Modelling is an important technique in the comprehension and management of complex systems. Queueing network models capture most relevant information from computer system and network behaviour. The construction and resolution of these models is constrained by many factors. Approximations contain detail lost for exact solution and/or provide results at lower cost than simulation. Information at the resource and interactive command level is gathered with monitors under ULTRIX'. Validation studies indicate central processor service times are highly variable on the system. More pessimistic predictions assuming this variability are in part verified by observation. The utility of the Generalised Exponential (GE) as a distribution parameterised by mean and variance is explored. Small networks of GE service centres can be solved exactly using methods proposed for Generalised Stochastic Petri Nets. For two centre. systems of GE type a new technique simplifying the balance equations is developed. A very efficient "building bglloocbka"l. is presented for exactly solving two centre systems with service or transfer blocking, Bernoulli feedback and load dependent rate, multiple GE servers. In the tandem finite buffer algorithm the building block illustrates problems encountered modelling high variability in blocking networks. A parametric validation study is made of approximations for single class closed networks of First-Come-First-Served (FCFS) centres with general service times. The multiserver extension using the building block is validated. Finally the Maximum Entropy approximation is extended to FCFS centres with multiple chains and implemented with computationally efficient convolution.

The physiological process of cold acclimation protects plants native to the temperate regions of the world from the deleterious effects of low and freezing temperatures. This is achieved by a series of transcriptional, regulatory, and metabolic changes that enable continued growth and survival. Within minutes of exposure to temperatures below ca. 10°C, a complex cascade of transcriptional events is initiated to accomplish these changes. The initial alarm phase favors the rapid induction of a library of stress proteins with protective functions (e.g. COR proteins). This is followed by a cold hardened phase, characterized by maximal freezing tolerance, which continues until either the stress is removed, or the plant's metabolic and/or developmental state can no longer support maximal resistance. We have studied some of the important transcription factors and transcriptional changes associated with the initial alarm and later hardened phases of cold acclimation in the herbaceous annual Arabidopsis thaliana and the woody perennial Populus spp. We confirmed the functionality of the CBF-mediated signaling cascade in Poplar overexpressing AtCBF1, but noted that regulon composition and endogenous poplar CBF ortholog induction appeared to be tissue-specific. The lack of statistically significant DRE enrichment in the Poplar AtCBF1 regulons led us to investige cis-element abundance in the cold-associated transcription factor regulons of publicly available microarray data from Arabidopsis, leading to the development of a gene voting method of microarray analysis that we used to test for regulatory associations between transcription factors and their downstream cis-elements and gene targets. This analysis resulted in a new transcriptional model of the ICE1-mediated signaling cascade and implicated a role for phytochrome A. Application of this same method to microarray data from arabidopsis leaves developed at low temperature allowed us to identify a new cis-element, called DDT, which possessed enhancer-blocking function during the alarm stage of cold stress, but was enriched in the promoters of genes upregulated during the later cold hardened stages. As leaf growth and development at low temperature correlated with the enhancement freeze tolerance in Arabidopsis, we compared the transcriptomes of rapidly growing and fully grown poplar leaves at night (when both low temperatures and PhyA status might play important roles in nature), in the hopes of comparing this data with that of cold-treated leaves in the future. We identified the nocturnal mode of leaf growth in Populus deltoides as predominantly proliferative as opposed to expansive, and potentially linked to cellular carbohydrate status.

Gravity waves have a significant dynamic effect in the mesosphere. In particular, they drive the mesospheric circulation and are the reason that the summer polar mesosphere is cooler than the winter polar mesosphere. This thesis examines whether the effects of gravity waves are largely determined by filtering effects which allow only gravity waves with certain properties to propagate into the atmosphere. The filtering of gravity waves above Scott Base, Antarctica is examined using a radiosonde derived gravity wave source function, an MF-radar derived mesospheric gravity wave climatology, and a model derived filtering function. Least squares fitting of the source function and filtering function to the observed mesospheric gravity wave climatology allows us to determine which gravity wave phase velocities and propagation direction are likely to be present in the mesosphere and the relative importance of filtering and sources in this region. It is concluded the blocking of eastward gravity waves is important in winter and westward waves in summer.

