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Evidence of histamine H3 receptor crosstalk with dopamine D1 receptors and group 1 metabotropic glutamate receptors in the brain : possible link with cocaine addiction-like behavior in rodents / Signalisation croisée entre les récepteurs H3 de l'histamine avec les récepteurs D1 de la dopamine et entre les récepteurs H3 et les récepteurs métabotropes du glutamate du groupe 1 dans le cerveau : lien possible avec un comportement d'addiction à la cocaïne chez le rongeurHoffmann, Hanne M. 05 November 2010 (has links)
La modification de l'activité neuronale peut engendrer des altérations dans des circuits neuronaux. L'activation des récepteurs couplés aux protéines G (RCPG) peux participer à des mécanismes à la base du développement de maladies comme l'addiction à la cocaïne. La consommation de cocaïne conduit à une augmentation de neurotransmetteurs tels que la dopamine, l'histamine et le glutamate qui activent des RCPG dans le cerveau. La signalisation des RCPG peut se faire au travers de monomères, d'homo- ou d'hétéromères de RCPG ainsi que par des interactions protéine - protéine, permettant entre autre une régulation croisée. Nous montrons que les récepteurs de la dopamine 1 (D1R) et de l'histamine 3 (H3R) induisent une signalisation croisée dans le striatum de rat vraisemblablement par la formation d'hétérodimères. Une administration chronique de cocaïne modifie la signalisation de ces récepteurs tant que la signalisation croisée des D1R et H3R. Les H3R et les récepteurs métabotropes du glutamate 1/5 (mGlu1/5R) sont fortement exprimés dans l'hippocampe et le striatum. Des expériences de comportement suggèrent que ces récepteurs seraient susceptibles de coordonner leurs signalisations par une régulation croisée. Nos expériences d'électrophysiologie, de mesure de Ca++ intracellulaire et de transduction du signal montrent effectivement une régulation croisée des récepteurs H3R et mGlu1/5R dans le cerveau de rat. De plus, nous montrons que la consommation chronique de cocaïne affecte la signalisation des H3R et mGlu1/5R de manière différente de son impacte sur leur signalisation croisée. Nos résultats démontrent l'existence d'une régulation croisée de certains RCPG dans le cerveau de rat. De plus, la consommation chronique de la cocaïne affecte différemment la signalisation induite par l'activation d'un récepteur et l'induction d'une signalisation croisée. / Alterations of neuronal activity, mediated by G-protein coupled receptors (GPCRs), can modulate neuronal circuits and are thought to be important in the development and expression of diseases as cocaine addiction. GPCR activity is regulated by various mechanisms, including protein-protein interactions in the membrane, permitting these receptors to crosstalk and form homo-and heteromers. Cocaine blocks monoamine reuptake leading to increased synaptic presence of various neurotransmitters including dopamine, histamine and glutamate in the brain. First we describe that dopamine D1 receptors (D1R) and histamine H3 receptors (H3R) crosstalk in the rodent brain. Chronic cocaine self-administration altered the crosstalk between D1R and H3R in the striatum, a brain structure involved in habit learning and motor control. The altered signaling was observed in both individual receptor signaling and by D1R-H3R crosstalk signaling. Both histamine H¬3R and metabotropic glutamate 1/5 receptors (mGlu1/5R) are highly expressed in the hippocampus and the striatum of rodents and they are involved in behaviors regulated by these structures. We describe that H3R and mGlu1/5R crosstalk in pyramidal neurons of the hippocampus and in the striatum of rats. In addition, we found that signaling through H3R and mGlu1/5R were differently affected by chronic cocaine self-administration than the apparent crosstalk between the receptors. These results show evidence of GPCR interactions in adult rodent brain and reveal that chronic cocaine self-administration differently affected crosstalk and single receptor mediated signaling.
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Exploiting crosstalk between growth and immunity in plants : the role of the Phytophthora infestans effector AVR2 in potato late blightTurnbull, Dionne January 2016 (has links)
Plants are fundamental to life on earth, crucially providing the basis of our food supply. As world population continues to grow, so too does the pressure on our agricultural systems, with one of the biggest challenges being the control of plant pathogens to ensure a healthy crop. The interaction between plant and pathogen is complex, with subtleties at the molecular level dictating the boundary between health and disease. This is exemplified by pathogen effectors; secreted proteins which enter the plant cell and interact with host targets to facilitate infection. AVR2 is one such effector, secreted by the oomycete pathogen Phytophthora infestans; the pathogen responsible for potato late blight. AVR2 interacts with a family of kelch-repeat containing phosphatases in potato, the BSLs, implicated in brassinosteroid pathway signalling – a major hormone signalling pathway in plants associated with growth and development. This work investigates the role of AVR2 and its host targets in pathogen virulence, with focus on the link between the brassinosteroid pathway and immunity in S. tuberosum. StBSL1 is shown to be a ‘susceptibility factor’ in P. infestans infection – a host protein with a positive effect on pathogen virulence. AVR2 stabilises BSL1 in planta, and both AVR2 and BSL1 are shown to suppress primary defence responses in the plant. Transcriptional analysis of brassinosteroid-treated S. tuberosum is used to identify a set of marker genes for active BR signalling. Strikingly, AVR2 is shown to upregulatethis pathway, and specifically upregulates the transcription factor StHBI1-like, identified as a suppressor of immunity. These findings reveal a novel mechanism in oomycete effector biology; the exploitation of crosstalk between the brassinosteroid pathway and immune signalling in plants.
