Structured emulsion gel systems for delivery of bioactive compounds : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Food Technology at Massey University, Manawatū, New Zealand

Figures are re-used with permission.The structure of solid/semi-solid foods greatly impacts on how the food is broken down and digested in the human body, which affects its sensory perception, and the bioaccessibility of nutrients. In this project, heat-set whey protein emulsion gel was used as a model system for solid/semi-solid foods for the delivery of capsaicinoids (CAP); the capsaicinoids were dissolved in the emulsion droplets. The aim was to investigate the effect of emulsion gel structure on the breakdown properties and sensory perception of the gel in human mouth and to understand how gel structure affects its digestion behaviour as well as the release of capsaicinoids during in vitro gastrointestinal digestion. Small and large deformation properties as well as the microstructure of the emulsion gel were evaluated. Eighteen human subjects were used to investigate in vivo oral processing behaviour and sensory perception. The Human Gastric Simulator (HGS) was used for in vitro dynamic gastric digestion and pH-stat for simulated intestinal digestion. Human intestinal epithelial cells Caco-2 were used to evaluate the irritation effect of gastric digesta by the quantification of human interleukin-8 (IL-8) production using enzyme-linked immunosorbent assay (Elisa). Based on the rheological properties, the gels were classified into three groups: semi-solid gel (whey proteins as emulsifier, 10 mM NaCl with d4,3 of ~ 0.2 µm); soft and elastic gels (whey proteins as emulsifier, 10 mM NaCl with d4,3 of ~ 4, 1 and 0.5 µm); hard and brittle gels (whey proteins as emulsifier, 100 mM NaCl with d4,3 of ~ 4, 1, 0.5 and 0.2 µm). Results from in vivo study indicated that the degree of gel fragmentation during mastication was positively correlated with gel hardness (represented by Young’s modulus). A higher degree of fragmentation led to a greater surface exposure during mastication and, therefore, a greater release of capsaicinoid molecules, resulting in greater mouth burn perception. Results from in vitro gastrointestinal digestion of CAP-loaded soft gel and CAP-loaded hard gel showed that the hard gel was disintegrated and hydrolysed slower than the soft gel during gastric digestion. The rate and extent of lipid digestion during intestinal digestion were affected by several factors, such as fat content, gel structure, gel particle size and initial oil droplet size of the gastric digesta. Generally, the soft gel had higher degree of lipid digestion, mainly because of its soft gel structure and lower fat content. The bioaccessibility of CAP was found to be positively correlated with the extent of lipid digestion. The effect of active (whey proteins as emulsifier) versus inactive (Tween 80 as emulsifier) filler particles of CAP-loaded emulsion gels was also investigated. CAP-loaded Tween-80-coated oil droplets were not bound within the whey protein matrix (i.e. emulsion gels containing inactive filler particles) and appeared to be flocculated and heterogeneously distributed in the gel matrix; this led to drastically decreased gel strength. On the other hand, the whey-protein-coated oil droplets had strong interactions with surrounding whey protein matrix contributing to gel strength, and the oil droplets were relatively evenly distributed in gel matrix in CAP-loaded whey protein emulsion gels (i.e. emulsion gels containing active filler particles). During in vivo oral processing, CAP-loaded Tween 80 emulsion gels were readily broken down into small fragments in the mouth at small deformations with less chewing and released large amounts of oil droplets from the gel matrix. In general, the mouth burn perception was positively correlated with degree of gel fragmentation. The large amounts of oil droplets released from the gel matrix during mastication and the inhomogeneous distribution of the oil droplets of the CAP-loaded Tween 80 emulsion gels also contributed to their greater mouth burn perception. During in vitro gastric digestion, the gel with inactive filler particles was disintegrated and emptied out faster than gel with active filler particles, due to its significantly smaller masticated particle size entering the stomach. Large amounts of oil droplets were released during gastric digestion from the gel with inactive filler particles while gel with active filler particles had minor release of oil droplets at the end of digestion. During intestinal digestion, the presence of Tween 80 in gel with inactive filler particles has slowed down the rate and extent of lipolysis, because Tween 80 had certain resistance against replacement by bile salts from the interface. Moreover, the Tween 80 molecules, once displaced by bile salts from the interface, would also participate in the formation of mixed micelles and help solubilize the released CAP molecules, therefore, leading to improved bioaccessibility of CAP. An in vitro method was developed to quantify the gastric irritation of CAP-loaded food formulations during gastric digestion. Results suggest that Caco-2 cells had immune responses to CAP-loaded samples by secreting significant amounts of IL-8, confirming that CAP molecules are inflammatory to Caco-2 cells. The emulsion gel structure was modified using different emulsifiers: whey proteins versus Tween 80. The gastric digesta from CAP-loaded Tween 80 emulsion gel was able to stimulate more IL-8 production than CAP-loaded whey protein emulsion gel. Tween 80 was found to be a proinflammatory factor to Caco-2 cells and could stimulate IL-8 secretion. Overall, this research provided new information on the use of solid/semi-solid systems for delivery of capsaicinoids and how food structure affects disintegration and digestion behaviour and eventually the release of capsacinoids. The outcomes have potential for designing functional foods containing capsaicinoids, with increased incorporation of capsaicinoids in the foods / pharmaceuticals, reduced irritation in the mouth and stomach and increased bioaccessibility in the intestine

