Proportional, integral and derivative (PID) controller tuning guidelines in process industry have been in place for over six decades. Nevertheless despite their long design history PID tuning has remained an ‘art’ and no single comprehensive solution yet exists. In this study various considerations, with new and different perspectives, have been taken into account in PID tuning design. This study explores the issue of PID tuning from a practical point of view with particular focus on robust design in the presence of typical problems in process industry: process changes, valve stiction effects and unmeasured disturbances. The IMC tuning rule is recommended for setpoint tracking, while in the case of regulation, a newly proposed tuning rule, based on a combination of IMC and Ziegler-Nichols method, is demonstrated to give satisfactory results. The results were evaluated by simulation and were also validated on a computer-interfaced pilot scale continuous stirred tank heater (CSTH) process. / Chemical Engineering

3-Chloro-4,4,5-trimethyl-3,5-diphenyl-4,5-dihydro-3H-pyrazole (3b) and 3-bromo-4,4,5-trimethyl-3,5-diphenyl-4,5-dihydro-3H-pyrazole (3c) were prepared for the thermolysis project. The thermal decompositions of 3b and 3c were monitored using 1H NMR spectroscopy. Plots of ln (% starting material) vs. time (sec) were linear for at least two half lives and the first order rate constants were determined over at least a 30o temperature range. The relative reactivity was found to be 3c > 3b. The activation parameters determined for the thermal decomposition of the pyrazoline at 150oC were found to be: for 3b &#;H‡ = 33 &#;1.0 kcal/mol, &#;S‡ = -2.4 &#; 0.07eu , k150 0 = 7.34 &#; 0.44 x 10 -5 s-1 ; for 3c &#;H‡ = 30&#;0.2 kcal/mol, &#;S‡ = -6.9 &#;0.03 eu, k150o = 42.3&#;0.7 x 10-5 s-1. Thermal decomposition of 3b both neat and in dibromobenzene (DBB) resulted in the formation of an intermediate 2,3-diphenyl-4-methyl-1,3-pentadiene (8) as a major product and minor isomers of 8. These intermediates then thermally decomposed to 1,1,3-trimethyl-2-phenyl-1H-indene (9) via an acid catalyzed process. In order to gain a mechanistic understanding (ionic vs. radical pathways) of the thermal decomposition of 3b, a product study was conducted in protic solvents. In methanol and ethanol, 3b underwent an ionic reaction (SN1-type) with the solvent to produce 3-methoxy/ethoxy-4,4,5-trimethyl-3,5-diphenyl-4,5-dihydro-3H-pyrazole (3/3d) in good yield. The reaction of 3b with refluxing protic solvents led to the development of new method for the synthesis of alkoxy-4,5-dihydro-3H-pyrazoles which is both safe and efficient.

Advances in the design and manufacturing technologies have greatly enhanced the utility of fiber reinforced composite materials in aircraft, helicopter and space- craft structural components. The special characteristics of composites such as high strength and stiffness, light-weight corrosion resistance make them suitable sub- stitute for metals/metallic alloys. However, composites are very sensitive to the anomalies induced during their fabrication and service life. Also, they are suscepti- ble to the impact and high frequency loading conditions because the epoxy matrix is at-least an order of magnitude weaker than the embedded reinforced carbon fibers. On the other hand, the carbon based matrix posses high electrical conductivity which is often undesirable. Subsequently, the metal matrix produces high brittleness. Var- ious forms of damage in composite laminates can be identified as indentation, fiber breakage, matrix cracking, fiber-matrix debonding and interply disbonding (delam- ination). Among all the damage modes mentioned above, delamination has been found to be serious for all cases of loading. They are caused by excessive interlaminar shear and normal stresses. The interlaminar stresses that arise in the case of composite materials due to the mismatch in the elastic constants across the plies. Delamination in composites reduce it’s tensile and compressive strengths by consid- erable margins. Hence the knowledge of these stresses is the most important aspect to be looked into. Basic theories like the Euler-Bernoulli’s theory and Timoshenko beam theory are based on many assumptions which poses limitation to determine these stresses accurately. Hence the determination of these interlaminar stresses accurately requires higher order theories to be considered. Most of the conventional methods of determination of the stresses are through the solutions, involving the trigonometric series, which are available only to small and simple problems. The most common method of solution is by Finite Element (FE) Method. There are only few elements existing in the literature and very few in the commercially available finite element software to determine the interlaminar stresses accurately in the composite laminates. Accuracy of finite element solution depends on the choice of functions to be used as interpolating polynomials for the field variable. In-appropriate choice will manifest in the form of delayed convergence. This delayed convergence and accuracy in predicting these stresses necessiates a formulation of elements with a completely new concept. The delayed convergence is sometimes attributed to the shear locking phenomena, which exist in most finite element formulation based on shear deformation theories. The present work aims in developing finite elements based on higher order theories, that alleviates the slow convergence and achieves the solutions at a faster rate without compromising on the accuracy. The accuracy primarily depends on the theory used to model the problem. Thus the basic theories (such as Elementary Beam theory and Timoshenko Beam theory) does not suffice the condition to accuratley determine the interlaminar stresses through the thickness, which is the primary cause for delamination in composites. Two different elements developed on the principle of super-convergence has been presented in this work. These elements are subjected to several numerical experiments and their performance is assessed by comparing the solutions with those available in literature. Spacecraft and aircraft structures are light in weight and are also lightly damped because of low internal damping of the material of construction. This increased exibility may allow large amplitude vibration, which might cause structural instability. In addition, they are susceptible to impact loads of very short duration, which excites many structural modes. Hence, structural dynamics and wave propagation study becomes a necessity. The wave based techniques have found appreciation in many real world problems such as in Structural Health Monitoring (SHM). Wave propagation problems are characterized by high frequency loads, that sets up stress waves to propagate through the medium. At high frequency, the wave lengths are small and from the finite element point of view, the element sizes should be of the same order as the wave lengths to prevent free edges of the element to act as a free boundary and start reflecting the stress waves. Also longer element size makes the mass distribution approximate. Hence for wave propagation problems, very large finite element mesh is an absolute necessity. However, the finite element problems size can be drastically reduced if we characterize the stiffness of the structure accurately. This can accelerate the convergence of the dynamic solution significantly. This can be acheived by the super-convergent formulation. Numerical results are presented to illustrate the efficiency of the new approach in both the cases of dynamic studies viz., the free vibration study and the wave propagation study. The thesis is organised into five chapters. A brief organization of the thesis is presented below, Chapter-1 gives the introduction on composite material and its constitutive law. The details of shear locking phenomena and the interlaminar stress distribution across the thickness is brought out and the present methods to avoid shear locking has been presented. Chapter-2 presents the different displacement based higher order shear deformation theories existing in the literature their advantages and limitations. Chapter-3 presents the formulation of a super-convergent finite element formulation, where the effect of lateral contraction is neglected. For this element static and free vibration studies are performed and the results are validated with the solution available in the open literature. Chapter-4 presents yet another super-convergent finite element formulation, wherein the higher order effects due to lateral contraction is included in the model. In addition to static and free vibration studies, wave propagation problems are solved to demonstrate its effectiveness. In all numerical examples, the super-convergent property is emphasized. Chapter-5 gives a brief summary of the total research work performed and presents further scope of research based on the current research.

