<p>One of the limiting factors in gas turbine design is the allowable metal temperatures and loads in critical components. Specially designed superalloys are used when the conditions are most severe. One of these superalloys is Inconel 718. To be able to design components for higher temperature and higher loads, an accurate understanding and computational model of the material is needed. In this thesis the deformation mechanisms of Inconel 718 have been investigated and a theoretical basis for modelling in a large deformation context has been established. Finally a viscoplastic nonlinear kinematic hardening material model with an Armstrong-Frederick backstress evolution law has been implemented as a first step in describing the constitutive behaviour of the material Inconel 718.</p>

Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / "May 2001." Typescript. Vita. Includes bibliographical references (leaves 66-80). Also available on the Internet.

published_or_final_version / Medicine / Master / Master of Research in Medicine

Cyclic adenosine monophosphate (cAMP) is an important intracellular secondary messenger. The major target of cAMP was traditionally considered as protein kinase (PK) A. This belief has been challenged by the discovery of exchange protein activated by cAMP 1 (Epac1), a cAMP-dependent guanine-nucleotide-exchange factor (GEF). Epac1 is ubiquitously expressed in all tissues and plays important roles particularly in the cardiovascular system. As cAMP activates both PKA and Epac1, the development of 8-pCPT-2'-O-Me-cAMP (8-pCPT), which has 107-fold higher affinity to bind and activate Epac1 than PKA, aids the researches on Epac1-mediated responses. In the present study, the protein expressions of Epac1 in the porcine coronary arteries and rat aortas were confirmed by Western blot analysis. In organ chambers, 8-pCPT induced acute relaxations in isolated porcine coronary arteries contracted to thromboxane receptor (TP-receptor) antagonists, and the relaxation was endothelium-independent. The 8-pCPT-induced Epac1 activation selectively altered the vasoactive responses to the TP-receptor agonists. The Epac1-mediated relaxation was found not related to PKA, PKG and the opening of ATP-sensitive potassium channels. Although Epac1 was first cloned as a Rap-linked GEF, in the porcine coronary artery, small GTPase Rac1 is the downstream target of Epac1 instead of Rap1 for relaxation. Activation of TP-receptors stimulates Rho-kinase to cause contraction, and the 8-pCPT-induced relaxation was Rho-kinase dependent, probably through pathway that is distinct from Rac1. Activation of Epac1 also inhibited the contraction to PKC, which is also downstream of TP-receptor but independent to Rho-kinase activity. On the contrary, in the aorta from male Sprague-Dawley rats aged 10-12 weeks, 8-pCPT induced relaxation in rings contracted to phenylephrine (PE) and the relaxation was endothelium-dependent. The relaxation depended mainly on endothelial nitric oxide synthase (eNOS) and partly on cyclooxygenase (COX). Western blot analysis found that 8-pCPT did not enhance eNOS phosphorylation, which is one of the mechanisms for eNOS activation. Activation of Epac1 also did not alter the phosphorylation of Akt and ERK1/2 which play important roles in cAMP-dependent eNOS. More experiments are needed to examine whether or not Epac1 alters nitric oxide (NO) and prostanoids synthesis, which are the major endothelium-derived mediators responsible for vascular tone regulation. In summary, the selective Epac activator 8-pCPT induced significant relaxations by distinct mechanisms in porcine coronary arteries and rat aortas. It is most likely that the relaxing effects of Epac1 activator are tissue and/or species specific. Owing to the effects of 8-pCPT on vascular relaxation, Epac1 might be an alternative therapeutic target for the treatment of vasospasm and hypertension. Further studies are necessary to explore the detailed mechanisms of Epac1 and its in vivo effects and in diseased models. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Philosophy

