No description available.

Plasma membrane derived microvesicles (MV) are nanoscale particles released from cells both constitutively and in response to stimuli including stress, apoptosis and oncogenic transformation. Due to their mechanism of biogenesis, the majority of MV expose phosphatidylserine (PS) on their surface and as such can be identified by staining with annexin V (AxV). First observed nearly 40 years ago as coagulant ‘dust’ originating from activated platelets, MV were initially studied for their role in thrombosis. In more recent years it has become apparent that MV release is increased in several diseases including cancer; this, in conjunction with their ability to carry cargo such as proteins and nucleic acid species, strongly implicates them in disease pathology. Given their small size it is considered likely that MV are able to travel to distal sites within the body allowing the widespread dissemination of effects otherwise not achievable by their parent cells. In the context of malignancy, the contribution of MV is especially important in that MV have been demonstrated to have roles in oncogenic transformation, promotion of tumour growth and increasing metastatic potential. Although clearly important in pathogenesis, their small size makes qualitative and quantitative analysis extremely difficult. Furthermore, the study of MV has been greatly hampered by a lack of standardised protocols for their isolation and as such the majority of studies have been in vitro. In line with this, the relevance of observed effects to in vivo systems is often questioned; given the high quantities of MV used in in vitro systems, the question of whether these concentrations bear any relevance in vivo remain to be answered. We hypothesise that the high rates of apoptosis observed in many tumours, most notably in the high grade B cell malignancy, Non-Hodgkin’s lymphoma (NHL), provides an environment whereby MV are continually released into the surrounding milieu allowing for an amplification of effects. As apoptosis has been previously implicated in promoting tumourigenesis we propose that this is extended to include MV released from apoptotic tumour cells (aMV). Given the numerous technical challenges involved in MV research, initial studies involved identifying the limitations of the instruments available for MV analysis. Preliminary experiments identified considerable resolution issues with the older style EPICS XL flow cytometer (Beckman Coulter) and so a newer flow cytometer, The Attune™ (Thermo Fisher), capable of higher resolution was utilised for the remainder of the project. Despite this improvement, flow cytometry was demonstrated to be less effective at quantifying MV than nanoparticle tracking analysis (NTA). As the fluorescent capacity of NTA is still in its infancy, it was used in concert with flow cytometry in order to quantify and phenotype MV as accurately as possible. As there is currently no concensus on an optimal method of MV isolation subsequent studies focused on determining a method of MV isolation that was appropriate for our experimental system. To this end, centrifugation, filtration and antibody coated magnetic bead-based methods were all tested and their limitations identified. In terms of bead-based isolation strategies, the generation of AxV, protein S, gla domain and gas 6 fusion proteins was attempted with the intention to conjugate to magnetic beads and provide a novel means to isolate aMV. Unfortunately this aspect of the project was ultimately abandoned due to time constraints and although commerically available antibody coated beads were tested for their ability to isolate MV, later co-culture experiments demonstrated that the beads had off target effects that were deleterious to cells. As a result, centrifugation and filtration methods were next researched and validated extensively. TEM analysis of MV morphology identified damage likely induced by the high-speed centrifugation of a fragile apoptotic cell population. As such, a protocol combining low speed centrifugation and filtration was designed and validated by several methods including TEM and staining with AxV. The surface levels of parent cell markers (CD19 and CD20) and apoptosis associated proteins were compared in aMV and vMV (MV released from viable tumour cells) and results demonstrated that B cell surface markers were off loaded into MV to a greater extent following apoptosis. Additional phenotypic studies extended previous work from the group demonstrating the presence of apoptotic cell associated molecular patterns (ACAMPs) capable of binding a panel of antibodies to LPS. Flow cytometry results confirmed the presence of ACAMPs on aMV and results from co-culture experiments with CD14 positive and negative cells suggested that unlike recognition of LPS, binding via ACAMPs was not CD14 dependent. The protein and nucleic acid content of MV was also studied and interestingly, results demonstrated significantly increased quantities of DNA and RNA in aMV compared to vMV. Furthermore, aMV were also shown to contain the matrix metalloproteinases, MMP2 and MMP12 alluding to a role for aMV in angiogenesis. The final stage of the project was focused on determining the roles of aMV in the tumour microenvironment and effects relating to cell growth, cell cycle and angiogenesis were studied and compared to vMV. Results showed that both aMV conditioned supernatant and aMV concentrated by the centrifugation were able to significantly increase the growth of the parent cell population. Further studies using DAPI staining to determine the cell cycle status of cells co-cultured with aMV demonstrated an increase in DNA synthesis and cell division upon incubation with aMV. An in vitro angiogenesis assay was designed to determine any pro-angiogenic capabilities of aMV given the earlier results demonstrating the presence of MMPs. These results provided some of the most interesting findings of the project and showed that aMV were able to increase the angiogenic potential of human endothelial cells (HUVECs); an effect that was shown to be greatly reduced following storage at either 4 or - 80°C. These results demonstrated that aMV possess factors capable of manipulating the tumour microenvironment to favour disease progression and that previously described pro-tumour functions of MV are increased as a result of apoptosis. These findings have implications both in terms of extending the previously described hallmarks of cancer and also when designing a course of therapy whereby in some instances the generation of large amounts of apoptosis may in fact serve to promote regeneration of the tumour cell population.

