In this thesis, a Thermal Model Tool (TMT) is developed for standard Avionic Transport Rack (ATR) chassis and thermal design of a standard ATR chassis is done using developed TMT. This ATR chassis is a Digital Moving Map (DMAP) of a helicopter and the tool is used to determine the cooling channel details of DMAP. TMT decreases design process steps and eliminates the complexity of the design. Experimental studies are conducted on one of the existing chassis produced in Aselsan Inc. for different operating conditions. There are two different operating conditions for the chassis as 25 &ordm / C and 55 &ordm / C, which are given, in military standard MIL-STD-810F. Critical temperature values are measured, which are used in analytical calculations, and results are represented. At the first step, outputs of the experimental studies are used in analytical calculation in order to develop TMT. Secondly, heat dissipation rate of two different chassis are v calculated easily by using the TMT, and without making effort for CFD analysis, the necessary number of plate fins of the chassis are assessed considering given geometrical constraints and heat loads. Finally, cooling channels are generated using the results of TMT. In the next step the chassis, which are designed using the results of TMT, are analyzed numerically by using Icepak Computational Fluid Dynamics (CFD) tool and results of TMT are verified. The cooling capacities of the decided plate fins, which are obtained by TMT, are checked whether or not the required heat dissipation rates are ensured. Consequently, TMT is tested under for two different operating conditions on two different chassis. Analytical and numerical studies for both conditions are compared and discussed in detail. Comparisons show that, developed TMT results are meaningful and close to numerical results, therefore TMT can be used in forthcoming ATR chassis designs.

<p>In order to extend the applications of aluminium, organic coatings may be applied on sheet materials, for instance for corrosion protection or aesthetic surface finish purposes in the automotive and construction industries, or on foil materials in the flexible packaging industry.</p><p>The most common mechanisms for deterioration and structural failure of organically coated aluminium structures are triggered by exposures to the surrounding environment. Despite the great importance to elucidate the influence of exposure parameters on a buried aluminium/polymer interface, there is still a lack of knowledge regarding the mechanisms that destabilise the structure. It is generally believed that a detailed <i>in situ</i> analysis of the transport of corroding species to the buried interface, or of surface processes occurring therein, is most difficult to perform at relevant climatic and real-time conditions.</p><p>In this work, Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR) in the Kretschmann-ATR configuration was successfully applied to <i>in situ</i> studies of the transport of water and ionic species through polymer films to the aluminium/polymer interface upon exposure to ultra pure deionised water and to a 1 M sodium thiocyanate (NaSCN) model electrolyte. Other main processes distinguished were the formation of corrosion products on the aluminium surface and swelling of the surface-near polymer network. Hence, <i>in situ</i> ATR-FTIR was capable to separate deterioration-related processes from each other.</p><p>To perform more unambiguous interpretations, a spectro-electrochemical method was also developed for<i> in situ</i> studies of the buried aluminium/polymer interface by integrating the ATR-FTIR technique with a complementary acting technique, Electrical Impedance Spectroscopy (EIS). While transport of water and electrolyte through the polymer film to the aluminium/polymer interface and subsequent oxidation/corrosion of aluminium could be followed by ATR-FTIR, the protective properties of the polymer as well as of processes at the aluminium surface were simultaneously studied by EIS. The integrated set-up provided complementary information of the aluminium/polymer sample investigated, with ATR-FTIR being sensitive to the surface-near region and EIS being sensitive to the whole system. While oxidation/corrosion and delamination are difficult to distinguish by EIS, oxide formation could be confirmed by ATR-FTIR. Additionally, while delamination and polymer swelling may be difficult to separate with ATR-FTIR, EIS distinguished swelling of the polymer network and also identified ultimate failure as a result of delamination.</p><p>The capability of the integrated ATR-FTIR / EIS <i>in situ</i> technique was explored by studying aluminium/polymer systems of varying characteristics. Differences in water and electrolyte ingress could be monitored, as well as metal corrosion, polymer swelling and delamination.</p>

