Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: heat fluxes; fire testing; composites; instrumentation; material properties. Includes bibliographical references.

Abstract The role of vacuolar H+-ATPase (V-ATPase) in exocytic and endocytic membrane transport processes was studied by using its specific inhibitor, bafilomycin A1 (Baf A1), as a tool. On the exocytic pathway, both brefeldin A- and nocodazole-induced retrograde transport of Golgi proteins to the endoplasmic reticulum (ER) were inhibited by Baf A1. Furthermore, p58/ERGIC-53, which normally cycles between the ER, the intermediate compartment (IC), and cis-Golgi, was arrested in pre-Golgi tubules and vacuoles, and the number of p58-positive 80-nm Golgi (COPI) vesicles was reduced, suggesting that the drug inhibits the vesicle-mediated retrieval of the protein from post-ER compartments. The small GTPase rab1p was efficiently recruited to the tubules, accumulating in the presence of Baf A1. In contrast, these tubules showed no enrichment of anterogradely transported proteins, indicating that they participate in retrograde transport. Interestingly, acidic lumenal pH could only be detected in the more central pre-Golgi elements. The forward (anterograde) transport of newly synthesized Semliki Forest virus (SFV) and vesicular stomatitis virus (VSV) glycoproteins from the ER to the cis-Golgi was largely unaffected by Baf A1. However, maturation processes occurring in the trans-Golgi were inhibited, and the amounts of viral glycoproteins appearing at the cell surface were reduced. Newly synthesized VSV glycoprotein accumulated into rab1p-positive Golgi membranes in the presence of Baf A1, indicating that the transport from cis-Golgi was affected. Furthermore, O-glycosylation of the expressed CD8 chimeras and lectin cytochemistry experiments indicate that Baf A1 affects the transport from cis-Golgi. Instead, Baf A1 did not affect the transport of viral glycoproteins from the trans-Golgi network to the cell surface. We propose, that anterograde intra-Golgi traffic may be affected indirectly by Baf A1, as it inhibits retrograde vesicle-mediated transport and thus cisternal maturation. Baf A1 inhibited the entry of SFV into BHK-21 cells. Thus, V-ATPase was responsible for the acidification of the endosomes needed for virus entry. In cells infected with VSV and subsequently treated with Baf A1, virus particles were found to be accumulated in tubular membrane structures, which also contained endocytosed BSA-gold. Neither VSV nor BSA-gold particles were detected in lysosomal glycoprotein (lgp) 120-positive lysosomes, however. Thus, secreted and further endocytosed virus particles accumulate into tubulated endocytic organelles, apparently early endosomes, in Baf A1-treated cells. We conclude that the transport from endosomes to lysosomes is inhibited by Baf A1. The bulk of rab7 GTPase, which participates in vesicle fusion to late endosomes, was localized to the ruffled border (RB) membrane of bone-resorbing osteoclast. This indicates that the membrane has some characteristics of late endosomal membranes and that endocytic membrane transport is oriented towards the RB. Consistently, both endocytosed lumenal horseradish peroxidase and receptor-bound transferrin were delivered to the RB. The delivery of membrane-associated transferrin to the RB further indicates that the RB has some endosomal characteristics and suggests that the endocytic pathway contributes to the maintenance of functional RB. The endocytic pathway could act in balancing the membrane traffic associated with transcytosis from the RB to the basal plasma membrane. Endocytic processes in osteoclasts appeared to be very sensitive to Baf A1. Thus, blocking of the endocytic membrane traffic towards the RB could explain the inactivation of cells by low concentrations of the drug.

No description available.

