Circadian rhythms are daily molecular oscillations within cells ranging from prokaryotes to humans. This rhythm is self sustaining, and receives external cues in order to synchronize an organism's behavior and physiology with the environment. Many metabolites utilized in metabolic processes seem to follow a pattern of circadian oscillation. Iron, an essential component in cellular processes such as respiration and DNA synthesis, is obtained almost exclusively through diet, yet little is known about how the clock governs iron metabolism. The regulation of iron within the cell is very tightly controlled, as iron is highly reactive in the generation of oxidative stress and the excretion of excess iron is very limited. There are limited findings indicating that there are molecular ties between the circadian clock and the regulation of iron metabolism. The first half of my dissertation focuses on the role of the circadian clock in modulating expression of iron metabolic components. We found that key components of iron import, in TFRC, and export, in SLC40A1, show altered expression in response to changes in the expression of clock transcription components. Furthermore, in circadian synchronized HepG2 hepatocytes TFRC and SLC40A1 showed rhythms in their mRNA expression, although expression of these genes was highly altered in conditions of high iron availability. We also examined IREB2, which expresses a master regulator of iron concentration in IRP2. IRP2 showed rhythms in phase with circadian component PER2, and IRP2's rhythmicity was lost under iron overload conditions. We observed that the ability of these three critical iron metabolic components to respond to sudden increases in available iron was mitigated in cells with clock impairment. Whole cistrome and transcriptome analysis was used to determine that rhythmicity in TFRC and SLC40A1 are not equal in their recruitment of circadian protein binding or in the stage of transcription in which circadian rhythms are generated. The cumulative effect of all of this regulation is that rhythmic variation in intracellular hepatic ferrous iron is clock controlled. The second half of my dissertation focuses on understanding how iron uptake influences clock resetting. Initially, iron was added to the cells in the form of ferrous sulfate, or chelated out of the cells using 2-2'-dipyridyl and clock gene expression was monitored. Altered rhythmicity of these components was seen at both the mRNA and protein level in cells with disrupted iron homeostasis. Then, we measured changes in period, phase, and amplitude of these rhythms, ultimately using a luciferase reporter cell line to demonstrate that even slight changes in cellular iron produce an effect on rhythmic period. We find that the circadian clock and iron metabolism pathway are intimately related, and that the intracellular iron concentration plays a role in circadian clock behavior. Overall, our research illustrates the importance of the circadian clock in liver metabolism and physiology. Improper iron metabolism due to genetic or dietary shortcomings is common in humans, and our work builds on the importance of chronotherapy in treatment of these conditions. Conversely, our research into the effect intracellular iron has on the clock contributes to the growing body of research into how circadian clocks, especially the peripheral clock of the liver, receive input from a range of metabolites in conjunction with signals from the master oscillator of the suprachiasmatic nucleus. / Ph. D.

La séquence des événements moléculaires engendrés par des perturbations de signaux externes qui peuvent affecter les horloges circadiennes, et générer des pathologies restait peu connue. Durant ma thèse, j’ai démontré au niveau moléculaire, comment déplacer l’horaire de l'alimentation chez la souris de la phase active à la phase de repos, altère le métabolisme à la suite d’une hypoinsulinémie durant la phase active, ce qui provoque une activation de PPARα qui reprogramme le métabolisme et l'expression de RevErbα et qui de ce fait décale l’horloge de 12h dans les tissus périphériques. Notamment, l’absence de PPARα dans le noyau suprachiasmatique empêche le décalage de l’horloge centrale. Ainsi, les phases d’activité et de repos contrôlées par l’horloge centrale ne sont plus alignées avec l'expression des gènes contrôlée par les horloges périphériques. Ce non-alignement crée un syndrome métabolique similaire à celui observé chez des individus soumis à des horaires de travail décalés. / The sequence of molecular events through which alterations in externals cues may impinge on circadian clocks, and generate pathologies, was mostly unknown. During my thesis work, I have molecularly deciphered, how switching feeding in mice, from the “active” to the "rest" phase [Restricted Feeding (RF)] , alters the metabolism through hypoinsulinemia during the “active” phase, leading to increased PPARα activity, thereby reprograming both metabolism and RevErbα expression and leads to a 12h circadian clock-shift in peripheral tissues.Most notably, the lack of PPARα expression in the suprachiasmatic nuclei (SCN) prevents a shift of the central clock. Therefore, the “active” and “rest” phases controlled by the SCN clock and gene expression controlled by the peripheral circadian clocks are misaligned. Most interestingly, this misalignment generates a metabolic syndrome-like pathology, similar to that associated with shiftwork schedules.

