A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Metastatic, treatment‐resistant pancreatic ductal adenocarcinoma (PDAC) is a rapidly fatal disease that typically carries a bleak prognosis. Contrast‐enhanced CT is the current standard of care tool for imaging evaluation, and repeat imaging is routinely performed in clinical trials. The availability of these imaging data render them exploitable for further analysis. CT texural analysis (CTTA), a quantitative tool for examining a region of interest on CT and generating statistical parameters based on gray‐level pixel data, is powerful technique that has been studied in other cancers and shown to correlate with features such as tumor grade, stage, and prognosis. However, the application of CTTA to PDAC has not been studied. Given the paucity of diagnostic tests to guide therapy, validated CTTA biomarkers could be immensely useful. Identifying PDAC variants that have a relative deficit in DNA repair might allow these cancers to be treated with targeted cytotoxic regimens sooner. Additionally, identifying prognostic CTTA parameters would be useful in gauging the severity of disease. We sought to perform quantitative textural analysis on CT imaging from a clinical trial cohort of patients with metastatic, treatment‐resistant PDAC. We aimed to correlate CTTA features to molecular profiling results (copy number variations obtained by array CGH) and clinical features (overall survival). Metastatic tumor sites from patients with treatment‐resistant PDAC were biopsied and molecularly profiled. Intrachromosal copy number were assessed by CGH in tumor specimens, and patients were treated based on these individual molecular profiling results. Pre‐biopsy portal‐venous phase and non‐contrast CT scans were obtained for retrospective analysis (n=15). CTTA was performed by drawing regions of interest around the primary pancreas adenocarcinoma and the normal pancreas tissue. CTTA parameters including mean positive pixels, entropy, kurtosis, and skewness were derived using the TexRAD platform at texture filtering densities of 0, 2, 3, 4, 5, and 6 pixels. CTTA values were then compared to intrachromosomal copy number variation (CNV) per tumor and overall survival (OS) post treatment using a Spearman’s rank correlation coefficient. Additional linear regression analysis was performed for positive correlations, and a Kaplan‐Meier statistic was generated for OS using median CTTA entropy. Multivariate analyses for CNV and OS were also performed. CNV were negatively correlated with the kurtosis value of the primary tumor mass using medium texture filtering (p=0.034, n=15). Linear regression revealed a significant negative correlation between kurtosis and CNV (p=0.038). Secondary analysis of the normal pancreas using coarse texture filtering revealed that increasing entropy was associated with decreased OS (p=0.0014, n=12). Using median entropy as a cutoff value (median: 4.165), median OS was greater in the entropy < 4.165 group versus the entropy > 4.165 group (179 days v 43 days; 95% CI 73.137 – 166.87; p=0.004, n=12). This exploratory study with admittedly limited sample size raises interesting questions about the use of CTTA parameters as diagnostic tools and/or biopsy adjuncts in assessing PDAC susceptibility to commercially available cytotoxics. Secondarily, entropy, a potential marker of heterogeneity and inflammation in the normal pancreas, represents an intriguing possibility for gauging prognosis.

Background: Manufacturers have used emulsifying salts universally in the processed cheese industry since James L. Kraft patented the first processed cheese in 1916. My objective was to find alternative ingredients to replace emulsifying salts in processed cheese formulations; the product would follow "clean-labeling" trends and lower the final formulation's sodium content. Materials and Methods: My experiments followed conventional processed cheese formulations to create experimental batches, which were compared to positive and negative controls for significance. Textural, rheological, and melting tests evaluated objective cheese parameters. We observed subjective sensory properties through qualitative descriptive analysis, consumer acceptance panels, and focus groups. Results: We found that aspartic acid, cysteine, and glutamic acid could functionally emulsify a processed cheese formulation, as seen in the Manuscript section of this thesis. Potential future applications can be found under the Optimization Research section of this thesis. Conclusions: Alternative ingredients can make a large change on the processed cheese industry to improve current manufacturing practices and the nutrition of food products. While optimization work can always improve upon formulations, we propose a few formulations that could serve to replace traditional processed cheese practices.