Introduction — Hyperkalemia, defined as serum potassium >6.0mmol/L, affects ±6% of people with kidney disease and is a contraindication to surgery due to the perioperative risk of potentially fatal cardiac dysrhythmia (1,2,3). When emergency surgery cannot be avoided, hyperkalemia must be managed perioperatively using a variety of traditional practice patterns which vary in efficacy (3,4,5). We present a case report of successful rapid correction of hyperkalemia in a 67-year- old man with a history of chronic kidney disease who presented to the emergency department for acute compartment syndrome in need of emergent fasciotomy to prevent loss of limb. Methods — Since emergent treatment of hyperkalemia is often managed through a combination of medications with multiple mechanisms of action, we reviewed available related literature in PubMed in order to present this educational case report. Patient Presentation — At the time of presentation, our patient’s serum potassium was 7.7mmol/L, creatinine kinase was 33,160U/L, and an ECG revealed a first-degree AV node block with slight ST depression. Following intubation, as a team of surgeons started extensive fasciotomy of his arm, our anesthesia team gave several medications in tandem—calcium gluconate to stabilize cardiac myocytes and prevent ventricular arrythmia, coadministration of dextrose and insulin to induce an intracellular shift of potassium, sodium bicarbonate to induce cellular hydrogen/potassium exchange, and albuterol to increase cellular uptake of potassium via β2 adrenergic receptors (1,6). The patient’s hyperkalemia improved from 7.7 to 3.7 (normal 3.5 – 5.1mmol/L) over 4 hours. Discussion and Conclusion — Our review of available literature identified several methods of treatment of hyperkalemia, some with limitations to use which we believe support our team’s approach to treatment in this case report (6). Calcium salts are integral to the treatment of hyperkalemia by stabilizing cardiac myocytes, however they do not directly influence serum or total body potassium levels. Our report adds to a growing pool of existing case reports and small studies documenting safe, efficacious emergent treatment of hyperkalemia. It also describes the utility of the anesthesiologist in providing safe, effective perioperative medical care.

Stochastic compartment models are widely used in modeling processes for biological populations. The residence time has been especially useful in describing the system dynamics in the models. The direct calculation of the distribution for the residence time of stochastic multi-compartment models is very complicated even with a relatively simple model and often impossible to calculate directly. This dissertation presents an analytical method to obtain the moment generating function for stochastic multi-compartment models and describe the distribution of the residence times, especially systems with nonexponential lifetime distributions. A common method for obtaining moments of the residence time is using the coefficient matrix, however it has a limitation in obtaining high order moments and moments for combined compartments in a system. In this dissertation, we first derive the bivariate moment generating function of the residence time distribution for stochastic two-compartment models with general lifetimes. It provides any order of moments and also enables us to approximate the density of the residence time using the saddlepoint approximation. The approximation method is applied to various situations including the approximation of the bivariate distribution of residence times in two-compartment models or approximations based on the truncated moment generating function. Special attention is given to the distribution of the residence time for multi-compartment semi-Markov models. The cofactor rule and the analytic approach to the two-compartment model facilitate the derivation of the moment generating function. The properties from the embedded Markov chain are also used to extend the application of the approach. This approach provides a complete specification of the residence time distribution based on the moment generating function and thus provides an easier calculation of high-order moments than the approach using the coefficient matrix. Applications to drug kinetics demonstrate the simplicity and usefulness of this approach.

Diss. (sammanfattning) Umeå : Umeå universitet, 2010.

