Lameness continues to cause significant problems in profitability, productivity, and animal welfare in the feedlot industry. Toe tip necrosis syndrome (TTNS) is a new name for a previously reported condition. By definition, TTNS is separation of the apical white line with tissue necrosis and clinical lameness. This definition includes complications such as pedal (P3) osteitis, middle (P2) and proximal (P1) phalangeal osteomyelitis, tendonitis, tenosynovitis, cellulitis, and embolic pneumonia. Anecdotal experiences from practitioners report this lameness in feedlot cattle will develop within weeks after feedlot entry. Often the hindlimbs, specifically the lateral claw, are affected where a separation of the dorsal wall and sole will be noticed. Secondary infections will progress deeper into the foot and become systemic. Unfortunately, despite treatment, these animals can become very lame and will need to be euthanized. The overall objective of this project was to describe the epidemiology of TTNS in western Canadian feedlot cattle. The specific objectives were 1) to use clinical examinations, imaging modalities, and necropsy findings to aid in description, classification, and characterization of TTNS lesions, 2) to describe the epidemiology of TTNS in feedlot cattle, and 3) to evaluate risk factors for TTNS. Upon further investigation into this arrival related condition it became apparent that there were many different descriptors: P3 necrosis, toe abscess, apicus necrotica, apical pedal bone necrosis or toe necrosis. These names and descriptors of toe tip lesions were based on anecdotal experiences and previous case reports. As a result, traditional epidemiological approaches that included field investigations, clinical and necropsy examinations were implemented to identify, characterize and describe this condition. Based on clinical findings, imaging modalities, and necropsy specimens examined during September to December 2012, inclusive, a more specific name and descriptive case definition were introduced. TTNS descriptive epidemiology was described by use of a retrospective database analysis from Feedlot Health Management Services (FHMS) with 702 veterinarian confirmed TTNS cases by necropsy examination. From this database, there were 30% (210/702) of necropsy cases treated for TTNS and 70% of cases (492/702) that were not treated. Of those animals treated, the mean and standard deviation (median) interval from feedlot arrival to first treatment was 18.9 ±1.7 d (12 d). The mean (standard deviation) days on feed until death from TTNS was the earliest in grass-fed calves (32.4 ± 22.1 d), followed by auction-derived (40.6 ± 40.6 d), ranch direct (44.1 ± 53.1 d), and back-grounded calves (69.0 ± 75.6 d) (P < 0.001). Yearlings were on feed for a mean (standard deviation) days of 37.1 ± 32.0 d when compared to calves at 49.5 ± 57.0 d before death (P < 0.001). The greatest proportion of deaths occurred from September to November. There were 96.2% (1,832/1,904) of lots without one case of TTNS and 3.8% (72/1,904) of lots had one or more TTNS cases. A prospective case-control study to identify TTNS risk factors consisted of 148 total necropsy submissions (82 cases, 66 controls) from three feedlot veterinary practices and 16 feedlots during October 2012 to January 2013, inclusive. Confirmation of feet samples by the principal investigator at the Western College of Veterinary Medicine reduced the total to 135 animals: 67 cases and 68 controls. The measure of agreement (kappa) on classification of TTNS cases and controls between the veterinary practice and WCVM was 0.778 (P < 0.001). Bacterial culture results revealed that 75% of pure isolates in TTNS cases were attributed to Escherichia coli, Streptococcus spp., Trueperella pyogenes, Fusobacterium necrophorum. TTNS cases were 3.8 times more likely than control animals to have BVDV isolated (95% CI 1.7-8.5; P < 0.001). TTNS animals were 2.2 times more likely than control animals to have histopathological evidence of vasculitis (95% CI 1.0-4.6; P = 0.04). BVDV samples were 11.2 times more likely to show histopathological evidence of vasculitis than non-BVDV samples (95% CI 4.7-27.0; P < 0.001). A decreased difference was found in sole thickness at the toe tip (P < 0.001). There was no evidence of pedal bone rotation between case and control animals (P = 0.15). In summary, TTNS is a specific term for apical white line separation with tissue necrosis and clinical lameness. A practitioner's field diagnosis of TTNS based on apical white line separation and tissue necrosis is accurate on clinical signs alone. TTNS is a transport or arrival related condition in feedlot cattle that has a propensity for cases to cluster together. Pure bacterial isolates provide an understanding of the pathogens responsible for TTNS and that environmental pathogens contribute to an ascending infection. BVDV, vasculitis and apical sole thickness were risk factors associated with TTNS; however, their exact role requires further investigation.

