The present study assessed olfactory and cognitive abilities in two strains of Alzheimer’s disease (AD) model mice and in healthy control mice over a four month time period. To this end an operant conditioning paradigm using an automated olfactometer and a spatial learning test with non-olfactory cues were employed and data on olfactory learning and memory, discrimination, and sensitivity as well as spatial learning and memory were collected. The mice were between 6 to 7 month old at the beginning of the study and 9 to 10 months old at the end of the data collection, that is, in the age range when the animals are supposed to display marked neuroanatomical changes typical of AD. The results demonstrate that there were no systematic differences in olfactory performance and spatial learning and memory abilities of AD model mice and the control mice up to the age they were tested. Further, there was no indication of an age-related decline in performance in any of the mouse strains across the testing period. Several reasons might account for the observed lack of difference in olfactory and cognitive performance between the mouse strains tested here: the AD model mice might not develop amyloid plaques and neurofibrillary tangles at all or they might develop them later than stated by the supplier. Alternatively, the AD model mice may have developed AD-typical neuroanatomical changes but these do not, or not yet, affect their olfactory performance and/or spatial learning and memory capabilities. Ongoing data collection will help to evaluate which of these explanations holds true.

La production de paires de quarks top se désintégrant en deux leptons dont au moins un lepton tau est étudiée dans le cadre de l'expérience CDF auprès du collisionneur proton-antiproton, Tevatron, a FNAL aux USA. La sélection exige un électron ou un muon produit par désintégration du lepton tau ou par désintégration d'un W. L'analyse utilise toutes les données enregistrées, 9 fb-1, avec un déclenchement basé sur un électron ou muon à faible moment transverse et une trace chargée isolée. La section efficace de production de paires de top a cette énergie obtenue est de 8,2+-1.7(+1.2-1.1)+-0,5 pb, et le rapport de branchement en leptons tau est de 0,120+-0,027(+0,022-0,019)+-0,007 avec erreur statistique, systématique et sur la luminosité respectivement. Ce sont à jour les résultats les plus précis dans ce canal de désintégration du top, en bon accord avec les résultats obtenus au Tevatron avec tous les autres canaux de désintégration du top. Le rapport de branchement est aussi mesuré en séparant les événements tau plus lepton et avec deux leptons tau avec une méthode de maximum de vraisemblance. C'est la première fois que ces modes de désintégration sont identifiés séparément. Par une méthode de maximum de vraisemblance appliquée pour séparer ces deux canaux une mesure alternative du rapport de branchement du top en lepton tau de 0,098+-0,022(stat.)+-0,014(syst.) est obtenue, en bon accord avec les prédictions du Modèle Standard. Une limite supérieure de 0,159 pour ce rapport de branchement, avec 95% de niveau de confiance est extraite donnant un indice de Physique au delà du Modèle Standard en particulier un possible boson de Higgs chargé.

It is essential to secure the implementation of cryptosystems in embedded devices agains side-channel attacks. Namely, in order to resist differential (DPA) attacks, randomization techniques should be employed to decorrelate the data processed by the device from secret key parts resulting in the value of this data. Among the countermeasures that appeared in the literature were those that resulted in a random representation of the key known as the binary signed digit representation (BSD). We have discovered some interesting properties related to the number of possible BSD representations for an integer and we have proposed a different randomization algorithm. We have also carried our study to the $\tau$-adic representation of integers which is employed in elliptic curve cryptosystems (ECCs) using Koblitz curves. We have then dealt with another randomization countermeasure which is based on randomly splitting the key. We have investigated the secure employment of this countermeasure in the context of ECCs.

It is essential to secure the implementation of cryptosystems in embedded devices agains side-channel attacks. Namely, in order to resist differential (DPA) attacks, randomization techniques should be employed to decorrelate the data processed by the device from secret key parts resulting in the value of this data. Among the countermeasures that appeared in the literature were those that resulted in a random representation of the key known as the binary signed digit representation (BSD). We have discovered some interesting properties related to the number of possible BSD representations for an integer and we have proposed a different randomization algorithm. We have also carried our study to the $\tau$-adic representation of integers which is employed in elliptic curve cryptosystems (ECCs) using Koblitz curves. We have then dealt with another randomization countermeasure which is based on randomly splitting the key. We have investigated the secure employment of this countermeasure in the context of ECCs.