When fires occur in domestic or commercial buildings it is the smoke from the fire that leads to far more injury and death than the heat produced from the flames. Understanding the movement of smoke within the fire compartment and through openings in the enclosure is critical for designing buildings to prevent fire fatalities. Prediction of the movement of smoke is a complex phenomenon and is a continued focus of research throughout the world. Work has been conducted in the past on the exchange flow rates through vertical openings, but very little has been done on horizontal ceiling openings. Current smoke transport calculations are most often carried out using standard vent flow models that do not accurately take in to account the buoyancy component of the flow. The fire zone model BRANZFire was developed with a ceiling vent flow algorithm based on the work of Cooper who found there was very little data on which to base his predictions. This report aims to provide additional experimental data on exchange flow rates through horizontal ceiling openings through the use of saltwater modelling and compare this to the work previously undertaken by Cooper. Taking measurements of fire phenomena in hot and smoky environments can be difficult and expensive because the sooty environment and high temperatures involved can damage equipment and make taking accurate readings a challenge. Herein this problem is overcome through the use of a saltwater analogue system to model the conditions in a real fire scenario. The density difference created by a fire between the hot fire gases and the ambient air is replicated by using fresh and saltwater. The orientation of the experiment is inverted compared to the real life scenario as the saltwater which has the higher density is added to the fresh water. The saltwater is injected from a source on the ‘floor’ of the compartment into a tank of fresh water which generates a buoyant plume that ‘rises’ to the ceiling forming a distinct upper layer. Fluid in this layer exchanges with the ambient fluid through the ceiling opening. The saltwater is dyed and Light Attenuation (LA) is used to discern the density of the fluid and hence the amount of mixing that has occurred. This can then be used to determine the amount of exchange flow through the ceiling vent. An integral model for the descent of the interface between the hot smoky zone and the cool ambient zone has been developed and was found to perform well when compared with the saltwater experiments and another predictive model developed by Turner and Baines. The model was then developed further using mass conservation conventions to calculate the exchange flow through the ceiling opening. The exchange rate through the ceiling opening was calculated and was found to compare well with Cooper’s algorithm when an equivalent fire size of 323 kW was used but differed significantly when a fire twice this size was considered. It was found that Cooper’s method did not adequately take into account the difference in fire sizes as the exchange flow predicted was almost identical between fire sizes for a particular ceiling vent. The implications of this are that the exchange, and hence the mixing and the amount of smoke, may be under predicted using larger fires in BRANZFire and this could lead to non-conservative design.

In fire, any information about the actual condition within the building could be essential for quick and safe response of both fire–fighters and occupants. In most cases, however, the emergency responders will rarely be aware of the actual conditions within a building and they will have to make critical decisions based on limited information. Recent buildings are equipped with numbers of sensors which may potentially contain useful information about the fire; however, most buildings do not have capability of exploiting these sensors to provide any useful information beyond the initial stage of warning about the possible existence of a fire. A sensor–linked modelling tool for live prediction of uncontrolled compartment fires, K– CRISP, has therefore been developed. The modelling strategy is an extension of the Monte– Carlo fire model, CRISP, linking simulations to sensor inputs which controls evolution of the parametric space in which new scenarios are generated, thereby representing real–time “learning” about the fire. CRISP itself is based on a zone model representation of the fire, with linked capabilities for egress modelling and failure prediction for structural members, thus providing a major advantage over more detailed approaches in terms of flexibility and practicality, though with the conventional limitations of zone models. Large numbers of scenarios are required, but computational demands are mitigated to some extent by various procedures to limit the parameters which need to be varied. HPC (high performance computing) resources are exploited in “urgent computing” mode. K–CRISP was demonstrated in conjunction with measurements obtained from two sets of full–scale fire experiments. In one case, model execution was performed live. The thesis further investigates the predictive capability of the model by running it in pseudo real–time. The approach adopted for steering is shown to be effective in directing the evolution of the fire parameters, thereby driving the fire predictions towards the measurements. Moreover, the availability of probabilistic information in the output assists in providing potential end users with an indication of the likelihood of various hazard scenarios. The best forecasts are those for the immediate future, or for relatively simple fires, with progressively less confidence at longer lead times and in more complex scenarios. Given the uncertainties in real fire development the benefits of more detailed model representations may be marginal and the system developed thus far is considered to be an appropriate engineering approach to the problem, providing information of potential benefit in emergency response. Thus, the sensor–linked model proved to be capable of forecasting the fire development super–real– time and it was also able to predict critical events such as flashover and structural collapse. Finally, the prediction results are assessed and the limitations of the model were further discussed. This enabled careful assessment of how the model should be applied, what sensors are required, and how reliable the model can be, etc.

