No description available.

The anatomical organization of the connections of the major components of the basal ganglia was investigated in detail. A sensitive procedure for the simultaneous study of afferents and efferents was carried out on the striatum (CP), globus pallidus (GP), and substantia nigra (SN). Previously well characterized connections of the CP were confirmed, additional evidence for a projection to the CP from the ventromedial nucleus of the thalamus was obtained and a topographically organized projection to the CP from the GP was discovered. A similar study of the SN revealed a nigral projection to the ipsilateral lateral dorsal nucleus of the thalamus and nigral input from the contralateral posterior lateral hypothalamus. The projection of the GP to the SN was found to be linked topographically to the striatonigral and pallidostriatal pathways. A study of the connections of the GP confirmed a massive projection from the CP and provided further evidence of a reciprocal connection. In addition, pallidal innervations of the entopeduncular nucleus and reticular nucleus of the thalamus were indicated. Because of the potential importance of a pallidostriatal projection and the significant number of technical difficulties associated with its demonstration, additional experiments were carried out to confirm the presence of this pathway and to determine its anatomical relationship to other basal ganglia connections. Retrograde labelling of pallidostriatal neurons, studied with electron microscopy and in combination with lesions of the striatum, confirmed that pallidal neurons project either to or through the striatum. Evidence for possibly two groups of pallidal neurons that project to the CP was obtained, and it was observed that both of these cell groups were congruent with the striatopallidal terminal fields. Comparisons of the distribution of cells retrogradely labelled after tracer injections into the cortex and CP in combination with histochemistry for acetylcholinesterase demonstrated that the population of pallidal neurons projecting to the CP was distinct from that of peripallidal cholinergic neurons which may project through the striatum to the cortex. Double retrograde fluorescent tracing experiments indicated that pallidal neurons which project to the CP also have collateral projections to the substantia nigra and perhaps to the subthalamic nucleus. The application of a new technique for studying, efferent projections allowed the confirmation and morphological description of the projection of the globus pallidus to the striatum. The characteristic morphology of this projection was shared by pallidal efferents which project to the entopeduncular nucleus, the reticular nucleus of the thalamus, the subthalamic nucleus and the substantia nigra. The fine morphological detail afforded by this method of anterograde tracing was utilized in combination with a histochemical protocol to show that pallidostriatal terminals end in part on somatostatin-containing neurons in the CP. / Graduate and Postdoctoral Studies / Graduate

The measurement of dopamine neurotransmission in the brain has evolved alongside techniques for measuring neuronal activity. This evolution has progressed from coarse physical inspection (using lesions or dialysis approaches) to measuring electrical signatures of the phenomena of interest. Most recently, an optical revolution has taken hold within the neurosciences. We present an optical dopamine measurement technique as a companion to burgeoning neural activity monitors such as GCaMP. The electrical consequences of individual glutamate molecules impinging upon a postsynaptic membrane can be captured in an electrophysiological trace. On the other hand, dopamine has no consistent, measureable postsynaptic effects and therefore cannot easily be measured electrophysiologically. Researchers have instead used the electrochemical features of dopamine to measure samples of it in physical space. This approach, termed cyclic voltammetry, has generated nearly all of the existing knowledge about the precise characteristics of dopamine release. While a reliable method for measuring dopamine release from heavily innervated areas, cyclic voltammetry lacks the resolving power to establish release from dopamine terminals in other areas of interest. One such area is the external globus pallidus (GPe), the focus of this work. Research performed nearly thirty years prior to this thesis established the presence of sparsely distributed dopamine varicosities within the GPe. Here, we leverage FFN102, a newly developed optical method used as a proxy for dopamine release, to measure dopamine release in this area. Based on previous literature showing that dopamine varicosities were present in the GPe and that dopamine receptors exist on principal cells in the area, we hypothesized that these dopamine varicosities were capable of releasing FFN102. Moreover, previous work had shown that anatomically, the most prominent dopaminergic innervation to the GPe came from the substantia nigra. By validating the FFN102 method in the GPe, we showed that a substance is released which likely reflects dopamine vesicle release. Moreover, the use of two dopamine depletion mouse models allowed us to conclude that FFN102 is released exclusively from dopamine terminals. Finally, we advanced the understanding of dopamine release in the area by examining whether pharmacological manipulation could alter the amount of FFN102 released from dopamine terminals.