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Optique adaptative par modulateur spatial de lumière en microscopie et holographie / Adaptative optics with spatial light modulator for microscopy and holographyGemayel, Pierre 18 February 2016 (has links)
Depuis les années 50, la récupération de la phase d’un faisceau optique diffracté par un objet quelconque, est un sujet important dans plusieurs domaines scientifiques, comme la microscopie, l’astronomie et bien d’autres. Généralement, les méthodes qui le permettent se divisent en deux grandes catégories : les méthodes interférométriques et les méthodes itératives basées sur la propagation du faisceau. L’intérêt de ces dernières, réside dans le fait qu’elles sont moins sensibles au bruit, et leur implémentation expérimentale est plus simple. Aussi, le développement des techniques informatiques a rendu cette approche plus rapide et plus intéressante. Cependant, même si l’efficacité de ces méthodes a été démontrée dans plusieurs domaines, leur utilisation est restée limitée à cause de certaines exigences sur les conditions expérimentales, et à la non-convergence de leur algorithme vers une solution unique dans un grand nombre de cas. Ceci est encore plus vrai pour les objets dits "objets complexes", possédant une amplitude et une phase, ce qui réduit fortement leur champ d’application. Afin de surmonter ces problèmes de convergence, diverses stratégies expérimentales ont été développées. Elles ont toutes comme principe d’introduire de nouvelles contraintes bien connues dans le plan de l’objet. Cela permet d’augmenter le nombre de spectres acquis, et donc accroitre et diversifier les sources d’informations sur l’objet de base, ce qui va aider l’algorithme itératif à converger plus rapidement vers une solution finale et unique. Comme exemple de ces stratégies expérimentales, on peut acquérir plusieurs spectres provenant de différentes zones de l’objet, ou moduler la longueur d’onde du faisceau incident, ou même enregistrer les spectres dans des plans parallèles, connectés entre eux par la transformée de Fresnel. Dans ce contexte, le présent travail vise à démontrer expérimentalement une technique connue sous SSPR (Spread Spectrum Phase Retrieval), proposé en 2007 par Zhang, tout en lui introduisant un certain nombre de modifications, afin de la rendre plus pratique. L’idée consiste à moduler le front d’onde de l’objet par M phases aléatoires, générées avec un modulateur spatial de lumière à base de cristaux liquides (LC-SLM), puis enregistrer dans le plan de Fourier les M spectres correspondants. Ces M spectres seront ensuite utilisés dans un algorithme itératif permettant de remonter au front d’onde de l’objet initial, en simulant la propagation du front d’onde entre les deux espaces, spatial et fréquentiel.La première partie de cette thèse comporte une étude détaillée sur les modulateurs spatiaux de lumière, afin de pouvoir choisir le mieux adapté à notre application. Une fois que le modulateur à base de cristaux liquides (LC-SLM) est sélectionné, on présentera ses caractéristiques techniques, ainsi que les tests et les étapes de calibrations nécessaires pour assurer son fonctionnement linéaire et optimal. Ensuite, on montrera plusieurs types d’applications possibles avec ce composant, et dans divers domaines scientifiques, comme l’holographie, la microscopie, l’optique adaptative ainsi que les méthodes interférométriques permettant de reconstruire la phase d’un faisceau lumineux. Dans la deuxième grande partie, on concentre notre travail autour de la méthode itérative SSPR. On montrera comment on peut rendre l’application de cette méthode plus simple en utilisant un modulateur spatial de lumière à base de cristaux liquides, et en travaillant dans le plan de Fourier à la place du plan de Fresnel. Cependant, après avoir appliqué expérimentalement cette méthode, on remarque que les résultats obtenus sont très mauvais par rapport aux résultats des simulations. On effectue donc, une étude détaillée concernant les sources de bruits pouvant être responsable de la dégradation de la qualité des reconstructions obtenues. [...] / Since the 50s, recovering the phase information of a diffracted beam has a major interest in several fields such as microscopy, astronomy and many others. Generally, the solutions fall into two broad categories: interferometric methods and iterative methods based on beam propagation. The advantage of the latter is that they are less sensitive to noise, and their experimental implementation is simpler. Also, the progress in computer technologies as well in digital imaging devices makes the application of this approach easier and more interesting. However, even if the effectiveness of these methods has been demonstrated in several fields, their use remained limited because of certain requirements on the experimental conditions and the non-convergence of their algorithm to a single solution in many cases. This is even more true for the so-called "complex objects", having an amplitude and a phase, which can greatly reduce their field of application. To overcome the convergence problems and improve the robustness of these methods, many experimental strategies have been employed. They are all based on the same principle, which consists