Critical bed shear stress and threshold of motion of maërl biogenic gravel

Critical bed shear stress for incipient motion has been determined for biogenic free-living coralline algae known as maërl. Maërl from three different sedimentary environments (beach, intertidal, and open marine) in Galway Bay, west of Ireland have been analysed in a rotating annular flume and linear flume. Velocity profile measurements of the benthic boundary layer, using an Acoustic Doppler Velocimeter, have been obtained in four different velocity experiments. The bed shear stress has been determined using three methods: Law of the Wall, Turbulent Kinetic Energy and Reynolds Stress. The critical Shields parameter has been estimated as a non-dimensional mobility number and the results have been compared with the Shields curve for natural sand. Maërl particles fall below this curve because its greater angularity allows grains to be mobilised easier than hydraulically equivalent particles. From previous work, the relationship between grain shape and the settling velocity of maërl suggests that the roughness is greatest for intertidal maërl particles. During critical shear stress determinations, beds of such rough particles exhibited the greatest critical shear stress probably because the particle thalli interlocked and resisted entrainment. The Turbulent Kinetic Energy methodology gives the most consistent results, agreeing with previous comparative studies. Rarely-documented maërl megaripples were observed in the rotating annular flume and are hypothesised to form at velocities ~10 cm s-1 higher than the critical threshold velocity, where tidal currents, oscillatory flow or combined-wave current interaction results in the preferential transport of maërl. A determination of the critical bed shear stress of maërl allows its mobility and rate of erosion and deposition to be evaluated spatially in subsequent applications to biological conservation management.

Studies of the role of nf-κb in controlling osteoclast differentiation and bone loss

Increased osteoclast (OC) bone resorption and/or decreased osteoblast (OB) bone formation contribute to bone loss in osteoporosis and rheumatoid arthritis (RA). Findings of the basic and translational research presented in this thesis demonstrate a number of mechanisms by which cytokine-induced NF-κB activation controls bone resorption and formation: 1) Tumour necrosis factor-α (TNF) expands pool of OC precursors (OCPs) by promoting their proliferation through stimulation of the expression of macrophage colony stimulating factor (M-CSF) receptor, c-Fms, and switching M-CSF-induced resident (M2) to inflammatory (M1) macrophages with enhanced OC forming potential and increased production of inflammatory factors through induction of NF-κB RelB; 2) Similar to RANKL, TNF sequentially activates transcriptional factors NF-κB p50 and p52 followed by c-Fos and then NFATc1 to induce OC differentiation. However, TNF alone induces very limited OC differentiation. In contrast, it pre-activates OCPs to express cFos which cooperates with interleukin-1 (IL-1) produced by these OCPs in an autocrine mechanism by interacting with bone matrix to mediate the OC terminal differentiation and bone resorption from these pre-activated OCPs. 3) TNF-induced OC formation is independent of RANKL but it also induces NF-κB2 p100 to limit OC formation and bone resorption, and thus p100 deletion accelerates joint destruction and systemic bone loss in TNF-induced RA; 4) TNF receptor associated factor-3 (TRAF3) limits OC differentiation by negatively regulating non-canonical NF-κB activation and RANKL induces TRAF3 ubiquitination and lysosomal degradation to promote OC differentiation. Importantly, a lysosomal inhibitor that inhibits TRAF3 degradation prevents ovariectomy-induced bone loss; 5) RelB and Notch NICD bind RUNX2 to inhibit OB differentiation and RelB:p52 dimer association with NICD inhibit OB differentiation by enhancing the binding of RBPjκ to Hes1. These findings suggest that non-canonical NF- κB signaling could be targets to develop new therapies for RA or osteoporosis. For example 1) Agents that degrade TNF-induced RelB could block M1 macrophage differentiation to inhibit inflammation and joint destruction for the therapy of RA; 2)Agents that prevent p100 processing or TRAF3 degradation could inhibit bone resorption and also stimulate bone formation simultaneously for the therapy of osteoporosis.

Thirty minutes of handgrip exercise enhances brachial artery flow-mediated dilation in response to two different shear stress profiles.