An increase in the co-operativity in the motion of particles and a growth of a suitably defined dynamical correlation length seem to be generic features exhibited by all liquids upon supercooling. These features have been observed both in experiments and in numerical simulations of glass-forming liquids. Specially designed NMR experiments have estimated that the rough magnitude of this correlation length is of the order of a few nanometers near the glass transition. Simulations also predict that there are regions in the system which are more liquid-like than other regions. A complete theoretical understanding of this behaviour is not available at present. In recent calculations, Berthier, Biroli and coworkers [1, 2] extended the simple mode coupling theory (MCT) to incorporate the effects of dynamic heterogeneity and predicted the existence of a growing dynamical correlation length associated with the cooperativity of the dynamics. MCT also predicts a power law divergence of different dynamical quantities at the mode coupling temperature and at temperatures somewhat higher than the mode coupling temperature, these predictions are found to be consistent with experimental and simulation results. The system size dependence of these quantities should exhibit finite size scaling (FSS) similar to that observed near a continuous phase transition in the temperature range where they show power law growth. Hence we have used the method of finite size scaling in the context of the dynamics of supercooled liquids. In chapter 2, we present the results of extensive molecular dynamics simulations of a model glass forming liquid and extract a dynamical correlation length ξ associated with dynamic heterogeneity by performing a detailed finite size scaling analysis of a four-point dynamic susceptibility χ4(t) [3] and the associated Binder cumulant. We find that although these quantities show the “normal” finite size scaling behaviour expected for a system with a growing correlation length, the relaxation time τ does not. Thus glassy dynamics can not be fully understood in terms of “standard” critical phenomena. Inspired by the success of the empirical Adam-Gibbs relation [4] which relates dynamics with the configurational entropy, we have calculated the configurational entropy for different system sizes and temperatures to explain the nontrivial scaling behaviour of the relaxation time. We find that the behaviour of the relaxation time τ can be explained in terms of the Adam-Gibbs relation [4] for all temperatures and system sizes. This observation raises serious questions about the validity of the mode coupling theory which does not include the effects of the potential energy (or free energy) landscape on the dynamics. On the other hand, in the “random first order transition” theory (RFOT), introduced by Wolynes and coworkers [5], the configurational entropy plays a central role in determining the dynamics. So we also tried to explain our simulation results in terms of RFOT. However, this interpretation has the drawback that the value of one of the exponents of this theory extracted from our numerical results does not satisfy an expected physical bound, and there is no clear explanation for the obtained values of other exponents. Thus we find puzzling values for the exponents relevant to the applicability of RFOT, which are in need of explanation. This can be due to the fact that RFOT focuses only near the glass transition, while all our simulation results are for temperatures far above the glass transition temperature (actually, above the mode coupling temperature). Interestingly, results similar to ours were obtained in a recent analysis [6] of experimental data near the laboratory glass transition, on a large class of glass-forming materials. Thus right now we do not have any theory which can explain our simulation data consistently from all perspectives. There have been some attempts to extend the RFOT analysis to temperatures above the mode coupling temperature [7, 8] and to estimate a length scale associated with the configurational entropy at such temperatures. We compare our results with the predictions arising from these analyses. In chapter 3, we present simulation results that suggest that finite size scaling analysis is probably the only feasible method for obtaining reliable estimates of the dynamical correlation length for supercooled liquids. As mentioned before, although there exists a growing correlation length, the behaviour of all measured quantities (specifically, the relaxation time) is not in accordance with the behaviour expected in “standard” critical phenomena. So one might suspect the results for the correlation length extracted from the scaling analysis. To find out whether the results obtained by doing finite size scaling are correct, we have done simulations of very large system sizes for the same model glass forming liquid. In earlier studies, the correlation length has been extracted from the wave vector dependence of the dynamic susceptibility in the limit of zero wave vector, but to estimate the correlation length with reasonable accuracy one needs data in the small wave vector range. This implies that one needs to simulate very large systems. But as far as we know, in all previous studies typical system sizes of the order of 10, 000 particles have been used to do this analysis. In this chapter we show by comparing results for systems of 28, 000 and 350, 000 particles that these previous estimates are not reliable. We also show that one needs to simulate systems with at least a million particles to estimate the correlation length correctly near the mode coupling temperature and this size increases with decreasing temperature. We compare the correlation length obtained by analyzing the wave vector dependence of the dynamic susceptibility for a 350, 000particle system with the results obtained from the finite size scaling analysis. We were only able to compare the results in the high temperature range due to obvious reasons. However the agreement in the high temperature range shows that the finite size scaling analysis is robust and also establishes the fact that finite size scaling is the only practical method to extract reliable correlation lengths in supercooled liquids. In chapter 4, we present a free energy landscape analysis of dynamic heterogeneity for a monodisperse hard sphere system. The importance of the potential energy landscape for particles interacting with soft potentials is well known in the glass community from the work of Sastry et al. [9] and others, but the hard sphere system which does not have any well defined potential energy landscape also exhibits similar slow dynamics in the high density limit. Thus it is not clear how to treat the hard sphere systems within the same energy landscape formalism. Dasgupta et al. [10, 11, 12, 13, 14, 15] showed that one can explain the slow dynamics of these hard core systems in term of a free energy landscape picture. They and other researchers showed that these system have many aperiodic local minima in its free energy landscape, with free energy lower than that of the liquid. Using the Ramkrishnan-Yussouff free energy functional, we have performed multi parameter variational minimizations to map out the detailed density distribution of glassy free energy minima. We found that the distribution of the widths of local density peaks at glassy minima is spatially heterogeneous. By performing hard sphere event driven molecular dynamics simulation, we show that there exists strong correlation between these density inhomogeneity and the local Debye-Waller factor which provides a measure of the dynamic heterogeneity observed in simulations. This result unifies the system of hard core particles with the other soft core particles in terms of a landscapebased description of dynamic heterogeneity. In chapter 5, we extend the same free energy analysis to a polydisperse system and show that there is a critical polydispersity beyond which the crystal state is not stable and glassy states are thermodynamically stable. We also found a reentrant behaviour in the liquid-solid phase transition within this free-energy based formalism. These results are in qualitative agreement with experimental observations for colloidal systems.

