A novel method of beam steering that utilizes a mass-produced Digital Micromirror Device (DMD) enables a large field of view and reliable single chip Light Detection and Ranging (LIDAR). Using a short pulsed laser, the micromirrors' rotation is frozen mid-transition which forms a programmable blazed grating which efficiently redistributes the light to a single diffraction order, among several. With a nanosecond 905nm laser and Si avalanche photo diode, measurement accuracy of < 1 cm for 3340 points/sec is demonstrated over a 1 m distance range and with a 48° full field of view.

No description available.

Duchenne muscular dystrophy (DMD) is the most devastating form of muscular dystrophy caused by a mutation in the dystrophin gene. Defects in the dystrophin gene in DMD, are homologous to that found in mdx mice, and result in profound muscle damage, inflammation and weakness in diaphragm and limb muscles. Dystrophin, a scaffolding protein located in the sarcolemmal cytoskeleton, helps cells to maintain their structural integrity and associates with critical cell signaling molecules that regulate cell growth and repair (e.g., nNOS). While the contributing mechanisms leading to DMD-induced degenerative muscle function and damage are multi-factorial, elevated oxidative stress has been proposed as a central mechanism. In contrast, antioxidants can attenuate muscle damage as well as improve contractile function in dystrophin-deficient muscles. However, it is unknown if oxidative stress is a causal factor in dystrophin-deficient diaphragm muscle pathology and specifically targeted antioxidant (e.g., EUK-134) treated early in the course of the disease (3-4 weeks) can modulate oxidative stress, functional damage and weakness in mdx diaphragm. Therefore, the purpose of this study was to determine the effects of catalase/superoxide dismutase mimetic EUK-134 on damage, inflammation, and contractile function of the diaphragm muscle in mdx mice. We hypothesized that (a) EUK-134 would attenuate muscle damage and oxidative stress in mdx diaphragm, (b) EUK-134 would reduce inflammatory cells and an important transcription factor including nuclear factor-kappaB (NF-kB) in mdx diaphragm and (c) EUK-134 would restore proteins that attach to dystrophin such as nNOS and cytoskeletal proteins back to sarcolemmal region and improve muscle contractility in mdx diaphragm. C57BL/10ScSn wild type and mdx mice were given EUK-134 (30mg/kg, i.p., injection) beginning at 20 days of age for 8 days. The mice were euthanized and the diaphragm muscle was harvested at 4 weeks of age, the time of peak inflammation, and analyzed to measure myofiber inflammation, NF-kB activation, cytoskeletal proteins and oxidative stress markers using Western immunoblotting, ELISA, immunofluoresence, and immunohistochemistry. We found that EUK-134 ameliorated muscle damage and oxidative stress in mdx diaphragm. EUK-134 protected against inflammation by decreasing NF-kB activation in the nucleosome fraction of mdx diaphragm. Further, EUK-134 partially rescued nNOS and k-1 syntrophin back to sarcolemmal membranes and recovered force generation even in acute application in vitro in mdx diaphragm. These results are the first to demonstrate a causal relationship between oxidative stress and pathology caused by dystrophin-deficient diaphragm muscle. Moreover, the data indicate that EUK-134 has a protective effect against muscle damage, inflammation, and contractility in mdx diaphragm. We believe that the results from our investigation will provide clinical significance, as we expect to elucidate mechanisms by which oxidative stress contribute to tissue damage and weakness in dystrophic diaphragm.