Gravity waves have a significant dynamic effect in the mesosphere. In particular, they drive the mesospheric circulation and are the reason that the summer polar mesosphere is cooler than the winter polar mesosphere. This thesis examines whether the effects of gravity waves are largely determined by filtering effects which allow only gravity waves with certain properties to propagate into the atmosphere. The filtering of gravity waves above Scott Base, Antarctica is examined using a radiosonde derived gravity wave source function, an MF-radar derived mesospheric gravity wave climatology, and a model derived filtering function. Least squares fitting of the source function and filtering function to the observed mesospheric gravity wave climatology allows us to determine which gravity wave phase velocities and propagation direction are likely to be present in the mesosphere and the relative importance of filtering and sources in this region. It is concluded the blocking of eastward gravity waves is important in winter and westward waves in summer.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The meteorological systems modulate the behavior of rainfall and temperature on large regions and must be correctly simulated by the climate models. The representation of these events should be good for the reliability model to be higher. This research therefore has the primary aim of examining how atmospheric blocks and frontal systems are being detected. Was used for this, the model of the British Center, HadGEM2-ES (Hadley Centre Global Environment Model version 2 Earth System) in two climate change scenarios, RCP4.5 and RCP8.5 in the future (2020-2049) projections series, comparing them with series of reference for the past 30 years (1975-2004). The results will be validated from those already found by other studies. For the blocks, the detection method proposed by Pelly e Hoskins (2003), in which find meridionaly anomalous variations of potential temperature in the dynamical tropopause. Frontal systems were found by frontogenetic function first proposed by Petterssen (1956). Moreover, the study of changes in rainfall, simulated by RegCM4 (Regional Climate Model version 4) model for the South and Southeast regions of Brazil is made. The main results show that there good agreement between the annual cycle and positioning of both systems by the model on past. There is a reduction of blocking systems on Central Pacific (170.0◦W-120◦W) and increased over the same region of the Southeast Pacific (117.5◦W-80◦W) and the Southwest Atlantic (77.5◦W-40◦W) in both future scenarios. The frontal systems, which also show a good agreement in the reference series, have a tendency to increase the frequency in the two studied regions. Likewise the accumulated rainfall simulated on RegCM4 indicating to be more significant in summer, fall and spring seasons and behavior similar to that reported previously for the winter months. / A atuação de sistemas meteorológicos modula o comportamento das chuvas e da temperatura de grandes regiões, devendo ser corretamente simulados pelos modelos climáticos. A representação dos sistemas deve ser consideravelmente boa para que a confiabilidade no modelo seja mais alta. Esta pesquisa, portanto, tem o principal objetivo de analisar como bloqueios atmosféricos e sistemas frontais estão sendo reproduzidos por estes modelos. Foi utilizado para isso, o modelo do centro britânico, o HadGEM2-ES (Hadley Centre Global Environment Model version 2 Earth System) em dois cenários de mudança climática, o RCP4.5 e o RCP8.5, em séries de projeções futuras (2020-2049), comparando-os com uma série de referência de 30 anos para o passado (1975-2004). Os resultados encontrados serão validados a partir daqueles já encontrados por outros estudos. Para os bloqueios, o método usado é o proposto por Pelly e Hoskins (2003), em que se buscam variações meridionalmente anômalas de temperatura potencial na tropopausa dinâmica. Já os sistemas frontais foram encontrados através da função frontogenética proposta inicialmente por Petterssen (1956). Além disso, é feito o estudo da alteração no regime de chuvas, simulados pelo modelo RegCM4 (Regional Climate Model version 4) para as regiões Sul e Sudeste do Brasil. Os principais resultados mostram que existe uma boa concordância entre o ciclo anual e o posicionamento de ambos os sistemas pelo modelo no passado. Verifica-se uma redução dos sistemas de bloqueio sobre a região do Pacífico Central (170.0◦W-120◦W) e um aumento dos mesmos sobre a região do Pacífico Sudeste (117.5◦W-80◦W) e do Atlântico Sudoeste (77.5◦W-40◦W) em ambos os cenários futuros. Já os sistemas frontais, que também mostram uma boa concordância na série de referência, possuem uma tendência de aumento em sua frequência nas duas regiões estudadas. Da mesma forma o regime de chuvas simuladas pelo RegCM4 indica acumulados mais significativos nas estações de verão, outono e primavera e um comportamento próximo ao observado para os meses de inverno.

