Molecular pathology of colorectal cancer.

Colorectal cancer (CRC) is one of the most intensively studied cancer types, partly because of its high prevalence but also because of the existence of its precursor lesions, tubular or villous adenomas, and more recently (sessile) serrated adenomas, which can be detected endoscopically and removed. The morphological steps in the adenoma-carcinoma sequence have been elucidated at a molecular level, which has been facilitated by identification of the genes responsible for familial intestinal cancer. However, apart from early detection of familial forms of CRC and its use in genetic counseling, until recently such detailed molecular knowledge has had little impact on clinical management of the disease. This has dramatically changed in the last decade. With drugs specifically targeting the epidermal growth factor receptor (EGFR) having been shown effective in CRC, mechanisms responsible for resistance have been explored. The finding that KRAS mutated cancers do not respond to anti-EGFR treatment has had a profound impact on clinical management and on molecular diagnostics of CRC. Additional genetic tests for mutations in NRAS, BRAF and PIK3CA contribute to determining who to treat, and others will follow. New therapies effective in patients with advanced CRC are under investigation. Remaining burning questions for optimal management are which patients will relapse after resection of the primary tumor and which patients will respond to the standard 5FU-oxaliplatin adjuvant treatment regimen. Predictive tests to address these issues are eagerly awaited. New classifications of CRC, based on molecular parameters, are emerging, and we will be confronted with new subtypes of CRC, for which the definition is based on combinations of gene expression patterns, chromosomal alterations, gene mutations and epigenetic characteristics. This will be instrumental in designing new approaches for therapy but will also be translated into molecular diagnostics. Both will contribute to improved clinical management of CRC.

Confocal and two-photon microscopy : image enhancement /

Confocal and two-photon microcopy have become essential tools in biological research and today many investigations are not possible without their help. The valuable advantage that these two techniques offer is the ability of optical sectioning. Optical sectioning makes it possible to obtain 3D visuahzation of the structiu-es, and hence, valuable information of the structural relationships, the geometrical, and the morphological aspects of the specimen. The achievable lateral and axial resolutions by confocal and two-photon microscopy, similar to other optical imaging systems, are both defined by the diffraction theorem. Any aberration and imperfection present during the imaging results in broadening of the calculated theoretical resolution, blurring, geometrical distortions in the acquired images that interfere with the analysis of the structures, and lower the collected fluorescence from the specimen. The aberrations may have different causes and they can be classified by their sources such as specimen-induced aberrations, optics-induced aberrations, illumination aberrations, and misalignment aberrations. This thesis presents an investigation and study of image enhancement. The goal of this thesis was approached in two different directions. Initially, we investigated the sources of the imperfections. We propose methods to eliminate or minimize aberrations introduced during the image acquisition by optimizing the acquisition conditions. The impact on the resolution as a result of using a coverslip the thickness of which is mismatched with the one that the objective lens is designed for was shown and a novel technique was introduced in order to define the proper value on the correction collar of the lens. The amoimt of spherical aberration with regard to t he numerical aperture of the objective lens was investigated and it was shown that, based on the purpose of our imaging tasks, different numerical apertures must be used. The deformed beam cross section of the single-photon excitation source was corrected and the enhancement of the resolution and image quaUty was shown. Furthermore, the dependency of the scattered light on the excitation wavelength was shown empirically. In the second part, we continued the study of the image enhancement process by deconvolution techniques. Although deconvolution algorithms are used widely to improve the quality of the images, how well a deconvolution algorithm responds highly depends on the point spread function (PSF) of the imaging system applied to the algorithm and the level of its accuracy. We investigated approaches that can be done in order to obtain more precise PSF. Novel methods to improve the pattern of the PSF and reduce the noise are proposed. Furthermore, multiple soiu'ces to extract the PSFs of the imaging system are introduced and the empirical deconvolution results by using each of these PSFs are compared together. The results confirm that a greater improvement attained by applying the in situ PSF during the deconvolution process.

Components of reaching and grasping an object may emerge following a single minimization process

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Plasma Polymerised Organic Thin Films-A Study on the Structural, Electrical and Nonlinear Optical Properties for Possible Applications