I present the results of a search for pair production of scalar top quarks (~t1) in an R-parity violating supersymmetric scenario using 322 pb_1 of pp collisions at ps = 1.96 TeV collected by the upgraded Collider Detector at Fermilab. I assume each ~t1 decays into a tau lepton and a b quark, with branching ratio B, and search for final states containing either an electron or a muon from a leptonic tau decay, a hadronically decaying tau lepton, and two or more jets. Two candidate events pass my final selection criteria, consistent with the expectation from standard model processes. I present upper limits on the cross section times branching ratio squared (~t1~t1)B2 as a function of the stop mass m(~t1). Assuming B = 1, I set a 95% confidence level limit m(~t1) > 153 GeV=c2. These limits are also fully applicable to the case of a pair produced third generation scalar leptoquark that decays into a tau lepton and a b quark.

Alzheimer¡¦s disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions and the presence of intracellular neurofibrillary tangles (NFT) and extraneuronal senile plaques (SP). The major component of NFT is the hyperphosphorylated microtubules-associated protein tau. SP is consistent of extracellular deposition of £]-amyloid (A£]), mainly A£]1-42 peptide (A£]42). Given the need of tools for early and accurate diagnosis and prediction of disease progression and monitoring the efficacy of therapeutic agents for AD, development of cerebrospinal fluid (CSF) biomarkers have become a rapidly growing research field. In our study, patients with AD (n=28), non-AD dementia (n=16), other neurological disorder (OND, n=14) and healthy controls (HC, n=21) were included. Our results revealed that AD patients have significant higher CSF total tau (t-tau) and lower A£]42 levels than HC and OND groups. There is no significant difference of both CSF t-tau and A£]42 levels between AD and non-AD dementia groups. These results suggest that both CSF t-tau and A£]42 are good biomarkers for distinguishing AD from non-dementia control subjects but demonstrate less discriminating power in differentiating AD from non-AD dementia. Moreover, our results show only CSF t-tau level but not A£]42 has an inverse correlation with the score of short-term memory patients with AD (spearman: r = -0.444; p=0.018). These data indicate the higher CSF t-tau level is associated with much NFT pathology and more severe impairment of short-term memory in AD patients. In the study of the moleacular mechanism of tau¡¦s hyperphosphorylation by glycogen synthase kinase 3b (GSK3b), we show that the T231 is the primary phosphorylation site for GSK3b and the tau227-237 (AVVRTPPKSPS) derived from tau containing T231P232 motif is identified as the GSK3b binding site with high affinity of a Kd value 0.82 ¡Ó 0.16 mM. Our results suggest that direct binding and phosphorylation of T231P232 motif by GSK3b induces conformational change of tau and consequentially alters the inhibitory activity of its N-terminus that allows the sequential phosphorylation of C-terminus of tau by GSK3b. Furthermore, hyperphosphorylation reduces tau¡¦s ability to promote tubulin assembly and to form bundles in N18 cells. T231A mutant completely abolishes tau phosphorylation by GSK3b and retains the ability to promote tubulin polymerization and bundle formation. Taken together, these results suggest that phosphorylation of T231 by GSK3b may play an important role in tau¡¦s hyperphosphorylation and functional regulation.

<p>Auto-tuning has become an important function in distributed control systems (DCS) and is especially appreciated in large industries that can have hundreds of controllers. In the DCS 800xA manufactured by ABB, there is an auto-tuning method implemented based on a relay experiment to determine the ultimate gain and the ultimate period, with which the PID parameters are obtained using the modified Ziegler-Nichols tuning rules. The tuning procedure can then proceed with a step identification experiment to get additional parameters for kappa-tau tuning. In the previous DCS, called Advant, there was another auto-tuning approach implemented. This method was based on dominant pole design, which included an identification of the process. The purpose of this thesis is to compare these auto-tuning methods, to investigate if the dominant pole placement method should be migrated to the 800xA system.</p> / <p>Automatisk trimning har blivit en viktig funktion i distribuerade styrsystem (DCS och är speciellt av intresse för stora industrier som kan ha flera hundra regulatorer. Den automatiska trimningen som idag är implementerad i ABB:s DCS 800xA är baserad på ett reläexperiment för att bestämma den ultimata förstärkningen och den ultimata periodtiden. Modifierade Ziegler-Nichols trimningsregler används sedan för att bestämma PID parametrarna. Vidare kan trimningen fortsätta med ett stegsvars-experiment för att erhålla ytterliggare parametrar och trimma med kappa-tau metoden. Den automatiska trimningsmetoden som var implementerad i tidigare DCS, Advant, var baserad på dominant polplacering med identifiering av processen. Syftet med detta examensarbete är att jämföra dessa automatiska trimningsmetoder för att undersöka om den tidigare trimningsmetoden baserad på dominant polplacering ska implementeras i 800xA systemet.</p>

Aligning two images by point to point correspondence is a hard optimization problem. It can be solved using t-Extremal Optimization or with a modification of this method called Fitness threshold accepting. In this work these two methods are tested and compared to see whether one of the methods should be preferred for image alignment. Since real image data is almost always noisy the performance of the methods under conditions like noisy and outlying data is analyzed too.