This paper will first focus on the theoretical definition of the term "atmospherics" and its elements. This will continue with the definition of seasonal influences. These parts will then serve as basis for concrete evaluation of atmospherics in hypermarket retail units Tesco and Globus. After that, the two units will be compared and contrasted and eventual suggestions for improvement will be offered. Responsible employees of the two units will then react to the evaluations and suggestions.

Práce je rozdělena do pěti kapitol. Teoretická část práce obsahuje kapitoly Cena, Image, Chování spotřebitele a Současné trendy v retailu, praktická část práce zahrnuje kapitolu Výzkum v hypermarketu Globus. Teoretická část práce vystihuje hlavní teoretické poznatky z oblasti problematiky tvorby a vnímání cen, vysvětluje pojem image a zabývá se způsoby jeho analýzy, popisuje faktory, které ovlivňují chování spotřebitele a vystihuje hlavní současné trendy v retailu zejména v České republice. Praktická část obsahuje výsledky cenového výzkumu a zhodnocení image hypermarketu Globus.

The striatopallidal (indirect) pathway is considered as the main modulatory locus for the basal ganglia control of motor functions. According to the classic basal ganglia model, the striatopallidal pathway inhibits motor activity mainly via its projection to globus pallidus (GPe). However, striatopallidal medium spiny neurons (MSNs) form extensive feedback and lateral inhibitory networks via their collaterals. Thus, the striatopallidal pathway may control motor activity either through its projections onto GPe or through the striatal collaterals. To further define the circuit mechanism whereby the striatopallidal pathway controls motor activity, we have developed two new optogenetic transgenic mouse lines expressing channelrhodospin-2 (ChR2) or archaerhodopsin-3 (Arch) selectively in the striatopallidal neurons under the Adora2a gene promoter. Consistent with previous optogenetic studies, we found that ChR2 activation and Arch silencing of the striatopallidal neurons in dorsolateral striatum (DLS) suppressed and increased motor activity, respectively. However, contrary to the prediction from the classical model, we found that selective activation of the striatopallidal axon projections in GPe increased locomotor activity. Thus, light stimulation of MSN cell bodies and collaterals in DLS, versus stimulation in GPe axon projections, produced opposite motor responses. This led us to reassess the function of the striatopallidal collaterals and to test the hypothesis that the profuse projections and collaterization within the striatum may contribute to striatopallidal pathway control of motor activity. We found that ChR2-mediated activation of the striatopallidal neurons in DLS induced c-Fos expression in ChR2/GFP-positive MSNs. Conversely, Arch-mediated silencing of the striatopallidal neurons induced c-Fos expression and MAPK phosphorylation in Arch/GFP-negative MSNs surrounding the Arch/GFP-positive MSNs. This c-Fos/pMAPK expression pattern in MSNs is consistent with the suppression of GABA release in GFP-positive cells, resulting in the induction of c-Fos in GFP-negative cells having collateral connections with the GFP-positive cells. Together, our findings revealed a previously unrecognized complexity and novel motor control mechanism of the striatopallidal pathway: activation of striatopallidal projections to GPe increases motor activity while activation of striatopallidal neurons and collaterals in the DLS may contribute to motor suppression. These findings call for a revisit of GPe as a potential locus for deep brain stimulation in Parkinson’s disease.