This proposed thesis is entitled “Plasma Polymerised Organic Thin Films: A study on the Structural, Electrical, and Nonlinear Optical Properties for Possible Applications. Polymers and polymer based materials find enormous applications in the realm of electronics and optoelectronics. They are employed as both active and passive components in making various devices. Enormous research activities are going on in this area for the last three decades or so, and many useful contributions are made quite accidentally. Conducting polymers is such a discovery, and eversince the discovery of conducting polyacetylene, a new branch of science itself has emerged in the form of synthetic metals. Conducting polymers are useful materials for many applications like polymer displays, high density data storage, polymer FETs, polymer LEDs, photo voltaic devices and electrochemical cells. With the emergence of molecular electronics and its potential in finding useful applications, organic thin films are receiving an unusual attention by scientists and engineers alike. This is evident from the vast literature pertaining to this field appearing in various journals. Recently, computer aided design of organic molecules have added further impetus to the ongoing research activities in this area. Polymers, especially, conducting polymers can be prepared both in the bulk and in the thinfilm form. However, many applications necessitate that they are grown in the thin film form either as free standing or on appropriate substrates. As far as their bulk counterparts are concerned, they can be prepared by various polymerisation techniques such as chemical routes and electrochemical means. A survey of the literature reveals that polymers like polyaniline, polypyrrole, polythiophene, have been investigated with a view to studying their structural electrical and optical properties. Among the various alternate techniques employed for the preparation of polymer thin films, the method of plasma polymerisation needs special attention in this context. The technique of plasma polymerisation is an inexpensive method and often requires very less infra structure. This method includes the employment of ac, rf, dc, microwave and pulsed sources. They produce pinhole free homogeneous films on appropriate substrates under controlled conditions. In conventional plasma polymerisation set up, the monomer is fed into an evacuated chamber and an ac/rf/dc/ w/pulsed discharge is created which enables the monomer species to dissociate, leading to the formation of polymer thin films. However, it has been found that the structure and hence the properties exhibited by plasma polymerized thin films are quite different from that of their counterparts produced by other thin film preparation techniques such as electrochemical deposition or spin coating. The properties of these thin films can be tuned only if the interrelationship between the structure and other properties are understood from a fundamental point of view. So very often, a through evaluation of the various properties is a pre-requisite for tailoring the properties of the thin films for applications. It has been found that conjugation is a necessary condition for enhancing the conductivity of polymer thin films. RF technique of plasma polymerisation is an excellent tool to induce conjugation and this modifies the electrical properties too. Both oxidative and reductive doping can be employed to modify the electrical properties of the polymer thin films for various applications. This is where organic thin films based on polymers scored over inorganic thin films, where in large area devices can be fabricated with organic semiconductors which is difficult to achieve by inorganic materials. For such applications, a variety of polymers have been synthesized such as polyaniline, polythiophene, polypyrrole etc. There are newer polymers added to this family every now and then. There are many virgin areas where plasma polymers are yet to make a foray namely low-k dielectrics or as potential nonlinear optical materials such as optical limiters. There are also many materials which are not been prepared by the method of plasma polymerisation. Some of the materials which are not been dealt with are phenyl hydrazine and tea tree oil. The advantage of employing organic extracts like tea tree oil monomers as precursors for making plasma polymers is that there can be value addition to the already existing uses and possibility exists in converting them to electronic grade materials, especially semiconductors and optically active materials for photonic applications. One of the major motivations of this study is to synthesize plasma polymer thin films based on aniline, phenyl hydrazine, pyrrole, tea tree oil and eucalyptus oil by employing both rf and ac plasma polymerisation techniques. This will be carried out with the objective of growing thin films on various substrates such as glass, quartz and indium tin oxide (ITO) coated glass. There are various properties namely structural, electrical, dielectric permittivity, nonlinear optical properties which are to be evaluated to establish the relationship with the structure and the other properties. Special emphasis will be laid in evaluating the optical parameters like refractive index (n), extinction coefficient (k), the real and imaginary components of dielectric constant and the optical transition energies of the polymer thin films from the spectroscopic ellipsometric studies. Apart from evaluating these physical constants, it is also possible to predict whether a material exhibit nonlinear optical properties by ellipsometric investigations. So further studies using open aperture z-scan technique in order to evaluate the nonlinear optical properties of a few selected samples which are potential nonlinear optical materials is another objective of the present study. It will be another endeavour to offer an appropriate explanation for the nonlinear optical properties displayed by these films. Doping of plasma polymers is found to modify both the electrical conductivity and optical properties. Iodine is found to modify the properties of the polymer thin films. However insitu iodine doping is tricky and the film often looses its stability because of the escape of iodine. An appropriate insitu technique of doping will be developed to dope iodine in to the plasma polymerized thin films. Doping of polymer thin films with iodine results in improved and modified optical and electrical properties. However it requires tools like FTIR and UV-Vis-NIR spectroscopy to elucidate the structural and optical modifications imparted to the polymer films. This will be attempted here to establish the role of iodine in the modification of the properties exhibited by the films

New compact microstrip antenna

A new microstrip antenna geometry with considerable reduction in size, with similar radiation characteristics to those of an equivalent rectangular patch antenna is proposed. A relationship has been suggested for fmding out the resonant frequency of the new geometry, and its validity has been established by the experimental results. Without increasing the aperture area, this geometry also offers a facility for considerably reducing the resonant frequency compared to conventional patches.