Tip growth, the mechanism by which hyphae, pollen tubes, root hairs, and algal rhizoids extend, is a complex and dynamic process that is characterised by localised extension at the extreme apex of the cell and morphological polarity. Its complexity suggests that high degree of regulation is needed to ensure that the characteristics of a particular cell type are maintained during growth. Regulation is likely to come about through bidirectional interplay between the cell wall and cytoplasm, although the mechanisms by which such cross-talk might occur are unknown. Results of this thesis present immunocytochemical data that indicate the presence of, and a close association between β4 integrin subunit-like proteins and proteins containing phosphorylated tyrosine residues in the oomycete Achlya bisexualis. When hyphae were plasmolysed, these proteins were present in wall-membrane attachment sites where there was also F-actin. A combination of immunoblots, ELISA, and a coupled enzyme assay suggest that phosphorylation may occur by both autophosphorylation and through the possible action of a tyrosine kinase. Tyrphostins, which are inhibitors of tyrosine kinases, abolished the anti-phosphotyrosine staining, inhibited the kinase activity, slowed tip growth and affected the organisation of the actin cytoskeleton, in a dose-dependent manner. In addition, results show A. bisexualis contains proteins epitopically similar to the rod domain of animal talin. However, these proteins do not co-localise with F-actin, and mainly locate at the sub-apical region in hyphae. For comparative purposes, Saccharomyces cerevisiae was also used to investigate the presence of β4 integrin subunit-like proteins and tyrosine phosphorylation. Immunoblotting showed that S. cereviaise contains a protein, which is found in the microsomal pellet fraction, that cross reacts with anti-β4 integrin subunit antibody. Furthermore, there are a number of proteins containing phosphotyrosine residues. Immunocytochemistry shows that this anti-β4 integrin staining is at the cortical site but anti-phosphotyrosine residues are distributed throughout cells. On the basis of an ELISA and a coupled enzyme assay, it is suggested that a soluble fraction of S. cerevisiae contains tyrosine kinase activity. This activity is strongly inhibited by tyrphostins.

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No / This paper presents and compares the most important and often used methods to measure turbine blade vibrations: use of strain gauges and telemetry system which is an intrusive method or, on the other site. The Blade Tip Timing (BTT) method known as Non-Intrusive Stress Measurement (System) NSMS. Both methods have advantages and disadvantages which are described below. This paper focused on synchronous vibrations, which are more important in terms of turbine blades fatigue prediction and design optimization.

A large-scale moving end-wall system has been designed and built at the Aerospace and Ocean Engineering Department of Virginia Tech. This system forms part of a low-speed linear compressor cascade wind tunnel, where it is used to simulate the effects of the relative motion between the blade tips and casing upon the flow. Detailed 4-sensor hot wire measurements were made at various locations downstream the cascade. The results are presented in term of mean flow field and turbulence flow field. In order to reveal the effects of moving end wall, the results also compared with the results obtained with stationary end wall. / Master of Science