The medial ganglionic eminence (MGE) is a progenitor domain in the subpallium that produces both locally-projecting interneurons which undergo tangential migration in structures such as the cortex as well as long-range projection neurons that occupy subcortical nuclei. Very little is known about the transcriptional mechanisms specifying the migratory behavior and axonal projection patterns of these two broad classes of MGE-derived neurons. In this study, I identify St18 as a novel transcriptional determinant specifying projection neuron fate in the MGE lineage. St18 is transiently expressed in the MGE subventricular zone (SVZ) and mantle, and I assessed its function using an ES cell-based model of MGE development. Induction of St18 is sufficient to direct ES-derived MGE neurons to adopt a projection neuron-like identity as defined by migration and morphology. Through gene expression analysis I identified a downstream effector of St18, Cbx7, which is a component of Polycomb repressor complex 1. I find that Cbx7 is essential for projection neuron-like migration and is not involved in St18-mediated projection neuron-like morphology. Using genetic loss-of-function in mice, I find that St18 is required for the production of globus pallidus pars externa (GPe) prototypic projection neurons. Single cell RNA sequencing revealed that St18 regulates MGE output of specific neuronal populations: in the absence of St18, I observe a large expansion of cortical interneurons at the expense of putative GPe neurons. I also find that, following St18 genetic loss of function, mouse walk cycles are disrupted downstream of a loss of a critical neuronal projection from the GPe to the sub thalamic nucleus (STN). These results characterize a novel transcriptional determinant that directs GPe prototypic projection neuron identity within the MGE lineage. Further, I have identified a downstream target of St18, Cbx7, which regulates only the migratory behavior of long-range projection neurons, suggesting that specific features of MGE projection neuron identity may be governed in a compartmentalized fashion by distinct transcriptional modules downstream of St18. I’ve also demonstrated the role of the GPe PV+ prototypic neurons in the production and maintenance of mouse locomotor gait.

The Grid has revolutionized the way computations are done on the Internet. Access to remote computational resources and ad hoc creation of virtual organizations across administrative domains opens new opportunities on the Grid. The newly developed web services based Open Grid Services Architecture makes the Grid more accessible by allowing the Grid to be constructed from distinct platform independent components. Together they provide an environment for application sharing (or trading), collaborations and access to remote data repositories. The application marketplace is a natural extension to this application sharing environment. The marketplace addresses the fact that the existing infrastructure is still incomplete without provisions for publishing and discovering applications and resources, including the application descriptors that must be moved between the market participants. This work demonstrates a web service instance-based infrastructure, the application market that allows the sellers, the application and the CPU providers to publish their applications for the users to find and use. The application market uses a portal architecture built on top of Globus toolkit 3.0 that interacts with the providers and the users. The market services provide distinct interfaces that allow providers to advertise applications and users to select, configure, and run these applications. The applications themselves are modeled as stateful objects represented using XML which can be exchanged between the providers and users when required. The marketplace, through its interfaces, effectively hides the compute resource and application complexity thus allowing end users to explore and use applications unfamiliar to them with ease.

Chen Lei. / "February 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 124-161). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Neste trabalho foi avaliada a utilização da grid computing em aspectos importantes para simulações em Física Computacional. Em particular, para aplicações de diagonalização de matrizes de grande porte. O projeto de código aberto Globus Toolkit foi utilizado para comparar o desempenho da biblioteca paralela de álgebra linear ScaLAPACK em duas versões baseadas na biblioteca de passagem de mensagens, a versão tradicional MPICH e a versão desenvolvida para um ambiente de grid computing MPICH-G2. Várias simulações com diagonalização de matrizes complexas de diversos tamanhos foram realizadas. Para um sistema com uma matriz de tamanho 8000 x 8000 distribuída em 8 processos, nos nós de 64 bits foi alcançado um speedup de 7,71 com o MPICH-G2. Este speedup é muito próximo do ideal que, neste caso, seria igual a 8. Foi constatado também que a arquitetura de 64 bits tem melhor desempenho que a de 32 bits nas simulações executadas para este tipo de aplicação / This work evaluates the use of grid computing in essential issues related to Computational Physics simulations. In particular, for applications with large scale matrix diagonalization. The Globus Toolkit open source project was used to compare the performance of the linear algebra parallel library ScaLAPACK in two different versions based on the message passing library, the traditional version MPICH and its version developed for a grid computing environment MPICH-G2. Several simulations within large scale diagonalization of complex matrix were performed. A 7.71 speedup was reached with the MPICH-G2 for a 8000 x 8000 size matrix distributed in 8 processes on 64 bits nodes. This was very close to the ideal speedup, that would be in this case, 8. It was also evidenced that the 64 bits architecture has better performance than the 32 bits on the performed simulations for this kind of application.