Excitation of low-profile equilateral-triangular dielectric resonator antenna using a conducting conformal strip

A new configuration that employs a conducting conformal strip to excite the low-profile equilaterial-triangular dielectric resonator antenna (DRA) of very high permittivity is proposed. As compared with the previous aperture-coupling configuration, the new configuration has a wider impedance bandwidth (- 5.5%) and a higher front-to-back radiation ratio. The return loss, radiation patterns, and antenna gain are measured and discussed

The tautomerism, solvatochromism and non-linear optical properties of fluorescent 3-hydroxyquinoxaline-2-carboxalidine-4-aminoantipyrine

The Schiff base, 3-hydroxyquinoxaline-2-carboxalidine-4-aminoantipyrine, was synthesized by the condensation of 3-hydroxyquinoxaline-2-carboxaldehyde with 4-aminoantipyrine. HPLC, FT-IR and NMR spectral data revealed that the compound exists predominantly in the amide tautomeric form and exhibits both absorption and fluorescence solvatochromism, large stokes shift, two electron quasireversible redox behaviour and good thermal stability, with a glass transition temperature of 104oC. The third-order non-linear optical character was studied using open aperture Z-scan methodology employing 7 ns pulses at 532 nm. The third-order non-linear absorption coefficient, b, was 1.48 x 10-6 cm W-1 and the imaginary part of the third-order non-linear optical susceptibility, Im c(3), was 3.36 x10-10 esu. The optical limiting threshold for the compound was found to be 340 MW cm-2.

The tautomerism, solvatochromism and non-linear optical properties of fluorescent 3-hydroxyquinoxaline-2-carboxalidine-4-aminoantipyrine

The Schiff base, 3-hydroxyquinoxaline-2-carboxalidine-4-aminoantipyrine, was synthesized by the condensation of 3-hydroxyquinoxaline-2-carboxaldehyde with 4-aminoantipyrine. HPLC, FT-IR and NMR spectral data revealed that the compound exists predominantly in the amide tautomeric form and exhibits both absorption and fluorescence solvatochromism, large stokes shift, two electron quasireversible redox behaviour and good thermal stability, with a glass transition temperature of 104 oC. The third-order non-linear optical character was studied using open aperture Z-scan methodology employing 7 ns pulses at 532 nm. The third-order non-linear absorption coefficient, b, was 1.48 x 10-6 cm W-1 and the imaginary part of the third-order non-linear optical susceptibility, Im c(3), was 3.36x10-10 esu. The optical limiting threshold for the compound was found to be 340 MW cm-2.

Fabrication and characterisation of polymer optical fibers for smart sensing and optical amplification

The thesis presented the fabrication and characterisation of polymer optical fibers in their applications as optical amplifier and smart sensors.Optical polymers such as PMMA are found to be a very good host material due to their ability to incorporate very high concentration of optical gain media like fluorescent dyes and rare earth compounds. High power and high gain optical amplification in organic dye-doped polymer optical fibers is possible due to extremely large emission cross sections of oyes. Dye doped (Rhodamine 6G) optical fibers were fabricated by using indigenously developed polymer optical fiber drawing tower. Loss characterization of drawn dye doped fibers was carried out using side illumination technique. The advantage of the above technique is that it is a nondestructive method and can also be used for studying the uniformity in fiber diameter and doping. Sensitivity of the undoped polymer fibers to temperature and microbending were also studied in its application in smart sensors.Optical amplification studies using the dye doped polymer optical fibers were carried out and found that an amplification of l8dB could be achieved using a very short fiber of length lOcm. Studies were carried out in fibers with different dye concentrations and diameter and it was observed that gain stability was achieved at relatively high dye concentrations irrespective of the fiber diameter.Due to their large diameter, large numerical aperture, flexibility and geometrical versatility of polymer optical fibers it has a wide range of applications in the field of optical sensing. Just as in the case of conventional silica based fiber optic sensors, sensing techniques like evanescent wave, grating and other intensity modulation schemes can also be efficiently utilized in the case of POF based sensors. Since polymer optical fibers have very low Young's modulus when compared to glass fibers, it can be utilized for sensing mechanical stress and strain efficiently in comparison with its counterpart. Fiber optic sensors have proved themselves as efficient and reliable devices to sense various parameters like aging, crack formation, weathering in civil structures. A similar type of study was carried out to find the setting characteristics of cement paste used for constructing civil structures. It was found that the measurements made by using fiber optic sensors are far more superior than that carried out by conventional methods. More over,POF based sensors were found to have more sensitivity as well.

