With more states revealed, and more reliable rates inferred, mechanistic schemes for ion channels have increased in complexity over the history of single-channel studies. At the forefront of single-channel studies we are faced with a temporal barrier delimiting the briefest event which can be detected in single-channel data. Despite improvements in single-channel data analysis, the use of existing methods remains sub-optimal. As existing methods in single-channel data analysis are unquantified, optimal conditions for data analysis are unknown. Here we present a modular single-channel data simulator with two engines; a Hidden Markov Model (HMM) engine, and a sampling engine. The simulator is a tool which provides the necessary a priori information to be able to quantify and compare existing methods in order to optimize analytic conditions. We demonstrate the utility of our simulator by providing a preliminary comparison of two event detection methods in single-channel data analysis; Threshold Crossing and Segmental k-means with Hidden Markov Modelling (SKM-HMM).

The objective of this study was to characterize water quality and hydrologic properties of urban streams in the Richmond metropolitan area. Water quality data were analyzed for six urban sites and two non-urban sites. Geomorphological surveys and conservative tracer studies were performed at four urban sites and one non-urban site to describe intra- and inter- site variability in transient storage, channel geomorphology, and related hydrologic parameters. Urban sites showed elevated concentrations of nitrogen and more variable TSS concentrations relative to reference sites. Urban channels were deeply incised with unstable banks and low sinuosity. Little Westham Creek exhibited the greatest transient storage. This site was characterized by large, deep pools and therefore it is likely that transient storage was associated with surface water storage. Transient storage was low at all other sites, particularly for the study reach at Reedy Creek, which flowed through a concrete channel. Lowest transient storage was observed at this site in spring, though higher values were measured in summer corresponding to the presence of biofilms, A lower, more naturalized section of the concrete channel was found to have greater transient storage suggesting the possibility of passive restoration of concrete channels in urban environments. This study documents variability in the structure and function of urban streams. Restoration projects should work to improve impairments that are specific to each site at both the reach and watershed scale to maximize the efficacy of restoration.

Les concepteurs de moteurs aéronautiques sont constamment sujets à la demande d’augmentation de puissance de la part des constructeurs d’aéronefs. Pour satisfaire à cette exigence, la température de sortie de la chambre de combustion peut être augmentée pour améliorer le rendement et la puissance de sortie du moteur. Cette élévation de température peut toutefois dépasser le point de fusion du matériau et, pour éviter les pannes de moteur, l’intégrité des aubes de la turbine repose notamment sur des systèmes de refroidissement internes,prélevant de l'air froid du compresseur. La conception de ces systèmes revient donc à maximiser l’amélioration du transfert de chaleur tout en minimisant le débit d’air via les pertes de charge afin d’éviter des pénalités de puissance du moteur. Or ces écoulements en canaux internes sont encore largement incontrôlés et mal compris. Dans le but de mieux comprendre ces écoulements en rotation se développant spatialement, ce travail porte sur l’étude via simulations numériques d’un canal de refroidissement droit, perturbé, en rotation. La configuration consiste en un canal carré équipé de 8 perturbateurs placés avec un angle de 90 degrés par rapport à l’écoulement principal. Pour les cas étudiés, des mesures PIV temporelles ont été effectuées à l'Institut VanKarman (VKI). Les conditions adiabatiques et isothermes ont été étudiées pour évaluer l’impact dela température de la paroi sur l’écoulement, en particulier dans les configurations en rotation. Les canaux statiques ainsi qu’en rotation positive et négative sont comparés avec, dans chaque cas,une prédiction d’écoulement adiabatique ou isotherme. Dans ce travail, les résultats de simulations aux grandes échelles (SGE) montrent que le modèle CFD haute fidélité est capable de reproduire les différences induites par la flottabilité sur la topologie de l'écoulement dans la région proche. Le modèle parvient également à prévoir l'augmentation (la diminution) de la turbulence autour des perturbateurs en rotation déstabilisante (stabilisante). Enfin et grâce à la SGE spatiale et temporelle complète, le développement spatial et l’instationnarité des écoulements secondaires sont analysés pour mieux comprendre leur origine et leurs différences potentielles entre les cas. Cette étude montre que la topologie du flux thermique en parois est déterminée par la structure des écoulements secondaires alors que l’intensité du flux thermique aux parois est déterminée par le niveau de fluctuations de l’écoulement dans l’espace interperturbateur / Aeronautical engine designers are constantly subject to increasing power demands from aircraft manufacturers. To satisfy this requirement, combustor outlet temperature can be increased to improve efficiency and output energy of the engine. This rise in temperature however can surpass the material melting point and to avoid engine failure, turbine blades rely on internal cooling systems. Turbine blade cooling often uses internal channels, taking cold air from the compressor flow. Design of these systems therefore resumes to maximizing heat transfer enhancement while minimizing airflow rate to avoid engine power penalties. However, such flows are still largely uncontrolled and miss-understood. In an attempt to better understand such spatially developing rotating flows, the present study deals with a computational investigation on a straight, rotating rib roughened cooling channel. The configuration consists in a squared channel equipped with 8 ribs turbulators placed with an angle of 90 degrees with respect to the flow direction. For the studied cases, time resolved two-dimensional Particle Image Velocimetry (PIV) measurements have been performed at the Van Karman Institute (VKI). Adiabatic as well as isothermal conditions have been investigated to evaluate the impact of the wall temperature on the flow, especially in the rotating configurations. Static as well as both positive and negative rotating channels are compared with, in each case, either an adiabatic or an isothermal flow prediction. In this work, Large Eddy Simulation (LES) results show that the high fidelity CFD model is able to reproduce the differences induced by buoyancy on the flow topology in the near rib region and resulting from an adiabatic or an isothermal flow in rotation. The model manages also to predict the turbulence increase (decrease) around the rib in destabilizing (stabilizing) rotation of the ribbed channels. Finally and thanks to the full spatial and temporal description produced by LES, the spatial development and the unsteadiness of secondary flows are analyzed to better understand their origin and potential differences in all a cases. This study shows that the wall heat flux topology is driven by the secondary flows structure and the wall heat flux intensity is driven by the level of flow fluctuations in the ribbed region

