A 9.4 T magnetic resonance imaging (MRI) system was used to evaluate the response of a human tumour xenograft model to radiation therapy. The apparent diffusion coefficient (ADC) and the transverse relaxation time (T2) of human glioblastoma multiforme (GBM) tumour xenografts in NIH-iii nude mice were measured before, and at multiple points after, treatment of the tumours with 200 kVp x-rays. The response was characterized as a function of a number of variables of interest in the clinical treatment of cancer with external beam radiation therapy. Mean tumour ADC and T2 responses after single fractions of radiation were investigated, with measurements being made until 14 days after treatment. Single fraction doses ranged from 50 cGy to 800 cGy. Fractionated treatments were used to deliver 800 cGy in two or three fractions with fraction spacings of 24 or 72 hours. The role of hypoxia on ADC and T2 response was investigated by using an externally-applied, suture-based ligature to induce a state of reduced oxygenation in tumours during treatment, after which ADC and T2 were measured using serial MRI. Finally, tumours were dissected in order to provide insight into possible pathophysiological mechanisms explaining the observed responses. Tissue sections were prepared and reviewed by a pathologist. This work adds to the body of literature describing tumour ADC and T2 response to anticancer therapy, and adds to the understanding of ADC and T2 response to radiation therapy in particular. This works supports that of others suggesting the use of ADC and T2 as potential biomarkers for tumour response to treatment. / Medical Physics

Live juvenile cobia (Rachycentron canadum) transport methods were examined to determine opportunities for increasing packing density in closed containers for temporal durations up to 24 hours. Juvenile cobia (27 to 46 days-post-hatch (dph)) were tested for salinity tolerance following abrupt transfer from 35 ppt salinity water to salinities ranging from 0 ppt to 55 ppt. Results indicate a wide range of tolerance, with 100% survival at 24 hours post-transfer in salinities between 11 ppt and 45 ppt. Salinity preference was also tested to determine a possible correlation between acclimation salinity and salinity preference using an experimental horizontal salinity gradient with juvenile cobia (87 dph) over a period of 24 hours. Results of the salinity preference trials showed that salinity preference was directly related to acclimation salinity. Using two different salinities within the range tested in the tolerance trials (12 ppt and 32 ppt), a 24 hour simulated shipping trial was conducted comparing final survival between the two salinities at each of four packing densities (5 kg/m3, 10 kg/m3, 15 kg/m3, and 20 kg/m3). Results indicated a significant relationship between salinity and stocking density on survival of juvenile cobia following a 24 hour simulated shipment. At packing densities above 10 kg/m3, survival was significantly higher in the low salinity (12 ppt) treatments as compared to survival rates in the higher salinity (32 ppt) treatments. To help aquaculture professionals make accurate and economical decisions regarding the shipment of live juvenile cobia in closed containers, a bioeconomic model was constructed using survival data at different packing densities (1 kg/m3 to 20 kg/m3) and salinities (12 ppt and 32 ppt) obtained in the experimental trials combined with shipping cost and fingerling price data. The resulting model enables cobia fingerling producers to optimize their shipping methods and protocols, allowing for reductions in labor and material costs.

There is extensive research focused on identifying predictors of autism, including biomarkers such as genes and neurophysiology. Because of inconsistent data, I explored these biomarkers as predictors of variability in behavioral outcomes (i.e., internalizing and externalizing symptoms), rather than indicators of the disorder per se. In a sample of children (ages 8-16) diagnosed with High Functioning Autism (HFA) and an age- and IQ- matched typically developing comparison group, individual differences in behavioral outcomes were assessed in relation to common genetic polymorphisms, 5-HTTLPR and DRD4, and neurophysiological (ERN) and behavioral (rate of self-correction) measures of response monitoring. Although the diagnostic groups did not differ on allele frequency for 5-HTTLPR, carriers of the L variant displayed attenuated ERN amplitudes at frontal-central sites, lower rates of self-correction following errors, and higher levels of parent-reported Somatization and Hyperactivity. With respect to DRD4, an overrepresentation of the 7-repeat allele was found in the HFA sample. Regardless of diagnostic group, 7-repeat allele carriers were rated as having more attention problems. These results suggest that genetics and neural correlates of response monitoring may explain interindividual variations in social emotional functioning of both HFA and typically developing children alike. However, contrary to hypothesis, response monitoring did not mediate the association between 5-HTTLPR or DRD4 and outcome measures. Future directions of this research may look at how genes and measures of response monitoring affect etiology, course, and treatment of autism and other related disorders.