Unstable Sn(III) intermediates generated in the Sn(IV)/Sn(II) redox reaction in 2 M HBr + 4 M NaBr media were detected by scanning electrochemical microscopy (SECM) and cyclic voltammetry (CV). In CV, the underpotential deposition of Sn(0) and its stripping peaks severely perturbed the analysis of diffusional reactions. In SECM, however, the detection of diffusional Sn(III) bromide species was clearly observed due to the absence of the perturbation from the surface reactions. The ECEC-DISP mechanism in both the reduction and oxidation reactions was proposed via Sn(III) bromide intermediates. CVs at different concentrations of Sn(IV) and at various scan rates were fit by numerical simulations based on the proposed mechanism with good agreement. Enhanced electrochemical reversibility in the Sn(IV)/Sn(II) redox reaction was observed at the elevated temperature of 80 °C. We attributed such observation to changes in the rate of bromide loss from Sn(IV)Br₆²⁻ to Sn(IV)Br₅⁻ based on the CV simulation. In a similar approach, a short-lived intermediate, presumably bromine anion radical Br₂⁻·, was detected in the Br⁻ /Br₃⁻ electro-oxidation reaction in nitrobenzene solution by SECM and CV. The reaction mechanism was proposed based on a detected Br₂⁻· intermediate as follows: (1) the one electron transfer of Br⁻ to Br·, (2) the dimerization of 2Br· to Br₂, (3) the bromide addition reaction of Br₂ to Br₃⁻ , (4) the bromide addition reaction of Br· to Br₂⁻·, and (5) the Br· addition reaction of Br₂⁻· to Br₃⁻. The simulation based on the proposed mechanism fitted well with the experimental SECM and CV results. At last, the applicability of the Sn/Br system as electrolyte for electrochemical energy storage was tested. A redox flow battery was constructed, where the Sn(IV)/Sn(II) reduction was carried out on the negative electrode, while the Br· /Br₂ oxidation was carried out on the positive electrode during charging. Cyclability was tested up to 35 charge/discharge cycles, and 100 % coulombic efficiency was observed in all cycles. However, only 40 % of voltage efficiency was obtained, mainly due to the large irreversibility of the Sn(IV)/Sn(II) redox reaction in the bromide media.

Το θέμα της παρούσας εργασίας αφορά την αποτίμηση της απόκρισης των τοιχοπληρωμένων πλαισίων οπλισμένου σκυροδέματος, έναν τομέα που έχει απασχολήσει πληθώρα ερευνητών τις τελευταίες δεκαετίες. Παρότι έχουν προταθεί πολλές διαφορετικές λύσεις για την προσομοίωση των τοιχοπληρώσεων, δεν έχει ακόμη προκύψει ένα ενιαίο και αξιόπιστο προσομοίωμα ικανό να αναπαραστήσει με ακρίβεια τα διαφορετικά χαρακτηριστικά της απόκρισης που εμφανίζονται κατά περίπτωση. Στην παρούσα εργασία προτείνεται ένα νέο απλοποιητικό προσομοίωμα για την ανάλυση των τοιχοπληρώσεων μετά την τροποποίηση του υπάρχοντος προσομοιώματος των Crisafulli and Carr (2007) και διερευνάται η εφαρμογή και η κατάλληλη βαθμονόμηση του για την ανελαστική ανάλυση τοιχοπληρωμένων πλαισίων οπλισμένου σκυροδέματος υπό την δράση πλευρικών ανακυκλιζόμενων φορτίων. Στο προτεινόμενο προσομοίωμα συνδυάζονται μία σειρά από μέλη/ελατήρια προκειμένου να ληφθούν υπόψη ανεξάρτητα η συμπεριφορά της τοιχοπλήρωσης σε διαγώνια θλίψη και διάτμηση. Η αξιοπιστία του προσομοιώματος επαληθεύεται με διαθέσιμα πειραματικά δεδομένα σε τοιχοπληρωμένα πλαίσια, επιδεικνύοντας ικανοποιητικό βαθμό συμφωνίας. Η πολυπλοκότητα των προσομοιωμάτων των τοιχοπληρώσεων έγκειται στην πληθώρα των παραμέτρων που απαιτούνται για τον ορισμό τους. Για το λόγο αυτό η αριθμητική εφαρμογή του προσομοιώματος συνοδεύεται από μία εκτεταμένη παραμετρική μελέτη που στοχεύει στην διερεύνηση της ευαισθησίας του προσομοιώματος σε κάθε μία από τις παραμέτρους που υπεισέρχονται στον ορισμό του επιτρέποντας εν τέλει την ταυτοποίηση των κρίσιμων ποσοτήτων και την καθοδήγηση του μέλλοντα χρήστη σχετικά με την επιλογή τους. / The assessment of the response of masonry infilled RC frame structures has been a major challenge over the last decades. While several modeling approaches have been proposed, none can cover all aspects observed in the tests. The present paper introduces a simplified model built on the approach established by Crisafulli and Carr (2007) and addresses its calibration and implementation in a nonlinear analysis software for the evaluation of the in-plane lateral response of infilled RC frames. The proposed model uses a set of elements/springs to account separately for the compressive and shear behavior of masonry. The efficiency of the modeling approach is validated with available experimental data, yielding satisfactory matching. The most intricate issue encountered when attempting to represent a masonry panel is the plethora of the material parameters involved and the lack of complete and available test results. Thus, the numerical investigation is accompanied by a parametric study on the sensitivity of the model to the various parameters to identify the critical modeling quantities and provide guidance on their selection.