of introducing new well-known constraints in the object plane. This increases the number of acquired spectrum, and therefore diversifies the sources of information about the starting object, which will help the iterative algorithm to converge more quickly towards the final solution. As examples of such experimental strategies, one can record several spectra from different areas of the object, or modulate the wavelength of the incident beam, or also acquire the spectrums across two or more parallel planes connected through Fresnel or Fourier transform.In this context, the present work aims to experimentally demonstrate a technique known as SSPR (Spread Spectrum Phase Retrieval), proposed in 2007 by Zhang, while modifying it in order to make it more flexible. The idea is to introduce, using a liquid crystal spatial light modulator M strong phase modulation into the object field, then record in the Fourier plane the M corresponding spectrums. These M acquisitions will then be used in an iterative algorithm what will allow us to recover the object wavefront by simulating the propagation of the light between spatial and frequency spaces. The first part of this thesis includes a complete study on spatial light modulators; in order to select which one will be best suited for our application. Once liquid crystal spatial light modulators are selected, we present their technical characteristics, as well as the calibration tests needed to ensure their linear and optimal functioning. Then we show several possible applications with this type of component, in various scientific fields, like holography, microscopy, adaptive optics and interferometric methods to reconstruct the phase of a beam.In the second part, we focus our work around the SSPR iterative method. We will show how to make the application of this method simpler by using a liquid crystal spatial light modulator, and by working in Fourier plane instead of Fresnel plane. However, after applying SSPR we have noticed that the quality of experimental results is very inferior to the quality of simulation results. Therefore, a detailed study of the noise sources is conducted. Each of these noise sources adds its own contribution, yet modulator cross-talk remains the factor that deteriorates the most the quality of reconstruction. In fact liquid crystal spatial light modulators are known to have a strong cross-talk between their pixels commonly recognized as fringing field effect. As the pixels are micrometric, each addressed one affects its neighbors, and thus, the phase retardation obtained from a pixel will not be uniform over its entire surface. This will result in a blurring effect of the desired sharp edge between the pixels; therefore, the real displayed phase map will be very different from the addressed one. [...]
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Estudo de amplificadores paramétricos para sistemas de comunicações ópticas de altas taxas de transmissão / Study of parametric amplifiers for high bit rate optical communication systemsMarconi, Jorge Diego 08 January 2006 (has links)
Orientador: Hugo Luis Fragnito / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin / Made available in DSpace on 2018-08-08T21:00:40Z (GMT). No. of bitstreams: 1
Marconi_JorgeDiego_D.pdf: 6438397 bytes, checksum: df80d0a6babab0366b1839d4344573fa (MD5)
Previous issue date: 2006 / Resumo: Esta tese apresenta um estudo teórico e experimental sobre Amplificadores Paramétricos a Fibra Óptica.
Mostramos primeiramente a potencialidade do amplificador em termos de largura de banda plana, necessária para aplicações em sistemas WDM. Foram desenvolvidas equações do ripple para os diferentes tipos de espectro de alto ganho possíveis. Usando fibras de dispersão deslocada e fibras altamente não-lineares curtas, construímos amplificadores de dois bombeios com uma banda plana de amplificação de 52 nm e 84 nm, respectivamente. Em ambos os casos, a banda obtida foi comparável à obtida com outras tecnologias como Érbio ou Raman.
Pesquisamos também o crosstalk entre canais em amplificadores paramétricos. Mostramos como as variações de ë 0 ao longo da fibra aumentam o crosstalk, pois se incrementam os processos de mistura de quatro ondas espúrios. Em amplificadores de dois bombeios, obtivemos os melhores resultados para aplicações WDM com fibras curtas (L ~ 0.8 km). Finalmente, a partir da análise da penalidade do fator de mérito Q do sinal, estudamos como os efeitos da modulação de fase do/s laser/s de bombeio, necessária para suprimir o espalhamento Brillouin estimulado, são prejudiciais para a performance destes amplificadores. Com base nesse resultado, procuramos eliminar o espalhamento Brillouin com um método alternativo que consiste na aplicação de distribuições de deformação mecânica ao longo da fibra. Obtivemos um aumento de 10.7 dB em 285 m de fibra altamente não-linear, o que é da ordem dos valores obtidos modulando a fase do/s bombeio/s. Aplicamos a técnica em dispositivos paramétricos obtendo um conversor de comprimento de onda com um sinal convertido de largura de banda estreito, sintonizável ao longo de 70 nm de comprimento de onda do sinal de entrada / Abstract: This thesis presents a theoretical and experimental study on fiber optics parametric amplifiers.