La migration et l'invasion tumorale sont des étapes clés de la cascade métastatique. Les microtubules (MT) contribuent à la division cellulaire et constitue la cible des agents de chimiothérapie anti-MT (ACM). Ce sont des structures dynamiques qui s'ancrent aux structures cellulaires périphériques. Durant ma thèse, j’ai étudié comment les protéines régulant le bout « + » des MT (+TIP) contribuent à la migration cellulaire et à la dégradation de la matrice extracellulaire. D’abord j’ai étudié l'impact de l'eribuline, un ACM dépolymérisant, sur la migration de cellules mammaires. L'éribuline s'est avérée empêcher l'ancrage des MT, modifier leur dynamique et inhiber la migration dirigée cellulaire, phénomène que nous avons expliqué par son action sur la +TIP EB1 mais surtout par la délocalisation de la tubuline polymérase ch-TOG de l'extrémité + des MT. Puis, nous avons examiné le rôle des +TIP dans la dégradation de la matrice, par les invadopodes, de petites protrusions riches en actine dégradant la matrice. La déplétion de EB1 et ses partenaires, APC et ACF7, régulaient négativement l’action des invadopodes, laissant supposer la présence d'un complexe fonctionnel : EB1, APC et ACF7 régulant négativement les invadopodes. En parallèle, par analyse protéomique systématique des composant des invadopodes, nous avons identifié de nouveaux proches voisins de TKS5, protéines indispensable à la formation des invadopodes, dont une protéine associée aux MT, MAP4. Au total, la régulation de la dynamique des +TIP est importante pour la migration et l'invasion et développer des stratégies ciblées contre ces acteurs pourrait améliorer la prise en charge du cancer du sein métastatique. / Migration and invasion are key steps in the metastatic cascade. Microtubules (MT) are involved in cell division and are dammaged by MT tagetting agents(MTA), a widely used chemotherapy drugs. MT are dynamic structures anchored to peripheral cell structures. During this work, I studied how proteins that regulates the "+" end of MT (+ TIP) cell migration and extracellular matrix degradation. First I adressed the impact of eribulin, a new depolymerizing MTA, on mammary cell migration. Eribulin was found to prevent the anchoring of MT to cell cortex, to modify their dynamics and to inhibit cell migration, a phenomenon that we explained by its action on +TIP EB1 but more precisely by the delocalization of tubulin polymerase ch-TOG. Next we investigated the role of TIPs in invadopodia matrix degradation , which are actin-rich protrusion specialized in matrix digestion. The depletion of EB1 and its partners, APC and ACF7, negatively regulated the action of invadopodia, assumed the presence of a complex complex: EB1, APC and ACF7 negatively regulating invadopodia activity. In parallel, by systematic proteomic analysis of the component of the invadopodia, we identified new close neighbors of TKS5, an essential proteins in invadopodia formation, including a MT associated protein MAP4. In conclusion, the regulation of + TIP dynamics is important for migration and invasion and developping targeted strategies against them could improve the management of metastatic breast cancer.