Breast cancer is a major global health problem and the most common form of cancer among women. Major advances in the technologies of imaging provide improved detection and sensitivity with fewer unnecessary biopsies. Commonly used imaging modalities include mammography, ultrasonography, magnetic resonance imaging (MRI), scintimammography, single photon emission computed tomography (SPECT) and positron emission tomography (PET). The current study is focused on breast MRI imaging, especially one of the most promising recent techniques, i.e. the Diffusion Weighted Imaging breast MRI (DWI). DWI is an unenhanced MRI technique, based on volume sequences on various b values (the b value identifies the measurement's sensitivity to diffusion and determines the strength and duration of the diffusion gradients) measuring the mobility of water molecules (Brownian motion) in vivo (in tissues) and provides different and potentially complementary information to Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) technique. As DWI based on the diffusive properties of water molecules, reflects their random motion resulting from thermal agitation. Water diffusion on breast can be quantified by measuring the mean diffusivity, which is the average of Apparent Diffusion Coefficient (ADC). The ADC can be calculated by making measurements at a low b factor, b1, and a higher b factor, b2. DWI allows the mapping of the diffusion process of molecules by the ADC map. ADC maps are calculated by collecting images with at least 2 different values, b1 and b2, of the b factor. The ADC map is a parametric image whose color scale or gray scale represents the ADC values of the voxels and is usually generated by proprietary or in house software. DWI apart from the 3D anatomical information, provides a noninvasive investigation of tissue vascularity, a novel contrast mechanism in MRI and has a high sensitivity in the detection of changes in the local biologic environment due to a pathologic process. Therefore, in addition to contrast enhancement-based characterization (DCE-MRI), measurement of the motion of water molecules in DWI provides an additional feature for lesion characterization that may further increase the specificity of MRI for classifying breast lesions. The diagnostic task that the current study deals with, accounts for the diagnosis of mass-like lesions in Diffusion Weighed Magnetic Resonance Imaging, based on low ADC values compared to high once in case of benign versus normal tissue. The hypothesis is that diffusivity of water molecules is restricted in environments of high cellularity, intracellular and extracellular edema, high viscosity, and fibrosis, such as malignant tumors, because these conditions become barriers to the movement of water molecules. Therefore, most of breast cancers show low ADC values compared with benign and normal tissue. Many studies have revealed the usefulness of ADC values in the differential diagnosis of breast lesions; however, the clinical effect remains limited because of the substantial overlap between benign and malignant lesions, which presents challenges for implementing a useful diagnostic ADC threshold. The majority of studies, similar to the current study, determined optimal cutoff levels of the ADC value between malignant and benign lesions by using ROC analysis, and ranged from 0.90 to 1.76 × 10-3 mm2/s while the sensitivity and specificity ranged from 63% to 100% and 46% to 97%, respectively. In addition, the methods for measuring ADC differ among reported studies, with the most representative method being the mean value of ADC (mean ± standard deviation) over a Region Of Interest representative of the breast lesion. The purpose of this study was to investigate the ability of histogram characteristics of Apparent Diffusion Coefficient (Apparent Diffusion Coefficient-ADC) to differentiate malignant from benign breast lesions in breast DWI. To this end the ADC maps of representative lesion ROIs were subjected to first order statistics analysis by calculating five first order textural features: Mean value, Standard Deviation, Kurtosis, Skewness and Entropy. This approach is intended to offer a more complete assessment of tumor texture and heterogeneity. The dataset analyzed is comprised of 92 histologically verified breast lesions, originating from 69 women with mammographically and/or ultrasonographically detected or palpable findings. Histology revealed 53 malignant