The walls of blood vessels are lined with a single-cell layer of endothelial cells. As blood flows through the arteries, a frictional force known as shear stress is sensed by mechanosensitive structures on the endothelium. Short and long term changes in shear stress can have a significant influence on the regulation of endothelial function. Acutely, shear stress triggers a pathway that culminates in the release of vasodilatory molecules from the endothelium and subsequent vasodilation of the artery. This endothelial response is known as flow mediated dilation (FMD). FMD is used as an index of endothelial function and is commonly assessed using reactive hyperemia (RH)-FMD, a method which elicits a large, short lived increase in shear stress following the release of a brief (5 min) forearm occlusion. A recent study found that a short term exposure (30 min) to a sustained elevation in shear stress potentiates subsequent RH-FMD. FMD can also result from a more prolonged, sustained increase in shear stress elicited by handgrip exercise (HGEX-FMD). There is evidence to suggest that interventions and conditions impact FMD resulting from sustained and transient shear stress stimuli differently, indicating that HGEX-FMD and RH-FMD provide different information about endothelial function. It is unknown whether HGEX-FMD is improved by short term exposure to shear stress. Understanding how exercise induced FMD is regulated is important because it contributes to blood flow responses during exercise. The study purpose was therefore to assess the impact of a handgrip exercise (intervention) induced sustained elevation in shear stress on subsequent brachial artery (BA) HGEX-FMD. Twenty healthy male participants (22±3yrs) preformed a 30-minute HGEX intervention on two experimental days. BA-FMD was assessed using either an RH or HGEX shear stress stimulus at 3 time points: pre-intervention, 10 min post and 60 min post. FMD and shear stress magnitude were determined via ultrasound. Both HGEX and RH-FMD increased significantly from pre-intervention to 10 min-post (p<0.01). These findings indicate that FMD stimulated by exercise induced increases in shear stress is potentiated by short term shear stress exposure. These findings advance our understanding regarding the regulation of endothelial function by shear stress.

Crack propagation in non-homogenous materials: Evaluation of mixed-mode SIFs, T-stress and kinking angle using a variant EFG method

A new variant of the Element-Free Galerkin (EFG) method, that combines the diffraction method, to characterize the crack tip solution, and the Heaviside enrichment function for representing discontinuity due to a crack, has been used to model crack propagation through non-homogenous materials. In the case of interface crack propagation, the kink angle is predicted by applying the maximum tangential principal stress (MTPS) criterion in conjunction with consideration of the energy release rate (ERR). The MTPS criterion is applied to the crack tip stress field described by both the stress intensity factor (SIF) and the T-stress, which are extracted using the interaction integral method. The proposed EFG method has been developed and applied for 2D case studies involving a crack in an orthotropic material, crack along an interface and a crack terminating at a bi-material interface, under mechanical or thermal loading; this is done to demonstrate the advantages and efficiency of the proposed methodology. The computed SIFs, T-stress and the predicted interface crack kink angles are compared with existing results in the literature and are found to be in good agreement. An example of crack growth through a particle-reinforced composite materials, which may involve crack meandering around the particle, is reported.

Stress på akutmottagningen ur ett sjuksköterskeperspektiv : En litteraturstudie

Sjuksköterskor som arbetar på akutmottagningar utsätts regelbundet för stress. Det medför psykiska och fysiska besvär för sjuksköterskor och försämrad omvårdnad för patienten. Studien avser att utifrån vetenskaplig litteratur sammanställa de faktorer som leder till stress för sjuksköterskor som arbetar på akutmottagningar och hur vården påverkas av stressade sjuksköteskor. Syfte Syftet med litteraturstudien var att beskriva vilka faktorer på akutmottagningen som upplevdes bidra till stress för sjuksköterskor som arbetar på en akutmottagning och hur stressen påverkar sjuksköterskors möjligheter att erbjuda en god vård för patienter på akutmottagningen. Metod Studien har genomförts som en litteraturstudie. I studien användes 15 artiklar som bestod av både kvalitativ och kvantitativ ansats. Materialet hämtades i databaserna CINAHL och PubMed. Resultat Resultatet visar att det finns flera olika faktorer som bidrar till stress för sjuksköterskor på akutmottagningen. Stressande faktorer visade sig utifrån studierna i resultatet vara; hög arbetsbelastning och låg bemanning, avsaknad av tid för reflektion för sjuksköterskan, att vårda barn i stressade situationer, hot och våld på akutmottagningen, kommunikation samt smärta och lidande. Hur vården påverkas av sjuksköterskors stress på akutmottagningen var utifrån studierna att patientsäkerheten blev försämrad och att vårdrelationen påverkades. Slutsats Författarna drar slutsatsen att stress påverkar sjuksköteskors arbetsuppgifter på akutmottagningen. Patienters möjlighet till patientsäker och god vård på akutmottagningen påverkas negativt av stressade sjuksköterskor. För att komma till rätta med sjuksköterskebristen på akutmottagningar så är det av betydelse för sjukhusledningen att arbeta preventivt mot stressade sjuksköterskor.