In 2010 and 2011 Christchurch, New Zealand experienced a series of earthquakes that caused extensive damage across the city, but primarily to the Central Business District (CBD) and eastern suburbs. A major feature of the observed damage was extensive and severe soil liquefaction and associated ground damage, affecting buildings and infrastructure. The behaviour of soil during earthquake loading is a complex phenomena that can be most comprehensively analysed through advanced numerical simulations to aid engineers in the design of important buildings and critical facilities. These numerical simulations are highly dependent on the capabilities of the constitutive soil model to replicate the salient features of sand behaviour during cyclic loading, including liquefaction and cyclic mobility, such as the Stress-Density model. For robust analyses advanced soil models require extensive testing to derive engineering parameters under varying loading conditions for calibration. Prior to this research project little testing on Christchurch sands had been completed, and none from natural samples containing important features such as fabric and structure of the sand that may be influenced by the unique stress-history of the deposit. This research programme is focussed on the characterisation of Christchurch sands, as typically found in the CBD, to facilitate advanced soil modelling in both res earch and engineering practice - to simulate earthquake loading on proposed foundation design solutions including expensive ground improvement treatments. This has involved the use of a new Gel Push (GP) sampler to obtain undisturbed samples from below the ground-water table. Due to the variable nature of fluvial deposition, samples with a wide range of soil gradations, and accordingly soil index properties, were obtained from the sampling sites. The quality of the samples is comprehensively examined using available data from the ground investigation and laboratory testing. A meta-quality assessment was considered whereby a each method of evaluation contributed to the final quality index assigned to the specimen. The sampling sites were characterised with available geotechnical field-based test data, primarily the Cone Penetrometer Test (CPT), supported by borehole sampling and shear-wave velocity testing. This characterisation provides a geo- logical context to the sampling sites and samples obtained for element testing. It also facilitated the evaluation of sample quality. The sampling sites were evaluated for liquefaction hazard using the industry standard empirical procedures, and showed good correlation to observations made following the 22 February 2011 earthquake. However, the empirical method over-predicted liquefaction occurrence during the preceding 4 September 2010 event, and under-predicted for the subsequent 13 June 2011 event. The reasons for these discrepancies are discussed. The response of the GP samples to monotonic and cyclic loading was measured in the laboratory through triaxial testing at the University of Canterbury geomechanics laboratory. The undisturbed samples were compared to reconstituted specimens formed in the lab in an attempt to quantify the effect of fabric and structure in the Christchurch sands. Further testing of moist tamped re- constituted specimens (MT) was conducted to define important state parameters and state-dependent properties including the Critical State Line (CSL), and the stress-strain curve for varying state index. To account for the wide-ranging soil gradations, selected representative specimens were used to define four distinct CSL. The input parameters for the Stress-Density Model (S-D) were derived from a suite of tests performed on each representative soil, and with reference to available GP sample data. The results of testing were scrutinised by comparing the data against expected trends. The influence of fabric and structure of the GP samples was observed to result in similar cyclic strength curves at 5 % Double Amplitude (DA) strain criteria, however on close inspection of the test data, clear differences emerged. The natural samples exhibited higher compressibility during initial loading cycles, but thereafter typically exhibited steady growth of plastic strain and excess pore water pressure towards and beyond the strain criteria and initial liquefaction, and no flow was observed. By contrast the reconstituted specimens exhibited a stiffer response during initial loading cycles, but exponential growth in strains and associated excess pore water pressure beyond phase-transformation, and particularly after initial liquefaction where large strains were mobilised in subsequent cycles. These behavioural differences were not well characterised by the cyclic strength curve at 5 % DA strain level, which showed a similar strength for both GP samples and MT specimens. A preliminary calibration of the S-D model for a range of soil gradations is derived from the suite of laboratory test data. Issues encountered include the influence of natural structure on the peak-strength–state index relationship, resulting in much higher peak strengths than typically observed for sands in the literature. For the S-D model this resulted in excessive stiffness to be modelled during cyclic mobility, when the state index becomes large momentarily, causing strain development to halt. This behaviour prevented modelling the observed re- sponse of silty sands to large strains, synonymous with “liquefaction”. Efforts to reduce this effect within the current formulation are proposed as well as future research to address this issue.

The cyclic nucleotide monophosphates (CNs), cAMP and cGMP, are second messengers that participate in the regulation of development, metabolism and adaptive responses. In plants, CNs are associated with the control of pathogen responses, pollen tube orientation, abiotic stress response, membrane transport regulation, stomatal movement and light perception. In this study, we hypothesize that cAMP and cGMP promote changes in the transcription level of genes related to photosynthesis, high light and membrane transport in Arabidopsis thaliana leaves and, that these changes at the molecular level can have functional biological consequences. For this reason we tested if CNs modulate the photosynthetic rate, responses to high light and root ion transport. Real time quantitative PCR was used to assess transcription levels of selected genes and infrared gas analyzers coupled to fluorescence sensors were used to measure the photosynthetic parameters. We present evidence that both cAMP and cGMP modulate foliar mRNA levels early after stimulation. The two CNs trigger different responses indicating that the signals have specificity. A comparison of proteomic and transcriptional changes suggest that both transcriptional and post-transcriptional mechanisms are modulated by CNs. cGMP up-regulates the mRNA levels of components of the photosynthesis and carbon metabolism. However, neither cAMP nor cGMP trigger differences in the rate of carbon assimilation, maximum efficiency of the photosystem II (PSII), or PSII operating efficiency. It was also demonstrated that CN regulate the expression of its own targets, the cyclic nucleotide gated channels - CNGC. Further studies are needed to identify the components of the signaling transduction pathway that mediate cellular changes and their respective regulatory and/or signaling roles.