ABSTRACT A PARAMETRIC INVESTIGATION OF TIP INJECTION FOR ACTIVE TIP VORTEX CONTROL Dedekarginoglu, Riza Can M.Sc., Department of Aerospace Engineering Supervisor :Asst. Prof. Dr. Oguz Uzol December 2010, 79 pages Wing tip vortex is a challenging phenomenon that reduces the lift generation at the tip region of the wing. For aerial vehicles, several methodologies were presented for the sake of controlling vortices and alleviating effects of tip loss. In this study, the effect of wing tip injection on wing tip vortex structure was investigated computationally. A NACA0015 profile rectangular wing was employed with an aspect ratio of 3, at a free stream Reynolds number of 67000. 10 identical ejection holes along the wing were prepared chordwise to provide cross sectional air flow in order to determine the net effect of ejection over wing tip vortices and wake flow field. Study setup consists of a wind tunnel that is 1.6m long, 0.6m wide and 0.6m high, which the wing is attached to one side of it as a cantilever beam. Chord length of the wing is 0.1m and span is 0.3m. A constant free stream air flow is maintained with 10 m/s of velocity. Computer aided drawing (CAD) and grid generation were carried out using commercial tools. Whole setup was drawn using Rhinoceros. Surface mesh was created using ANSYS Gambit, ANSYS T-Grid software was used for generating the viscous mesh over the wing and finally for volume mesh ANSYS Gambit was utilized once more. FLUENT was chosen to be the flow solution tool with k-&omega / SST turbulence model. For 3 different angles of attack cases, respectively, 4&deg / , 8&deg / and 12&deg / , several injection scenarios were defined. There are 3 steady injection cases for each angle of attack case namely, no injection case, uniform injection case, triangular waveform injection case where there is no injection at the leading edge tip whereas there is injection which is equal to the uniform injection velocity at the trailing edge tip. Moreover there are 5 additional scenarios for 8&deg / angle of attack case that are, sinusoidal waveform injection case which consists of a chordwise velocity distribution shape that is a quarter sinus wave where maximum injection velocity is the same as the uniform velocity, reverse triangular waveform injection case where injection velocities were reversed with respect to triangular waveform case, two cases consisting of angled injections having both +15&deg / and -15&deg / with respect to the flapping axis of the wing. The effect of tube walls on the jet injection was neglected for all cases, therefore for the last case, in order to simulate pipe flow, a case is provided with uniform injection velocity. In that way, regardless of the solution method, a parametric study was performed. Considering each case, non-dimensional 3-axis velocity components, turbulent kinetic energy, vorticity magnitude, pressure, lift and drag values were computed and having the exactly same cases as an experimental study for 8&deg / angle of attack, a comparison of aerodynamic data series was presented. As results, it&rsquo / s observed that, vortex core locations were shifted upwards and away from the tip region. Increasing the turbulence level of the tip flow by tip injection, inherently the pressure difference became larger, however as the vortices ascend, tip loss decreases. In that way, a significant increase in the lift was observed while drag values are slightly increased, as well.

The development of nanoscale patterns has a vast variety of applications going from biology to solid state devices. In this research we present a new direct patterning technique in which laser photoreduction of silver from a liquid is controlled by a scanning atomic force microscope tip. While pursuing the formation of patterns using the plasmonic field enhancement of an electromagnetic wave incident on a metallic Atomic Force Microscope (AFM) tip, our group discovered that contrary to expectations, the tip suppresses, rather than enhances, deposition on the underlying substrate, and this suppression persists in the absence of the tip. Experiments presented here exclude three potential mechanisms: purely mechanical material removal, depletion of the silver precursor, and preferential photoreduction on existing deposits. An example of a nano-scaled pattern was generated to show the possibilities of this work. These results represent a first step toward direct, negative tone, tip-based patterning of functional materials.

This thesis presents the results of a study performed in the Virginia Tech low speed linear cascade wind tunnel operating at a Reynolds number of 382,000 designed to model an axial compressor rotor. To simulate the flow created by the junction of a set of inlet guide vanes and the compressor casing, vortex generators were glued to a moving end wall. In this investigation, the tip clearance was varied from 0.83% to 12.9% chord. Measurements of the midspan and the tip blade loading were made using static pressure taps. The tip loading shows that the minimum suction surface pressure coefficient increases in magnitude linearly up to a tip clearance of 7.9% chord. Unsteady pressure was measured on the pressure and suction surfaces at the tip of two cascade blades using an array of 23 microphones mounted subsurface. These measurements reveal that the unsteady pressure at the blade tip is a linear function of tip clearance height. The instantaneous pressure shows that the surface pressure at the blade tip has the same character regardless of whether or not the blade is disturbed by the inflow vortices. This suggests that the vortex generators simply stimulate and organize the existing response of the blade. Single sensor hot-wire measurements were made within the tip clearance on the suction side of the blade 1mm from the tip gap exit. These measurements show that the mass flux through the tip clearance is closely related to the pressure difference across the tip gap. / Master of Science