Validação da Versão Portuguesa da Center for Epidemiologic Studies Depression Scale for Children (CES-DC)

A Depressão na infância e adolescência, tal como na população adulta, é uma das perturbações mentais mais comuns. Uma vez que o seu aparecimento nestas faixas etárias conduz a graves consequências na idade adulta, é fundamental identificar os sintomas depressivos precocemente. Desta forma, os instrumentos de autorrelato têm um papel fundamental, uma vez que permitem com facilidade, de forma fidedigna e válida, ter acesso a formas de pensar, sentir e agir dos sujeitos. O objetivo do presente trabalho consistiu na tradução, adaptação e estudo da Center for Epidemiological Studies Depression Scale for Children (CES-DC) (Weissman, Orvash & Padian, 1980) para os adolescentes portugueses. A amostra é constituída por 417 adolescentes, com idades compreendidas entre os 12 e os 18 anos a frequentar o 3º ciclo do ensino básio e ensino secundário. Para o estudo da validade convergente e divergente da CES-DC, foram utilizados a Depression Anxiety Stress Scales (DASS 21) (Lovibond & Lovibond, 1995), o Children's Depresssion Inventory (CID) (Marujo, 1994) e a Students' Life Satisfaction Scale (SLSS) (Marques, Pais-Ribeiro & Lopez, 2007) que avaliam, respetivamente, os estados emocionais negativos (depressão, ansiedade e stress), a sintomatologia depressiva e a satisfação global com a vida. Os resultados obtidos mostram que a escala possui uma boa consistência interna, uma estabilidade temporal adequada, assim como uma boa validade. Sugerem, ainda, tratar-se de uma escala tridimensional: fator humor, fator interpessoal e fator felicidade. Estes dados permitem o avanço da Psicologia, no que diz respeito à avaliação e prática clínica com adolescentes. A utilidade do questionário deve ser verificada noutras faixas etárias, principalmente, nas de menos de 12 anos de idade, e também numa amostra clínica. Não obstante as limitações apontadas, os resultados sugerem que a CES-DC é um questionário útil na avaliação de sintomas depressivos nos adolescentes. / Depression in children and adolescents, as well as in adults, is one of the most common mental disorders. Since its appearance in these age groups leads to serious consequences in adulthood, it is critical to identify depressive symptoms in early stages. Therefore, self-report instruments play a key role in this contexto since they allow to easily, reliably and validly have access to ways the subject thinks, feels and acts. The aim of this study was to translate, adapt and study the Center for Epidemiological Studies Depression Scale for Children (CES-DC) (Weissman, Orvash & Padian, 1980) for portuguese adolescents. The sample consists of 417 adolescents, aged between 12 and 18 years old, attending the 3rd cycle of basic education and secondary education schools. To study the convergent and divergent validity of the CES-DC, the Depression Anxiety Stress Scales (DASS 21) (Lovibond & Lovibond, 1995) was used, along with the Children's depression Inventory (CDI) (Sailor, 1994) and the Students' Life Satisfaction Scale (SLSS) (Marques, Pais-Ribeiro & Lopez, 2007) that evaluate, respectively, the negative emotional states (depression, anxiety and stress), depressive symptoms and overall satisfaction with life. The results show that the evaluated scale presents a good internal consistency, an adequate temporal stability as well as good validity. They also suggest that this is a three-dimensional scale: humor factor, interpersonal factor and happiness factor. These data allow for the progress of psychology, regarding the assessment and clinical practice among adolescents. The usefulness of the questionnaire should be verified in other age groups, especially in children with less than 12 years old and in a clinical sample. Despite these limitations, the results suggest that CES-DC is useful in the assessment questionnaire of depressive symptoms in adolescents.