No description available.

In this work two ways of processing controlled-source magnetotelluric (MT) data were tried and compared against each other. The aim was to evaluate the differences between a multivariate-based processing method to a bivariate processing method. The software KMSProTF represents conventional processing using bivariate and robust statistics. MsDEMPCA utilizes a multi-variate Criss-Cross regression scheme to improve the condition of the data-matrix before robustly decomposing it into principal components. Data from the FENICS-19 survey in northern Scandinavia was processed to transfer functions (TF) using the respective method. The TFs were visually interpreted in KMSProTF. There were no significant differences found between the methods. In addition a calibration between instruments was carried out, which caused an exclusion of parts of the data-set.

Marine vibrio MV-1 is a magnetotactic bacterium capable of aligning its cell in response to the Earth’s magnetic field. This ability is due to the presence of chainlike structures comprising magnetosomes, magnetite particles enclosed in a lipid membrane with associated proteins. Strain MV-1 differs from other, bettercharacterized strains of magnetotactic bacteria as the cells produce higher amounts of biomagnetite per litre of culture and its magnetosomes are unique in shape. This study investigates the presence and organisation of a gene cluster termed a “magnetosome island” within the genome of MV-1. In other magnetotactic bacteria this genomic region has been shown to contain many of the genes associated with magnetosome formation but has not been previously investigated for MV-1. One of the conserved fragments of this region was amplified using degenerate primers followed by extension of the known sequence using inverse PCR based technique and constructing plasmid libraries. Sequencing of the genome of strain MV-1 was accomplished as a part of this study. Significant work was done on comparison of the sequence quality obtained from SOLEXA, 454 and Sanger sequencing technologies. A number of obtained contigs were joined manually and the resulting sequence was automatically annotated using RAST. The obtained genome sequence of 3.6 Mb with a G+C content of 54.3 % was preliminarily analysed and used to search for magnetosome related genes. This study also analysed proteins associated with the magnetosomes of strain MV-1 using MALDI-TOF, LC-MS and Orbitrap mass spectrometry. These approaches allowed the identification of a number of proteins in the isolated magnetosome membrane fraction. Some of these proteins have very low similarity with other characterized proteins (either in magnetotactic bacteria or in other organisms). Another significant point is that genes that code for proteins such as MamR, MamK and MmsF were found to be present in several homologous copies within the “magnetosome island” of MV-1. Interestingly, this study shows that all homologous copies of these proteins were identified in the magnetosome membrane fraction. Generation of knock-out mutants of several specific genes from the “magnetosome island” of strain MV-1 was attempted; constructs were made based on suicide plasmids carrying the cre-lox or I-SceI systems. Despite altering numerous experimental conditions it was not possible to obtain conclusive evidence of the isolation of MV-1 transconjugants containing the integrated constructs. In order to investigate the cell localization of the magnetosome associated protein CAV30779.1, an enhanced green fluorescent protein (EGFP) fusion based construct was generated and transferred into MV-1 cells. The EGFP fluorescent protein fusions within the cells were detected by microscopy. This study reveals novel information about magnetosome formation in marine vibrio MV-1. The obtained results provide an important foundation for further investigation of this organism and contribute towards broadening the knowledge of the complex process of magnetosome formation in bacteria.

A Varian 2100C 18 MV photon beam has been modeled in this work using the MCNP5 Monte Carlo particle transport user code. The subsequent beam irradiation was also delivered to a water phantom and benchmarked against experimentally measured depth dose data. The model presented in this work establishes the foundation to which further beam characteristics tuning is required in order to realistically model the beam mentioned above. It has been determined in this work that the initial electron beam energy of this beam model is sufficiently close to the electron beam energy from the linear accelerator used to obtain the benchmark depth dose data.

Through ¡§Economic Value Added¡¨ (EVA) approach, this study tries to observe the correlation between formation process of king stocks and their market prices. We hope to provide a useful tool to investors, which helps to realize value of king stocks and conditions of finding king stocks among numerous of listed companies, in order to make investment decisions efficiently and more precisely, and to obtain a good margin of profit. We gather financial information of those listed companies, which they had ever deemed as king stocks between 1992 and 2011. They basically have some features in common, i.e. companies with positive prospects, high market price, and newly listed. In this research, we utilize WACC, MV, COV and FGV to analyze EVA of king stocks, and find out the following empirical results: 1.When WACC of a king stock trends up in the long-run, it has a greater opportunity to improve and trigger COV trending up as well. 2.When COV of a king stock trends up, it brings stable performances of MV continuously. 3.FGV has a positive correlation with market price. When FGV of a king stock trends up, it triggers its market price to go up. In this research, we see that when MV and COV are convergent, we¡¦re able to use FGV to anticipate future trend of the stock. We also expect this study further facilitates king-stock companies themselves to set up workable market price stabilizing plans and select the best timing for stock buybacks. Keywords: King Stock, EVA, WACC, MV, COV, FGV, Stock Buybacks.