Thesis (Ph.D.)--University of Delaware, 2006. / Principal faculty advisor: Ratna Nandakumar, School of Education. Includes bibliographical references.

Thesis (M. Communication Pathology)--University of Pretoria, 2005. / Summary in English and Afrikaans. Includes bibliographical references.

Phosphorus is an essential element for plant growth and development. Due to its low availability, solubility and mobility, phosphate is often the limiting macronutrient for crops and other plants. Plants have evolved several responses to phosphate deficiency. However, very little is known about the molecular basis of these responses. Here, I study the expression of PAP12, its role in the phosphate starvation response and the interaction of its promoter with nuclear factors. Analysis of a PAP12 T-DNA insertion line (pap12-1) revealed PAP12 is responsible for the majority of the acid phosphatase activity detected by the standard in-gel assay. RNA gel blots showed that PAP12 was induced only by Pi deficiency, and not by general nutrient stress. PAP12 expression, at the RNA and protein level, reflected endogenous phosphate levels in two mutants with altered phosphate accumulation. In the pho1 mutant, PAP12 expression and activity were up-regulated with respect to wild-type plants, and in the pho2 mutant, PAP12 expression and activity were reduced. Analysis of the PAP12 promoter using promoter-GUS fusions revealed expression in leaves, roots, flowers, hydathodes, root tips, and pollen grains. This broad pattern of expression suggests that PAP12 functions throughout the plant in response to low phosphate concentrations. The results showed PAP12 does not play a major role in phosphate remobilization, acquisition or in helping plants cope with low phosphate environments. Instead, the major phenotype associated with PAP12 deficiency was a significant delay in flowering in the low-phosphate pho1 background and a slight acceleration of flowering in the high-phosphate pho2 background over-expressing PAP12. These results suggest that PAP12 may have a role in linking phosphate status with the transition to flowering. Finally, I used promoter deletion and DNA-protein interaction assay to understand PAP12 expression upon phosphate starvation. A 35-bp region of the PAP12 promoter was identified as an important phosphate regulatory cis-element required for induction during phosphate starvation. We isolated a 23.5 kDa nuclear factor, which binds to this 35-bp region of the PAP12 promoter in a phosphate-dependent manner. The work presented here will add to our knowledge about the molecular processes that regulate phosphate nutrition.