For the double-pumped case, we show the performance of the amplifier in terms of spectral bandwidth and gain uniformity, both fundamental properties for WDM applications. By using short dispersion shifted fibers and highly non-linear fibers, we made parametric amplifiers with 52 and 84 nm of flat bandwidth, respectively. In both cases, the bandwidth is similar to the one obtained with optical amplifiers based on other technologies such as doped fibers, Raman gain or semiconductors.
We also deduced equations of the gain ripple for all the possible types of high gain spectra. We also investigated the inter-channel crosstalk in parametric amplifiers. We showed that the variations of the zero dispersion wavelength along the fiber increase the crosstalk because those variations enhances the spurious four wave mixing tones.
Finally, the degradation of the signal quality factor (Q) was studied for both, single and double-pumped parametric amplifiers. We showed that the phase modulation applied to the pump lasers to suppress the stimulated Brillouin backscattering can strongly degrade the performance of the amplifier. One alternative technique that we developed was based on applying different mechanical stress distributions along the fiber length. We experimentally demonstrated, using 285 m of highly non-linear fibers, that the backscattering threshold can be increased by 10.7 dB. This value is similar to that obtained using the phase modulation schema. The method was successfully applied to parametric devices. In particular we made a narrow linewidth wavelength converter with 70 nm of signal tuning band / Doutorado / Física / Doutor em Ciências
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Etude du rôle de AHP6 dans le contrôle de la phyllotaxie chez la plante modèle Arabidopsis thaliana : robustesse et coordination spatio-temporelle au cours du développement de structures auto-organisées / Study of the role of AHP6 in the control of phyllotaxis in Arabidopsis thaliana : robustness and spatio-temporal coordination in the development of self-organized organismsBesnard, Fabrice 21 October 2011 (has links)
En se développant, les plantes produisent des organes le long des tiges suivant des organisations stéréotypées, appelées phyllotaxies. Ces structures se forment dans les méristèmes, qui abritent une niche de cellules souches : les organes y sont produits successivement et leur positionnement dépendrait d'interactions dynamiques avec les organes pré-existants. Ces interactions seraient notamment dues à des champs inhibiteurs générés par le transport polaire de l'hormone végétale auxine. Afin de rechercher si d'autres facteurs que l'auxine contrôlent la phyllotaxie chez Arabidopsis thaliana, nous nous sommes intéressés au rôle possible des cytokinines, une autre hormone végétale. Nous avons développé des nouvelles méthodes statistiques pour analyser la structure de la phyllotaxie. Cette approche nous a permis d'identifier des anomalies de phyllotaxie chez des plantes mutantes pour le gène AHP6 (ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER protein 6), un inhibiteur de la signalisation des cytokinines. Notre analyse suggérait des possibles perturbations du plastochrone, la période de temps séparant l'initiation de deux organes, ce que nous avons alors confirmé par imagerie confocale en temps réel. Nos données montrent que AHP6 contrôle la régularité du plastochrone, et suggèrent que les perturbations de phyllotaxies sont dues à l'initiation simultanée de deux à trois organes dans le méristème. De plus, AHP6 est exprimé dans les organes et sa protéine établit des champs qui inhibent la signalisation des cytokinines au delà des organes. Pour mieux comprendre les rôles possibles de ces champs, nous avons généré un modèle numérique théorique de la phyllotaxie. Notre étude suggère que le plastochrone pourrait être déstabilisé par du bruit affectant le seuil d'activation nécessaire aux cellules méristématiques pour se différencier en organe. Des champs inhibiteurs pourraient filtrer les effets de ce bruit en influant sur la cinétique d'émergence des organes. Les propriétés observées des champs de AHP6 sont en accord avec ce modèle et nos données expérimentales suggèrent en effet que AHP6 et les cytokinines peuvent moduler la signalisation auxine lors de l'émergence des organes. Nous proposons comme modèle que le transport et la signalisation de l'auxine positionnent de manière robuste les organes mais génèrent un plastochrone irrégulier en présence de bruit. Des champs inhibiteurs de cytokinines stabiliseraient le plastochrone, assurant un couplage plus robuste entre le temps et l'espace lors de l'établissement de la phyllotaxie. / During development, plant aerial organs are produced along the stems following stereotyped patterns. This so-called phyllotaxis is initiated at the shoot meristem, which contains the stem cell niche: organs are produced iteratively and their precise position is thought to depend on dynamic interactions with preexisting organs. These interactions would notably result from inhibitory fields generated by the polar transport of the plant hormone auxin. To investigate whether other factors than auxin regulate phyllotaxis, we studied the potential role of cytokinin signaling. We developed a new pipeline of methods based on statistics to analyze phyllotactic patterns. This approach allowed us to identify phyllotactic perturbations in mutants of the AHP6 (ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER protein 6), an inhibitor of cytokinin signaling that suggested perturbations in the plastochron, the time between two organ initiations. This was further confirmed using confocal live-imaging. We demonstrated that AHP6 controls the regularity of the plastochron, and our results suggest that the defective phyllotaxis in ahp6 is caused by concomitant initiations of two or three organs in the meristem. Interestingly, AHP6 is expressed in organs and the protein can move beyond these domains, generating cytokinin signaling inhibitory fields. To explore further the putative role of these secondary fields, we generated a mathematical model of phyllotaxis. This suggested that plastochron instabilities could be caused by noise affecting the threshold at which meristematic cells are recruited into organs. Inhibitory fields generated by AHP6 could filter out the effect of noise by modifying the kinetics of early organ emergence. Consistently, the properties of AHP6 fields fit the model predictions and our experimental data show that AHP6 and cytokinin modulate auxin signaling during organ emergence. We thus propose a model in which auxin transport and signaling robustly control organ positioning but generates plastochron instablities in noisy backgrounds. In this scenario cytokinin inhibitory fields would stabilize the rhythmicity of organ initiation, ensuring a robust coupling of space and time during pattern formation.