Third order nonlinear optical studies in europium naphthalocyanine using degenerate four wave mixing and Z-scan

Third order nonlinear susceptibility χ(3) and second hyperpolarizability (γ) of a bis-naphthalocyanine viz. europium naphthalocyanines, Eu(Nc)2, were measured in dimethyl formamide solution using degenerate four wave mixing at 532 nm under nanosecond pulse excitation. Effective nonlinear absorption coefficient, βeff and imaginary part of nonlinear susceptibility, Im(χ(3)) were obtained using open aperture /Z-scan technique at the same wavelength. Optical limiting property of the sample was also investigated. The role of excited state absorption in deciding the nonlinear properties of this material is discussed.

Strategies for Inverse Profiling of Two Dimensional Dielectric Scatterers Using Electromagnetic Illumination

Electromagnetic tomography has been applied to problems in nondestructive evolution, ground-penetrating radar, synthetic aperture radar, target identification, electrical well logging, medical imaging etc. The problem of electromagnetic tomography involves the estimation of cross sectional distribution dielectric permittivity, conductivity etc based on measurement of the scattered fields. The inverse scattering problem of electromagnetic imaging is highly non linear and ill posed, and is liable to get trapped in local minima. The iterative solution techniques employed for computing the inverse scattering problem of electromagnetic imaging are highly computation intensive. Thus the solution to electromagnetic imaging problem is beset with convergence and computational issues. The attempt of this thesis is to develop methods suitable for improving the convergence and reduce the total computations for tomographic imaging of two dimensional dielectric cylinders illuminated by TM polarized waves, where the scattering problem is defmed using scalar equations. A multi resolution frequency hopping approach was proposed as opposed to the conventional frequency hopping approach employed to image large inhomogeneous scatterers. The strategy was tested on both synthetic and experimental data and gave results that were better localized and also accelerated the iterative procedure employed for the imaging. A Degree of Symmetry formulation was introduced to locate the scatterer in the investigation domain when the scatterer cross section was circular. The investigation domain could thus be reduced which reduced the degrees of freedom of the inverse scattering process. Thus the entire measured scattered data was available for the optimization of fewer numbers of pixels. This resulted in better and more robust reconstructions of the scatterer cross sectional profile. The Degree of Symmetry formulation could also be applied to the practical problem of limited angle tomography, as in the case of a buried pipeline, where the ill posedness is much larger. The formulation was also tested using experimental data generated from an experimental setup that was designed. The experimental results confirmed the practical applicability of the formulation.

Nonlinear optical absorption in silver nanosol

Nonlinear optical absorption in silver nanosol was investigated at selected wavelengths (456 nm, 477 nm and 532 nm) using open aperture Z-scan technique. It was observed that nature of nonlinear absorption is sensitively dependent on input fluence as well as on excitation wavelength. Besides, the present sample was found to exhibit reverse saturable absorption (RSA) and saturable absorption (SA) at these wavelengths depending on excitation fluence. RSA is attributed to enhanced absorption resulting from photochemical changes. SA observed for fluence values lower and higher than those corresponding to RSA are, respectively, attributed to plasmon bleach and saturation of RSA.

Radar cross-section enhancement of dihedral corner reflector using fractal-based metallo-dielectric structures

Effective use of fractal-based metallo-dielectric structures for enhancing the radar cross-section (RCS) of dihedral corner reflectors is reported. RCS enhancement of about 30 dBsm is obtained for corner reflectors with corner angles other than 90deg. This may find application in remote sensing and synthetic aperture radar.

Studies on underwater propagation development of programmable arrays

The thesis presented here includes the designing of underwater transducer arrays, taking into account the ‘interaction effects’ [30] among the closely packed radiators. Methods of minimizing the ‘interaction effects‘ by modifying the radiating aperture, are investigated. The need for this study arises as it is one of the important peculiar limitations that stands in the way of achieving maximum range of transmission of acoustic signals. Application of the modified array format for the generation of narrow beam low frequency sound waves, through nonlinear interactions, is discussed. Other techniques that can be advantageously exploited in array synthesis are also investigated

Modifications of secondary reflector antenna patterns due to shaped beams from flanged primary horn feeds

With the advent of satellite communication and radio astronomy, the need for large and efficient reflector antennas had triggered a widespread investigation in reflector feed design techniques. Major improvements sought are reduction in spill-over, cross polarization losses and the enhancement of aperture efficiency. The search for such a feed culminated in the corrugated horn. The main idea behind the present work is to use the H-plane sectoral horns fitted with,corrugated flanges as feeds of a paraboloid and see how the secondary pattern of the reflector antenna varies with different parameters of the feed. An offset paraboloid is used as the secondary reflector in order to avoid the adverse effect of aperture ‘blocking by the feed horn structure on the secondary radiation pattern. The measurements were repeated for three different H-plane sectoral horns with the same set of corrugated flanges at various X-band frequencies. The following parameters of the whole system are studied: (a) Beam shaping. (b) Gain. (c) Variation of VSWR and (d) Cross polarization