The main goals of this research were to synthesize nitrogen oxide releasing diazeniumdiolates and their prodrugs and to evaluate their pharmacological effects. The different projects and their results are described below. i. Comparison of HNO and NO donating properties of cyclic amine diazeniumdiolates Diazeniumdiolates are an attractive class of donor compounds as they can be tuned to release NO or both NO and HNO depending upon the amine backbone. Isopropylamine (IPA/NO) and cyclohexylamine (CHA/NO) diazeniumdiolates are currently the only examples of primary amine based diazeniumdiolates. A series of structurally related cyclic amine based diazeniumdiolates were synthesized and characterized. An acetoxymethyl derivative was also synthesized to facilitate cellular uptake and to achieve higher HNO levels in cells. ii. Nitrogen oxide releasing diazeiumdiolate based adducts of N-des-methyl-tamoxifen Nitrogen oxide (NO/HNO) donating diazeniumdiolate adducts of N-desmethyltamoxifen (a key metabolite of the breast cancer drug tamoxifen) were synthesized. DEA/NO-AcOM, an NO donor was also synthesized to monitor the effect of NO on breast cancer cell survival. Derivatives of N-desmethyltamoxifen were found to be effective towards estrogen receptor positive (ER+) cells only. DEA/NO-AcOM was found to be cytotoxic towards estrogen-dependent and independent cell lines, in combination with tamoxifen, or by itself. iii. Synthesis and characterization of nitrogen oxide adducts with non-steroidal anti-inflammatory drugs (NSAIDs) Our group has shown HNO releasing diazeniumdiolate derivatized aspirin to be comparably effective in preventing gastric ulceration to NO-releasing diazeniumdiolate based aspirin analogues. Series of such NSAID adducts were further extended by synthesizing such derivatives of indomethacin and niflumic acid. NO/HNO releasing analogues of aspirin and indomethacin were cytotoxic towards two different breast cancer cell lines, irrespective of estrogen dependence.iv. Chlorambucil analogue of PABA/NOChlorambucil, an alkylating agent is used in leukemia treatment. Tumor cells resistant to alkylating agents often have increased glutathione levels and increased activity of glutathione-S-transferase (GST). PABA/NO is an NO donor with a promising anticancer profile. The chlorambucil analogue of PABA/NO was synthesized to utilize GST for releasing NO and to potentially overcome cellular resistance.

Low-density parity-check (LDPC) codes have been intensively studied in the past decade for their capacity-approaching performance. LDPC code implementation complexity and the error-rate floor are still two significant unsolved issues which prevent their application in some important communication systems. In this dissertation, we make efforts toward solving these two problems by introducing the design of a class of LDPC codes called structured irregular repeat-accumulate (S-IRA) codes. These S-IRA codes combine several advantages of other types of LDPC codes, including low encoder and decoder complexities, flexibility in design, and good performance on different channels. It is also demonstrated in this dissertation that the S-IRA codes are suitable for rate-compatible code family design and a multi-rate code family has been designed which may be implemented with a single encoder/decoder.The study of the error floor problem of LDPC codes is very difficult because simulating LDPC codes on a computer at very low error rates takes an unacceptably long time. To circumvent this difficulty, we implemented a universal quasi-cyclic LDPC decoder on a field programmable gate array (FPGA) platform. This hardware platform accelerates the simulations by more than 100 times as compared to software simulations. We implemented two types of decoders with partially parallel architectures on the FPGA: a circulant-based decoder and a protograph-based decoder. By focusing on the protograph-based decoder, different soft iterative decoding algorithms were implemented. It provides us with a platform for quickly evaluating and analyzing different quasi-cyclic LDPC codes, including the S-IRA codes. A universal decoder architecture is also proposed which is capable of decoding of an arbitrary LDPC code, quasi-cyclic or not. Finally, we studied the low-floor problem by focusing on one example S-IRA code. We identified the weaknesses of the code and proposed several techniques to lower the error floor. We successfully demonstrated in hardware that it is possible to lower the floor substantially by encoder and decoder modifications, but the best solution appeared to be an outer BCH code.