The amyloid beta peptide particularly the 40 and 42 amino acid residues are the responsible for plaque formation in Alzheimer's disease (AD) patients. Extra cellular plaque formation has been recognized after incessant investigations along with the formation of intracellular tau protein tangles as the hallmarks of AD. Furthermore, the plaque formation has been linked mostly as a cause of the disease and the tangles mostly as a consequence. Our investigation is focused on studying the formation of AD plaques. The amyloid beta (A[beta]) is a physiological peptide secreted from neurons under normal conditions, along with other soluble forms cleaved from the amyloid precursor protein (APP). These soluble forms of APP have neuroprotective and neurotrophic functions, while the A[beta] is considered an unwanted by-product of the APP processing. Under normal conditions there is an anabolic/catabolic equilibrium of the A[beta] peptide; therefore, it is believed that the formation of the plaque does not take place. On the other hand, the neurons' surface may play an important role in the adhesion mechanisms of the A[beta] peptide. Our experiments show that the neuron surfaces along with the media conditions may be the most important causes for progressive formation of plaques. We have incubated rigid supports (mica) and soft biomimetic substrates (lipid bilayers on top of a PEG cushion layer drafted onto a silica surface) with the three different conformations of the A[beta] peptide (monomeric, oligomeric and fibrils structures) to determine the adhesion mechanisms associated with in situ plaque formation. The soft biomimetic substrates have been assembled first by depositing and activating a thin film of silica (i.e., to create surface silanol groups). This film is then reacted with polyethylene glycol (PEG), which is a biocompatible polymer, to create a cushion-like layer that supports and allows the lipid bilayer to have high mobility. A lipid bilayer is then deposited on this soft support to reproduce a cell membrane using the Langmuir Blodgett deposition technique. The characterization of such biomimetic membranes has been studied by using Atomic Force Microscopy (AFM) in liquid environments. Our results show that these lipid bilayers are highly mobile. Additionally the structure and topography characteristics of the A[beta] conformations have been followed with atomic force microscopy (AFM). The kinetics and rates of adhesion have been measured with attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. Our results show the progress of the plaques' formation with time where simple monomers deposit on the substrates and allow the development of oligomeric species.

This dissertation shows the performance of adaptive waveforms when applied to two radar applications. One application is automatic target recognition (ATR) and the other application is range-Doppler ambiguity mitigation. The adaptive waveforms are implemented via a feedback loop from receiver to transmitter, such that previous radar measurements affect how the adaptive waveforms proceed. For the ATR application, adaptive transmitter can change the waveform's temporal structure to improve target recognition performance. For range-Doppler ambiguity mitigation application, adaptive transmitter can change the pulse repetition frequency (PRF) to mitigate range and Doppler ambiguity. In the ATR application, commercial electromagnetic software is used to create high-fidelity aircraft target signatures. Realistic waveform constraints are applied to show radar performance. The radar equation is incorporated into the waveform design technique and template-based classification is performed. Translation invariant feature is used for inaccurately known range scenario. The performance of adaptive waveforms is evaluated with not only a monostatic radar, but also widely separated MIMO radar. In MIMO radar, multiple transmit waveforms are used, but spectral leakage caused by constant-modulus constraint shows minimal interference effect. In the range-Doppler ambiguity mitigation application, particle-filter-based track-before-detect for a single target is extended to track and detect multiple low signal-to-noise ratio (SNR) targets, simultaneously. To mitigate ambiguity, multiple PRFs are used and improved PRF selection technique is implemented via predicted entropy computation when both blind and clutter zones are considered.

A broadband coupling approach applied to a single mode, sol-gel, planar integrated optical waveguide (IOW) was used to create a multichannel attenuated total reflection (ATR) spectrometer. Initial attempts to create an achromatic coupling element for sol-gel waveguides, based upon previous work applied to vacuum deposited glass devices, did not lead to an easily achievable design. Instead a simplified, non-achromatic approach based upon impinging an incident light beam with a large numerical aperture onto an incoupling prism was used. This simplified broadband coupling approach was used to create a sol-gel IOW-ATR spectrometer that transmitted light down to at least 400 nm, and produced a measurable bandwidth of ~ 250 nm; both phenomena are marked improvements upon the capabilities of previously reported devices. An experimental demonstration of this device proved it capable of measuring the visible spectrum of a thin film of horse heart cytochrome c adsorbed to the sol-gel surface at a submonolayer coverage. The broadband spectral capabilities of this sol-gel device were also used to experimentally validate a new method for determining the angular orientation of molecules bound to an arbitrary waveguide surface. In addition to the sol-gel IOW work, the simplified broadband coupling approach was applied to a previously reported multilayered electroactive waveguide device, which was used to collect electrically modulated, broadband spectra for thin films of cytochrome c, as well as a dicarboxyferrocene moiety. Both of these IOW-ATR spectrometers represent improved tools for probing the near-surface chemical environments of molecular assemblies.

The aim of the research is to examin the specialists from the Early Rehabilitation services (ERS) and the patients parents‘ attitude towards services for children quality, and introduce recommendations how to improve parents‘ and specialists‘ cooperation while accomplishing the services for children. Methodology. The anonymous questioning was made with 100 parents whose children were visiting specialists of Early Rehabilitation in 3 public medical institutions in Kaunas. The questionnaire used in the research was composed on the base of SERVQUAL methodology. One part of the questionnaire gave possibility to find parents‘ expectations towards servises for children quality, the next part satisfaction in services they get. The evaluation was made in differences which are in parents‘ expectations and satisfaction in the quality of servises they get in the aspect of dimensions (evidence, response, security, empathy). Linkert scale was used for answers. The statistical package SPSS version 13.0 for Windows was used to conduct data analysis. Results. In parent‘s opinion, services quality expectations got less point (mean score 2,80±0,44) than their satisfaction of the service provided (mean score 2,80±0,44) Therefore, the satisfaction of the service provided by ERS was beyond expectations. The largest quality gap was observed in the response, the smallest – in the dimensions of evidence. The parents‘ expectations were: to consult specialists of ERS at the desirable time... [to full text]

