way for the construction of highly efficient MOF-based materials that can serve as the light harvesting and energy-transfer components in solar energy conversion devices.

Un des plus grands défis de la neuroscience moderne pour parvenir à comprendre et diagnostiquer les maladies du cerveau est de déchiffrer les détails des interactions neuronales dans le cerveau vivant. Pour ce faire, on doit être capable d'observer des populations de cellules vivantes dans leur matrice d'origine avec une bonne résolution spatiale et temporelle. La microscopie à deux photons se prête bien à cet exercice car elle permet d'exciter des fluorophores à de grandes profondeurs dans les tissus biologiques et elle offre une résolution spatiale de l'ordre du micron. Malheureusement, la très bonne résolution tridimensionnelle diminue la résolution temporelle, car l'effet de sectionnement optique causé par la faible profondeur de champ du microscope nous oblige à balayer les échantillons épais une multitude de fois avant de pouvoir compléter l'acquisition d'un grand volume. Dans ce projet de doctorat, nous avons conçu, construit et caractérisé un microscope à deux photons avec une profondeur de champ étendue afin de faciliter l'imagerie fonctionnelle de neurones dans un échantillon épais. Pour augmenter la profondeur de champ du microscope à deux photons, nous avons modifié le faisceau laser entrant dans le système optique afin de générer une aiguille de lumière, orientée axialement, dans l'échantillon au lieu d'un point. Nous modifions le faisceau laser avec un axicon, une lentille en forme de cône qui transforme le faisceau gaussien en un faisceau quasi non-diffractant, de type Bessel-Gauss. Le faisceau d'excitation conserve donc la même résolution transverse à différentes profondeurs dans l'échantillon, éliminant le besoin de balayer l'échantillon à répétition afin de sonder un volume complet. Dans cette thèse, nous démontrons que le microscope à grande profondeur de champ fonctionne effectivement tel que nous l'avons conçu et nous l'utilisons pour faire de l'imagerie calcique dans un réseau tridimensionnel de neurones vivants. Nous présentons aussi les différents avantages de notre système par rapport à la microscopie à deux photons conventionnelle. / One of the greatest challenges of modern neuroscience that will lead to a better understanding and earlier diagnostics of brain sickness is to decipher the details of neuronal interactions in the living brain. To achieve this goal, we must be capable of observing populations of living cells in their original matrix with a good resolution, both spatial and temporal. Two-photon microscopy offers the right tools for this since it presents with a spatial resolution in the order of the micron. Unfortunately, this very good three-dimensional resolution lowers the temporal resolution because the optical sectioning caused by the microscope's small depth of field forces us to scan thick samples repeatedly when acquiring data from a large volume. In this doctoral project, we have designed, built and characterized a two-photon microscope with an extended depth of field with the goal of simplifying the functional imaging of neurons in thick samples. To increase the laser scanning microscope's depth of field, we shaped the laser beam entering the optical system in such a way that a needle of light is generated inside the sample instead of a spot. We modify the laser beam with an axicon, a cone-shaped lens that transforms a gaussian beam into a quasi non-diffractive beam called Bessel-Gauss beam. The excitation beam therefore maintains the same transverse resolution at different depths inside the sample, eliminating the need for many scans in order to probe the entire volume of interest. In this thesis, we demonstrate that the extended depth of field microscope effectively works as we designed it, and we use it to image calcium dynamics in a three-dimensional network of live neurons. We also present the different advantages of our system in comparison with standard two-photon microscopy.

