Background: Adherent-invasive Escherichia coli (AIEC) is a pathogen isolated from the ileum of patients with CD. IFNγ is a key mediator of immunity, which regulates inflammatory responses to microbial infections. Previously, we showed enterohemorrhagic E. coli prevents STAT1 activation. Aims: To determine; 1) whether activation of STAT1 by IFNγ was prevented following AIEC infection, and 2) define the mechanisms used. Methods: Human epithelial cells were infected with AIEC strains or other pathogenic and commensal E. coli strains. Following infection, cells were stimulated with IFNγ. Activation of STAT1, was monitored by immunoblotting. Results: AIEC strains prevented STAT1 phosphorylation in response to IFNγ. Effect required live bacteria with active protein synthesis. A bacterial product was responsible for blocking STAT1 signalling and interfered with downstream signalling cascades. Conclusion: Suppression of epithelial cell STAT1 signal transduction by AIEC strains represents a novel mechanism by which the pathogen evades host immune responses to the infection.

Background: Adherent-invasive Escherichia coli (AIEC) is a pathogen isolated from the ileum of patients with CD. IFNγ is a key mediator of immunity, which regulates inflammatory responses to microbial infections. Previously, we showed enterohemorrhagic E. coli prevents STAT1 activation. Aims: To determine; 1) whether activation of STAT1 by IFNγ was prevented following AIEC infection, and 2) define the mechanisms used. Methods: Human epithelial cells were infected with AIEC strains or other pathogenic and commensal E. coli strains. Following infection, cells were stimulated with IFNγ. Activation of STAT1, was monitored by immunoblotting. Results: AIEC strains prevented STAT1 phosphorylation in response to IFNγ. Effect required live bacteria with active protein synthesis. A bacterial product was responsible for blocking STAT1 signalling and interfered with downstream signalling cascades. Conclusion: Suppression of epithelial cell STAT1 signal transduction by AIEC strains represents a novel mechanism by which the pathogen evades host immune responses to the infection.

Acoustic micro-sensors have already been applied in mass sensing including surface acoustic wave (SAW), flexural plate wave (FPW), thickness shear mode (TSM) and shear horizontal acoustic plate mode (SH-APM). The FPW micro-sensor is very suitable for liquid-sensing and bio-sensing applications due to the high mass-sensitivity and low phase-velocity in liquid. However, the conventional FPW micro-sensors presented a high insertion-loss (IL) and a low signal-to-noise ratio so it is difficult to combine with IC into a micro-system. To overcome these drawbacks, this study combine the Microelectromechanical System (MEMS) technology and the high C-axis orientation ZnO piezoelectric thin-film to develop a low insertion loss, low operation frequency, and high electromechanical coupling coefficient FPW device. In this study, a high C-axis orientation ZnO piezoelectric thin-film with a 20944A.U. X-Ray diffraction intensity at 34.200 degree and a 0.573 degree full width at half maximum (FWHM) was deposited by a commercial magnetic radio-frequency (RF) sputter system. The total processes of the FPW micro-sensor included five photolithography and seven thin-film depositions. In this study a low operation frequency (0.1MHz), low insertion loss (11dB to 14dB) and high electromechanical coupling coefficient (11%) FPW sensor was developed and fabricated.

In this thesis, numerical and experimental design of a multi-frequency underwater acoustic transducer with cylindrical piezoelectric ceramic tubes is studied. In the numerical design, the acoustic, mechanical and thermal performances of the transducer are investigated by means of finite element method (FEM) in ANSYS. The design of the transducer that meets the acoustic requirements is checked in terms of the mechanical and thermal performances. After the completion of the numerical design, the transducer is manufactured and some performance tests such as impedance test, hydrostatic pressure test and full-power operation test are applied to it. Finally, the results of the numerical and experimental design are compared. As a result, the design of an underwater acoustic transducer that operates at two frequency bands centered at about 30 and 60 kHz under a hydrostatic pressure of 30 bars is accomplished. This transducer also resist to a shock loading of 500g for 1 millisecond.