One of the purposes of allergen-specific immunotherapy (SIT) is to modulate the humoral immune response against allergens with significant increases in allergen-specific IgG1 and IgG4 levels. These antibodies are associated with blocking activity by preventing IgE binding to allergen and leading to reduced inflammatory responses. This study aimed to investigate in vitro blocking activity of allergen-specific IgG antibodies on IgE reactivity to D. pteronyssinus (Dpt) in sera from atopic patients. Dpt-specific IgG antibodies were obtained from atopic sera and irrelevant IgG from non-atopic sera. IgG antibodies were purified by ammonium sulfate precipitation followed by Protein-G affinity chromatography and evaluated with regards to purity by SDS-PAGE and immunoreactivity by slot-blot and immunoblot assays. The blocking activity was evaluated by inhibition ELISA. The electrophoretical profile after salting-out precipitation showed an enrichment of high molecular weight proteins in the precipitated fraction and strongly stained bands in the ligand fraction after chromatography, compatible with molecular weight of human IgG. It was detected strong immunoreactivity to IgG, negligible to IgA, and no reactivity to IgE and IgM. Dpt-specific IgG fraction was capable to significantly reduce levels of IgE anti-Dpt, resulting in 35-51% inhibition of IgE reactivity to Dpt in atopic patient sera. Allergen-specific IgG antibodies purified using available and standardized methodology are able to inhibit IgE reactivity to Dpt allergen extract. In addition to the clinical symptoms improvement (subjective parameter), this approach reinforces that the intermittent measurement of serum allergen-specific IgG antibodies will be an important objective laboratorial parameter that will help specialists to follow their patients under SIT. / Uma das propostas da imunoterapia alérgeno específica é a de modular a resposta imune humoral contra alérgenos, com aumento significativo nos níveis de IgG1 e IgG4 específicos. Esses anticorpos estão associados com uma atividade bloqueadora, impedindo a ligação de anticorpos IgE ao alérgeno e levando a uma redução nas respostas inflamatórias. Esse estudo objetivou investigar a atividade bloqueadora, in vitro, de anticorpos IgG específicos sobre a reatividade de IgE a D. pteronyssinus (Dpt) em soros de pacientes atópicos. Anticorpos IgG específicos foram obtidos de soros de pacientes atópicos, e IgG irrelevante a partir de soros de não atópicos, e depois purificados por precipitação com sulfato de amônio, seguido de cromatografia de afinidade em Proteina G-agarose. A pureza desses anticorpos foi avaliada por SDS-PAGE, a imunoreatividade por ensaios de slot-blot e immunoblot, e a atividade bloqueadora por ELISA inibição. O perfil eletroforético, após precipitação com sulfato de amônio, mostrou um enriquecimento de proteínas de alto peso molecular na fração precipitada,e bandas fortemente coradas na fração ligante após a cromatografia, compatíveis com o peso molecular de IgG humana. Foi detectada uma forte imunoreatividade para IgG, leve para IgA, e nenhuma reatividade para IgE e IgM. A Fração IgG específica foi capaz de reduzir significantemente os níveis de IgE anti-Dpt, resultando em 35-51% de inibição da reatividade de IgE a Dpt em pools de soros de pacientes atópicos. Anticorpos IgG específicos purificados, através de uma metodologia disponível e padronizada, são capazes de inibir a reatividade de IgE ao extrato alergênico Dpt. Além da melhoria da sintomatologia clínica, considerada um parâmetro subjetivo, essa abordagem reforça que a avaliação intermitente de anticorpos IgG alérgeno-específicos pode ser uma ferramenta importante, auxiliando especialistas a acompanharem seus pacientes em processo de imunoterapia específica. / Mestre em Ciências da Saúde

abstract: This dissertation presents a novel current source converter topology that is primarily intended for single-phase photovoltaic (PV) applications. In comparison with the existing PV inverter technology, the salient features of the proposed topology are: a) the low frequency (double of line frequency) ripple that is common to single-phase inverters is greatly reduced; b) the absence of low frequency ripple enables significantly reduced size pass components to achieve necessary DC-link stiffness and c) improved maximum power point tracking (MPPT) performance is readily achieved due to the tightened current ripple even with reduced-size passive components. The proposed topology does not utilize any electrolytic capacitors. Instead an inductor is used as the DC-link filter and reliable AC film capacitors are utilized for the filter and auxiliary capacitor. The proposed topology has a life expectancy on par with PV panels. The proposed modulation technique can be used for any current source inverter where an unbalanced three-phase operation is desires such as active filters and power controllers. The proposed topology is ready for the next phase of microgrid and power system controllers in that it accepts reactive power commands. This work presents the proposed topology and its working principle supported by with numerical verifications and hardware results. Conclusions and future work are also presented. / Dissertation/Thesis / Ph.D. Electrical Engineering 2013