Numerical simulations of the Navier-Stokes equations are conducted to achieve a better understanding of the behavior of wakes generated by the wind turbines. The simulations are performed by combining the in-house developed code EllipSys3D with the actuator line technique. In step one of the project, a numerical study is carried out focusing on the instability onset of the trailing tip vortices shed from a 3-bladed wind turbine. To determine the critical frequency, the wake is perturbed using low-amplitude excitations located near the tip spirals. Two basic flow cases are studied; symmetric and asymmetric setups. In the symmetric setup a 120 degree flow symmetry condition is dictated due to the confining the polar computational grid to 120 degree or introducing identical excitations. In the asymmetric setup, uncorrelated excitations are imposed near the tip of the blades. Both setups are analyzed using proper orthogonal decomposition (POD) and dynamic mode decomposition (DMD). By analysing the dominant modes, it was found that in the symmetric setup the amplification of specific waves (traveling structures) traveling along the tip vortex spirals is responsible for triggering the instability leading to wake breakdown, while by breaking the symmetry almost all the modes are involved in the tip vortex destabilization. The presence of unstable modes in the wake is related to the mutual inductance (vortex pairing) instability where there is an out-of-phase displacement of successive helix turns. Furthermore, using the non-dimensional growth rate, it is found that the mutual inductance instability has a universal growth rate equal to Π/2. Using this relationship, and the assumption that breakdown to turbulence occurs once a vortex has experienced sufficient growth, an analytical relationship is provided for determining the length of the stable wake. This expression shows that the stable wake length is inversely proportional to thrust, tip speed ratio and the logarithmic of the turbulence intensity. In second study, large eddy simulations of the Navier-Stokes equations are also performed to investigate the wake interaction. Previous actuator line simulations on the single model wind turbine show that the accuracy of the results is directly related to the quality of the input airfoil characteristics. Therefore, a series of experiments on a 2D wing are conducted to obtain high quality airfoil characteristics for the NREL S826 at low Reynolds numbers. The new measured data are used to compute the rotor performance. The results show that the power performance as well as the wake development behind the rotor are well-captured. There are, however, some difficulties in prediction of the thrust coefficients. The continuation of this work considers the wake interaction investigations of two turbines inline (full-wake interaction) and two turbines with spanwise offset (half wake interaction). It is demonstrated that the numerical computations are able to predict the rotor performances as well as the flow field around the model rotors, and it can be a suitable tool for investigation of the wind turbine wakes. In the last study, an evaluation of the performance and near-wake structure of an analytical vortex model is presented. The vortex model is based on the constant circulation along the blades (Joukowsky rotor) and it is able to determine the geometry of the tip vortex filament in the rotor wake, allowing the free wake expansion and changing the local tip vortex pitch. Two different wind turbines have been simulated: a wind turbine with constant circulation along the blade and the other setup with a realistic circulation distribution, to compare the outcomes of the vortex model with real operative wind turbine conditions. The vortex model is compared with the actuator line approach and the presented comparisons show that the vortex method is able to approximate the single rotor performance and qualitatively describe the flow field around the wind turbine but with a negligible computational effort. This suggests that the vortex model can be a substitute of more computationally-demanding methods like actuator line technique to study the near-wake behavior. / <p>QC 20141010</p>

Duchenne muscular dystrophy (DMD) is an X-linked lethal condition associated with high morbidity and mortality. There is currently no cure for this disease. Several gene-based therapeutic approaches for treating DMD are currently under development but all are dependent on the knowledge of the causative dystrophin gene mutation. A combined mutation detection approach consisting of a quantitative PCR based analysis and DNA sequencing of the dystrophin gene resulted in a mutation etection rate of 96% in the New South Wales (NSW) DMD cohort. The proportion of exon duplication mutations was twice that generally reported for similar patient opulations. The clinical utility of the combined mutation protocol for DMD carrier testing clarified the carrier status of an additional one-third (33%) of female relatives compared to a conventional approach of biochemical, pedigree and linkage studies. The generally accepted view that two-thirds of mothers of isolated cases of DMD are themselves mutation carriers is challenged. Although this assumption is valid for duplication and DNA sequence mutations, it is not valid for deletion mutations in the NSW cohort. The incidence of new cases of DMD in the New South Wales population was educed from approximately 1 in 3594 live male births to 1 in 6022 live male births over a 25 year period, indicative of a significant effect of the combination of genetic counselling and improved methods of carrier detection over that period. In a study of a cohort of boys with DMD, who had both psychological and mutational analysis, it was shown that mutations affecting the shorter, C-terminal isoforms of dystrophin are associated with decreased mean intellectual function. A hypothesis is presented that mutations within the long 5' untranslated region of the Dp140 isoform are unlikely to significantly affect expression of this brain-expressed isoform. During the course of studying the NSW DMD cohort a family was identified which exhibited X-linkage and a unique clinical presentation involving episodes of severe and prolonged muscle weakness. A novel variant in the pyruvate dehydrogenase E1 alpha subunit (PDHA 1) was identified. The phenotypic effect of this variant is not proven but a body of evidence implicates this as likely to be causative of the observed phenotype.