Lithium has been used for more than 50 years as a primary therapy for bipolar affective disorder (BPD) and has proven highly effective for both acute and long-term phases of the disease. Unfortunately, the molecular and cellular mechanisms underlying the mood-stabilizing action of lithium for the treatment of BPD remains largely unknown. In an effort towards understanding the complexities of lithium's action in the nervous system, I have utilized the Drosophila neurological mutant Shudderer (Shu). Previous findings have suggested that the adult Shu phenotypes may be improved by providing a diet containing millimolar concentrations of lithium. Using well-established genetic techniques and behavioral paradigms I thoroughly characterized the Shu mutant phenotypes. I found that the mutant displays morphological and behavioral abnormalities indicative of dysregulated neuronal excitability that include: down-turning wings and indented dorsal thorax, defects in negative geotaxis, deficits in locomotion, abnormal sleep architecture and unusual patterns of leg-shaking behaviors upon recovery of ether anesthetics. Furthermore, I confirmed that lithium was able to significantly improve many aspects of Shu behaviors. Recombination-based mutation mapping in Shu revealed that the genetic lesion lies somewhere within the gene CG9907, which encodes the voltage-gated sodium channel á-subunit paralytic (para). Subsequent genetic experiments using para hypomorphic mutant alleles as well as a UAS-RNAi/GAL4 system showed that a reduction in sodium channel levels resulted in a drastic improvement of the mutant defects. Together, these data suggest that the lithium-responsive Shu mutant is likely a gain-of-function allele of para. Sequencing of the entire para coding region identified a missense mutation in a highly conserved region of the para coding sequence, in transmembrane segment S2 of homology domain III ((M1350I). To date, this is the first known discovery of a sodium channel mutant allele in Drosophila which causes hyperactivity. These data suggest that the Shu phenotypes are somehow caused by an increase in sodium channel activation. Lastly, I identified a number of genes likely to functionally interact with the Shu mutation. Of note, the Ca2+/calmodulin-activated Ser/Thr protein phosphatase alpha subunit gene CanA-14F is up-regulated in Shu and reduction of its activity suppresses the mutant phenotypes. Furthermore, a large percentage of genes encoding anti-microbial peptides (AMP) were also significantly up-regulated in Shu, possibly acting downstream of CanA-14F. A genetic deficiency screen looking for genes that alter the Shu phenotypes has identified that the gene Glutathione S-transferase S1 (Gsts1) suppresses the morphological and behavioral defects in the lithium-responsive mutant. Overall, these genes will help decipher how the gain-of-function sodium channel Shu mutation alters nervous system function. In addition, they will shed light on those mechanisms responsible for lithium's mood-stabilizing effects in the brain.