Biologics for the treatment of chronic rhinosinusitis with nasal polyps : state of the art

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex upper airway disease affecting up to 11% of the population of Western Europe. In these western countries, 85% of the CRSwNP disease reveals a type 2 inflammatory pattern. In the last 15 years, several randomized double-blind studies on monoclonal antibodies in CRSwNP were performed. These studies demonstrated for the first time that biologics targeting type 2 immune reactions might be successful in nasal polyps. The target proteins, interleukin (IL)-4, IL-5, IL-13, and IgE were previously identified as key mediators in studies using nasal polyp tissues to measure and to interact in ex-vivo settings. No biomarkers have been identified to predict response to a specific biologic or to monitor treatment success. These studies were characterized by small numbers of patients and heterogeneous populations. They did, however, pave the way for currently performed and analyzed phase 3 studies, which will possibly lead to the registration of the first biologic drug with the indication CRSwNP. The studies already provide indications on the effects to be expected from those biologics; the results of phase-3 studies in larger populations will be decisive for the indications, patient selection, and finally the stopping rules for those drugs in subjects with severe nasal polyps, in whom the current standard of care including topical and oral glucocorticosteroids, antibiotics and surgical procedures failed to control the disease. We may expect that those biologics will open new perspectives for those patients with severe polyposis with, but also independent of asthma, allowing to avoid the possible adverse events resulting from systemic glucocorticosteroids and surgery

Thermal Bremsstrahlung Radiation in a Two-Temperature Plasma

In the normal one-temperature plasma the motion of ions is usually neglected when calculating the Bremsstrahlung radiation of the plasma. Here we calculate the Bremsstrahlung radiation of a two-temperature plasma by taking into account of the motion of ions. Our results show that the total radiation power is always lower if the motion of ions is considered. We also apply the two-temperature Bremsstrahlung radiation mechanism for an analytical Advection-Dominated Accretion Flow (ADAF) model; we find the two-temperature correction to the total Bremsstrahlung radiation for ADAF is negligible.Comment: 5 pages, 4 figures, accepted for publication in CHJAA. Some discussions and references adde

Enhanced CNN for image denoising

Owing to flexible architectures of deep convolutional neural networks (CNNs), CNNs are successfully used for image denoising. However, they suffer from the following drawbacks: (i) deep network architecture is very difficult to train. (ii) Deeper networks face the challenge of performance saturation. In this study, the authors propose a novel method called enhanced convolutional neural denoising network (ECNDNet). Specifically, they use residual learning and batch normalisation techniques to address the problem of training difficulties and accelerate the convergence of the network. In addition, dilated convolutions are used in the proposed network to enlarge the context information and reduce the computational cost. Extensive experiments demonstrate that the ECNDNet outperforms the state-of-the-art methods for image denoising.Comment: CAAI Transactions on Intelligence Technology[J], 201

Automated Lensing Learner: Automated Strong Lensing Identification with a Computer Vision Technique