Student Number ; 9901384G - MPharm dissertation - School of Pharmacy and Pharmacology - Faculty of Health Sciences / A lyophilized polymeric wafer system was formulated for the provision of rapid drug release in the oramucosal region. Lyophilization produced a porous sponge-like matrix which allowed simulated saliva to be rapidly imbibed into the hydrophilic structure. This surge of simulated saliva resulted in rapid disintegration of the wafer. Hydroxypropyl cellulose (HPC) was selected as the polymeric platform based on its low gelation potential. Other excipients incorporated into the system were lactose and mannitol as diluents, and glycine as a collapse protectant. A Face Centred Central Composite Design was chosen to establish the significant effects of the independent formulation variables on the physicochemical and physicomechanical properties of the wafer. The formulation variables investigated were, HPC concentration, type of diluent (lactose, mannitol or mixture), concentration of diluent, quantity of glycine and fill volume. An analysis of these variables elucidated the influential factors that may be controlled to form an ‘ideal’ wafer. The concentration of HPC significantly affected the disintegration rate (p=0.003), influx of simulated saliva (p=0.011) and friability (p=0.023). The quantity of diluent present in the system also had significant effect on matrix tolerance (p=0.029) and friability (p=0.032). Statistical optimization was undertaken using stepwise forward and backward regression, and Artificial Neural Networks to predict the ideal combination of the independent variables that would produce an ideal formulation. This wafer was required to produce a matrix disintegration of 3.33%/s, friability of 0.1% loss and maximum matrix resilience. Formulations manufactured with and without model drug, diphenhydramine hydrochloride, reflected no significant differences in their physicomechanical and physicochemical properties. In an attempt to expand the scope of this technology, a preliminary investigation was undertaken to develop a prolonged release wafer system. This was successfully achieved trough the application of crosslinking technology. It was possible to achieve drug released over a period of 6 hours.

In this study conducted at Food Science Australia (FSA) and Berlin University of Technology (BUT), the effects of pulsed electric field (PEF) treatment, a novel non-thermal processing technology on bovine milk microflora and native enzymes and on the rheological and textural properties of rennet-induced milk gels was investigated. The PEF treatments were conducted at field intensities of 25-37 kV cm-1 (up to 50 kV cm-1)and temperature range of 30°C to 75ºC. Native milk enzymes selected for the study included alkaline phosphatase, lipase, xanthine oxidase and plasminand microbiological study included determining Total Plate Count (TPC) and Pseudomonas and Enterobacteriaceae counts in skim milk. At 30ºC PEF treatment at maximum field intensity inactivated AlP by 42% while at 60oC inactivation was higher (67%). Under these treatment conditions less than1 log reduction in TPC and Pseudomonas count and 2.1 logs reduction in the Enterobacteriaceae count was achieved at 30oC while at 60ºC TPC dropped by 2.4 logs and Pseudomonas and Enterobacteriaceae counts were reduced by 5.9 and 2.1 logs, respectively to below the detection limit of 1 CFU mL-1. Combining PEF treatment with heat increased the inactivation level of all enzymes which showed an increasing trend with increasing field intensity and temperature. Treatment time (4.8, 9.6, 19.2, 28.8 and 38.4 µs) was controlled by either changing the pulse frequencies (100-400 Hz) or product flow rate (30-240 mL min-1) at a constant field intensity of 31 kV cm-1 and it was found that changing the flow rate was a more effective way of enzyme inactivation than changing the frequency due to longer exposure time of enzymes to heat and field intensity. The size of casein micelles and fat globules was not affected by PEF treatment while severe heating of milk at 97oC for 10 min decreased both micelle and fat globule sizes marginally. The coagulation time of rennet-induced gels made from PEF-treated (35 to 50 kV cm-1) milks (whole and skim) increased as the treatment intensity increased, but remained shorter than gels made from pasteurised milk. The PEF treatment of milk at various field intensities and temperatures adversely affected the G′, G′′ and firmness of gels, but the effects were less pronounced than in gels made from pasteurised milks. This study concludes that for successful application in milk processing the PEF treatment needs to be combined with mild heat treatment. This approach could achieve safer milk with less damage to milk functionality. However, the quest for a suitable quality assurance indicator enzyme will need more extensive studies.