Un code de résolution des équations de Navier-Stokes pour un fluide incompressible a été développé en utilisant une approche mixte spectral/différences finies, compatible avec une mise en oeuvre dans un environnement massivement parallèle. On procède, grâce à ce nouvel outil, à des simulations directes de la turbulence dans une configuration où l'agitation est synthétisée à l'aide d'un forçage aléatoire. La production de turbulence est confinée dans une couche centrale du domaine et s'auto-diffuse en direction d'une surface libre ou d'une paroi adhérente. Dans cette configuration on obtient un état statistiquement stationnaire où le cisaillement moyen, généralement à l'origine de la production de la turbulence, est nul. Ces conditions permettent de mieux comprendre l'origine du transfert intercomposantes, caractéristique de la partie lente du terme de corrélation pression-déformation dans les équations-bilan des tensions de Reynolds. L'accent est mis sur l'analyse de ce transfert lorsqu'il s'effectue sous l'influence de l'effet de blocage au voisinage d'une surface. Les résultats obtenus permettront de mieux appréhender la modélisation des termes de corrélation pression-déformation au voisinage d'une paroi dans les modèles de fermeture au second ordre. / A Navier-Stokes solver for incompressible flow has been developed using a mixed spectral/finite-difference approach, while being compatible with a massively parallel environment. We use it to perform direct numerical simulations in a situation where the turbulent agitation is synthesized under the action of a random forcing. The turbulence production is confined in a central layer and self-diffuses towards a free-slip or no-slip surface. With this set-up, we obtain a statistical steady state in which the mean shear, usually associated with the turbulence production, is zero. These conditions allow a better understanding of the intercomponent energy transfer, induced by the slow part of the pressure-strain correlation in the Reynolds tensor budget. We focus on this transfer when it occurs in combination with the blocking effect, in the vicinity of the surface. The results will help to model the pressure-strain correlation in a second- order-closure context.

Refrigerated Stability of Diluted Succinylcholine, Pancuronium, and Atracurium. T. Archibald1, S. Brown1, A. Gonzalez-Estrada2 1College of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN2Quillen College of Medicine, Allergy and Clinical Immunology, East Tennessee State University, Johnson City, TN The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely succinylcholine, pancuronium, and atracurium, for skin prick/intradermal testing. Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Each drug was prepared with an n = 5 for each dilution, using a different newly opened product for each series. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days (day 0, 1, 2, 4, 7, and 14), one milliliter aliquots of each dilution were removed, filtered, and analyzed against freshly prepared set of reference dilutions. The results are expressed as beyond use date (BUD), defined as recovery of drug versus the reference (90-110%). Based on the LC-MS/MS data, the BUD for succinylcholine diluted by 10x and 100x is 48 and 24 hours, respectively. The1000x dilution is also stable for 24 hours.Higher dilutions of succinylcholine (10,000x to100,000x) should be used immediately following preparation (within less than 24 hours), as the potency of these dilutions had decreased below 90% at the 24 hr sampling. .Pancuronium diluted by 10x and 100x, had a BUD of 48 hours, and the1,000x dilution was stable for 24 hours.As with the succinylcholine, the 10,000x and 100,000x dilutions expressed potency of <90% at 24 hours. .Atracurium diluted to 10x had a BUD of 96 hours, the100x dilution is stable for 24 hours yet higher dilutions (1,000x to 10,000x) do not persist beyond 24 hours. . The 100,000x dilution of atracurium was unknown, given than the signal intensity was too weak to monitor by our LC-MS/MS method. With increasing dilution factors, the stability of these drugs in saline decreases, associated with an increasing deviation between samples and freshly prepared references. The most stable dilutions for each of the drugs tested were 10x and 100x. Stability of these drugs is likely compromised by hydrolysis of the ester bonds in the drug molecules.

abstract: Modern manufacturing systems are part of a complex supply chain where customer preferences are constantly evolving. The rapidly evolving market demands manufacturing organizations to be increasingly agile and flexible. Medium term capacity planning for manufacturing systems employ queueing network models based on stationary demand assumptions. However, these stationary demand assumptions are not very practical for rapidly evolving supply chains. Nonstationary demand processes provide a reasonable framework to capture the time-varying nature of modern markets. The analysis of queues and queueing networks with time-varying parameters is mathematically intractable. In this dissertation, heuristics which draw upon existing steady state queueing results are proposed to provide computationally efficient approximations for dynamic multi-product manufacturing systems modeled as time-varying queueing networks with multiple customer classes (product types). This dissertation addresses the problem of performance evaluation of such manufacturing systems. This dissertation considers the two key aspects of dynamic multi-product manufacturing systems - namely, performance evaluation and optimal server resource allocation. First, the performance evaluation of systems with infinite queueing room and a first-come first-serve service paradigm is considered. Second, systems with finite queueing room and priorities between product types are considered. Finally, the optimal server allocation problem is addressed in the context of dynamic multi-product manufacturing systems. The performance estimates developed in the earlier part of the dissertation are leveraged in a simulated annealing algorithm framework to obtain server resource allocations. / Dissertation/Thesis / Doctoral Dissertation Industrial Engineering 2020