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Action dynamics in multitasking: the impact of additional task factors on the execution of the prioritized motor movementScherbaum, Stefan, Gottschalk, Caroline, Dshemuchadse, Maja, Fischer, Rico 18 January 2016 (has links)
In multitasking, the execution of a prioritized task is in danger of crosstalk by the secondary task. Task shielding allows minimizing this crosstalk. However, the locus and temporal dynamics of crosstalk effects and further sources of influence on the execution of the prioritized task are to-date only vaguely understood. Here we combined a dual-task paradigm with an action dynamics approach and studied how and according to which temporal characteristics crosstalk, previously experienced interference and previously executed responses influenced participants' mouse movements in the prioritized task's execution. Investigating continuous mouse movements of the prioritized task, our results indicate a continuous crosstalk from secondary task processing until the endpoint of the movement was reached, although the secondary task could only be executed after finishing execution of the prioritized task. The motor movement in the prioritized task was further modulated by previously experienced interference between the prioritized and the secondary task. Furthermore, response biases from previous responses of the prioritized and the secondary task in movements indicate different sources of such biases. The bias by previous responses to the prioritized task follows a sustained temporal pattern typical for a contextual reactivation, while the bias by previous responses to the secondary task follows a decaying temporal pattern indicating residual activation of previously activated spatial codes.
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SYNTHESIS AND CHARACTERIZATION OF NOVEL EXCITED STATE INTRAMOLECULAR PROTON TRANSFER (ESIPT) CYANINE DYES WITH NEAR INFRARED (NIR) EMISSION FOR BIOLOGICAL APPLICATIONSDahal, Dipendra, Dahal 06 September 2019 (has links)
No description available.
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Crosstalk between the Jak-Stat and Wingless pathways is mediated by Mad in Drosophila melanogaster larval hematopoiesis.Rush, Craig Michael January 2013 (has links)
No description available.
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FUNCTIONAL CHARACTERIZATION OF FAM210A PROTEIN IN SKELETAL MUSCLE AND MUSCLE STEM CELLSJingjuan Chen (18290026) 02 April 2024 (has links)
<p dir="ltr">Skeletal muscle accounts for 40% of total body weight and the homeostasis of muscle tissue is critical in maintaining proper body function. Skeletal muscle develops during the embryonic stages from the muscle progenitor cells derived from the dermomyotome structure. The myogenic progenitor cells contribute to the primary myogenesis by forming the primary myotubes which are the founding structures that the secondary myogenesis continues to build on. A portion of the myogenic progenitor cells makes up the adult muscle stem cells residing in homeostatic muscle tissue. The adult muscle stem cells contribute substantially for the adult muscle regeneration. Due to the significance of the muscle tissue and the importance of muscle stem cells, dysregulation of the muscle homeostasis or the muscle stem cell homeostasis will result in severe pathological conditions such as myopathy.</p><p dir="ltr">Mitochondria are cellular organelles that are responsible for generating energy needed for cellular processes, especially for muscle tissue where muscle contraction requires the presence of ATP. On the other hand, mitochondria also serve as signaling molecules and provide macromolecules for the biosynthesis. FAM210A (Family With Sequence Similarity 210 Member A) protein was shown to impact the lean mass of human subjects yet a detailed study on the effect of FAM210A in skeletal muscle was not performed, nor has the molecular mechanisms through which FAM210A function been elucidated. Therefore, I take on the task to unveil the function of FAM210A in muscle development, muscle homeostasis and muscle stem cell behavior by using a combination of mouse models with different myogenic promoters to target <i>Fam210a</i> at different developmental stages.