Tous les êtres vivants présentent un arsenal de défenses contre les pathogènes, et la réponse inflammatoire constitue le processus initial de cette défense, qui s’achève par la réparation des tissus lésés. Paradoxalement, un processus inflammatoire prolongé est également associé à de nombreuses pathologies comme l’athérosclérose, l’asthme, les maladies auto-immunes mais aussi certains cancers. Le recrutement excessif de leucocytes au site de l’inflammation est un processus commun à ces pathologies. Dès lors, la compréhension et la maîtrise du phénomène complexe et finement orchestré de la migration sélective des populations leucocytaires, appelée chimiotactisme, sont des enjeux majeurs de la recherche médicale contemporaine. Les récepteurs aux peptides formylés bactériens et mitochondriaux (FPRs) forment la première famille de récepteurs chimiotactiques identifiée. Elle comprend trois membres, FPR1, 2 et 3, présentant un haut niveau de similitude et partageant certains de leurs multiples ligands. Le troisième membre de ce groupe, FPR3, reste actuellement le moins bien connu. Récemment, un agoniste de FPR3, affin et spécifique, a été identifié dans le laboratoire. Il s’agit du peptide F2L, qui correspond aux 21 premiers acides aminés de la protéine intracellulaire HEBP1. Dans le cadre de ce travail de thèse, nous nous sommes attelé à la caractérisation approfondie du récepteur FPR3 et son ligand peptidique F2L. Dans un premier temps, et à l’aide d’anticorps validés dans le cadre de ce travail, nous avons montré que le peptide F2L induit le chimiotactisme d’un ensemble de populations leucocytaires qui expriment FPR3, dont les sous-populations de macrophages des poumons, du colon et de la peau, les éosinophiles et les cellules dendritiques plasmacytoïdes. Cette distribution suggère, pour FPR3, une fonction dans la réponse inflammatoire. Nous avons pu montrer ensuite que F2L peut être généré par la protéolyse de son précurseur, HEBP1, sous l’action de la cathepsine D des macrophages. La cathepsine D est une aspartique protéase lysosomiale impliquée dans l’homéostasie cellulaire, les processus apoptotiques et inflammatoires physiologiques et pathologiques, et dans le développement tumoral. Il s’agit désormais d’identifier dans quel compartiment et sous quelles conditions F2L est produit et sécrété. Enfin, parallèlement à ces travaux, nous avons démontré que la cathepsine G, une sérine protéase contenue dans les granules azurophiles des neutrophiles, active également le récepteur FPR3. Des résultats préliminaires suggèrent un mode d’activation alternatif du récepteur, impliquant la protéolyse d’un troisième partenaire et la génération d’un agoniste actuellement non identifié. Le couple FPR3-F2L semble dès lors impliqué dans l’induction ou la résolution de la réponse inflammatoire en recrutant les éosinophiles, monocytes, macrophages et cellules dendritiques au site de la lésion.

Quorum sensing (QS) is a type of cell-to-cell communication that allows the bacteria to communicate via small molecules to coordinate activities such as growth, biofilm formation, virulence, and stress response as a population. QS depends on the accumulation of signal molecules as the bacterial population increases. After a critical threshold of the signal molecules are reached, the bacteria induce a cellular response allowing the bacteria to coordinate their activities as a population. In Vibrio anguillarum, three parallel quorum-sensing phosphorelay systems channels information via three hybrid sensor kinases VanN, VanQ, and CqsS that function as receptors for signal molecules produced by the synthases VanM, VanS, and CqsA, respectively. The phosphorelay systems converge onto a single regulatory pathway via the phosphotransferase VanU, which phosphorylates the response regulator VanO. Together with the alternative sigma factor RpoN, VanO activates the expression of a small RNA, Qrr1 (Quorum regulatory RNA), which in conjunction with the small RNA chaperone Hfq, destabilizes vanT mRNA, which encode the major quorum-sensing regulator in V. anguillarum. This thesis furthers the knowledge on the quorum-sensing phosphorelay systems in V. anguillarum. In this study, three additional qrr genes were identified, which were expressed during late logarithmic growth phase. The signal synthase VanM activated the expression of the Qrr1-4, which stands in contrast to Qrr regulation in other vibrios. Moreover, in addition to VanO, we predict the presence of a second response regulator which can be phosphorylated by VanU and repress Qrr1-4 expression. Thus, VanU functions as a branch point that can regulate the quorum-sensing regulon by activating or repressing VanT expression. Furthermore, VanT was shown to directly activate VanM expression and thus forming a negative regulatory loop, in which VanM represses VanT expression indirectly via Qrr1-4. In addition, VanM expression was negatively regulated post-transcriptionally by Hfq. Furthermore, a universal stress protein UspA repressed VanM expression via the repression of VanT expression. We showed that UspA binds Hfq, thus we suggest that UspA plays a role in sequestering Hfq and indirectly affect gene expression. This thesis also investigated the mechanism by which V. anguillarum can attach to and colonize fish skin tissue. We show unequivocally that fish skin epithelial cells can internalize bacteria, thus keeping the skin clear from pathogens. In turn, V. anguillarum utilized the lipopolysaccharide O-antigen to evade internalization by the fish skin epithelial cells. This study provides new insights into the molecular mechanism by which pathogen interacts with marine animals to cause disease.