The pedigree of voltage-gated sodium channels spans the millennia from eukaryotic members that initiate the action potential firing in excitable tissues to primordial ancestors that act as enviro-protective complexes in bacterial extremophiles. Eukaryotic sodium channels (eNavs) are central to electrical signaling throughout the cardiovascular and nervous systems in animals and are established clinical targets for the therapeutic management of epilepsy, cardiac arrhythmia and painful syndromes as they are inhibited by local anesthetic compounds. Alternatively, bacterial voltage-gated sodium channels (bNavs) likely regulate the survival response against extreme pH conditions, electrophiles and hypo-osmotic shock and may represent a founder of the voltage-gated cation channel family. Despite apparent differences between eNav and bNav channel physiology, gating and gene structure, the discovery that bNavs are amenable to crystallographic study opens the door for the possibility of structure-guided rational design of the next generation of therapeutics that target eNavs. Here I summarize the gating behavior of a bacterial channel NaChBac and discuss mechanisms of local anesthetic inhibition in light of the growing number of bNav structures. Also, an interesting novel observation on cross-lineage modulation of NaChBac by eNav beta subunit is reported. This auxiliary subunit modulation is isoform specific and I show the discrete effects of each isoforms on NaChBac, with functional and biochemical analysis. I also report a novel mutation that alters inactivation kinetic drastically and a possible mechanism of NaChBac inactivation is discussed.

Neurological disorders, such as epilepsy, often result from inherited or newly acquired genetic mutations. However, individuals possessing the exact same disease-causing mutations can exhibit dramatic differences in the severity of their symptoms. These differences can be explained in part by environmental factors, such as the microbes in our gut, that play an important role in the manifestation of disease symptoms. Within the last decade, microbes living in the gut have established themselves as an environmental factor with profound effects on our health and well-being. Of special interest is the relationship between the gut microbiota and neurological disease. The goal of my thesis was to: 1) characterize the gut microbiota composition and 2) understand how the gut microbiota modulates seizure-like behavior using Shudderer, a fruit fly (Drosophila melanogaster) model of epilepsy. Shudderer flies possess a mutation in the voltage-gated sodium channel gene and display seizure-like behavioral abnormalities including spontaneous tremors and heat-induced seizures. We identified differences in the microbial composition of the gut microbiota between Shudderer and control (healthy) flies. We also found that by removing the gut microbiota we could improve seizure-like behavior of Shudderer flies as well as another Drosophila mutant harboring a similar genetic mutation. Together, these findings provide evidence that a bidirectional interaction exists between the gut microbiota and neurological function. Since the molecular and cellular mechanisms controlling basic biological processes are highly conserved between fruit flies and humans, these findings are expected to be applicable to mammalian systems, including humans, and may lead to the future development of novel therapeutics to treat epilepsy and other neurological disorders.

A promising feedstock for biofuels is microalgae. The most economical means of cultivating microalgae is via open raceway ponds. However, a large gap in economic feasibility exists between algae-based biofuels and traditional petroleum fuels. Recent research at Utah State University has focused on increasing biomass growth by implementing Delta Wings (DWs). DWs are placed facing the incoming flow, with a 40 degree angle of attack to create large vortices which travel downstream. The trailing vortices increase vertical mixing, which in turn increases algal growth. Past researchers at USU quantified vertical mixing with new metrics, optimized various raceway operating conditions, and established a positive correlation between the newly defined metrics and algal growth. Research was performed with the aid of a small-scale clear acrylic raceway. Both stereo particle image velocimetry (SPIV) and acoustic Doppler velocimetry (ADV) were used to estimate the recently defined mixing metric: the vertical mixing index (VMI). The focus of this work is to ascertain additional preferred operating conditions, in particular those unique to large scale raceways, with the aid of a computational fluid dynamics (CFD) model validated by experimental data. Three case studies are presented herein, which analyze the DW vertical position (VP), array spacing ratio (ASR), and the projected height to depth ratio (PHDR). The criteria for these studies are the VMI and power consumption. While it was previously assumed that vertically centering the DW centroid was optimal, the first case study revealed the ideal VP to be far lower. The lowest possible VP allows the trailing vortices to travel further downstream, resulting in increased vertical mixing. The second case study entails modeling complete arrays of DWs with various spacing. This model was the first to account for an increase in the number of allowable DWs with a decrease in array spacing. The ASR study revealed the ideal array spacing to be approximately half a DW, as opposed to the initial estimate of a full DW. The third case study confirmed the largest allowable DW to be superior.