The PEF treatments were conducted at field intensities of 25-37 kV cm-1 (up to 50 kV cm-1)and temperature range of 30°C to 75ºC. Native milk enzymes selected for the study included alkaline phosphatase, lipase, xanthine oxidase and plasminand microbiological study included determining Total Plate Count (TPC) and Pseudomonas and Enterobacteriaceae counts in skim milk. At 30ºC PEF treatment at maximum field intensity inactivated AlP by 42% while at 60oC inactivation was higher (67%). Under these treatment conditions less than1 log reduction in TPC and Pseudomonas count and 2.1 logs reduction in the Enterobacteriaceae count was achieved at 30oC while at 60ºC TPC dropped by 2.4 logs and Pseudomonas and Enterobacteriaceae counts were reduced by 5.9 and 2.1 logs, respectively to below the detection limit of 1 CFU mL-1. Combining PEF treatment with heat increased the inactivation level of all enzymes which showed an increasing trend with increasing field intensity and temperature. Treatment time (4.8, 9.6, 19.2, 28.8 and 38.4 µs) was controlled by either changing the pulse frequencies (100-400 Hz) or product flow rate (30-240 mL min-1) at a constant field intensity of 31 kV cm-1 and it was found that changing the flow rate was a more effective way of enzyme inactivation than changing the frequency due to longer exposure time of enzymes to heat and field intensity. The size of casein micelles and fat globules was not affected by PEF treatment while severe heating of milk at 97oC for 10 min decreased both micelle and fat globule sizes marginally. The coagulation time of rennet-induced gels made from PEF-treated (35 to 50 kV cm-1) milks (whole and skim) increased as the treatment intensity increased, but remained shorter than gels made from pasteurised milk. The PEF treatment of milk at various field intensities and temperatures adversely affected the G′, G′′ and firmness of gels, but the effects were less pronounced than in gels made from pasteurised milks. This study concludes that for successful application in milk processing the PEF treatment needs to be combined with mild heat treatment. This approach could achieve safer milk with less damage to milk functionality. However, the quest for a suitable quality assurance indicator enzyme will need more extensive studies.

L’objet de cette thèse porte sur le développement de technologies efficaces pour le recyclage du béton. Le béton est le plus utilisé des matériaux conçus par l’homme, et par voie de conséquence, sa fabrication consomme plus de ressources naturelles que n’importe quelle autre industrie. Le béton est responsable de 7% des émissions anthropiques de CO2, la moitie provenant de la décarbonatation du calcaire. Compte-tenu des quantités de matières utilisées et de déchets produits, le recyclage du béton est un enjeu environnemental majeur, et une priorité grandissante. Le principal défi au développement et à la mise en oeuvre d’un procède de recyclage du béton concerne la difficulté à séparer ses constituants, les graviers et la pâte de ciment. Le chauffage microonde est un candidat idéal pour parvenir à ce résultat, de par sa capacité à chauffer sélectivement les différentes phases d’un matériau multiphasique, induisant ainsi des fractures aux interfaces entre phases et conduisant à leur libération. Les effets du chauffage microonde sur le béton ont donc été étudies dans cette thèse avec l’objectif de conclure quant au bien-fondé de développer un procède de recyclage qui intègre les microondes. Les effets ont été mesures par des analyses classiques d’échelle macroscopique qui ont mises en évidence une corrélation significative entre le chauffage, l’augmentation de porosité et la diminution des propriétés mécaniques du béton. Pour mieux comprendre les changements mesures à une échelle macroscopique, une technique d’analyse locale d’images de la texture du béton, base sur la microscopie électronique, a été développée. L’analyse locale des changes induits par le chauffage du béton a révélé la présence d’une porosité de fractures, qui a permis d’expliquer les changements observes des propriétés du béton les plus pertinentes vis-à-vis du recyclage. L’analyse de la texture du béton soumis au chauffage par microondes a mis en évidence la formation de deux réseaux de fractures dans la pâte de ciment, dont le développement est dicte par les conditions du chauffage microonde. Les propriétés texturales de ces réseaux de fractures ont été corrélées directement aux variations des propriétés macroscopiques du béton, ainsi qu’à la libération des