Behavior of Granular Materials Under Triaxial Compression with Pulsating Deviator Stress, HR-131, Special Report

Behavior of granular material subjected to repeated load triaxial compression tests is characterized by a model based on rate process theory. Starting with the Arrhenius equation from chemical kinetics, the relationship of temperature, shear stress, normal stress and volume change to deformation rate is developed. The proposed model equation includes these factors as a product of exponential terms. An empirical relationship between deformation and the cube root of the number of stress applications at constant temperature and normal stress is combined with the rate equation to yield an integrated relationship of temperature, deviator stress, confining pressure and number of deviator stress applications to axial strain. The experimental program consists of 64 repeated load triaxial compression tests, 52 on untreated crushed stone and 12 on the same crushed stone material treated with 4% asphalt cement. Results were analyzed with multiple linear regression techniques and show substantial agreement with the model equations. Experimental results fit the rate equation somewhat better than the integrated equation when all variable quantities are considered. The coefficient of shear temperature gives the activation enthalpy, which is about 4.7 kilocalories/mole for untreated material and 39.4 kilocalories/mole for asphalt-treated material. This indicates the activation enthalpy is about that of the pore fluid. The proportionality coefficient of deviator stress may be used to measure flow unit volume. The volumes thus determined for untreated and asphalt-treated material are not substantially different. This may be coincidental since comparison with flow unit volumes reported by others indicates flow unit volume is related to gradation of untreated material. The flow unit volume of asphalt-treated material may relate to asphalt cement content. The proposed model equations provide a more rational basis for further studies of factors affecting deformation of granular materials under stress similar to that in pavement subjected to transient traffic loads.

Relação entre Vulnerabilidade ao Stress e Estratégias de Coping: estudo de caso numa empresa de venda a retalho da Região Centro do País

As situações indutoras de stress são uma constante imutável no dia-a-dia do ser humano e quando esta perturbação não é gerida de forma adequada, acarreta graves prejuízos na saúde dos indivíduos refletindo-se em diversas áreas das suas vidas nomeadamente no trabalho. O presente estudo tem como finalidade identificar a relação entre o stress e as estratégias de coping e perceber se os indivíduos com vulnerabilidade ao stress diferem dos indivíduos sem stress no que concerne às estratégias de coping utilizadas. A vulnerabilidade ao stress foi medida pela escala 23QVS, enquanto as estratégias de coping foram avaliadas pelo Inventário de Resolução de Problemas (IRP), tendo sido, ainda, utilizado um questionário sociodemográfico. A amostra foi composta por 62 trabalhadores de uma empresa de venda a retalho com idades compreendidas entre os 20 e os 44 anos (M=32,02 DP=5,770). Os resultados obtidos revelaram que a vulnerabilidade ao stress se correlaciona de forma negativa e altamente significativa com as estratégias de coping e que indivíduos com e sem vulnerabilidade ao stress não diferem quanto ao uso destas estratégias. / The stress-induction situations are a constant unchanging in human being life, and if this disturbance is not managed adequately can be harmful to the health of individuals and reflected in many areas of their lives including their work. The present study aims to analyze the relationship between stress and coping strategies, and understand if individuals with stress vulnerability differs from individuals without stress in respect to the use of coping strategies. Stress vulnerability was measured by the 23QVS scale and coping strategies by the Inventário de Resolução de Problemas – IRP (Inventory of Problem Solving), and we also used a sociodemographic questionnaire. The sample consisted of 62 workers of a retailing company with ages between 20 and 40 years old (M = 32,02; DP = 5,770). Our research studies reveal that stress vulnerability correlates negatively and highly with coping strategies, and individuals with and without stress vulnerability not differ in the use of these strategies.

Preschoolers’ Executive Control and Diurnal Cortisol as Mediators of the Relations of Prenatal Stress to Child Adjustment

Thesis (Ph.D.)--University of Washington, 2016-08

Stress ocupacional e estratégias de coping em fisioterapeutas e terapeutas ocupacionais

Mestrado em Segurança e Higiene no Trabalho

Transcriptome-Wide Mapping of Pea Seed Ageing Reveals a Pivotal Role for Genes Related to Oxidative Stress and Programmed Cell Death

Understanding of seed ageing, which leads to viability loss during storage, is vital for ex situ plant conservation and agriculture alike. Yet the potential for regulation at the transcriptional level has not been fully investigated. Here, we studied the relationship between seed viability, gene expression and glutathione redox status during artificial ageing of pea (Pisum sativum) seeds. Transcriptome-wide analysis using microarrays was complemented with qRT-PCR analysis of selected genes and a multilevel analysis of the antioxidant glutathione. Partial degradation of DNA and RNA occurred from the onset of artificial ageing at 60% RH and 50 degrees C, and transcriptome profiling showed that the expression of genes associated with programmed cell death, oxidative stress and protein ubiquitination were altered prior to any sign of viability loss. After 25 days of ageing viability started to decline in conjunction with progressively oxidising cellular conditions, as indicated by a shift of the glutathione redox state towards more positive values (>-190 mV). The unravelling of the molecular basis of seed ageing revealed that transcriptome reprogramming is a key component of the ageing process, which influences the progression of programmed cell death and decline in antioxidant capacity that ultimately lead to seed viability loss.