No description available.

No description available.

The purpose of this study was to develop a SNaPshot® assay to simultaneously discriminate between the dystrophic and wild type (wt) alleles in mdx mice. The mdx mouse is an animal model for Duchenne muscular dystrophy (DMD), a severe and fatal muscle wasting disease. To evaluate possible treatments and to carry out genetic studies, it is essential to distinguish between mice that carry the mutant dystrophic or wt allele(s). The current Amplification-Resistant Mutation System (ARMS) assay used to genotype mdx mice is labor intensive and sometimes fails to yield typing results, which reduce its efficiency as a screening tool. An alternative assay based on single nucleotide polymorphism (SNP) extension technology (i.e., SNaPshot®) would be advantageous because its specificity and capability to be automated would reduce the labor involved and increase the fidelity of each assay. A SNaPshot® assay has been developed that provides a robust and potentially automatable assay that discriminates between the wt and dystrophic alleles. The assay has been optimized to use: an undiluted DNA in the PCR, a 0.1 µM PCR primer concentration, a full PCR product for the SNP extension reaction, a 50ºC annealing temperature for the SNP extension in accordance with standard SNaPshot® conditions, and a 0.4 µM concentration of the SNP extension primer. The advantages of the resultant SNaPshot® assay over the ARMS assay include higher fidelity, robustness, and more consistent performance within and among laboratories, and reduced risk of human error. / Master of Science