agrégats. L’analyse texturale a montré que la croissance de la fracture à l’interface entre les agrégats et la pâte de ciment survient durant les premiers instants du chauffage, et que la libération des agrégats dans le béton, appelée libération texturale, est significativement plus grande que la libération mesurée après fracture du béton par impact. Cette observation a démontré l’importance de choisir un mode de fragmentation capable de tirer parti de la fracture sélective des interfaces agrégat-ciment. De plus, le travail réalise a établi qu’il existe des relations de causalité entre les variations de la porosité de fractures présente dans le béton et les propriétés du béton les plus significatives pour son recyclage, revelant ainsi la possibilite de concevoir un procede de valorisation des dechets de béton en manipulant la texture du béton. En etablissant que le chauffage microonde permet de modifier la porosite de fractures du béton, ce travail conclut que le chauffage du béton par microondes est une technologie prometteuse pour concevoir un procede de recyclage du béton. Au-dela du seul objectif du recyclage du béton, la demonstration de l’existence de relations de causalite entre les proprietes de texture du béton et les criteres de performance associes a sa fragmentation ouvre des perspectives nouvelles pour analyser et concevoir des procedes de broyage des minerais. / This thesis is concerned with the development of efficient concrete recycling technology. Concrete is the most used manufactured material on the planet and as a consequence uses more natural resources than any other industry and is responsible for 7% of the world’s carbon dioxide production, 50% of that originating from the decarbonisation of limestone. Given the magnitude of materials used and the waste produced the recycling of concrete would be a major environmental boon and should be made a priority. The main obstacle to the development and implementation of a concrete recycling process is the necessity of separating concrete components, aggregate and cement paste before recycling. Microwave heating stands as an ideal candidate due to its capacity to selectively heat different phases in a multiphase material, thus producing phase boundary fracture and increasing the liberation of the component phases. The effects of microwave heating on concrete samples were investigated with the intent of concluding on the possibility of deriving a microwave-based recycling process for concrete. The effects were measured using standard macroscopic techniques and found a strong correlation between heating, increased porosity and decreased mechanical strength for concrete. In order to better understand the changes measured at the macroscopic scale, a dedicated image analysis technique was developed using electron microscopy to investigate local microscopic changes in concrete texture. Local investigation of the changes of heat treated concrete identified the presence of fracture porosity, which has significant explanatory power for observed changes in concrete properties most relevant to recycling. Textural analysis of concrete subjected to microwave heating showed the growth of two different networks of fractures throughout the cement paste matrix, whose development is associated with the microwave settings. These textural fracture properties correspond directly to the observed changes in mechanical properties as well as the observed liberation of aggregate particles. Textural analysis shows that phase boundary fracture growth occurs rapidly in the early stages of microwave treatment and that the absolute value of textural liberation is significantly higher than that of physical liberation. This highlights the importance of choosing an appropriate comminution method to make efficient use of phase boundary fracture. Moreover, the work established causal relationships between variations in fracture porosity and changes in properties of concrete most relevant to recycling, revealing the possibility of designing a concrete waste beneficiation process through manipulating concrete texture. Since microwave heating was found to be able to manipulate the form taken by the fracture porosity, this work concludes that microwave heating of concrete is a promising technology for designing a concrete recycling scheme. Moreover, through demonstration of causal links between textural properties and processing performance criteria, this work opens the possibility of an alternative approach for analysing and designing comminution process for minerals.