O presente estudo foi realizado no reservatório Rio Grande (Complexo Billings), estado de São Paulo, com o objetivo de analisar a heterogeneidade espacial ao longo de seu eixo principal e com isso também saber se a comunidade zooplanctônica varia junto com o gradiente de condições ambientais encontrado no reservatório. Para tal, o reservatório foi dividido em quatro porções com base em informações anteriores a este estudo que mostravam um gradiente de trofia variando de eutrófico próximo de seus tributários a oligotrófico próximo à barragem. Assim, em cada porção foram escolhidos três pontos, totalizando 12 pontos de coleta amostrados em duas épocas do ano. Algumas variáveis como clorofila-a, fósforo total, materiais em suspensão e condutividade elétrica diminuíram em direção a barragem, outras como a transparência e profundidade aumentaram, o que indica também uma diminuição da eutrofização na porção próxima à barragem onde há captação de água para abastecimento, embora os valores do IET tenham indicado em geral um ambiente eutrófico, chegando a ser mesotrófico próximo à barragem. O zooplâncton apresentou maior riqueza de espécies e abundância total na parte alta do reservatório, diminuindo em direção à barragem. Os Rotifera foram os organismos com maior número de espécies, foram quase sempre mais abundantes e seguiram o padrão geral de heterogeneidade na abundância, já os Copepoda, formados apenas pela ordem Cyclopoida, apresentaram padrões diferentes do geral em ambos os períodos. Os Cladocera foram pouco presentes. Assim, a presença de certas espécies ou grupos do zooplâncton apontaram para um ambiente eutrofizado e instável, com a presença de espécies oportunistas. Sendo assim, a comunidade zooplanctônica acompanhou o gradiente de condições ambientais do reservatório com alterações em sua abundância e composição, mostrando ser um bom indicador de mudanças ambientais. Esse gradiente ao longo do eixo principal é comum em reservatórios por ser um sistema de transição, mas no reservatório Rio Grande também pode haver influência antrópica vinda do despejo de cargas poluidoras ou do manejo, com a aplicação de algicidas para tratamento da água. Por meio de ACPs, as variáveis limnológicas e as características do zooplâncton dividiram o reservatório em três compartimentos dentro desse gradiente encontrado; tais compartimentos variam suas dimensões constantemente com o passar do tempo, mostrando assim um ambiente dinâmico, mas com compartimentos bem definidos. / The present study was done in the Rio Grande reservoir (Billings Complex), São Paulo state, with the aim to analyze the spatial heterogeneity in the main axis and also to know if the zooplankton community varies with the gradient of environmental conditions found in the reservoir. To this end , the reservoir was divided in four portions based on previous information to this study that showed a trophic gradient varying from eutrophic near of its tributaries to oligotrophic near of the dam. Thus, in each portion it was chosen three points, totalizing 12 points sampled in two seasons. Some variables as chlorophyll-a, total phosphorus, suspension materials and electric conductivity decreased towards the dam, others such as the transparency and depth increased, what indicates a decrease of the eutrophication in the dams portion where there is a captation point for water supply, although the IET values have indicated, in general, a eutrophic environment being mesotrophic near of the dam. The zooplankton presented large richness of species and total abundance in the upstream zone of the reservoir decreasing towards the dam. The Rotifera were the organisms with the largest number of species, being almost always the most abundant group and followed the general pattern of the heterogeneity in the abundance. On the other hand, the Copepoda, only formed by the order Cyclopoida, presented different patterns of heterogeneity in both periods. The Cladocera were rarely present. Therefore, the presence of some species or groups of zooplankton pointed to a eutrophic and instable environment, with the presence of opportunist species. Hence, the zooplankton community accompanied the gradient of environmental conditions of the reservoir with abundance and composition changes showing to be a good indicator of the environmental changes. This gradient along the main axis is common in reservoirs inasmuch as it is a transitional system, but in the Rio Grande reservoir can also have anthropic influence due to the discharge of pollutant loads or management applying algicides to water treatment. Through PCAs, the limnological variables and zooplankton characteristics divided the reservoir in three compartments inside this gradient found; such compartments vary their sizes constantly during the time showing thus a dynamic environment, but still with well-defined compartments.