by Chan Lung Anthony, Ho Shun-Wah Montgomery. / Thesis (M.B.A.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references. / TABLE OF CONTENTS --- p.i / CHAPTERS / Chapter I. --- INTRODUCTION --- p.1 / Chapter II. --- METHOD --- p.5 / Chapter III. --- MARKET PROFILE --- p.7 / Chapter IV. --- PRODUCT PROFILE --- p.12 / Chapter V. --- CUSTOMER PROFILE --- p.16 / Chapter VI. --- COMPANY PROFILE --- p.20 / Chapter VII. --- PRODUCT POSITIONING AND TARGET MARKET SELECTION --- p.22 / Chapter VIII. --- COMPANY'S MISSION AND GOALS --- p.27 / Chapter IX. --- MARKETING OBJECTIVES --- p.28 / Chapter X. --- PRODUCT OBJECTIVES AND STRATEGIES --- p.29 / Chapter XI. --- PRICE OBJECTIVES AND STRATEGIES --- p.33 / Chapter XII. --- PROMOTION OBJECTIVES AND STRATEGIES --- p.36 / Chapter XIII. --- SALES FORCE OBJECTIVES AND STRATEGIES --- p.40 / Chapter XIV. --- DISTRIBUTION OBJECTIVES AND STRATEGIES --- p.43 / Chapter XV. --- CONTROL --- p.47 / Chapter XVI. --- ADVERTISING PLAN --- p.48 / APPENDIX / Chapter 1. --- FINDINGS OF QUESTIONNAIRE ON TARGET GROUP --- p.53 / Chapter 2. --- QUESTIONNAIRE --- p.56 / Chapter 3. --- SUMMARY OF INTERVIEW WITH HENRY DUONG --- p.63 / Chapter 4. --- EFFECTIVE COMPARISON AMONG MEDIA --- p.64 / Chapter 5. --- EFFECTIVENESS COMPARISON AMONG NEWSPAPERS --- p.65 / Chapter 6. --- EFFECTIVENESS COMPARISON AMONG MEDIA PRODUCT --- p.66 / Chapter 7. --- SPECIALISED/VERTICAL PUBLICATION --- p.67 / Chapter 8. --- READERSHIP PROFILE --- p.68 / Chapter 9. --- FIELD SURVEY OF PRICES OF WATCHES IN HONG KONG --- p.71 / BIBLIOGAPHY --- p.72

[Truncated abstract] This thesis is split into two parts. In part one; A 50 K dual mode oscillator, the aim of the project was to build a 50 K precision oscillator with frequency stability on the order of 1014 from 1 to 100 seconds. A dual-mode temperature compensation technique was used that relied on a turning point in the frequency-temperature relationship of the difference frequency between two orthogonal whispering gallery modes in a single sapphire crystal. A cylindrical sapphire loaded copper cavity resonator was designed, modelled and built with a turning point in the difference frequency between an E-mode and H-mode pair at approximately 52.5 K . . . The frequencies and Q-factors of whispering spherical modes in the 3-12 GHz range in the fused silica resonator are measured at 6, 77 and 300 K and the Q-factor is used to determine the loss tangent at these temperatures. The frequency and Q-factor temperature dependence of the TM2,1,2 whispering gallery mode at 5.18 GHZ is used to characterise the loss tangent and relative permittivity of the fused silica from 4-300 K. Below 22 K the frequency-temperature dependence of the resonator was found to be consistent with the combined effects of the thermal properties of the dielectric and the influence of an unknown paramagnetic impurity, with a spin resonance frequency at about 138 ± 31 GHz. Below 8 K the loss tangent exhibited a 9th order power law temperature dependence, which may be explained by Raman scattering of Phonons from the paramagnetic impurity ions. A spherical Bragg reflector resonator made from multiple concentric dielectric layers loaded in a spherical cavity that enables confinement of field in the centre of the resonator is described. A set of simultaneous equations is derived that allow the calculation of the required dimensions and resonance frequency for such a resonator and the solution is confirmed using finite element analysis. A spherical Bragg reflector resonator is constructed using Teflon and free-space as the dielectric materials. A Q-factor of 22,000 at 13.87 GHz was measured and found to compare well with the design values.