lesions originating from 45 women and 39 benign lesions originating from 26 women. All of the breast MR examinations were performed with a 3T MR scanner, for b= 0, 900 s/mm2. Diagnostic performances of these parameters were compared by receiver operating characteristic (ROC) curve analysis. The mean of ADC of benign lesions [(1.470 ± 0.342) × 10-3 mm2/s] was found to be significantly higher than that of malignant tumours, [(0.965 ± 0.268) × 10-3 mm2/s, (p<0.00001)]. The standard deviation of ADC of benign lesions [(0.184 ± 0.999) × 10-3 mm2/s] was not significantly different from that of malignant tumours, [(0.192 ± 0.151) × 10-3 mm2/s, (p=0.6581)]. The skewness of ADC of benign [-0.303 ± 0.584] was significantly different than that of malignant tumours, 0.210 ± 0.725. (p = 0.0008)]. The kurtosis of ADC of benign [3.003 ± 1.065] was not significantly different from that of malignant tumours, [3.337 ± 1.334. (p=0.0987)]. The entropy of ADC of benign [4.794 ± 0.665] was significantly lower than that of malignant tumours, [5.569 ± 0.649, (p<0.00001)] The corresponding area under the empirical receiver operating characteristic curve was: 0.862 ± 0.042 (95% confidence interval: 0.754, 0.925) for mean of ADC, 0.705 ± 0.054 (95% confidence interval: 0.589, 0.800) for skeweness of ADC, 0.800 ± 0.046 (95% confidence interval: 0.691, 0.874) for entropy of ADC, resulting a good diagnostic performance of DWI for these parameters. On the other hand, an AUC of 0.527 ± 0.063 (95% confidence interval: 0.393, 0.640) and 0.601 ± 0.061 (95% confidence interval: 0.470, 0.707) for Standard deviation and kurtosis respectively, suggests a degree of overlap in ADC values between benign and malignant tumors. In an effort to identify optimal threshold values for differentiating benign versus malignant lesions these were selected to correspond to the points of highest accuracy of the ROC curves. In our study, we obtained two threshold values of mean ADC, both with an accuracy of 83.15%: 1.21 x 10-3 mm2/s with a sensitivity of 86.27% and specificity of 78.95%; and 1.32 x 10-3 mm2/s with a sensitivity of 92.16% and specificity of 71.05%. The threshold value of skeweness was -0.06 with an accuracy of 68.54%, a sensitivity of 66.03% and specificity of 66.67%. Finally, we found two threshold values of entropy, both with an accuracy of 76.40%: 5.17 with a sensitivity of 75.47% and specificity of 71.80%; and 5.21 with a sensitivity of 73.59% and specificity of 74.36%. In conclusion, results of the current study suggest the contribution of texture analysis methods in Diffusion-weighted MRI breast imaging for the quantification of tissue heterogeneity, providing important information for breast cancer diagnosis. Histogram analysis of ADC values in breast cancer has potential for differentiating benign and malignant tumors, providing information about the entire tumor. The mean, skewness and entropy of ADC are valuable parameters that are correlated with pathologic characterization of breast tumors. These 3 ADC parameters significantly elevated the quantitative diagnostic performance of breast DWI and would be effective parameters in distinguishing between malignant and benign breast lesions. Finally, future efforts will also focus on investigating the correlation of extracted texture features with histopathological findings, in order to verify the potential of the proposed texture analysis of ADC map in providing non-invasive prognostic factors of breast cancer. / Ο καρκίνος του μαστού είναι ένα σημαντικό παγκόσμιο πρόβλημα υγείας και η πιο διαδεδομένη μορφή καρκίνου στον γυναικείο πληθυσμό. Η ολοένα και πιο έγκαιρη διάγνωση του καρκίνου του μαστού έχει οδηγήσει σε σημαντική βελτίωση του ρυθμό θεραπείας της νόσου. Σημαντικές πρόοδοι στην τεχνολογία της απεικόνισης παρέχουν τη βελτιωμένη ανίχνευση και ευαισθησία του καρκίνου και οδηγούν σε όλο ένα και λιγότερες περιττές βιοψίες. Οι πιο συνηθισμένες μέθοδοι απεικόνισης, που χρησιμοποιούνται, περιλαμβάνουν την Μαστογραφία, την Υπερηχογραφία, την Μαγνητική Τομογραφία (MRI), την σπινθηρομαστογραφία, την Τομογραφία Εκπομπής Φωτονίων (SPECT) και την Τομογραφία Εκπομπής Ποζιτρονίων (PET). Η παρούσα μελέτη επικεντρώνεται στην τεχνολογία της Απεικόνισης Μαγνητικού Συντονισμού ειδικά σε μία πρόσφατη και ελπιδοφόρα τεχνική απεικόνισης του καρκίνου του μαστού, που ονομάζεται Απεικόνιση Σταθμισμένης Διάχυσης στη Τομογραφία Πυρηνικού Μαγνητικού Συντονισμού (Diffusion Weighted Imaging breast MRI (DWI)). Η DWI είναι μια MRI ακολουθία χωρίς χρήση σκιαγραφικής ουσίας, η οποία βασίζεται σε αλληλουχίες για διάφορες τιμές του παράγοντα διάχυσης b (η τιμή b προσδιορίζει την διαχυτότητα και καθορίζει την ένταση και τη διάρκεια των βαθμωτών πεδίων διάχυσης). Η DWI ποσοστικοποιεί την κινητικότητα των μορίων του νερού (Brownian κίνηση) in vivo (σε ιστούς) και παρέχει διαφορετικές και ενδεχομένως συμπληρωματικές πληροφορίες στην μαστογραφία μαγνητικής τομογραφίας με χρήση σκιαγραφικού (Dynamic Contrast-Enhanced Magnetic Resonance Imaging: DCE-MRI). Η DWI με βάση τις ιδιότητες διάχυσης των μορίων του νερού, αντανακλά την τυχαία κίνησής τους λόγω της θερμικής τους ενέργειας. Η διάχυση του νερού στον μαστό μπορεί να ποσοτικοποιηθεί με τη μέτρηση της μέσης διαχυτότητας, η οποία αναφέρεται ως Φαινόμενος Συντελεστής Διάχυσης (Apparent Diffusion Coefficient-ΑDC). Ο ADC υπολογίζεται ύστερα από μετρήσεις για δυο b τιμές, μια χαμηλή b1 και μια υψηλότερη b2 τιμή. Η DWI επιτρέπει την χαρτογράφηση της διάχυσης των μορίων του νερού μέσω του ADC χάρτη. Ο ADC χάρτης είναι μια παραμετρική εικόνα της οποίας η κλίμακα χρωμάτων ή κλίμακα των τόνων του γκρι, αντιπροσωπεύει τις ADC τιμές των voxels και συνήθως παράγεται από λογισμικό. Οι παραμετρικοί ADC χάρτες απεικόνισης DWI αναπαριστούν τη μικροδομή των ιστών για διάφορους συνδυασμούς τιμών της παραμέτρου b. Η DWI εκτός από 3D ανατομική πληροφορία, παρέχει μια μη επεμβατική διερεύνηση της αγγειοβρίθειας του ιστού, έναν νέο μηχανισμό αντίθεσης στην MRI, και χαρακτηρίζεται από υψηλή ευαισθησία στην ανίχνευση ενδεχόμενων αλλαγών στο τοπικό βιολογικό περιβάλλον, οι οποίες οφείλονται σε παθολογία. Ως εκ τούτου, εκτός από τον χαρακτηρισμό αλλοιώσεων βάση σκιαγραφικής ενίσχυσης (DCE - MRI), η ποσοτικοποίηση της κίνησης των μορίων του νερού στην DWI παρέχει επιπλέον στοιχεία για τον χαρακτηρισμό της αλλοίωσης, κάτι το οποίο μπορεί να αυξήσει περαιτέρω την ειδικότητα της MRI για την ταξινόμηση των αλλοιώσεων του μαστού. Το διαγνωστικό πρόβλημα το οποίο αντιμετώπισε/εστίασε η παρούσα διπλωματική εργασία, αφορά στο χαρακτηρισμό/διάγνωση χωροκατακτητικών αλλοιώσεων (mass-like) του μαστού στην Απεικονιση Μαγνητικου Συντονισμου Σταθμισμενης Διαχυσης (DWI) και την ποσοτικη αναλυση του Φαινομενου Συντελεστη Διαχυσης (ADC) για διαγνωση καρκινου του μαστου. Η ικανότητα διάχυσης των μορίων του νερού περιορίζεται σε περιβάλλον υψηλής κυτταροβρίθιας, ενδοκυττάριων και εξωκυττάριων οιδημάτων, υψηλού ιξώδους και ίνωσης, όπως συμβαίνει στους κακοήθεις όγκους, διότι οι παράγοντες αυτοί εμποδίζουν την κυκλοφορία των μορίων του νερού. Αποτέλεσμα αυτού είναι οι περισσότεροι καρκίνοι του μαστού να παρουσιάζουν χαμηλές ADC τιμές σε σύγκριση με τους καλοήθεις όγκους ή τον φυσιολογικό ιστό. Πολλές μελέτες έχουν δείξει τη χρησιμότητα των ADC τιμών στη διαφορική διάγνωση των αλλοιώσεων του μαστού. Εν τούτοις, το κλινικό αποτέλεσμα παραμένει περιορισμένο λόγω της σημαντικής επικάλυψης καλοήθων και κακοήθων αλλοιώσεων, γεγονός που αποτελεί πρόκληση για την εφαρμογή ενός χρήσιμου διαγνωστικού ορίου της μέσης ADC. Στη πλειοψηφία των μελετών, όπως και στη παρούσα μελέτη, τα βέλτιστα επίπεδα αποκοπής της ADC μεταξύ κακοήθων και καλοήθων αλλοιώσεων προσδιορίστηκαν με τη χρήση ROC ανάλυσης. Στις μέχρι τώρα μελέτες τα διαγνωστικά όρια της μέσης ADC κυμαίνονται από 0.90 έως 1.76 × 10-3 mm2 / s, με ευαισθησία και ειδικότητα να κυμαίνονται από 63% έως 100% και 46% έως 97%, αντίστοιχα. Γεγονός αποτελεί, επίσης, η διαφορετική μέθοδος υπολογισμού της ADC που ακολουθεί η κάθε μελέτη, με πιο συχνή μέθοδο, ο υπολογισμός της μέσης τιμής της ADC (μέση τιμή ± τυπική απόκλιση) σε μια περιοχή ενδιαφέροντος (ROI) μιας αλλοίωσης του μαστού. Σκοπός της παρούσας μεταπτυχιακής διπλωματικής εργασίας ήταν να διερευνηθεί η ικανότητα των χαρακτηριστικών ιστογράμματος του Φαινόμενου Συντελεστή Διάχυσης (Apparent Diffusion Coefficient-ADC) να διαφοροποιούν κακοήθεις από καλοήθεις αλλοιώσεις του μαστού στην Απεικόνιση Μαγνητικού Συντονισμού Σταθμισμένης Διάχυσης (Diffusion Weighted MRI-DWI). Για το σκοπό αυτό, δημιουργήθηκε ο ADC παραμετρικός χάρτης ο οποίος αποτέλεσε τη βάση για την εφαρμογή μεθόδου ανάλυσης υφής εικόνας, και τον υπολογισμό πέντε χαρακτηριστικών υφής πρώτης τάξης: την μέση τιμή, την τυπική απόκλιση, την κύρτωση, την λοξότητα και την εντροπία. Η προσέγγιση αυτή θεωρήθηκε ότι θα προσφέρει μια πιο ολοκληρωμένη αξιολόγηση της υφής του όγκου και της ετερογένειας. Η προσέγγιση εφαρμόσθηκε σε κλινικό δείγμα 92 ιστολογικά