Thesis advisor: Seth C. Kruckenberg / Quantitatively describing the deformational behavior (i.e. the rheology) of lower crustal materials has proven challenging due to the highly variable nature of structural and compositional fabrics in the lower crust. Further, many flow laws describing the rheology of monophase aggregates are experimentally derived and do not necessarily apply to polyphase materials, such as gabbro, that dominate the lower crust. Here, we present the results of integrated microstructural analysis and electron backscatter diffraction (EBSD) textural analysis from exhumed lower crustal granulites in the Mount Hay block of central Australia. The preservation of heterogeneous mafic and felsic granulites containing monophase and/or polyphase mixtures of anorthite, pyroxene, and quartz (interlayered on the mm- to m-scale) make this region uniquely suited for advancing our knowledge of the processes that affect deformation and the rheology of the lower crust. Forty-two samples from distinct structural and compositional domains were chosen to compare the microstructural record of deformation, the development of crystallographic textures, and to provide estimates of lower crustal rheology and deformation conditions. Full thin-section maps of crystallographic texture were produced using EBSD methods. The resultant orientation maps were processed to characterize crystallographic textures in all constituent phases, and all other quantifiable aspects of the rock microstructure (e.g., grain size, grain shape, misorientation axes). The EBSD analysis reveals the presence of strong crystallographic preferred orientations (CPO) in nearly all constituent phases, suggesting deformation dominated by dislocation creep. Differential stresses during deformation are calculated using grain size piezometry for all major phases, and range between 34-54 MPa in quartz within monophase layers. Two-pyroxene geothermometry was used to constrain deformation temperatures to ca. 780-810 C. Based on the estimated CPO patterns, stress, and temperature, we quantify strain rates and effective viscosities of all major phases through application of monophase flow laws. Monophase strain rates range from 2.10 x 10-12 s-1 to 1.56 x 10-11 s-1 for quartz, 4.68 x 10-15 s-1 to 2.48 x 10-13 s-1 for plagioclase feldspar, 1.56 x 10-18 s-1 to 1.64 x 10-16 s-1 for enstatite, and 5.66 x 10-16 s-1 to 1.00 x 10-14 s-1 for diopside. The determined flow law variables used for monophase calculations were subsequently applied to two different models – the Minimized Power Geometric model of Huet et al. (2014) and the Asymptotic Expansion Homogenization (AEH) method of Cook (2006) – in order to calculate a bulk aggregate viscosity of the polyphase material. At a strain rate of 10-14 s-1, polyphase effective viscosities for our samples range from 3.07 x 1020 to 2.74 x 1021 Pa·s. We find that the bulk viscosity of heterogeneous, gabbroic lower crust in the Mount Hay region lies between that of monophase plagioclase and monophase quartz, and varies as a function of composition. These results are consistent with past modeling studies and geophysical estimates. / Thesis (MS) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Earth and Environmental Sciences.

Background: Manufacturers continue to look for methods to save time in aging cheese. Complex reactions occur during cheese ripening that produce characteristic flavors and aromas. The addition of exogenous lipase enzymes is one accelerated ripening method that has been studied. Our objective was to document and compare the flavor profiles of cheddar cheeses created with either microbial lipase or animal lipase. Materials and Methods: The experiment followed a conventional formulation to create experimental batches of cheddar cheese. Kid goat lipase and three microbial lipase treatments were compared against a control. Other animal lipases were evaluated in preliminary research but were omitted in the final experiment due to bitter and unfavorable flavor development. Objective cheese parameters evaluated were texture, moisture, volatile, and free fatty acid (FFA) analysis. We observed subjective sensory properties through quantitative descriptive analysis. Results: The results of the current study showed that the addition of exogenous lipases caused minimal changes in cheese moisture and a reduction in firmness in cheese samples. Various levels of microbial and animal lipase in Cheddar cheese showed significant differences in the FFA profile of the aged cheese. Microbial lipases tended to liberate more medium and long-chain fatty acids while animal lipases tended to liberate more short-chain fatty acids. Mucor javanicus lipase was an exception among microbial lipases and liberated relatively greater amounts of short-chain fatty acids. The addition of exogenous lipase had significant impacts on cheese volatiles. Acetic acid levels decreased in the lipase-treated samples and there were changes in odd-numbered FFA. In terms of sensory analysis, the lipase-treated cheeses showed an increase in FFA flavor notes. Conclusions: If a microbial lipase were to replace kid goat lipase in the production of Cheddar cheese, the results of the current study show that Mucor javanicus microbial lipase would result in the closest free fatty acid profile and sensory characteristics to that of kid goat gastric lipase. Future studies could investigate the addition of animal lipases in cheese that traditionally makes use of exogenous lipases, such as Blue cheese, Emmental Parmesan, Romano, Provolone, and Feta cheeses.