With the present drive in turbomachine engine developmenttowards thinner and lighter bladings, closer spaced blade rowsand higher aerodynamic loads per blade row and blade, advanceddesign criteria and accurate prediction methods for vibrationalproblems such as forced response become increasingly importantin order to be able to address and avoid fatigue failures ofthe machine early in the design process. The present worksupports both the search for applicable design criteria and thedevelopment of advanced prediction methods for forced responsein transonic turbine stages. It is aimed at a betterunderstanding of the unsteady aerodynamic mechanisms thatgovern forced response in transonic turbine stages and furtherdevelopment of numerical methods for rotor stator interactionpredictions. The investigation of the unsteady aerodynamic excitationmechanisms is based on numerical predictions of thethree-dimensional unsteady flow field in representative testturbine stages. It is conducted in three successive steps. Thefirst step is a documentation of the pressure perturbations onthe blade surface and the distortion sources in the bladepassage. This is performed in a phenomenological manner so thatthe observed pressure perturbations are related to thedistortion phenomena that are present in the blade passage. Thesecond step is the definition of applicable measures toquantify the pressure perturbation strength on the bladesurface. In the third step, the pressure perturbations areintegrated along the blade arc to obtain the dynamic bladeforce. The study comprises an investigation of operationvariations and addresses radial forcing variations. With thehelp of this bottom-up approach the basic forcing mechanisms oftransonic turbine stages are established and potential routesto control the aerodynamic forcing are presented. For the computation of rotor stator interaction aerodynamicsfor stages with arbitrary pitch ratios a new numerical methodhas been developed, validated and demonstrated on a transonicturbine test stage. The method, which solves the unsteadythree-dimensional Euler equations, is formulated in thefour-dimensional time-space domain and the derivation of themethod is general such that both phase lagged boundaryconditions and moving grids are considered. Time-inclination isutilised to account for unequal pitchwise periodicity bydistributing time co-ordinates at grid nodes such that thephase lagged boundary conditions can be employed. The method isdemonstrated in a comparative study on a transonic turbinestage with a nominal non integer blade count ratio and anadjusted blade count ratio with a scaled rotor geometry. Thepredictions show significant differences in the blade pressureperturbation signal of the second vane passing frequency, whichwould motivate the application of the new method for rotorstator predictions with non-integer blade count ratios.

Arlanda är Sveriges största internationella flygplats och har en stor betydelse när det kommer till jobb, näringsliv, kunskap, turism, kultur och därmed hela Sveriges välfärd. Flygplatsen ligger i Sigtuna kommun och runt omkring Arlanda ligger ytterligare tre kommuner; Vallentuna, Knivsta och Upplands Väsby.  Alla dessa arbetar aktivt med åtgärder för en hållbar utveckling av sina organisationer. Kommunerna och Arlanda har tre huvudsakliga gemensamma intressen som samverkar och är beroende av varandra.  För att tillsammans organisera, strukturera och försöka hitta gemensamma hållbara lösningar på de problem och möjligheter som uppstår runt intressena har kommunerna och Arlanda en väl utvecklad dialog. Dialogen idag beskrivs som god och samtalsklimatet positivt. Kommunerna är delaktiga i Arlandas utveckling och samarbete sker i flera forum. För drygt tio år sedan var bilden en annan. Samtalsklimatet uppfattades som kyligt, verksamheten var sluten och det togs ingen hänsyn till vilken påverkan man hade på omgivningen. Litteratur som rör dialog mellan en organisation och dess intressenter poängterar ofta vikten av att man förstår varandra och delar uppfattning om vad organisationens ansvar består i om relationen ska vara värdefull.  För att få en större kunskap om hur det samförståndet ser ut i Arlandas fall har en rad intervjuer med representanter från de olika kommunerna samt Arlanda genomförts. Resultatet visar att förändringar i omgivningen och inom organisationen har påverkat hur både kommunerna och Arlanda ser på flygplatsens roll i samhället, hur man kommunicerar med varandra och relationen mot att bli mer utvecklande.