Forthcoming surveys such as the Large Synoptic Survey Telescope (LSST) and Euclid necessitate automatic and efficient identification methods of strong lensing systems. We present a strong lensing identification approach that utilizes a feature extraction method from computer vision, the Histogram of Oriented Gradients (HOG), to capture edge patterns of arcs. We train a supervised classifier model on the HOG of mock strong galaxy-galaxy lens images similar to observations from the Hubble Space Telescope (HST) and LSST. We assess model performance with the area under the curve (AUC) of a Receiver Operating Characteristic (ROC) curve. Models trained on 10,000 lens and non-lens containing images images exhibit an AUC of 0.975 for an HST-like sample, 0.625 for one exposure of LSST, and 0.809 for 10-year mock LSST observations. Performance appears to continually improve with the training set size. Models trained on fewer images perform better in absence of the lens galaxy light. However, with larger training data sets, information from the lens galaxy actually improves model performance, indicating that HOG captures much of the morphological complexity of the arc finding problem. We test our classifier on data from the Sloan Lens ACS Survey and find that small scale image features reduces the efficiency of our trained model. However, these preliminary tests indicate that some parameterizations of HOG can compensate for differences between observed mock data. One example best-case parameterization results in an AUC of 0.6 in the F814 filter image with other parameterization results equivalent to random performance.Comment: 18 pages, 14 figures, summarizing results in figure

A coupled mitral valve - left ventricle model with fluid-structure interaction

Understanding the interaction between the valves and walls of the heart is important in assessing and subsequently treating heart dysfunction. This study presents an integrated model of the mitral valve (MV) coupled to the left ventricle (LV), with the geometry derived from in vivo clinical magnetic resonance images. Numerical simulations using this coupled MV–LV model are developed using an immersed boundary/finite element method. The model incorporates detailed valvular features, left ventricular contraction, nonlinear soft tissue mechanics, and fluid-mediated interactions between the MV and LV wall. We use the model to simulate cardiac function from diastole to systole. Numerically predicted LV pump function agrees well with in vivo data of the imaged healthy volunteer, including the peak aortic flow rate, the systolic ejection duration, and the LV ejection fraction. In vivo MV dynamics are qualitatively captured. We further demonstrate that the diastolic filling pressure increases significantly with impaired myocardial active relaxation to maintain a normal cardiac output. This is consistent with clinical observations. The coupled model has the potential to advance our fundamental knowledge of mechanisms underlying MV–LV interaction, and help in risk stratification and optimisation of therapies for heart diseases

Modelling mitral valvular dynamics–current trend and future directions

Dysfunction of mitral valve causes morbidity and premature mortality and remains a leading medical problem worldwide. Computational modelling aims to understand the biomechanics of human mitral valve and could lead to the development of new treatment, prevention and diagnosis of mitral valve diseases. Compared with the aortic valve, the mitral valve has been much less studied owing to its highly complex structure and strong interaction with the blood flow and the ventricles. However, the interest in mitral valve modelling is growing, and the sophistication level is increasing with the advanced development of computational technology and imaging tools. This review summarises the state-of-the-art modelling of the mitral valve, including static and dynamics models, models with fluid-structure interaction, and models with the left ventricle interaction. Challenges and future directions are also discussed

Measuring Exocytosis Rate Using Corrected Fluorescence Recovery After Photoconversion

Exocytosis plays crucial roles in regulating the distribution and function of plasma membrane (PM) and extracellular matrix proteins. However, measuring the exocytosis rate of a specific protein by conventional methods is very difficult because of exocytosis-independent trafficking such as endocytosis, which also affects membrane protein distribution. Here, we describe a novel method, corrected fluorescence recovery after photoconversion, in which exocytosis-dependent and -independent trafficking events are measured simultaneously to accurately determine exocytosis rate. In this method, the protein-of-interest is tagged with Dendra2, a green-to-red photoconvertible fluorescent protein. Following the photoconversion of PM-localized Dendra2, both the recovery of the green signal and the changes in the photoconverted red signal are measured, and the rate of exocytosis is calculated from the changing rates of these two signals