αποδεδειγμένων αλλοιώσεων του μαστού, οι οποίες προέρχονται από 69 γυναίκες οι οποίες είχαν νωρίτερα ανιχνευθεί μέσω μαστογραφίας ή/και υπερηχογραφίας ή από ψηλαφητά ευρήματα. Η ιστολογική εξέταση αποκάλυψε 53 κακοήθεις αλλοιώσεις που προέρχονταν από 45 γυναίκες και 39 καλοήθεις αλλοιώσεις από 26 γυναίκες. Όλες οι εξετάσεις μαγνητικής τομογραφίας του μαστού έγιναν με σύστημα MRI 3T και για b=0 και 900 s/mm2. Η διαγνωστική απόδοση/επίδοση των παραμέτρων αυτών συγκρίθηκε με την ανάλυση λειτουργικού χαρακτηριστικού δέκτη (ROC analysis). Τα αποτελέσματα υποδεικνύουν τον σημαντικό ρόλο της ανάλυσης ADC ιστογράμματος χρησιμοποιώντας τα 5 παραπάνω χαρακτηριστικά υφής για την ταυτοποίηση των αλλοιώσεων του μαστού. Οι μετρήσεις της μέσης τιμής, της λοξότητας και της εντροπία της ADC των καλοήθων και κακοήθων αλλοιώσεων του μαστού είχαν στατιστικώς σημαντική διαφορά. Ειδικότερα, η μέση ADC τιμή των καλοήθων όγκων [(1.470 ± 0.342) × 10-3 mm2/s] ήταν σημαντικά υψηλότερη από εκείνη των κακοήθων, [(0.965 ± 0.268) × 10-3 mm2/s, (ρ < 0.00001)]. Η λοξότητα της ADC των καλοήθων όγκων [-0.303 ± 0.584], διέφερε σημαντικά από εκείνη των κακοήθων, [0.210 ± 0.725. (ρ= 0.0008)]. Και η εντροπία της ADC των καλοήθων όγκων [4.794 ± 0.665], ήταν σημαντικά χαμηλότερη από εκείνη των κακοήθων, [5.569 ± 0.649, (ρ < 0.00001)]. Ωστόσο, η τυπική απόκλιση και η κύρτωση της ADC των καλοήθων και κακοήθων αλλοιώσεων του μαστού δεν είχαν στατιστικώς σημαντική διαφορά. Συγκεκριμένα, η τυπική απόκλιση της ADC των καλοήθων όγκων ήταν [(0.184 ± 0.999) × 10-3 mm2/s] ενώ των κακοήθων ήταν [(0.192 ± 0.151) × 10-3 mm2/s, (ρ = 0.6581)] και η κύρτωση της ADC των καλοήθων όγκων ήταν [3.003 ± 1.065] ενώ των κακοήθων ήταν [3.337 ± 1.334, (ρ = 0.0987)]. Η περιοχή κάτω από την ROC καμπύλη (AUC) για τη μέση ADC τιμή ήταν 0.862 ± 0.042 (95% διάστημα εμπιστοσύνης: 0.754, 0.925), για την λοξότητα της ADC ήταν 0.705 ± 0.054 (95% διάστημα εμπιστοσύνης: 0.589, 0.800) και για η εντροπία της ADC ήταν 0.800 ± 0.046 (95% διάστημα εμπιστοσύνης: 0.691, 0.874), και είχαν ως αποτέλεσμα μια καλή διαγνωστική απόδοση/ επίδοση της DWI για τις παραμέτρους αυτές. Από την άλλη πλευρά, η AUC με 0.527 ± 0.063 (95% διάστημα εμπιστοσύνης: 0.393, 0.640) και με 0.601 ± 0.061 (95% διάστημα εμπιστοσύνης: 0.470, 0.707) για την τυπική απόκλιση και την κύρτωση, αντίστοιχα, υποδηλώνει ένα βαθμό επικάλυψης στις ADC τιμές μεταξύ καλοήθων και κακοήθων όγκων. Τα βέλτιστα κατώφλια αποκοπής για διαφοροποίηση καλοήθων έναντι κακοήθων αλλοιώσεων καθορίστηκαν με τον εντοπισμό των σημείων όπου η ακρίβεια ήταν μέγιστη στις καμπύλες ROC. Από τη συγκεκριμένη μελέτη, προέκυψαν δύο τιμές κατωφλίου αποκοπής της μέσης ADC, με την ίδια ακρίβεια 83.15%. Το πρώτο κατώφλι με τιμή 1.21 x 10-3 mm2/s χαρακτηρίζεται με ευαισθησία 86.27% και ειδικότητα 78.95%. Και το δεύτερο κατώφλι με τιμή 1.32 x 10-3 mm2/s χαρακτηρίζεται με ευαισθησία 92.16% και ειδικότητα 71.05%. Το κατώφλι για την λοξότητα της ADC ήταν στα -0.06 με ακρίβεια 68.54%, ευαισθησία 66.03% και ειδικότητα 66.67%. Τέλος, προέκυψαν δύο τιμές κατωφλίου αποκοπής της εντροπίας της ADC με την ίδια ακρίβεια ακρίβεια 76.40%. Το πρώτο κατώφλι με τιμή 5.17 χαρακτηρίζεται με ευαισθησία 75.47% και ειδικότητα 71.80%. Και το δεύτερο κατώφλι με τιμή 5.21 χαρακτηρίζεται με ευαισθησία 73.59% και ειδικότητα 74.36%. Συμπερασματικά, τα αποτελέσματα της παρούσας μελέτης δείχνουν τη συνεισφορά των μεθόδων ανάλυσης υφής εικόνας στη Απεικονιση Μαγνητικου Συντονισμου Σταθμισμενης Διαχυσης (DWI) του μαστού για την ποσοτικοποίηση της ετερογένειας του ιστού, παρέχοντας σημαντικές πληροφορίες για τη διάγνωση του καρκίνου του μαστού. Η ανάλυση ιστογράμματος των ADC τιμών στον καρκίνο του μαστού έχει τη δυνατότητα διαφοροποίησης καλοήθων και κακοήθων όγκων, παρέχοντας πληροφορίες για το σύνολο του όγκου. Η μέση τιμή, η λοξότητα και η εντροπία του ADC είναι πολύτιμες παράμετροι που συσχετίζονται με παθολογικό χαρακτηρισμό των όγκων του μαστού. Αυτές οι 3 ADC παράμετροι αύξησαν σημαντικά την ποσοτική διαγνωστική απόδοση της DWI του μαστού και πιθανότατα να είναι αποτελεσματικές παράμετροι όσον αφορά τη διάκριση μεταξύ καλοήθων και κακοήθων αλλοιώσεων του μαστού Μελλοντικές προσπάθειες πρόκειται να εστιάσουν στη διερεύνηση της συσχέτισης των εξαχθέντων χαρακτηριστικών υφής με ιστοπαθολογικούς δείκτες, με σκοπό την περαιτέρω επιβεβαίωση των προτεινόμενων προσεγγίσεων και ενδεχομένως την χρήση συγκεκριμένων χαρακτηριστικών υφής ως μη επεμβατικών προγνωστικών δεικτών καρκίνου του μαστού.