Investigation of properties affecting controlled release of macromolecules from PLGA microspheres

Poly(lactide-co-glycolide), or PLGA, microspheres offer a widely-studied biodegradable option for controlled release of therapeutics. An array of fabrication methodologies have been developed to produce these microspheres with the capacity to encapsulate therapeutics of various types; and produce microspheres of a wide range of sizes for different methods of delivery. The encapsulation, stability, and release profiles of therapeutic release based on physical and thermodynamic properties has also been studied and modeled to an extent. Much research has been devoted to tailoring formulations for improved therapeutic encapsulation and stability as well as selective release profiles. Despite the breadth of available research on PLGA microspheres, further analysis of fundamental principles regarding the microsphere degradation, formation, and therapeutic encapsulation is necessary. This work aims to examine additional fundamental principles related to PLGA microsphere formation and degradation from solvent-evaporation of preformed polymer. In particular, mapping the development of the acidic microenvironment inside the microsphere during degradation and erosion is discussed. Also, the effect of macromolecule size and conformation is examined with respect to microsphere diameter and PLGA molecular weight. Lastly, the effects of mechanical shearing and protein exposure to aqueous media during microsphere formation are examined. In an effort to better understand the acidic microenvironment development across the microsphere diameter, pH sensitive dye conjugated to protein that undergoes conformational change at different acidic pH values was encapsulated in PLGA microspheres of diameters ranging from 40 µm to 80 µm, and used in conjunction with fluorescence resonance energy transfer to measure the radial pH change in the microspheres. Qualitative analysis of confocal micrographs was used to correlate fluorescence intensity with pH value, and obtain the radial pH across the center of the microsphere. Therapeutic encapsulation and release from polymeric microspheres is governed by an interconnected variety of factors, including the therapeutic itself. The globular protein bovine serum albumin, and the elongated and significantly smaller enzyme, lysozyme, were encapsulated in PLGA microspheres ranging from 40 µm to 80 µm in diameter. The initial surface morphology upon microsphere formation, release profiles, and microsphere erosion characteristics were explored in an effort to better understand the effect of protein size, conformation, and known PLGA interaction on the formation and degradation of PLGA microspheres and macromolecule release, with respect to PLGA molecular weight and microsphere diameter. In addition to PLGA behavior and macromolecule behavior, the effect of mechanical stresses during fabrication was examined. Two similar solvent extraction techniques were compared for the fabrication of albumin loaded microspheres. In particular, the homogeneity of the microspheres as well as capacity to retain encapsulated albumin were compared. This preliminary study paves the way for a more rigorous treatment of the effect of mechanical forces present in popular microsphere fabrication. Several factors affecting protein release from PLGA microspheres are examined herein. The technique explored for spatial resolution of the pH inside the microsphere proved mildly effective in producing a reliable method of mapping microsphere pH changes. However, notable trends with respect to microsphere size, PLGA molecular weight, and microsphere porosity were observed. Proposed methods of improving spatial resolution of the acidic microenvironment are also provided. With respect to microsphere formation, studies showed that albumin and lysozyme had little effect on the internal homogeneity of the microsphere. Rather, ionic interactions with PLGA played a more significant role in the encapsulation and release of each macromolecule. Studies also showed that higher instances of mechanical stress led to less homogeneous microspheres with lower protein encapsulation. This suggests that perhaps instead of or in addition to modifying the microsphere formation formulation, the fabrication technique itself should be more closely considered in achieving homogeneous microspheres with desired loading.