Mitochondrial dysfunction plays a pivotal role in the development of aging phenotypes and aging-associated neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS). Strategies that restore mitochondrial dysfunction may rescue the deficits of central metabolism in these disorders and improve cell survival. For example, we found that modulating the mTOR signaling pathway in a tissue culture model of aging-induced mitochondrial DNA mutation enhanced mitochondrial function as evidenced by increased oxygen consumption. Our previous melatonin studies also led us to hypothesize that caloric restriction and the hormone melatonin would reverse brain mitochondrial dysfunction in animal models of AD. Although caloric restriction did not improve mitochondrial function in a transgenic P301L tau model of AD, novel insight into the regulation of F0-F1 ATP synthase activity under CR was gained that may help explain the protective effects of CR in other disease models. In addition, we determined the effects of melatonin treatment on brain mitochondrial cytochrome c oxidase (COX) activity using the transgenic APPSWE mouse model of AD bred to double melatonin receptor (MT1 and MT2) knockout mice. COX activity declined with aging in control mice, but increased with aging in AD mice, most likely as a response to mitochondrial reactive oxygen species (ROS) induced by amyloid-beta generated through APP proteolysis. Both effects were blunted by melatonin treatment. The effects of melatonin were partially dependent on the G-protein coupled melatonin receptors. We also used PD models to identify therapies that restore mitochondrial dysfunction. We showed that overexpression of wild-type alpha synuclein (α-syn) in human neuroblastoma M17 cells resulted in mitochondrial oxygen consumption deficits; similar to the levels observed when PD mutant forms (A30P α-syn, E46K α-syn, and, A53T α-syn) were overexpressed. Mitochondria from cells overexpressing α-syn were more sensitive to a high iron environment, mimicking the physiological conditions in which dopaminergic neurons are found. Diethyl oxaloacetate, succinate, and several amino acids were protective, suggesting the possibility for effective dietary interventions for PD. Lastly, we delineated the level of mitochondrial complex IV activity between gray and white matter in human cervical and lumbar spinal cord, as well as mitochondrial aggregation in the entire neurovascular units (NVU) as a consequence of ALS. At the conclusion of these projects a better understanding of the molecular mechanisms leading to mitochondrial dysfunction in AD, PD, ALS, and aging was gained and promising strategies to delay or reverse these dysfunctions were developed.

Auto-tuning has become an important function in distributed control systems (DCS) and is especially appreciated in large industries that can have hundreds of controllers. In the DCS 800xA manufactured by ABB, there is an auto-tuning method implemented based on a relay experiment to determine the ultimate gain and the ultimate period, with which the PID parameters are obtained using the modified Ziegler-Nichols tuning rules. The tuning procedure can then proceed with a step identification experiment to get additional parameters for kappa-tau tuning. In the previous DCS, called Advant, there was another auto-tuning approach implemented. This method was based on dominant pole design, which included an identification of the process. The purpose of this thesis is to compare these auto-tuning methods, to investigate if the dominant pole placement method should be migrated to the 800xA system. / Automatisk trimning har blivit en viktig funktion i distribuerade styrsystem (DCS och är speciellt av intresse för stora industrier som kan ha flera hundra regulatorer. Den automatiska trimningen som idag är implementerad i ABB:s DCS 800xA är baserad på ett reläexperiment för att bestämma den ultimata förstärkningen och den ultimata periodtiden. Modifierade Ziegler-Nichols trimningsregler används sedan för att bestämma PID parametrarna. Vidare kan trimningen fortsätta med ett stegsvars-experiment för att erhålla ytterliggare parametrar och trimma med kappa-tau metoden. Den automatiska trimningsmetoden som var implementerad i tidigare DCS, Advant, var baserad på dominant polplacering med identifiering av processen. Syftet med detta examensarbete är att jämföra dessa automatiska trimningsmetoder för att undersöka om den tidigare trimningsmetoden baserad på dominant polplacering ska implementeras i 800xA systemet.