</p><p dir="ltr">In the first part of the thesis, I investigated the role of FAM210A in post differentiation myofibers. Using the <i>Myl1</i><sup><em>Cre</em></sup> driven deletion of <i>Fam210a</i>, I found that <i>Fam210a</i><sup><em>MKO</em></sup> had normal development before 3 weeks of age, but the growth was stagnant from 4 weeks on, and the mice did not survive past 8 weeks of age. I found that the assembly of the ribosomes in the <i>Fam210a</i><sup><em>MKO</em></sup> was defective, leading to impaired translation which attenuated the muscle atrophy phenotype. I identified through proteomics that the mitochondrial autophagy and proteostatic control pathways were significantly induced yet mitochondrial organization and energetic proteins were downregulated. Metabolomics analysis showed that the signaling metabolite acetyl-CoA was increased in the <i>Fam210a</i><sup><em>MKO</em></sup> which led to increased protein acetylation, specifically, we showed that the ribosomal proteins were hyperacetylated, and that the acetylation increase was elicited by the <i>Fam210a</i>-null mitochondria.</p><p dir="ltr">In the second part of the thesis, I investigated the function of FAM210A in muscle progenitor cells. In the <i>FamMKO</i> mice, I found that deletion of <i>Fam210a</i> from embryonic myogenic progenitor cells led to developmental arrest and postnatal death at day 6. In the <i>FamPKO</i> mice, I found that <i>Fam210a</i> is needed for adult muscle stem cell to contribute to regeneration. Loss of <i>Fam210a</i> leads to the regenerative defects when the muscle was exposed to injury cues. We further showed that <i>Fam210a</i> deletion in muscle stem cells resulted in disruption of the proteostatic control over muscle stem cell activation, thereby forbidding the translational increase necessary to facilitate activation and proliferation. Furthermore, I showed that <i>Fam210a</i> deletion leads to excessive OPA1 cleavage, which contributes to the regenerative failure of muscle stem cells as fusion is required for the mitochondrial network remodeling during regeneration. Therefore, <i>Fam210a</i> safeguards the mitochondrial network and proteostasis during regeneration.</p><p dir="ltr">In summary, my studies characterized the functional contribution of FAM210A during embryonic muscle development, muscle mass maintenance and adult muscle stem cell homeostasis. The regulation of FAM210A in these three processes impinge on the translational regulation. My studies further demonstrated the importance of mitochondrial regulated protein translation in skeletal muscle and muscle stem cells.</p>
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Αλγόριθμοι κατανομών ισχύος και ρυθμού μετάδοσης δεδομένων για πολυκαναλικά συστήματα / Rate and power allocation algorithms for multicarrier communication systemsΠαπανδρέου, Νικόλαος Ι. 25 June 2007 (has links)
Το αντικείµενο αυτής της διδακτορικής διατριβής είναι η σχεδίαση και η ανάλυση νέων αλγορίθµων υπολογισµού των κατανοµών ισχύος και πληροφορίας σε πολυκαναλικά συστήµατα τεχνολογίας ψηφιακών συνδροµητικών γραµµών DSL. Η αρχή λειτουργίας των πολυκαναλικών συστηµάτων βασίζεται στη διαίρεση του συνολικού φάσµατος σε επιµέρους υποκανάλια χαµηλού ρυθµού µετάδοσης, τα οποία µεταφέρουν τη συνολική πληροφορία µέσω ειδικών τεχνικών διαµόρφωσης. Ο υπολογισµός των κατανοµών της ισχύος εκποµπής και της πληροφορίας στα υποκανάλια του συστήµατος βασίζεται σε αλγορίθµους που είναι γνωστοί µε τον όρο αλγόριθµοι bit-loading. Η πλειοψηφία των αλγορίθµων bit-loading που χρησιµοποιούνται σήµερα είναι αλγόριθµοι ενός χρήστη, δηλαδή εκτελούνται στο δέκτη της γραµµής ενδιαφέροντος, χωρίς να λαµβάνουν υπόψη τα χαρακτηριστικά των πηγών θορύβου (π.χ. παρεµβολή διαφωνίας από γειτονικά συστήµατα στην ίδια δέσµη), παρά µόνο το αποτέλεσµα αυτών (µείωση του λόγου σήµατος-προς- θόρυβο). Για τα πολυκαναλικά συστήµατα ορίζονται δύο βασικές κατηγορίες προβληµάτων bitloading: το πρόβληµα µεγιστοποίησης του ρυθµού µετάδοσης για δεδοµένη ισχύ εκποµπής και το πρόβληµα ελαχιστοποίησης της συνολικής ισχύος για δεδοµένο ρυθµό µετάδοσης. Σε κάθε περίπτωση ένα σύνολο από περιορισµούς (π.