Large eddy simulation of shock boundary layer interaction control using micro-vortex generators

The performance of supersonic engine inlets and external aerodynamic surfaces can be critically affected by shock wave / boundary layer interactions (SBLIs), whose severe adverse pressure gradients can cause boundary layer separation. Currently such problems are avoided primarily through the use of boundary layer bleed/suction which can be a source of significant performance degradation. This study investigates a novel type of flow control device called micro-vortex generators (µVGs) which may offer similar control benefits without the bleed penalties. µVGs have the ability to alter the near-wall structure of compressible turbulent boundary layers to provide increased mixing of high speed fluid which improves the boundary layer health when subjected to flow disturbance. Due to their small size,µVGs are embedded in the boundary layer which provide reduced drag compared to the traditional vortex generators while they are cost-effective, physically robust and do not require a power source. To examine the potential of µVGs, a detailed experimental and computational study of micro-ramps in a supersonic boundary layer at Mach 3 subjected to an oblique shock was undertaken. The experiments employed a flat plate boundary layer with an impinging oblique shock with downstream total pressure measurements. The moderate Reynolds number of 3,800 based on displacement thickness allowed the computations to use Large Eddy Simulations without the subgrid stress model (LES-nSGS). The LES predictions indicated that the shock changes the structure of the turbulent eddies and the primary vortices generated from the micro-ramp. Furthermore, they generally reproduced the experimentally obtained mean velocity profiles, unlike similarly-resolved RANS computations. The experiments and the LES results indicate that the micro-ramps, whose height is h≈0.5δ, can significantly reduce boundary layer thickness and improve downstream boundary layer health as measured by the incompressible shape factor, H. Regions directly behind the ramp centerline tended to have increased boundary layer thickness indicating the significant three-dimensionality of the flow field. Compared to baseline sizes, smaller micro-ramps yielded improved total pressure recovery. Moving the smaller ramps closer to the shock interaction also reduced the displacement thickness and the separated area. This effect is attributed to decreased wave drag and the closer proximity of the vortex pairs to the wall. In the second part of the study, various types of µVGs are investigated including micro-ramps and micro-vanes. The results showed that vortices generated from µVGs can partially eliminate shock induced flow separation and can continue to entrain high momentum flux for boundary layer recovery downstream. The micro-ramps resulted in thinner downstream displacement thickness in comparison to the micro-vanes. However, the strength of the streamwise vorticity for the micro-ramps decayed faster due to dissipation especially after the shock interaction. In addition, the close spanwise distance between each vortex for the ramp geometry causes the vortex cores to move upwards from the wall due to induced upwash effects. Micro-vanes, on the other hand, yielded an increased spanwise spacing of the streamwise vortices at the point of formation. This resulted in streamwise vortices staying closer to the wall with less circulation decay, and the reduction in overall flow separation is attributed to these effects. Two hybrid concepts, named “thick-vane” and “split-ramp”, were also studied where the former is a vane with side supports and the latter has a uniform spacing along the centerline of the baseline ramp. These geometries behaved similar to the micro-vanes in terms of the streamwise vorticity and the ability to reduce flow separation, but are more physically robust than the thin vanes. Next, Mach number effect on flow past the micro-ramps (h~0.5δ) are examined in a supersonic boundary layer at M=1.4, 2.2 and 3.0, but with no shock waves present. The LES results indicate that micro-ramps have a greater impact at lower Mach number near the device but its influence decays faster than that for the higher Mach number cases. This may be due to the additional dissipation caused by the primary vortices with smaller effective diameter at the lower Mach number such that their coherency is easily lost causing the streamwise vorticity and the turbulent kinetic energy to decay quickly. The normal distance between the vortex core and the wall had similar growth indicating weak correlation with the Mach number; however, the spanwise distance between the two counter-rotating cores further increases with lower Mach number. Finally, various µVGs which include micro-ramp, split-ramp and a new hybrid concept “ramped-vane” are investigated under normal shock conditions at Mach number of 1.3. In particular, the ramped-vane was studied extensively by varying its size, interior spacing of the device and streamwise position respect to the shock. The ramped-vane provided increased vorticity compared to the micro-ramp and the split-ramp. This significantly reduced the separation length downstream of the device centerline where a larger ramped-vane with increased trailing edge gap yielded a fully attached flow at the centerline of separation region. The results from coarse-resolution LES studies show that the larger ramped-vane provided the most reductions in the turbulent kinetic energy and pressure fluctuation compared to other devices downstream of the shock. Additional benefits include negligible drag while the reductions in displacement thickness and shape factor were seen compared to other devices. Increased wall shear stress and pressure recovery were found with the larger ramped-vane in the baseline resolution LES studies which also gave decreased amplitudes of the pressure fluctuations downstream of the shock.