<p>The objectives of the thesis work were to study theinteraction between embedded piezoceramic transducers andcomposite structures as well as determine techniques tosimplify the Lamb waves analysis. Firstly, this studyconsidered the design of the embedded piezoceramic transducers.Secondly, the effect of the embedded transducer on thecomposite strength as well as the influence of the mechanicallyloaded composite on the characteristics of the embeddedtransducer were investigated. Finally, to simplify the analysisof such complex Lamb wave responses, two techniques weredeveloped. They were based on the wavelet technique and amodelling technique, respectively.</p><p>The design of the embedded piezoceramic transducers wasimproved by reducing the stress concentrations in the compositeas well as in all components constituting the piezoceramictransducer, that is, the piezoceramic element, interconnectorand conductive adhesive. The numerical analysis showed that thethickness of the interconnector had no significant influence onthe stress state of the piezoceramic transducer. It was alsofound that a compliant conductive adhesive reduced the stressconcentration located at the edge of the piezoceramic element.The structural integrity of composites embedded with theimproved piezoceramic transducer was investigated. Theexperiments, performed in tensile and compressive staticloading, indicated that the strength of the composite was notsignificantly reduced by the embedded piezoceramic transducer.Further investigations were conducted to evaluate theperformance of the improved piezoceramic transducer used as aLamb wave generator embedded in composites subjected tomechanical loading. The tests were conducted in tensile andcompressive static loading as well as fatigue loading. Thestudy showed a large working range of the embedded piezoceramictransducer. A post processing technique based on the waveletswas further assessed in the detection of damage and in thedamage size evaluation. A new wavelet basis was developedspecially for processing the Lamb wave response. This method,focused on the wavelet coefficients from the decomposition Lambwave response, showed promising results in evaluating thedamage size. The wavelets offered a sensitive tool to detectsmall damage, compared to other detection methods, improvingthe damage detection capabilities. The other technique wasdevoted to the simplification of the generated Lamb waves bythe use of multi-element transducers. The transducers weredesigned using both a normal-mode expansion and a FE-method.This technique allowed reducing the effect of a Lamb wave modetowards another. This technique was successfully implemented ina damage detection system in composites.</p><p><b>Keywords:</b>Embedded piezoceramic, transducer, composite,structural integrity, health monitoring, damage detection, Lambwaves, wavelets, normal-mode expansion, FE-method</p>

Cytokine and growth factor signaling pathways involving STAT3 are frequently constitutively activated in many human primary tumors, and are known for the transcriptional role they play in controlling cell growth and cell cycle progression. However, the extent of STAT3's reach on transcriptional control of the genome as a whole remains an important question. We predicted that this persistent STAT3 signaling affects a wide variety of cellular functions, many of which still remain to be characterized. We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome-wide gene expression profile by microarray, using cells expressing constitutively-activated STAT3. Using computational analysis, we were able to define the gene expression profiles of cells containing activated STAT3 and identify candidate target genes with a wide range of biological functions. Among these genes we identified Necdin, a negative growth regulator, as a novel STAT3 target gene, whose expression is down-regulated at the mRNA and protein levels when STAT3 is constitutively active. This repression is STAT3 dependent, since inhibition of STAT3 using siRNA restores Necdin expression. A STAT3 DNA-binding site was identified in the Necdin promoter and both EMSA and chromatin immunoprecipitation confirm binding of STAT3 to this region. Necdin expression has previously been shown to be down-regulated in a melanoma and a drug-resistant ovarian cancer cell line. Further analysis of Necdin expression demonstrated repression in a STAT3-dependent manner in human melanoma, prostate and breast cancer cell lines. These results suggest that STAT3 coordinates expression of genes involved in multiple metabolic and biosynthetic pathways, integrating signals that lead to global transcriptional changes and oncogenesis. STAT3 may exert its oncogenic effect by up-regulating transcription of genes involved in promoting growth and proliferation, but also by down-regulating expression of negative regulators of the same cellular processes, such as Necdin.