La ligne directrice de nos expériences a été l'hypothèse que l'apparition et/ou la persistance des fluctuations de longue durée entre les états silencieux et actifs dans les réseaux néocorticaux et une excitabilité neuronale modifiée sont les facteurs principaux de l'épileptogenèse, menant aux crises d’épilepsie avec expression comportementale. Nous avons testé cette hypothèse dans deux modèles expérimentaux différents. La déafférentation corticale chronique a essayé de répliquer la déafférentation physiologique du neocortex observée pendant le sommeil à ondes lentes. Dans ces conditions, caractérisées par une diminution de la pression synaptique et par une incidence augmentée de périodes silencieuses dans le système cortico-thalamique, le processus de plasticité homéostatique augmente l’excitabilité neuronale. Par conséquent, le cortex a oscillé entre des périodes actives et silencieuses et, également, a développé des activités hyper-synchrones, s'étendant de l’hyperexcitabilité cellulaire à l'épileptogenèse focale et à des crises épileptiques généralisées. Le modèle de stimulation sous-liminale chronique (« kindling ») du cortex cérébral a été employé afin d'imposer au réseau cortical une charge synaptique supérieure à celle existante pendant les états actifs naturels - état de veille ou sommeil paradoxal (REM). Dans ces conditions un mécanisme différent de plasticité qui s’est exprimé dans le système thalamo-corticale a imposé pour des longues périodes de temps des oscillations continuelles entre les époques actives et silencieuses, que nous avons appelées des activités paroxysmiques persistantes. Indépendamment du mécanisme sous-jacent de l'épileptogenèse les crises d’épilepsie ont montré certaines caractéristiques similaires : une altération dans l’excitabilité neuronale mise en évidence par une incidence accrue des décharges neuronales de type bouffée, une tendance constante vers la généralisation, une propagation de plus en plus rapide, une synchronie augmentée au cours du temps, et une modulation par les états de vigilance (facilitation pendant le sommeil à ondes lentes et barrage pendant le sommeil REM). Les états silencieux, hyper-polarisés, de neurones corticaux favorisent l'apparition des bouffées de potentiels d’action en réponse aux événements synaptiques, et l'influence post-synaptique d'une bouffée de potentiels d’action est beaucoup plus importante par rapport à l’impacte d’un seul potentiel d’action. Nous avons également apporté des évidences que les neurones néocorticaux de type FRB sont capables à répondre avec des bouffées de potentiels d’action pendant les phases hyper-polarisées de l'oscillation lente, propriété qui peut jouer un rôle très important dans l’analyse de l’information dans le cerveau normal et dans l'épileptogenèse. Finalement, nous avons rapporté un troisième mécanisme de plasticité dans les réseaux corticaux après les crises d’épilepsie - une diminution d’amplitude des potentiels post-synaptiques excitatrices évoquées par la stimulation corticale après les crises - qui peut être un des facteurs responsables des déficits comportementaux observés chez les patients épileptiques. Nous concluons que la transition incessante entre des états actifs et silencieux dans les circuits cortico-thalamiques induits par disfacilitation (sommeil à ondes lentes), déafférentation corticale (épisodes ictales à 4-Hz) ou par une stimulation sous-liminale chronique (activités paroxysmiques persistantes) crée des circonstances favorables pour le développement de l'épileptogenèse. En plus, l'augmentation de l’incidence des bouffées de potentiels d’actions induisant une excitation post-synaptique anormalement forte, change l'équilibre entre l'excitation et l'inhibition vers une supra-excitation menant a l’apparition des crises d’épilepsie. / The guiding line in our experiments was the hypothesis that the occurrence and / or the persistence of long-lasting fluctuations between silent and active states in the neocortical networks, together with a modified neuronal excitability are the key factors of epileptogenesis, leading to behavioral seizures. We addressed this hypothesis in two different experimental models. The chronic cortical deafferentation replicated the physiological deafferentation of the neocortex observed during slow-wave sleep (SWS). Under these conditions of decreased synaptic input and increased incidence of silent periods in the corticothalamic system the process of homeostatic plasticity up-regulated cortical cellular and network mechanisms and leaded to an increased excitability. Therefore, the deafferented cortex was able to oscillate between active and silent epochs for long periods of time and, furthermore, to develop highly synchronized activities, ranging from cellular hyperexcitability to focal epileptogenesis and generalized seizures. The kindling model was used in order to impose to the cortical network a synaptic drive superior to the one naturally occurring during the active states - wake or rapid eye movements (REM) sleep. Under these conditions a different plasticity mechanism occurring in the thalamo-cortical system imposed long-lasting oscillatory pattern between active and silent epochs, which we called outlasting activities. Independently of the mechanism of epileptogenesis seizures showed some analogous characteristics: alteration of the neuronal firing pattern with increased bursts probability, a constant tendency toward generalization, faster propagation and increased synchrony over the time, and modulation by the state of vigilance (overt during SWS and completely abolished during REM sleep). Silent, hyperpolarized, states of cortical neurons favor the induction of burst firing in response to depolarizing inputs, and the postsynaptic influence of a burst is much stronger as compared to a single spike. Furthermore, we brought evidences that a particular type of neocortical neurons - fast rhythmic bursting (FRB) class - is capable to consistently respond with bursts during the hyperpolarized phase of the slow oscillation, fact that may play a very important role in both normal brain processing and in epileptogenesis. Finally, we reported a third plastic mechanism in the cortical network following seizures - a decreasing amplitude of cortically evoked excitatory post-synaptic potentials (EPSP) following seizures - which may be one of the factors responsible for the behavioral deficits observed in patients with epilepsy. We conclude that incessant transitions between active and silent states in cortico-thalamic circuits induced either by disfacilitation (sleep), cortical deafferentation (4-Hz ictal episodes) and by kindling (outlasting activities) create favorable circumstances for epileptogenesis. The increase in burst-firing, which further induce abnormally strong postsynaptic excitation, shifts the balance of excitation and inhibition toward overexcitation leading to the onset of seizures.