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Este trabalho de pesquisa descreve três estudos de utilização de métodos quimiométricos para a classificação e caracterização de óleos comestíveis vegetais e seus parâmetros de qualidade através das técnicas de espectrometria de absorção molecular no infravermelho médio com transformada de Fourier e de espectrometria no infravermelho próximo, e o monitoramento da qualidade e estabilidade oxidativa do iogurte usando espectrometria de fluorescência molecular. O primeiro e segundo estudos visam à classificação e caracterização de parâmetros de qualidade de óleos comestíveis vegetais utilizando espectrometria no infravermelho médio com transformada de Fourier (FT-MIR) e no infravermelho próximo (NIR). O algoritmo de Kennard-Stone foi usado para a seleção do conjunto de validação após análise de componentes principais (PCA). A discriminação entre os óleos de canola, girassol, milho e soja foi investigada usando SVM-DA, SIMCA e PLS-DA. A predição dos parâmetros de qualidade, índice de refração e densidade relativa dos óleos, foi investigada usando os métodos de calibração multivariada dos mínimos quadrados parciais (PLS), iPLS e SVM para os dados de FT-MIR e NIR. Vários tipos de pré-processamentos, primeira derivada, correção do sinal multiplicativo (MSC), dados centrados na média, correção do sinal ortogonal (OSC) e variação normal padrão (SNV) foram utilizados, usando a raiz quadrada do erro médio quadrático de validação cruzada (RMSECV) e de predição (RMSEP) como parâmetros de avaliação. A metodologia desenvolvida para determinação de índice de refração e densidade relativa e classificação dos óleos vegetais é rápida e direta. O terceiro estudo visa à avaliação da estabilidade oxidativa e qualidade do iogurte armazenado a 4C submetido à luz direta e mantido no escuro, usando a análise dos fatores paralelos (PARAFAC) na luminescência exibida por três fluoróforos presentes no iogurte, onde pelo menos um deles está fortemente relacionado com as condições de armazenamento. O sinal fluorescente foi identificado pelo espectro de emissão e excitação das substâncias fluorescentes puras, que foram sugeridas serem vitamina A, triptofano e riboflavina. Modelos de regressão baseados nos escores do PARAFAC para a riboflavina foram desenvolvidos usando os escores obtidos no primeiro dia como variável dependente e os escores obtidos durante o armazenamento como variável independente. Foi visível o decaimento da curva analítica com o decurso do tempo da experimentação. Portanto, o teor de riboflavina pode ser considerado um bom indicador para a estabilidade do iogurte. Assim, é possível concluir que a espectroscopia de fluorescência combinada com métodos quimiométricos é um método rápido para monitorar a estabilidade oxidativa e a qualidade do iogurte / This research work describes three studies of chemometric methods employed for the classification and characterization of edible oils and its quality parameters through Fourier Transform mid infrared spectroscopy and near infrared spectroscopy, and for the monitoring the oxidative stability and quality of yogurt using fluorescence spectroscopy . The first and second studies aimed the classification and characterization of edible oil and its quality parameters using Fourier Transform mid infrared spectroscopy (FT-MIR) and near infrared spectroscopy (NIR) measurements, respectively. Kennard-Stone algorithm was used for selecting the training set, after a principal component analysis (PCA) was applied. The discrimination of canola oils from sunflower, corn and soybean was investigated using SVM-DA, SIMCA and PLS-DA. The quality parameters refraction index and relative density of edible oil was investigated using partial least squares (PLS), iPLS, LS- SVM multivariate calibration of FT-MIR and NIR data were evaluated. Several preprocessing alternatives (first derivative, multiplicative scatter correction, mean centering, orthogonal signal correction and standard normal variate) were investigated by using the root mean square error of validation cross validation (RMSECV) and prediction (RMSEP), as control parameters. In fact, the methodology developed is proposed for direct relative density and refraction index in edible oils and their classification, requiring a few minutes per sample without any previous treatment. The third study aimed to evaluate the oxidative stability and quality of yogurt stored at 40C with light or dark using the combined parallel factor (PARAFAC) analysis and fluorescence spectroscopy. PARAFAC analysis of the fluorescence landscapes exhibited three fluorophores present in the yogurt, where, at least one of them was strongly related to the storage conditions. The fluorescence signal was resolved into excitation and emission profiles of the pure fluorescent compounds, which are suggested to be vitamin A, tryptophan and riboflavin. Regression model based on PARAFAC scores for riboflavin were built using the scores obtained in the first day as dependent variable and the scores obtained during the storage as independent variable. It was clear demonstrated that the slope of the analytical curve has become smaller throughout the experiment. Therefore, riboflavin level could be considered a good indicator for the yogurt stability. Thus, it is concluded that fluorescence spectroscopy in combination with chemometrics has a potential as a fast method for monitoring the oxidative stability and quality of yogurt

The modal satisfiability problem has to date been solved using either a specifically designed algorithm, or by translating the modal logic formula into a different class of problem, such as a first-order logic, a propositional satisfiability problem or a constraint satisfaction problem. These approaches and the solvers developed to support them are surveyed and a synthesis thereof is presented. The translation of a modal K formula into a constraint satisfaction problem, as developed by Brand et al. [18], is further enhanced. The modal formula, which must be in conjunctive normal form, is translated into layered propositional formulae. Each of these layers is translated into a constraint satisfaction problem and solved using the constraint solver ECLiPSe. I extend this translation to deal with reflexive and transitive accessibility relations, thereby providing for the modal logics KT and S4. Two of the difficulties that arise when these accessibility relations are added are that the resultant formula increases considerably in complexity, and that it is no longer in conjunctive normal form (CNF). I eliminate the need for the conversion of the formula to CNF and deal instead with formulae that are in negation normal form (NNF). I apply a number of enhancements to the formula at each modal layer before it is translated into a constraint satisfaction problem. These include extensive simplification, the assignment of a single value to propositional variables that occur only positively or only negatively, and caching the status of the formula at each node of the search tree. All of these significantly prune the search space. The final results I achieve compare favorably with those obtained by other solvers. / Computing / M.Sc. (Computer Science)