The role of intracellular calcium perturbations in muscle damage and dysfunction in mouse models of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the dystrophin gene. DMD is clinically characterized by severe, progressive and irreversible loss of muscle function, in which most patients lose the ability to walk by their early teens and die by their early 20’s. Impaired intracellular calcium (Ca2+) regulation and activation of cell degradation pathways have been proposed as key contributors to DMD disease progression. This dissertation research consists of three studies investigating the role of intracellular Ca2+ in skeletal muscle dysfunction in different mouse models of DMD. Study one evaluated the role of Ca2+-activated enzymes (proteases) that activate protein degradation in excitation-contraction (E-C) coupling failure following repeated contractions in mdx and dystrophin-utrophin null (mdx/utr-/-) mice. Single muscle fibers from mdx/utr-/- mice had greater E-C coupling failure following repeated contractions compared to fibers from mdx mice. Moreover, protease inhibition during these contractions was sufficient to attenuate E-C coupling failure in muscle fibers from both mdx and mdx/utr-/- mice. Study two evaluated the effects of overexpressing the Ca2+ buffering protein sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1 (SERCA1) in skeletal muscles from mdx and mdx/utr-/- mice. Overall, SERCA1 overexpression decreased muscle damage and protected the muscle from contraction-induced injury in mdx and mdx/utr-/- mice. In study three, the cellular mechanisms underlying the beneficial effects of SERCA1 overexpression in mdx and mdx/utr-/- mice were investigated. SERCA1 overexpression attenuated calpain activation in mdx muscle only, while partially attenuating the degradation of the calpain target desmin in mdx/utr-/- mice. Additionally, SERCA1 overexpression decreased the SERCA-inhibitory protein sarcolipin in mdx muscle but did not alter levels of Ca2+ regulatory proteins (parvalbumin and calsequestrin) in either dystrophic model. Lastly, SERCA1 overexpression blunted the increase in endoplasmic reticulum stress markers Grp78/BiP in mdx mice and C/EBP homologous protein (CHOP) in mdx and mdx/utr-/- mice. Overall, findings from the studies presented in this dissertation provide new insight into the role of Ca2+ in muscle dysfunction and damage in different dystrophic mouse models. Further, these findings support the overall strategy for improving intracellular Ca2+ control for the development of novel therapies for DMD.

The impacts of environmental and anthropogenic stressors on largemouth bass: an integration of field and laboratory studies

Several environmental stressors can impact the physiology and survival of fishes. Fish experience natural fluctuations in temperature and dissolved oxygen, but variations in these parameters due to anthropogenic sources are typically greater in magnitude and duration. Changes in temperature and oxygen of anthropogenic origins may therefore have larger negative impacts on fish than those occurring during natural events. Physiological parameters are sensitive indicators of the impacts of stressors by providing insight into the manner in which fish are disturbed by the stressor. Fish may display cumulative physiological responses to successive stressors, but the concept of synergy among multiple thermal stressors is poorly understood. Further, some fish species can be subjected to competitive angling events, which expose fish to an array of additional stressors that can increase mortality. The impacts of these events may change over seasons as fish display seasonal changes in behavior and physiology. Latitudinal origin may also affect the physiological response and mortality of fish exposed to common environmental stressors as individual populations are adapted to local environmental conditions. This thesis focuses on addressing these potential impacts on physiological parameters and mortality of largemouth bass (Micropterus salmoides) and provides implications for management and conservation. Largemouth bass were relatively robust to abrupt changes in temperature and oxygen, but were perturbed from physiological homeostasis during large (12°C) temperature shocks and low (< 4 mg O2/L) levels of dissolved oxygen. Cumulative physiological impacts of multiple cold shocks were only slightly greater than the disturbances sustained during a single cold shock, suggesting largemouth bass are able to tolerate successive thermal stressors. Largemouth bass exhibited seasonal changes in physiological parameters but the responses of fish to angling tournaments were relatively similar across seasons when compared with seasonal controls. Mortality was low during angling tournaments held during four seasons and no apparent seasonal trends were observed. Lastly, largemouth bass from two latitudinally separated populations exhibited differences in their physiological responses to acute cold stressors and overwinter mortality, characterized by greater mortality and physiological disturbances of southern fish than northern fish. Knowledge gained from this study can be used to make management and conservation decisions regarding a host of environmental factors and provides insight into the mechanisms by which fish species can persist over large latitudinal ranges.