Orientador: Michel Georges Albert Vincentz / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-25T14:21:25Z (GMT). No. of bitstreams: 1 Viana_AmericoJoseCarvalho_D.pdf: 5804951 bytes, checksum: a3c65fa34ad298641a9b177952050af3 (MD5) Previous issue date: 2014 / Resumo: O fator de transcrição do tipo basic leucine leucine zipper (bZIP) de Arabidopsis thaliana AtbZIP63 faz parte da via de resposta a carência energética coordenada pelas quinases KIN10/11, integradoras centrais dos sinais relacionados ao estado de privação de energia. O mutante de inserção de T-DNA atbzip63-2 apresenta uma redução do crescimento e desenvolvimento das folhas assim como um atraso do florescimento em comparação ao tipo selvagem (TS, acesso Ws) quando cultivado em fotoperíodo de dia curto (10 h/14 h). Condições de fotoperíodo de dia longo ou luz contínua promoveram uma reversão parcial ou completa, respectivamente, do fenótipo mutante para o tipo selvagem, levantando a possibilidade de que este fenótipo seja o resultado de uma carência energética. Plantas silenciadas para expressão de AtbZIP63 por RNAi apresentaram características similares a do mutante atbzip63-2 confirmando o envolvimento deste fator de transcrição no crescimento. O perfil de expressão gênica e os níveis de alguns metabólitos do mutante atbzip63-2 indicaram que AtbZIP63 participa do controle da degradação do amido, pois a expressão de alguns genes centrais na degradação deste carboidrato de reserva está desregulada neste mutante. Mostramos que as oscilações no nível do transcrito AtbZIP63 são reguladas pelo relógio circadiano e a fase da oscilação do AtbZIP63 é aparentemente influenciada pela disponibilidade de carboidratos na célula. Além de estar sob o controle do relógio, AtbZIP63 também atua como um ativador direto da expressão de PRR7, que codifica um dos componentes chave do oscilador central do relógio. Portanto, evidenciamos uma interação recíproca entre o relógio e AtbZIP63 que possivelmente está impactando o processo de degradação do amido à noite. Este conjunto de evidências revela novos aspectos do ajuste do relógio circadiano pelo status de açúcar na célula que estão de acordo com trabalhos recentes mostrando que os açúcares afetam diretamente o funcionamento do relógio. Nossa hipótese é que o AtbZIP63 está agindo como um mediador entre a disponibilidade de viii açúcar e o mecanismo oscilatório do relógio circadiano de A. thaliana. Adicionalmente, verificamos que o perfil de transcritos no final do dia no mutante atbzip63-2 é diferente do observado no final da noite, sugerindo a participação do AtbZIP63 na regulação de genes envolvidos em redes regulatórias distintas em função do período do dia. Dentre os genes desregulados no atbzip63-2 no final do dia, observamos um enriquecimento para genes relacionados com metabolismo secundário e síntese de trealose, o que sugere a participação do AtbZIP63 na regulação da síntese destes compostos durante o dia, e possivelmente reflete a ocorrência de stress no mutante / Abstract: he Arabidopsis thaliana basic leucine zipper domain (bZIP) AtbZIP63 transcription factor is part of the response pathway to energy shortage coordinated by kinases KIN10/11. The T-DNA insertion mutant atbzip63-2 shows a reduction in the growth and development of leaves, as well as a delay in flowering compared to wild type (WT; ecotype Ws), when grown in short-day conditions. Long day or continuous light conditions promoted a partial or complete reversion, respectively, of the mutant to wild-type phenotype, raising the possibility that this phenotype is the result of an energy shortage. Plants silenced for AtbZIP63 showed similar characteristics to the atbzip63-2 mutant, confirming the involvement of this transcription factor in the growth. The gene expression profile and the levels of some metabolites of the atbzip63-2 indicated that AtbZIP63 takes part in the control of starch