Nanoscale materials have great applications in many areas. One of these applications is for manufacturing ultra-compact and efficient sensors for chemical and biological molecule detection. Noble metals, such as gold (Au) and silver (Ag), because of their distinguished optical property"localized surface plasmon resonances (LSPRs) that exhibit low loss, are ideal materials to fabricate these nanoscale plasmonic particles or structures. This work addresses the synthesis, characterization, and sensing applications of Au and Ag nanoparticles (NPs). The progress on certain subjects related to our work"NP synthesis, surface functionalization, Au sphere-film structure and two-photon fluorescence"are reviewed in Chapter 1. We also show the calculation results of LSPRs of Au nanosphere suspensions using Mie theory. The measured extinction spectra of Au nanosphere suspensions agree with the calculated results very well. Chapter 2 is a chapter describing the chemical synthesis of a variety of NPs, such as Ag prisms and cubes, Au spheres, rods, and bipyramids. These experiments involved different synthetic mechanisms and methods which enabled us to prepare NPs with desired shapes and optical properties. To put these NPs into application, it is desirable and sometimes necessary to functionalize their surfaces. In Chapter 3, we present the functionalization of Ag cubes with poly(allylamine hydrochloride) (PAH) and poly(allylamine hydrochloride)-dithiocarbamate (PAH-DTC), which follows our previous work on Au NPs. The purpose of studying Ag instead of Au is to use the stronger plasmonic enhancement in Ag when applied to two-photon imaging applications. However, we found that PAH-DTC shrank the Ag cubes. We also functionalized the cationic hexadecyltrimethylammonium bromide (CTAB)-stabilized Au NRs with anionic poly(sodium 4-styrenesulfonate) (PSS). Coated with the strong polyelectrolyte PSS, the NRs become more manageable and can be stable for over six months and are easily immobilized onto positively charged substrate. We put PSS-functionalized Au NPs into use and studied their adsorption process onto PAH-coated optical fiber tapers by monitoring the transmission light through the fiber. When the diameter of the fiber taper gets smaller, stronger coupling occurred between transmitted light inside the taper and the Au NPs on the taper surface (cylinder). This coupling resulted in a loss of the guided light at the plasmon resonance wavelength of the NPs. By monitoring this loss, we can study the adsorption rate of Au NPs onto the fiber. In Chapter 4, we used Au nanospheres to study the adsorption rate on substrates with different curvatures. We also established a theoretical model to explain this phenomenon for cylindrical surface as well as planar and spherical surfaces. Our results fit well with the theory, which predicts that particle adsorption rates depend strongly on surface geometry, and can exceed the planar surface deposition rate by over two orders of magnitude when the diffusion length of the particle is large compared to the surface curvature. In Chapter 5, we studied the optical properties of Au nanospheres separated from a thick Au film by a polyelectrolyte multilayer (PEM) film assembled from PAH and PSS under specific pH condition. The PEM film undergoes swelling and shrinking when the environmental pH is changed as a result of charging and discharging of the polyelectrolytes. Therefore, the PEM film provides an efficient means to tune the distance between Au spheres and Au film. The extinction peak blue-shifted as much as 100 nm when the pH of the water changed from pH 10 to pH 3 for 100 nm diameter Au spheres on a PEM film assembled at pH 9.5. Our preliminary estimates that the gap between sphere and surface can be as small as a few nm even though the film itself is tens of nm thick when it is not constrained by Au spheres. We studied two-photon excitation fluorescence (TPEF) from Ag triangles in Chapter 6. The triangles were fabricated by nanosphere lithography, which used convective self-assembly to make the nanosphere mask. The LSPRs of the nanotriangles were tuned to be in the 800--900 nm range to match with the Ti:Sapphire pulse laser at 880 nm. We found that certain spots on the fluorescence images gave rise to larger fluorescence intensity than rest of the area. SEM imaging reveals that the unusually bright spots seen on the surface were related to regions where the triangles transformed to spherical particles. The larger intensity is tentatively ascribed to the plasmon resonance of those spherical particles in ~400 nm range. / Ph. D.