Particle separation is of great interest to many biological and biomedical applications. Flow-based methods have been used to sort particles and cells. However, the main challenge with flow based particle separation systems is the need for a sheath flow for successful operation. Existence of the sheath liquid dilutes the analyte, necessitates precise flow control between sample and sheath flow, requires a complicated design to create sheath flow and separation efficiency depends on the sheath liquid composition. In addition, current gold standard active separation techniques are only capable of separation based on particle size; hence, separation cannot be achieved for same-size particles with different densities. In this dissertation, a sheathless acoustic-based microfluidic platform using surface acoustic wave for not only size-dependent but also density-dependent particle separation has been investigated. In this platform, two different functions were incorporated within a single microfluidic channel with varying the number of pressure node and position. The first function was to align particles on the center of the microfluidic channel without adding any external sheath flow. The second function was to separate particles according to their size or density. Two different size-pairs of polystyrene particles with different diameters (3 µm and 10 µm for general size-resolution, 3 µm and 5 µm for higher size-resolution) were successfully separated. Also, the separation of two 10 µm diameter, different-density particle streams (polystyrene: 1.05 g/cm3, melamine: 1.71 g/cm3) was successfully demonstrated. The effects of the input power, the flow rate, and particle concentration on the separation efficiency were investigated. A range of high separation efficiencies with 94.8-100 % for size-based separation and 87.2 - 98.9 % for density-based separation were accomplished. In this dissertation, an acoustic-based microfluidic platform using dual acoustic streaming for active mixing has also been investigated. The rapid and high efficiency mixing of a fluorescent dye solution and deionized water in a microfluidic channel was demonstrated with single acoustic excitation by one interdigital transducer (IDT) as well as dual excitation by two IDTs. The mixing efficiencies were investigated as a function of applied voltage and flow rates. The results indicate that with the same operation parameters, the mixing efficiency with dual-IDT design increased to 96.7 % from 69.8 % achievable with the traditional single-IDT design. The effect of aperture length of the IDT on mixing efficiency was also investigated. Additionally, the effects of the polydimethylsiloxane (PDMS) channel wall thickness on the insertion loss and the particle migration to the pressure node due to acoustic radiation forces induced by SAW have been investigated. The results indicate that as the PDMS channel wall thickness decreased, the SAW insertion loss is reduced as well as the velocity of the particle migration due to acoustic forces increased significantly. As an example, reducing the side wall thickness of the PDMS channel from 8 mm to 2 mm in the design results in 31.2 % decrease in the insertion loss at the resonant frequency of 13.3 MHz and 186 % increase the particle migration velocity at the resonant frequency of 13.3 MHz with input power of 27 dBm. Lastly, a novel acoustic-based method of manipulating the particles using phase-shift has been proposed and demonstrated. The location of the pressure node was adjusted simply by modulating the relative phase difference (phase-shift) between two IDTs. As a result, polystyrene particles of 5 µm diameter trapped in the pressure node were manipulated laterally across the microfluidic channel. The lateral displacements of the particles from -72.5 µm to 73.1 µm along the x-direction were accomplished by varying the phase-shift with a range of -180° to 180°. The relationship between the particle displacement and the phase-shift of SAW was obtained experimentally and shown to agree with theoretical prediction of the particle position.

Visibly Pushdown Languages (VPLs), recognized by Visibly Pushdown Automata (VPAs), are a nicely behaved family of context-free languages. It has been shown that VPAs are equivalent to Extended Document Type Definitions (EDTDs), and thus, they provide means for elegantly solving various problems on XML. One of the important problems about XML that can be addressed using VPAs is the validation problem in which we need to decide whether an XML document con- forms to the schema specification given by an EDTD. In this thesis, we are interested in solving the approximate version of this problem, which is to decide whether an XML document can be modified by a tolerable number of edit operations to yield a valid one with respect to a given EDTD. For this, we define Edit Visibly Pushdown Transducers (EVPTs) that give us the framework for solving this problem ([23]). We propose two algorithms; the first algorithm solves the approximate validation for any EDTD in PTIME. The second algorithm solves the same problem for an interesting subclass of EDTDs (those rec- ognizable by FSA) in constant space using only a single pass over the document.