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Au cours de ma thèse au sein du laboratoire du Professeur Michelle Debatisse, je me suis intéressé aux mécanismes maintenant la stabilité du génome et contrôlant la dynamique de réplication dans les cellules de mammifères. J'ai étudié le rôle des kinases ATR (" Ataxia Telangectasia and Rad3 related ") et Chk1 (" Checkpoint Kinase 1 "), du point de contrôle intra-S (" checkpoint "), dans le contrôle de la dynamique de réplication. Cette première étude m'a amené à étudier la relation entre les dommages à l'ADN et la dynamique de réplication, dans des modèles cellulaires déficients pour des facteurs de la réponse aux dommages à l'ADN (DDR), appartenant soit au " checkpoint ", soit à la voie de réparation par recombinaison homologue (HR), tels que Rad51 et BRCA2. Je montre ici, que le ralentissement des fourches de réplication et l'augmentation de la densité d'événements d'initiation, observés dans des cellules déficientes pour Chk1 ou Rad51, sont la conséquence indirecte des lésions apparaissant spontanément dans de telles cellules. Le ralentissement des fourches dans ces cellules dépend d'une perturbation de la disponibilité en précurseurs de nucléotides qui dépend de la sur-expression et/ou de la re-localisation de la sous-unité p53R2 de la ribonucléotide réductase (RNR). De plus, contrairement à ce qui était proposé, je montre que Chk1 n'a pas de rôle actif dans la répression des origines latentes, mais que c'est la vitesse des fourches qui détermine l'espacement entre les origines actives, par un mécanisme de compensation découvert auparavant au laboratoire (Anglana, 2003 ; Courbet, 2008). L'ensemble de mes résultats permet de proposer un mécanisme général de communication entre la réplication et la réparation. Ce mécanisme confère un avantage aux cellules, puisque le ralentissement des fourches stabilise la machinerie de réplication qui voyage sur une matrice endommagée, et l'activation d'origines latentes procure une source de sauvetage pour les fourches bloquées.

Frankfurt (Main), Universiẗat, Diss., 2008.

Ewing Sarcoma (ES) is an aggressive pediatric solid tumor. Even though overall-survival for localized patients is approximately 70%, the overall-survival for high risk ES patients has not improved in the last 20 years. Therefore, there is a need for exploration of new therapeutic agents in ES. Recent evidence has demonstrated that ES cells behave like BRCA-deficient tumor types which renders them sensitive to PARP inhibitors in vitro and in vivo. However, a phase II study of the efficacy of single-agent PARP inhibition in patients with relapsed ES did not significantly improve outcome. As single-agent therapy is rarely expected to result in significant clinical responses, in this study, we plan to validate potential targeted combination therapies with PARP inhibitors in ES. Since ES appears to demonstrated BRCA-deficient biology with impaired homologous recombination, cells are expected to be sensitive to both PARP inhibitors and ATR inhibitors, drugs which have a role in regulating DNA damage and impairing homologous recombination. In breast cancer and ovarian cell lines with genetic BRCA-deficiency, PARP and ATR inhibitors have synergistic activity. We hypothesize that these inhibitors will also have synergistic anti-Ewing activity. Furthermore, we recognize that ES cells demonstrate remarkably quiet genomes suggesting that there is minimal ongoing DNA-damage when cells are growing unperturbed. Therefore, we also plan to test the effect of adding low-dose genotoxic chemotherapy to induce additional sensitivity to the combination of PARP and ATR inhibitors in ES. The specific aims of this study were to explore the possible anti-tumor effect of PARP inhibitors combined with ATR inhibitors in ES cell lines, and to explore whether low dose genotoxic chemotherapy with SN38 can potentiate the anti-tumor effect of combined PARP and ATR inhibition in ES cell lines. We studied the anti-Ewing Sarcoma effect of the combination of a PARP inhibitor, AZD2281, and an ATR inhibitor, AZD6738, across a range of doses with and without low doses of a DNA damaging agent, SN38 (irinotecan metabolite), in two ES cell lines. We analyzed synergy by determining the Combination Index (CI) and Fractional Inhibition (FA) of each combination. We found that the ATR inhibitor, AZD6738, was synergistic across large range of concentrations when combined with the PARP inhibitor, AZD2281, in ES cell lines. We also found that treatment of cells with low doses of SN38 increases ES cell sensitivity to treatment with the PARP inhibitor and ATR inhibitor combination. This study provides preclinical support for additional studies exploring these combinations in ES. Given the low number of pediatric patients with ES compared to adult cancer patients, there will be limited attempts in combining these agents in clinical trials. Therefore, the development of an in vivo trial testing the safety and efficacy of this combination in ES mouse models is proposed. / 2020-07-03T00:00:00Z