χ. µέγιστη ισχύς ανά υποκανάλι, ακέραιες τιµές στην κατανοµή της πληροφορίας) ορίζουν τη βέλτιστη λύση, η οποία ικανοποιεί όλες τις συνθήκες. Οι αλγόριθµοι που έχουν προταθεί βασίζονται σε µεθόδους τύπου greedy bit-filling, οι οποίες υπολογίζουν τη βέλτιστη λύση µε ακέραιες τιµές στην κατανοµή πληροφορίας, και σε µεθόδους τύπου water-filling, οι οποίες οδηγούν σε λύση µε πραγµατικές τιµές στην κατανοµή πληροφορίας, οπότε η τελική “ηµι-βέλτιστη” λύση προκύπτει µε κατάλληλη διακριτοποίηση. Η ραγδαία εξάπλωση των συνδέσεων DSL, καθώς και η ανάγκη για παροχή υψηλότερων ρυθµών µετάδοσης έχει οδηγήσει την επιστηµονική και βιοµηχανική κοινότητα στη διερεύνηση µεθόδων για τη διαχείριση ολόκληρου του φάσµατος µιας δέσµης αγωγών µε στόχο τη βελτιστοποίηση της απόδοσης του συνολικού δικτύου. Ο σηµαντικότερος παράγοντας που περιορίζει τον προσφερόµενο ρυθµό µετάδοσης στα συστήµατα DSL είναι ο θόρυβος διαφωνίας µεταξύ γειτονικών συστηµάτων που λειτουργούν στην ίδια δέσµη. Στα πλαίσια αυτά ανήκει και η σχεδίαση κεντρικών αλγορίθµων bit-loading πολλών χρηστών, µε στόχο τον υπολογισµό των βέλτιστων κατανοµών όλων των συνδέσεων της δέσµης, ώστε να ελαχιστοποιούνται οι συνολικές παρεµβολές διαφωνίας. Σε αντίθεση µε τους αλγορίθµους ενός χρήστη, η διατύπωση του προβλήµατος bit-loading της δέσµης απαιτεί τη γνώση των συναρτήσεων διαφωνίας, ώστε να ορισθεί η αλληλεπίδραση µεταξύ των σηµάτων στις επιµέρους γραµµές. Οι αλγόριθµοι bit-loading πολλών χρηστών που έχουν παρουσιαστεί µέχρι σήµερα βασίζονται στις αρχές λειτουργίας των µεθόδων ενός χρηστή και θεωρούν ότι οι συναρτήσεις διαφωνίας είναι γνωστές. Για τον υπολογισµό των τελευταίων οι τεχνικές που συναντώνται στη βιβλιογραφία δεν εκτελούνται στις διατάξεις µετάδοσης, αλλά βασίζονται στη συλλογή και επεξεργασία σηµάτων σε εξωτερικά συστήµατα. Στα πλαίσια της διδακτορικής διατριβής έγινε ανάλυση των πολυκαναλικών συστηµάτων δέσµης ψηφιακών συνδροµητικών γραµµών (τεχνολογίας ADSL) και προτάθηκαν νέοι αλγόριθµοι bit-loading ενός χρήστη και πολλών χρηστών. Ειδικότερα, παρουσιάζονται λύσεις που αφορούν τα παρακάτω θέµατα: Ανάπτυξη νέου ταχύ αλγόριθµου bit-loading ενός χρήστη. Ο νέος αλγόριθµος επιλύει το πρόβληµα ελαχιστοποίησης της συνολικής ισχύος εκποµπής για δεδοµένο ρυθµό µετάδοσης και ανήκει στην κατηγορία των βέλτιστων αλγορίθµων. ∆ιερεύνηση της απόδοσης συστηµάτων δέσµης συνδροµητικών γραµµών, ως προς την εκµετάλλευση της συνολικής χωρητικότητας της δέσµης, όταν εφαρµόζεται αυτόνοµη διαχείριση του φάσµατος σε κάθε σύνδεση µέσω αλγορίθµων bit-loading ενός χρήστη. Ανάπτυξη νέου κεντρικού αλγόριθµου bit-loading πολλών χρηστών. Ο νέος αλγόριθµος αντιµετωπίζει το πρόβληµα της ανισοκατανοµής των ρυθµών µετάδοσης µεταξύ των συνδέσεων µιας δέσµης, εξ αιτίας της µη κεντρικής διαχείρισης του φάσµατος. Ανάπτυξη νέας µεθόδου για την αναγνώριση των συναρτήσεων διαφωνίας µεταξύ των αγωγών µιας δέσµης συνδροµητικών γραµµών. Η νέα µέθοδος εκτελείται στις διατάξεις µετάδοσης και βασίζεται σε κυκλώµατα επεξεργασίας πραγµατικού χρόνου. Οι νέοι αλγόριθµοι που προτείνονται αποτελούν πρωτότυπες λύσεις στην περιοχή των ψηφιακών επικοινωνιών για πολυκαναλικά συστήµατα µετάδοσης και βασίζονται σε µεθόδους, οι οποίες παρουσιάζουν συγκριτικά πλεονεκτήµατα µε άλλες υφιστάµενες λύσεις. Ειδικότερα: Ο νέος αλγόριθµος bit-loading ενός χρήστη υπολογίζει τη βέλτιστη λύση µε όλους τους περιορισµούς του συστήµατος επικοινωνίας, σε αντίθεση µε άλλους αλγορίθµους που υποστηρίζουν µόνο µέρος των περιορισµών. Επιπλέον, εµφανίζει µικρή πολυπλοκότητα και µεγάλη ταχύτητα εκτέλεσης συγκριτικά µε άλλες µεθόδους. Η διερεύνηση των συστηµάτων δέσµης, ως προς τη µεγιστοποίηση των ρυθµών µετάδοσης όταν δεν εφαρµόζεται κεντρική διαχείριση του φάσµατος, αναδεικνύει το πρόβληµα της ανισοκατανοµής της συνολικής χωρητικότητας στις επιµέρους συνδέσεις. Ο νέος κεντρικός αλγόριθµος bit-loading πολλών χρηστών αντιµετωπίζει το πρόβληµα της µη δίκαιης κατανοµής των ρυθµών µετάδοσης και ταυτόχρονα εξασφαλίζει ένα ελάχιστο περιθώριο µείωσης του λόγου σήµατος-προς-θόρυβο σε κάθε σύνδεση. Η νέα µέθοδος αναγνώρισης των συναρτήσεων διαφωνίας εκτελείται στις συσκευές µετάδοσης σε πραγµατικό χρόνο σε αντίθεση µε άλλες µεθόδους, οι οποίες εκτελούνται σε εξωτερικά συστήµατα µετρήσεων, και βασίζεται σε µια νέα µέθοδο εκτίµησης και αναγνώρισης των σηµάτων παρεµβολής. / The objective of this dissertation is the development of new algorithms for the calculation of the power and rate distributions in multicarrier systems with application in the Asymmetric Digital Subscriber Line (ADSL) technology. In multicarrier systems the spectrum is divided into narrowband subchannels and the total data-load