In this thesis we will introduce multioperator weighted monadic datalog (mwmd), a formal model for specifying tree series, tree transformations, and tree languages. This model combines aspects of multioperator weighted tree automata (wmta), weighted monadic datalog (wmd), and monadic datalog tree transducers (mdtt). In order to develop a rich theory we will define multiple versions of semantics for mwmd and compare their expressiveness. We will study normal forms and decidability results of mwmd and show (by employing particular semantic domains) that the theory of mwmd subsumes the theory of both wmd and mdtt. We conclude this thesis by showing that mwmd even contain wmta as a syntactic subclass and present results concerning this subclass.

Doctor of Philosophy(PhD) / Soil Stiffness is an important parameter for any geotechnical engineering design. In laboratory tests it can be derived from stress-strain curves or from dynamic measurement based on wave propagation theory. The second method is a more accurate and direct method for measuring stiffness at very small strains. Until now dynamic measurements have usually been obtained manually from the triaxial test. Attempts have been made to automate the procedure but have apparently failed due to the high level of variability in dynamic measurements. Moreover, triaxial tests of soil can be very lengthy and manual dynamic measurements can be very tedious and impractical for long stress-path tests. In this research a computer program has been developed to automate the stiffness measurement (using bender elements) based on the cross- correlation technique. In this method the program records all the peaks and corresponding arrival times in the cross-correlation signal during the test. The stiffness is calculated and displayed on the screen continuously. The Bender Element enabled to get the small strain shear modulus. An arbitrary “Chirp” waveform of 4 kHz frequency was used for this purpose. Subsequently Bender Element test results were checked by ‘Sine’ waveforms of frequencies 5kHz to 20kHz, as well as by manual inspection of the arrival time. This thesis discusses the method and some of the difficulties in truly automating the process. Finally some results from a number of stress path tests on uncemented and cemented calcareous sediments are presented. Bender elements have been used by many researchers to determine the shear modulus at small strain. Most previous studies have used visual observation of arrival time, which is time consuming and often requires some judgement from the operator. This thesis will describe the use of cross-correlation as a method for automation of Gmax measurement. Cross-correlation has been claimed to be unreliable in the past. However, it will be shown that provided several peaks in the cross-correlation signal are monitored it is possible to follow the variation of Gmax throughout consolidation and shearing. The measurement can be made at regular intervals within the software controlling a stress-path apparatus. Details of the apparatus used and practical considerations including selection of waveform and frequency are discussed. A series of drained cyclic triaxial tests was carried out on artificially cemented and uncemented calcareous soil of dry unit weights 13, 15, and 17 kN/m3 and sheared with constant effective confining stress 300 kPa. Gypsum cement contents of 10%, 20% and 30% of the dry soil weight were used. In addition a series of stress path tests were performed on Toyuora sand samples. Results will be presented for two uncemented and one cemented sand. In addition to the bender elements, all tests had internal instrumentation to monitor axial and lateral strains. Results will be presented for Toyura sand to show that the measurements are consistent with those obtained by other methods. Results will also be presented for carbonate sand subjected to a wide range of stress paths. Finally, results will be presented for the carbonate sand cemented with gypsum. The degradation of Gmax of the cemented soil subjected to variety of monotonic and cyclic stress-paths is presented. Analysis of the results includes assessment of the factors influencing Gmax for uncemented sand. Preliminary analysis indicates that in order of importance these are the mean effective stress, the stress history, void ratio and stress ratio. For cemented sand, Gmax is initially constant and independent of stress path. After yielding the modulus degrades, becoming increasingly stress level dependent and eventually approaches the value for uncemented sand. Factors influencing the rate of degradation are discussed. For the Toyuora sand samples the effects of end restraint on the stress-strain response at small strains were investigated. The conventional method of mounting triaxial specimen has the effect of introducing friction between sample and end platen during a compression test. This inevitably restricts free lateral movement of the specimen ends. Frictional restraint at the sample ends causes the formation of 'dead zones' adjacent to the platens, resulting in non-uniform distribution of stress and strain (and of pore pressure if undrained). On the other hand the specimen with 'free' ends maintain an approximate cylindrical shape instead of barrelling when subjected to compression, resulting in a more uniform stress distribution.