Text in English / This research explores the meaning of the first and second-order therapeutic stances with reference to the therapist's professional and personal development. The dominant positivist paradigm was reflected in the therapist's initial position of expert observer, outside of the observed. The observed phenomena were a group of children suffering from thalassemia major, a terminal genetic disease, and their mothers. The initial idea of short-term intervention and focus on the observed evolved into six-year journey where the observer and the observed became an interconnected unit of observation, understanding and change. A first-order stance led to therapeutic stuckness, where the therapist's confrontation with her therapeutic failure and the limitations of the dominant paradigm provoked a deconstruction of the expert position and promoted a self-reflexive therapeutic stance. The author's self-searching process took her back to her personal self, her family of origin and the ''wounded healer". The researcher moved from an initial disconnection between her professional and personal selves to an awareness of the interface between the two and, ultimately, to a unification of her professional and personal selves. Such development involved an individuation process moving from a narcissistic belief in her objective stance towards a therapeutic stance where she sees herself less as a powerful agent of change and moves to an increasingly higher order of integration of the professional and personal selves (Skovholt & Ronnestad, 1992). The process with the children and mothers shifted from a focus on compliance and medical issues to more personal and emotional stories. The therapist's participation and collaborative stance created a context for change, where greatly improved medical compliance was just one of the many transformations experienced by all the participants. The researcher speculates that development of a second-order stance requires second-order change, which comes "at the end of long, often frustrating mental and emotional labor" (Watzlawick et al., 1974, p. 23), promoting integration between the professional and personal selves of the therapist. The researcher therefore contends that this process has important implications for psychotherapy training, supervision and continuing education. / Psychology / D. Litt. et Phil. (Psychology)

Este trabalho de pesquisa descreve três estudos de utilização de métodos quimiométricos para a classificação e caracterização de óleos comestíveis vegetais e seus parâmetros de qualidade através das técnicas de espectrometria de absorção molecular no infravermelho médio com transformada de Fourier e de espectrometria no infravermelho próximo, e o monitoramento da qualidade e estabilidade oxidativa do iogurte usando espectrometria de fluorescência molecular. O primeiro e segundo estudos visam à classificação e caracterização de parâmetros de qualidade de óleos comestíveis vegetais utilizando espectrometria no infravermelho médio com transformada de Fourier (FT-MIR) e no infravermelho próximo (NIR). O algoritmo de Kennard-Stone foi usado para a seleção do conjunto de validação após análise de componentes principais (PCA). A discriminação entre os óleos de canola, girassol, milho e soja foi investigada usando SVM-DA, SIMCA e PLS-DA. A predição dos parâmetros de qualidade, índice de refração e densidade relativa dos óleos, foi investigada usando os métodos de calibração multivariada dos mínimos quadrados parciais (PLS), iPLS e SVM para os dados de FT-MIR e NIR. Vários tipos de pré-processamentos, primeira derivada, correção do sinal multiplicativo (MSC), dados centrados na média, correção do sinal ortogonal (OSC) e variação normal padrão (SNV) foram utilizados, usando a raiz quadrada do erro médio quadrático de validação cruzada (RMSECV) e de predição (RMSEP) como parâmetros de avaliação. A metodologia desenvolvida para determinação de índice de refração e densidade relativa e classificação dos óleos vegetais é rápida e direta. O terceiro estudo visa à avaliação da estabilidade oxidativa e qualidade do iogurte armazenado a 4C submetido à luz direta e mantido no escuro, usando a análise dos fatores paralelos (PARAFAC) na luminescência exibida por três fluoróforos presentes no iogurte, onde pelo menos um deles está fortemente relacionado com as condições de armazenamento. O sinal fluorescente foi identificado pelo espectro de emissão e excitação das substâncias fluorescentes puras, que foram sugeridas serem vitamina A, triptofano e riboflavina. Modelos de regressão baseados nos escores do PARAFAC para a riboflavina foram desenvolvidos usando os escores obtidos no primeiro dia como variável dependente e os escores obtidos durante o armazenamento como variável independente. Foi visível o decaimento da curva analítica com o decurso do tempo da experimentação. Portanto, o teor de riboflavina pode ser considerado um bom indicador para a estabilidade do iogurte. Assim, é possível concluir que a espectroscopia de fluorescência combinada com métodos quimiométricos é um método rápido para monitorar a estabilidade oxidativa e a qualidade do iogurte / This research work describes three studies of chemometric methods employed for the classification and characterization of edible oils and its quality parameters through Fourier Transform mid infrared spectroscopy and near infrared spectroscopy, and for the monitoring the oxidative stability and quality of yogurt using fluorescence spectroscopy . The first and second studies aimed the classification and characterization of edible oil and its quality parameters using Fourier Transform mid infrared spectroscopy (FT-MIR) and near infrared spectroscopy (NIR) measurements, respectively. Kennard-Stone algorithm was used for selecting the training set, after a principal component analysis (PCA) was applied. The discrimination of canola oils from sunflower, corn and soybean was investigated using SVM-DA, SIMCA and PLS-DA. The quality parameters refraction index and relative density of edible oil was investigated using partial least squares (PLS), iPLS, LS- SVM multivariate calibration of FT-MIR and NIR data were evaluated. Several preprocessing alternatives (first derivative, multiplicative scatter correction, mean centering, orthogonal signal correction and standard normal variate) were investigated by using the root mean square error of validation cross validation (RMSECV) and prediction (RMSEP), as control parameters. In fact, the methodology developed is proposed for direct relative density and refraction index in edible oils and their classification, requiring a few minutes per sample without any previous treatment. The third study aimed to evaluate the oxidative stability and quality of yogurt stored at 40C with light or dark using the combined parallel factor (PARAFAC) analysis and fluorescence spectroscopy. PARAFAC analysis of the fluorescence landscapes exhibited three fluorophores present in the yogurt, where, at least one of them was strongly related to the storage conditions. The fluorescence signal was resolved into excitation and emission profiles of the pure fluorescent compounds, which are suggested to be vitamin A, tryptophan and riboflavin. Regression model based on PARAFAC scores for riboflavin were built using the scores obtained in the first day as dependent variable and the scores obtained during the storage as independent variable. It was clear demonstrated that the slope of the analytical curve has become smaller throughout the experiment. Therefore, riboflavin level could be considered a good indicator for the yogurt stability. Thus, it is concluded that fluorescence spectroscopy in combination with chemometrics has a potential as a fast method for monitoring the oxidative stability and quality of yogurt