degradation, regulating the expression of some key genes in starch degradation. Diurnal AtbZIP63 mRNA level fluctuation is regulated by the circadian clock, and the phase oscillation is influenced by the availability of carbohydrates. In addition, to be controlled by the circadian clock, AtbZIP63 directly regulates the expression of PRR7 which encodes one of the key regulators of the core clock. We have therefore identified a reciprocal interaction between the clock and AtbZIP63 which is probably affecting the starch degradation process. This set of evidence reveals new aspects of the entrainment of the circadian clock by sugars, and is consistent with recent studies showing that sugars directly regulate the circadian clock. Our hypothesis is that AtbZIP63 is acting as a mediator between the energy status (availability of sugar) and the oscillatory mechanism of the A. thaliana circadian clock. Additionally, we found that the profile of transcripts at the end of the day in atbzip63-2 mutant is different from that observed in the end of the night, suggesting the involvement of AtbZIP63 in the regulation of genes involved in distinct regulatory networks according to the period of day. Among the genes deregulated in atbzip63-2 at the end of the x day, an enrichment for genes related to secondary metabolism and trehalose biosynthesis was observed. Suggesting the involvement of AtbZIP63 in regulating the synthesis of these compounds during the day, and probably reflects the occurrence of stress in the mutant / Doutorado / Genetica Vegetal e Melhoramento / Doutor em Genetica e Biologia Molecular

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This Master thesis deals with synchronization of sensor nodes in wireless sensor net. It is used event ordering by the implementation of logical clocks . Lamport's algorithm is used here for synchronization, which is trying to order events within the given system. The thesis also evaluates how appropriate this principle for synchronization is. The implementation has been carried out in agent-oriented language AgentSpeak on the Jason platform. Samson environment has been used and modified for observation of this synchronization's behaviour and testing purposes.

Data race in parallel programs can be difficult to precisely detect, and doing so manually can often prove unsuccessful. Task parallel programming models can help reduce defects introduced by the programmer by restricting concurrent functionalities to fork-join operations. Typical data race detection algorithms compute the happens-before relation either by tracking the order that shared accesses happen via a vector clock counter, or by grouping events into sets that help classify which heap locations are accessed sequentially or in parallel. Access sets are simple and efficient to compute, and have been shown to have the potential to outperform vector clock approaches in certain use cases. However, they do not support arbitrary thread synchronization, are limited to fork-join or similar structures, and do not support mutual exclusion. Vector clock approaches do not scale as well to many threads with many shared interactions, rendering them inefficient in many cases. This work combines the simplicity of access sets with the generality of vector clocks by grouping heap accesses into access sets, and attaching the vector clock counter to those groupings. By combining these two approaches, access sets can be utilized more generally to support programs that contain mutual exclusion. Additionally, entire blocks can be ordered with each other rather than single accesses, producing a much more efficient algorithm for data race detection. This novel algorithm, ZipperOTF, is compared to the Computation Graph algorithm (an access set algorithm) as well as FastTrack (a vector clock algorithm) to show comparisons in empirical results and in both time and space complexity.