The channel catfish, Ictalurus punctatus (Rafinesque), was first introduced into Utah Lake in the summer of 1911, and has since been stocked in the lake on numerous occasions. It has only been in the last few years that the channel catfish has become an important game fish in Utah. As the value of the channel catfish, as a game fish, increased, it has become increasingly important to the state to maintain this species for present and future generations. This study was initiated in 1958 and completed in 19 60, and was financed by the Utah State Department of Fish and Game. Data on certain phases of the channel catfish life history were investigated to provide information to aid in management of this species. The following phases were studied: age and rate of growth; age composition of the population; reproduction success; food habits; movements; and extent of the fishing pressure.

The purpose of this research study was to compile regional profiles of the consumers who intend to consume grass-fed beef in the U.S. and to create marketing strategies that would assist producers in marketing their product to consumers. The researcher sent an online survey to a panel of 484 consumers across the U.S. to learn about their perceptions of and intention to purchase grass-fed beef. Respondents had a weak, positive attitude toward purchasing grass-fed beef but had low knowledge of production practices. These consumers had a desire to eat healthier; however, they wanted meat that was priced right and had a desirable leanness. Consumers were divided based on U.S. regions (Northeast, Midwest, South, and West) to determine any differences in their knowledge, attitudes, subjective norm, importance of quality cues, meat and beef consumption habits, beef consumption habits, and meal preparations. The information gathered from respondents was used to create a marketing plan for each region of the U.S. Recommendations for future research included exploring how the processing of meat, environmental attitudes, and eating habits influence consumers’ intention to purchase grass-fed beef. Information about consumer willingness to pay would also be helpful for grass-fed beef producers who are creating a marketing plan.

Since the early 20th century, river channels of the Colorado River basin have narrowed, decreasing available riparian and aquatic habitat. Changes are considered to be the result of three major factors: wide-spread water development, increasing hydroclimate variability and the invasion of non-native tamarisk (Tamarix spp.), altering flow regime and sediment supply. Different studies have reached different conclusions about the relative roles of flow regime, sediment supply and tamarisk in causing narrowing. I investigated channel change in the lower Green River within Canyonlands National Park to describe channel changes in the 20th century and understand the roles of shifting flow regime and changing vegetation communities on 20th century channel narrowing. The lower Green River within Canyonlands National Park has narrowed substantially since the late 1800s, resulting in narrower channel. Changes to flood magnitude, rate and timing since 1900, driven by increased water storage and diversion in the Green River basin and declines in annual precipitation, was responsible for inset floodplain formation documented in this study. I used multiple datasets to reconstruct the history of channel narrowing in the lower Green River and identify processes of floodplain formation. In the field, analyses of a floodplain trench were described to identify rate, timing and magnitude of floodplain formation. Channel and floodplain surveys were conducted to determine possible changes in bed elevation. Additionally, I analyzed existing aerial imagery, hydrologic data, and sediment transport data. I applied these techniques to determine how floodplain formation occurred at multiple spatial and temporal scales. My investigation shows that the floodplains of the contemporary lower Green River began forming in the late 1930s and continued to form in the 20th century by inset floodplain formation. During this time period, peak flow and total runoff declined due to climatic changes and human water development. Since the mid-1980s, inset floodplains continued to develop along the lower Green River since the mid-1980s, narrowing the river by an additional 9.4%. Analysis of aerial imagery shows that changes to the floodplain identified in the trench occurred throughout the 61 km of river I studied. Non-native tamarisk (Tamarix spp.) did not drive channel narrowing, though dense stands stabilized banks and likely promoted sediment deposition. Inset floodplain formation reflects changes to flooding resulting from water development and climate change. My findings have implications for the long-term management of the lower Green River and endangered endemic native fishes –particularly the Colorado pikeminnow (Ptychocheilus lucius) and the razorback sucker (Xyrauchen texanus). Collaboration with upstream stakeholders and managers is necessary to preserve elements of the flow regime that preserve channel width and limit channel narrowing.