O presente estudo foi realizado no reservatório Rio Grande (Complexo Billings), estado de São Paulo, com o objetivo de analisar a heterogeneidade espacial ao longo de seu eixo principal e com isso também saber se a comunidade zooplanctônica varia junto com o gradiente de condições ambientais encontrado no reservatório. Para tal, o reservatório foi dividido em quatro porções com base em informações anteriores a este estudo que mostravam um gradiente de trofia variando de eutrófico próximo de seus tributários a oligotrófico próximo à barragem. Assim, em cada porção foram escolhidos três pontos, totalizando 12 pontos de coleta amostrados em duas épocas do ano. Algumas variáveis como clorofila-a, fósforo total, materiais em suspensão e condutividade elétrica diminuíram em direção a barragem, outras como a transparência e profundidade aumentaram, o que indica também uma diminuição da eutrofização na porção próxima à barragem onde há captação de água para abastecimento, embora os valores do IET tenham indicado em geral um ambiente eutrófico, chegando a ser mesotrófico próximo à barragem. O zooplâncton apresentou maior riqueza de espécies e abundância total na parte alta do reservatório, diminuindo em direção à barragem. Os Rotifera foram os organismos com maior número de espécies, foram quase sempre mais abundantes e seguiram o padrão geral de heterogeneidade na abundância, já os Copepoda, formados apenas pela ordem Cyclopoida, apresentaram padrões diferentes do geral em ambos os períodos. Os Cladocera foram pouco presentes. Assim, a presença de certas espécies ou grupos do zooplâncton apontaram para um ambiente eutrofizado e instável, com a presença de espécies oportunistas. Sendo assim, a comunidade zooplanctônica acompanhou o gradiente de condições ambientais do reservatório com alterações em sua abundância e composição, mostrando ser um bom indicador de mudanças ambientais. Esse gradiente ao longo do eixo principal é comum em reservatórios por ser um sistema de transição, mas no reservatório Rio Grande também pode haver influência antrópica vinda do despejo de cargas poluidoras ou do manejo, com a aplicação de algicidas para tratamento da água. Por meio de ACPs, as variáveis limnológicas e as características do zooplâncton dividiram o reservatório em três compartimentos dentro desse gradiente encontrado; tais compartimentos variam suas dimensões constantemente com o passar do tempo, mostrando assim um ambiente dinâmico, mas com compartimentos bem definidos. / The present study was done in the Rio Grande reservoir (Billings Complex), São Paulo state, with the aim to analyze the spatial heterogeneity in the main axis and also to know if the zooplankton community varies with the gradient of environmental conditions found in the reservoir. To this end , the reservoir was divided in four portions based on previous information to this study that showed a trophic gradient varying from eutrophic near of its tributaries to oligotrophic near of the dam. Thus, in each portion it was chosen three points, totalizing 12 points sampled in two seasons. Some variables as chlorophyll-a, total phosphorus, suspension materials and electric conductivity decreased towards the dam, others such as the transparency and depth increased, what indicates a decrease of the eutrophication in the dams portion where there is a captation point for water supply, although the IET values have indicated, in general, a eutrophic environment being mesotrophic near of the dam. The zooplankton presented large richness of species and total abundance in the upstream zone of the reservoir decreasing towards the dam. The Rotifera were the organisms with the largest number of species, being almost always the most abundant group and followed the general pattern of the heterogeneity in the abundance. On the other hand, the Copepoda, only formed by the order Cyclopoida, presented different patterns of heterogeneity in both periods. The Cladocera were rarely present. Therefore, the presence of some species or groups of zooplankton pointed to a eutrophic and instable environment, with the presence of opportunist species. Hence, the zooplankton community accompanied the gradient of environmental conditions of the reservoir with abundance and composition changes showing to be a good indicator of the environmental changes. This gradient along the main axis is common in reservoirs inasmuch as it is a transitional system, but in the Rio Grande reservoir can also have anthropic influence due to the discharge of pollutant loads or management applying algicides to water treatment. Through PCAs, the limnological variables and zooplankton characteristics divided the reservoir in three compartments inside this gradient found; such compartments vary their sizes constantly during the time showing thus a dynamic environment, but still with well-defined compartments.