Recent studies have utilized spanwise traveling waves to alter the turbulent boundary layer with the aim of reducing skin friction drag. Spanwise traveling waves are a promising active drag reduction technique; however, the wave generation methods used in previous studies are bulky and could not be practically implemented. This research has developed an implementable traveling wave generation method and then fundamentally demonstrated how it changes the turbulent boundary layer, which is in a manner consistent with skin friction/shear stress reduction. Traveling waves were generated on a two-dimensional surface using low-profile piezoelectric actuators, in an open-loop fashion, and with minimal frequency limitations. The wave generation method was developed to generate tailored traveling wave patterns; thus, yielding control over the propagation direction, number of wave-fronts, and regions of the surface containing traveling waves. These tailored traveling waves have the capacity not just for affecting the boundary layer, but also for other applications such as propulsion. The implementable traveling wave generation method was then tested in a low-speed wind tunnel and shown to alter the structure of the turbulent boundary layer. The boundary layer is pushed off the wall, and the viscous sublayer is thickened, indicating a reduction in shear stress. Analysis of the boundary layer at positions phase-locked to the wave oscillation suggests that the traveling waves induce a phase-lag effect in the flow. This phase-lag produces a stretching of the viscous sublayer and may contribute to the skin friction reduction. The effects of standing waves on the turbulent boundary layer were also investigated and compared with traveling waves. The results indicate that both wave types alter the boundary layer in the same manner. Standing waves are simpler to generate than traveling waves, suggesting that standing waves may be an effective skin friction reduction method. Before traveling or standing waves can be implemented, further research is necessary to investigate the interaction between the wave pattern and the turbulent phenomena and also to quantify the skin friction reduction and overall net energy usage. / Ph. D. / Recent studies have utilized spanwise traveling waves to alter the turbulent boundary layer with the aim of reducing skin friction drag. Spanwise traveling waves are a promising active drag reduction technique; however, the wave generation methods used in previous studies are bulky and could not be practically implemented. This research has developed an implementable traveling wave generation method and then fundamentally demonstrated how it changes the turbulent boundary layer, which is in a manner consistent with skin friction/shear stress reduction. Traveling waves were generated on a two-dimensional surface using low-profile piezoelectric actuators, in an open-loop fashion, and with minimal frequency limitations. The wave generation method was developed to generate tailored traveling wave patterns; thus, yielding control over the propagation direction, number of wave-fronts, and regions of the surface containing traveling waves. These tailored traveling waves have the capacity not just for affecting the boundary layer, but also for other applications such as propulsion. The implementable traveling wave generation method was then tested in a low-speed wind tunnel and shown to alter the structure of the turbulent boundary layer. The boundary layer is pushed off the wall, and the viscous sublayer is thickened, indicating a reduction in shear stress. Analysis of the boundary layer at positions phase-locked to the wave oscillation suggests that the traveling waves induce a phase-lag effect in the flow. This phase-lag produces a stretching of the viscous sublayer and may contribute to the skin friction reduction. The effects of standing waves on the turbulent boundary layer were also investigated and compared with traveling waves. The results indicate that both wave types alter the boundary layer in the same manner. Standing waves are simpler to generate than traveling waves, suggesting that standing waves may be an effective skin friction reduction method. Before traveling or standing waves can be implemented, further research is necessary to investigate the interaction between the wave pattern and the turbulent phenomena and also to quantify the skin friction reduction and overall net energy usage.