is transmitted by modulating a set of independent subcarriers. The allocation of the total rate and power into the subchannels is based on bit-loading algorithms. The bit-loading algorithms used in multicarrier modems are mainly single-user algorithms: they do not take into account the decisions of the neighboring lines in the binder. In multicarrier systems two bit-loading problems are of main interest: rate-maximization subject to a total power constraint and margin-maximization subject to a given data rate. In both cases, a number of system constraints (e.g. power spectral density mask, integer bit values) determine the unique optimum solution. The bit-loading algorithms presented in the literature are based either on greedy methods, which provide the optimum discrete bit-allocation, or on water-filling methods, which in general provide non-integer bit-allocation. In this case, a final sub-optimum solution is provided using bit rounding. The rapid growth of the DSL users as well as the increasing demand for higher speed services has led the research and industry community in the investigation of methods for dynamic spectrum control of the modems operating in the same binder. In DSL systems, crosstalk interference induced by adjacent lines is one of the largest noise impairments that reduce the performance of services supported by the same binder. Therefore dynamic management incorporates methods for modem coordination and multi-user bit-loading in order to calculate the rate and power allocations of all activated lines, so that the total interference is reduced for a common global-binder benefit. In contrast to the single-user case, the formulation of the multi-user bit-loading problem requires the knowledge of the crosstalk transfer functions between the lines of the binder. The multi-user bitloading algorithms presented in the literature assume that the crosstalk transfer functions are known. In addition, the methods presented for crosstalk identification in DSL systems are based on data collection and processing in third-party systems. In this dissertation, the multicarrier system of an ADSL binder is studied and new single-user and multi-user bit-loading algorithms are developed. In particular, this dissertation presents solutions in the following problems: .. Development of a new computationally efficient single-user bit-loading algorithm. The proposed algorithm provides the optimum discrete solution to the margin-maximization problem. .. Investigation of the capacity and rate-region performance of ADSL binder systems when no overall spectrum control and no modem coordination are used (each modem performs single-user bit-loading). .. Development of a new multi-user bit-loading algorithm. The proposed algorithm resolves the problem of the non-uniform distribution of the achievable data rates experienced for a region of target-rate values, as a result of the no modem-coordination strategy. .. Development of a new crosstalk identification method for DSL binder systems. The proposed method is executed in the operating modems and is based on real time signal processing. This dissertation presents new algorithms which provide advantages compared to other solutions in the multicarrier DSL technology. In particular: .. The new single-user bit-loading algorithm provides the optimum discrete solution under the complete set of system constraints, in contrast to other solutions that consider only a subset of constraints. Moreover, the new algorithm is of low computational complexity compared with other methods. .. The investigation of the rate-region performance of ADSL binder systems under no overall spectrum control reports the problem of the non-uniform distribution of the achievable data rates. This “unfairness” is experienced as a result of the no modemcoordination strategy. .. The new multi-user bit-loading algorithm resolves the problem of the non-uniform distribution of the achievable data rates and guarantees a minimum SNR margin for each activated link in the binder. .. The new crosstalk identification method is based on a new technique for estimating the interference signals and is executed in the operating modems using real-time signal processing, in contrast to other methods which are executed in third-party systems.
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