Every fall, Northeastern America monarch butterflies (Danaus plexippus) undergo an extraordinary migration to their overwintering site in Central Mexico. During their long migration, monarch migrants use sun compass to navigate. To maintain a southward flying direction, monarch migrants compensate for the continuously changing position of the sun by providing timing information to the compass using their circadian clock. Animal circadian clocks depend primarily on a negative transcriptional feedback loop to track time. I started my work to re-construct the monarch butterfly circadian clock negative feedback loop in cell culture, focusing on homologs of Drosophila clock genes. It turned out that in addition to a Drosophila-like cryptochrome (cry1) gene, a second mammalian-like cry2 gene exists in monarch butterflies and many other insects, except in Drosophila. The two CRYs showed distinct functions in our initial assays in cultured Drosophila Schneider 2 (S2) cells. CRY2 functions as a potent transcriptional repressor, while CRY1 is light sensitive but shows no obvious transcriptional activity. The existence of two cry genes in insects changed the Drosophila-centric view of insect circadian clock. During the course of my study, our lab obtained a monarch cell line called DpN1 cells. These cells possess a light-driven clock and contributed tremendously to the research on monarch circadian clock. Using this cell line, I provided strong evidence supporting monarch CRY2’s role as a major circadian clock repressor and identified a protein-protein protective interaction cascade underlying the CRY1-mediated resetting of the molecular oscillator in DpN1 cells. I continued my work trying to understand how insect CRY2 inhibits transcription. I provided evidence suggesting the involvement of monarch PER in promoting CRY2 nuclear entry in both S2 cells and DpN1 cells. Finally, I mapped CRY2’s transcriptional inhibitory activity onto its N-terminal domain. Collectively, my research helped to change our view of insect clocks from a Drosophila-centric standpoint to a much more diverse picture. My studies also advanced the understanding of monarch circadian clock mechanism, and provides a foundation for further studies.

The existence of distributed real-time systems calls for protocols for high accuracy time synchronization between devices. One such protocol, the Precision Time Protocol (PTP) reaches sub microsecond synchronization precision. PTP can be implemented both in hardware and software. This study aimed to analyze how system stress could affect the accuracy and precision of software implemented PTP between two devices. This was done using two Intel Galileo Generation 2 running Linux systems. Software was used to simulate CPU, I/O, network, and OS usage. Data was extracted from software logs and summarized in charts and then analyzed. The results showed that PTP synchronization accuracy and precision does suffer under certain types of system load, most notably under heavy I/O load. However the results might not be applicable to real-world scenario due to limitations in hardware and the synthetic stress tests do not correspond to real-world usage. Further research is required to analyze why and how different types of system load affects PTPs accuracy and precision. / Förekomsten av distribuerade realtidssystem kräver protokoll för noggrann tidssynkronisering mellan enheter. Ett sådant protokoll, Precision Time Protocol (PTP), kan uppnå en precision på under mikrosekunden under synkronisering. PTP kan implementeras i både hårdvara och mjukvara. Den här rapporten fokuserar på att analysera hur systembelastning kan påverka precision och noggrannheten hos mjukvaruimplementerad PTP mellan två enheter. Testen utfördes på två stycken Intel Galileo Generation 2 kö- randes Linux. Mjukvara användes sedan för att simulera belastning på olika system såsom CPU, I/O, nätverk och på operativsystemet. Data extraherades ifrån loggar från mjukvaran, vilken sammanfattades i grafer för att sedan analyseras. Resultaten visade att precisionen och noggrannheten hos PTP försämras under vissa typer av systembelastningar, mest märkbart under tung I/O belastning. Resultaten är dock potentiellt inte applicerbara på verklighetscenarion på grund av begränsingar i hårdvaran samt att syntetiska stresstest inte motsvarar normal belastning. Ytterligare forskning krävs för att analysera hur och varför olika typer av systembelastning påverkar PTPs precision och noggrannhet.