The Sultanate of Oman is a rapidly modernizing country with a significant length of its coastline slated for development. Much of the coastline is still in its natural state and basic studies describing the sedimentary systems need to be conducted in order to plan effectively for their sustainable development and to monitor changes in them with time. For such purposes, sediment samples (surface and sub-surface), elevation data, and serial sediment cores were collected at Sur Lagoon during three field seasons. The research objectives, procedures, results, and analyses for Sur lagoon are presented in three chapters. The first chapter compares textural facies, identified on the basis of particle-size distribution (PSD) of surface sediments from Sur Lagoon and evaluated using multi-variate cluster analysis, for their value in recognizing modem sedimentary environments. Clustering the full PSD size spectrum (0.0375- 1888 μm) shows that facies identification is possible is closely tied to surface elevation, particle-size decreasing with increasing elevation above mean sea level. This analytical technique should be tested under different conditions to assess further its utility. The second chapter discusses the taphonomically distinct and laterally extensive (> 1 km2) bivalve shell bed deposited by a tsunami on November 28th, 1945. Taphonomic characteristics of this unit are compared to those of the shell-rich tsunamite from Caesarea, Israel, and resulted in the identification of three generic, tsunamigenic-specific traits in shell beds: 1) thickly bedded and laterally extensive shell deposit, 2) presence of allochthonous articulated bivalves not in life position, and 3) extensive angular fragmentation. When these three traits are found together, a tsunamigenic origin should be considered for the shell bed. The third chapter analyzes the PSD of the tsunamite in eight sediment cores for digested and undigested samples. Cluster analysis of the PSD extended the upper or lower tsunamite contacts in four cores, but in general, the tsunamite thickness is consistent with the previously identified shell beds (Chapter 3). The tsunamigenic processes that resulted in the deposition of the shell bed were complex, and deposition occurred during run-up, flooding, and backwash stages of the tsunami, incorporating marine, lagoonal, and terrestrial (wadi) sediment into the tsunamite. The results of this study provide baseline sedimentological data for an understudied region of the world. New applications of cluster analysis of PSD and taphonomic analysis have the potential to identify previously unknown tsunamites in the geological record, and lithological facies using textural analysis. / Thesis / Doctor of Philosophy (PhD)

<p>St. Joseph peninsula is situated on the panhandle of Florida west coast in the northeastern Gulf of Mexico at N29°50‘ and W85°20‘ and is located at the west edge of the westernmost portion of the Apalachicola Barrier Island Complex (ABIC) on the Gulf of Mexico shoreline. Three vibra-cores were collected on Saint Joseph Bay side of Cape San Blas which is part of St. Joseph peninsula to determine its evolution in context of previous work by Rink and Lopez (2010). The study uses detailed textural analysis (PSD - Particle Size Distribution plots), multivariate statistics on the PSDs (Q-mode cluster analysis) and organic matter geochemistry (C/N and δ13C). In addition, Ground Penetrating Radar (GPR) profiles are used to provide broader stratigraphic context.</p> <p>The stratigraphic analysis found that CSB has an older nucleus of strandplain deposits dating to >12 Ka that were subsequently flooded and modified through Holocene sea-level rise at ≈ 2.2 Ka. Actual barrier formation began sometime between 2.2. Ka and 0.6 Ka which is the oldest beach ridge measured by Rink and Lopez (2010). Progradation of the barrier on the St Joseph Bay side began at least by 0.3 Ka and likely earlier. There is no evidence to indicate a higher than present sea-level in our core data and our data follows that of other sea-level studies using submerged offshore samples</p> / Master of Science (MSc)