The main focus of this present work is to study how mechanical steady state traveling waves can be generated and propagated through one dimensional media by applying forces. By steady state traveling waves we refer to propagating mechanical waves in a finite medium that never exhibit reflections at the boundaries and continuously move from one end of the structure to the other. Mechanical waves can be classified as traveling, standing and hybrid waves that are the results of the interplay of excitation forces, applied force locations, and the boundary conditions of the structure. Traveling waves carry energy through a defined medium while standing waves keep energy at certain areas that are associated with the modes of excitation. To understand the interaction of systems that exhibit traveling waves with their surrounding media (i.e., swimming flagella, manta ray locomotion), it is crucial to first understand the wave propagation and what is desired in these structural systems. The parameters that affect the generation and propagation of waves should be welldefined to control and manipulate the desired system’s response. One-dimensional string and rod equations are studied with various boundary conditions to generate steady-state traveling waves in a string and longitudinal traveling waves in a rod. Two excitation forces are applied to a string and a rod near the boundaries to understand the generation and propagation of traveling and standing waves at various frequencies. The work examines the quality of the wave propagation in a string, and in a rod. A cost function approach is applied to identify the quality of such waves. Furthermore, steady-state square traveling waves are generated in a string and in-plane in a rod, both theoretically and experimentally. To the authors’ knowledge this is the first time this has been attempted in the literature. Determining the quality of traveling waves and understanding the parameters on the wave propagation of a string and rod can lead to further understand and leverage various engineering disciplines such as mechanical actuation mechanisms, propulsion of flagella, and the basilar membrane in the ear’s cochlea. / Master of Science

In this thesis, an output-only experimental modal testing and analysis technique known as the Natural Excitation Technique (NExT) is examined for use with large residential structures and interior cavities. The technique which assumes a random, stationary input causing the response data is reviewed and extended for the first time to include the assumption of an impulse input. This technique is examined with respect to the experimental modal analysis of single and two room residential structures. Each structure is first tested using conventional modal testing methods. Then, NExT is applied using each structure's response to a simulated sonic boom, an impulsive input. The results of these analyses along with the results obtained from a finite element model are compared. Then, the interior cavities enclosed by the residential structures are examined using NExT. Therefore, this thesis also demonstrates the successful use of NExT on acoustic systems for the first time. Three configurations of the interconnected cavities enclosed by the two room structure are considered to study physical phenomena. Both interior pressure response to random, stationary inputs and the sonic boom response are used with NExT to determine modal properties. The results of these analyses are compared to a theoretical analysis. Advantages to using NExT with both the response to a random, stationary input and an impulsive input are demonstrated for structural and acoustic systems. / Master of Science

No / Most inhibitory signals are mediated via γ-aminobutyric acid (GABA) receptors whereas glutamate receptors mediate most excitatory signals (Trends Neurosci 14:515–519, 1991; Annu Rev Neurosci 17:31–108, 1994). Many factors influence the regulation of excitatory and inhibitory synaptic inputs on a given neuron. One important factor is the subtype of neurotransmitter receptor present not only at the correct location to receive the appropriate signals but also their abundance at synapses (Pharmacol Rev 51: 7–61, 1999; Cold Spring Harb Perspect Biol 3, 2011). GABAB receptors are G-protein-coupled receptors and different subunits dimerise to form a functional receptor. GABAB receptor subunits are widely expressed in the brain and by assembling different isoform combinations and accessory proteins they produce variety of physiological and pharmacological profiles in mediating both inhibitory and excitatory neurotransmission. This chapter will describe the understanding of the molecular mechanisms underlying GABAB receptor regulation of glutamate and GABAA receptors and how they modulate excitatory and inhibitory neurotransmission.

This thesis presents a comprehensive modal analysis on an asphalt roller, focusing on optimizing excitation and measurement point selection for accurate characterization of the structure’s dynamic behavior. The thesis aims to find out how to select excitation points that ex-cite all mode shapes within a specific frequency range and to find out how to select measurement points that capture the dynamic behavior and mode shapes of the structure within the same frequency range. The method used is an action research method that includes four phases: planning, action, observation, and reflection. The planning phase involves numerical modal analysis, simulations, and selection of excitation and measurement points. The action phase includes experimental measurements preliminary tests, and the actual testing of the structure. The observation covers extracting modal parameters from measurement data and comparing results with simulation predictions. Reflection focuses on evaluating results and adapting the decision-making accordingly. The EODP method provides practical excitation points that successfully active modes consistent with the simulations. The minMAC GA approach identifies measurement points that capture the asphalt roller’s essential dynamic behavior, despite challenges with modal parameter extraction. Even though the mode shapes are not well separated due to the complexity of the structure, high-quality identification of mode shapes was achieved considering impact excitation which gives great insight into the asphalt roller’s dynamic properties. Overall, this research contributes to the understanding of modal analysis on complex mechanical structures, providing effective methods for excitation and measurement point selection. The findings in the study can inform the design and maintenance of similar structures in various engineering applications.