As distrofias musculares constituem um grupo de doenças caracterizadas por degeneração progressiva e irreversível da musculatura. A Distrofia Muscular de Duchenne (DMD) é uma miopatia letal causada pela deficiência da distrofina, proteína integrante do citoesqueleto muscular, cujo gene possui característica recessiva e localiza-se na porção p21 do cromossomo X. Avanços nos cuidados terapêuticos dos pacientes afetados pela DMD têm aumentado a expectativa e qualidade de vida dos mesmos. Por este motivo, questões de ordem fisiológica e/ou ética, antes não pensadas, dentre elas possibilidades reprodutivas destes pacientes, começaram a ser discutidas. Os modelos animais são muito úteis para se traçar paralelos entre achados morfológicos, fisiológicos, prognósticos e tratamentos de determinadas doenças que acometem o homem. A Distrofia Muscular do Golden Retriever (GRMD) é uma doença que naturalmente acomete esta raça, podendo ser um ótimo modelo animal para estudos da DMD, pois apresenta fisiopatologia semelhante. O objetivo deste estudo foi investigar a existência de possíveis alterações morfológicas do trato reprodutivo masculino e relacioná-las com o quadro espermático destes cães. Para tanto foram utilizados 5 cães com GRMD e 4 cães sadios, tendo sido realizadas ao todo 37 colheitas de sêmen, a intervalos aproximados de 30 dias entre elas. Após espermiograma de rotina, o sêmen foi avaliado quanto à integridade da membrana acrossomal (FITC-PSA), à atividade mitocondrial (JC-1) e à estrutura da cromatina (SCSA) utilizando-se a técnica da citometria de fluxo e quanto à resistência ao estresse oxidativo pela dosagem de TBARS. Fragmentos de testículo, epidídimo e próstata de cinco animais com GRMD e de 1 animal sadio foram coletados para avaliação histológica. As avaliações seminais não demonstraram diferença significativa (p>0,05) entre os grupos afetado e controle, embora as avaliações histológicas tenham mostrado alterações significativas em todos os tecidos analisados. Isto sugere que ejaculados de homens com DMD podem ser obtidos com estimulação apropriada e, utilizando técnicas de fecundação in vitro, combinada com diagnóstico genético pré-implantacional de desordem genética para um único gene, podem satisfazer o desejo de paternidade de pacientes portadores de DMD, com o nascimento de crianças não afetadas. / Muscular dystrophies constitute a group of diseases characterized by progressive and irreversible muscle degeneration. Duchenne´s Muscular Dystrophy (DMD) is a lethal myopathy caused by dystrophin deficiency, a muscular cell cytoskeleton protein. The dystrophin gene have recessive characteristic and is located in the p21 portion of the X chromosome. Advancements in the therapeutic cares of the affected by the DMD have been increasing their life expectancy and quality. For this motive, physiologic and/or ethics questions, like reproductive means of these patients, began to be discussed. Animal models are very useful in drawing parallels between morphologic and physiologic findings, predictions and treatments of diseases that affect man. The Golden Retrievers Muscular Dystrophy (GRMD) is a natural disease of this race, being the best animal model for DMD studies, since it presents similar physiopathology. The aim of this study was to investigate the existence of possible morphological alterations of the male reproductive tract and their connection with the sperm qualities of these dogs. For so, thirty seven ejaculates from 5 GRMD affected dogs and 4 non-affected Golden Retrievers were collected monthly and evaluated in five different replicates. After routine spermogram, the acrosome integrity (FITC-PSA), the mitochondrial activity (JC-1) and the DNA structure (SCSA) were evaluated by flow cytometry technique. The resistance to the oxidative stress was measured by the TBARS dosage. Fragments of testicle and epididymis of five GRMD affected animals and 1 healthy animal were collected for histological evaluation. No significant difference were found in seminal evaluations (p> 0,05) between affected and control groups, though significant alterations have been seen in the histological evaluations of all the analyzed cloths. This animal model suggests that ejaculates of DMD men can be obtained by the proper stimulation, and that the conventional in vitro fertilization techniques combined with pre-implantation genetic diagnosis for single gene disorders may be efficient to satisfy the desire of paternity of DMD patients with the birth of non-affected children.

Une des pistes majeures pour obtenir des turbines à gaz moins polluantes est l'utilisation de chambres de combustion fonctionnant en régime prémélangé pauvre. Cependant, dans de tels régimes de fonctionnement, la flamme obtenue est cependant plus facilement sujette aux instabilités thermo-acoustiques.Dans cette thèse, un brûleur étagé swirlé fonctionnant au propane a été employé pour illustrer une méthode d'analyse de la combustion prémélangée. Cette installation a été étudiée à l'aide de diagnostics classiques (micros, PLIF, film à haute cadence de la flamme).La stratégie de post-traitement développée dans cette thèse utilise par contre des outils eux aussi classiques (PSD, moyenne de phase) mais aussi une méthode d'analyse avancée, la Décomposition en Modes Dynamiques. Celle-ci est notamment étudiée em détail afin d'en cerner les avantages et les limitations dans le cadre de l'analye des instabilités de combustion. / One of the major ways of reducing pollutant emissions in gas turbines is using combustion chambers with lean premixed mixtures. However, in such operating conditions the flame is more susceptible to thermo-acoustic instabilities. In the present work, a propane-fed swirled burner using two injection stages is used to illustrate a post-processing strategy for premixed combustion analysis. This model burner has been studied using classic diagnostics (microphones, PLIF, highspeed imaging).The strategy developed in the present work uses both classic postprocessing tools (PSD, phase averaging) and an advanced method, the Dynamic Mode Decomposition. In particular, this method is studied in detail and compared to more lassic ones in order to clearly point its advantages as well as its shortcomings when used to study combustion instabilities.