This thesis presents methods for voltage management in distribution systems with high photovoltaic (PV) power production. The high PV penetration leads to both new challenges such as voltage profile violation and reverse power flow, and also new opportunities. Traditionally, the voltage control in the distribution network is achieved by common devices in the networks such as capacitor banks, static synchronous compensators (STATCOMs) and on-load tap changers (OLTCs). This thesis has considered existing reactive power capable solar PV inverters together with STATCOMs to provide voltage support for the distribution network. In this thesis, two effective coordination methods using the STATCOM and PV inverters are developed in order to study their interaction and how they together can stabilize the voltage level. Data from existing low-voltage (LV) and medium-voltage (MV) networks are used for a case study. The first control method is developed for LV network’s voltage control by means of PV inverter and STATCOM. The second control method is developed for both LV and MV networks’ voltage control, where reactive power control in PV inverters and STATCOMs are used in the LV network and only STATCOMs in the MV network. The control methods follow a hierarchical structure where reactive power compensation using PV inverters are prioritized. The STATCOMs, first in the LV and thereafter in the MV network in the second control method, are used only when the PV inverters are not able to provide or consume enough reactive power. This is beneficial due to the significant reduction in numbers of STATCOMs and their operation. The simulation results indicate that the proposed method is able to control both the over- and undervoltage situations for the test distribution networks. It is also shown that reactive power supply at night by the PV inverters can be an important resource for effective voltage regulation by using the proposed coordinated voltage control method.

Esta tesis está dividida en dos partes. La primera parte está dedicada al estudio de la variedad MMV de las MV-álgebras monádicas y de sus subreductos implicativos. En primer lugar, demostramos que MMV está generada por sus miembros finitos, caracterizamos los miembros indescomponibles por medio del álgebra de Boole monádica de sus elementos complementados y describimos el fragmento del reticulado de subvariedades que se encuentra contenido en V([0; 1]k), para cada k entero positivo, dando una axiomatización para dichas subvariedades. Estudiamos, además, las subvariedades simples que no están contenidas en V([0; 1]k) para ningún k. Nuestro segundo objetivo es extender el funtor �� de Mundici a la categoría de las MV-álgebras monádicas. En tal sentido, definimos el concepto de l-grupo monádico y establecemos una equivalencia natural entre la categoría de los l-grupos monádicos y la categoría de las MV-álgebras monádicas. También estudiamos las congruencias de un l-grupo monádico y las caracterizamos por medio de ciertos l-ideales que llamamos l-ideales monádicos. Probamos que el reticulado de l-ideales monádicos de un l-grupo monádico G es isomorfo al reticulado de l-ideales de EG. Demostramos que todo l-grupo monádico es producto subdirecto de una familia de l-grupos monádicos {Gi : iE I} donde EGi es una cadena para todo i E I. Por último, damos algunas aplicaciones de la equivalencia obtenida. Dedicamos un capítulo al estudio de la clase de los {O, -, A,1}-subreductos de lasMV-álgebras monádicas, esto es, la clase de los subreductos hoop monádicos de las MV-álgebras monádicas. Demostramos que esta clase forma una variedad, e introducimos una axiomática para estos subreductos hoop monádicos. Caracterizamos a los miembros subdirectamente irreducibles de la variedad y determinamos las subvariedades de ancho k.En el último capítulo de esta primera parte, estudiamos la clase de los subreductos implicativos monádicos de las MV-álgebras monádicas, esto es, los{O, -,A,1}-subreductos de las MV-álgebras monádicas. Demostramos que esta clase forma una variedad, e introdu-cimos una axiomática para la misma. Caracterizamos sus miembros subdirectamente irreducibles, describimos el reticulado de subvariedades y damos una base ecuacional para cada una de las subvariedades propias.La segunda parte de esta tesis está dedicada a obtener representaciones topológicas de ciertas álgebras de implicación. En primer lu-gar, obtenemos una representación topológica para las álge-bras de implicación monádicas, extendiendo la representación topológica de las álgebras de implicación. Toda álgebra de implicación monádica es representada como una unión de una familia única de filtros monádicos, dentro de una adecuada álgebra de Boole monádica. Introducimos la noción de espacio implicativo monádico, y probamos que existe una equivalencia dual entre la categoría de las álgebras de implicación monádi-cas y la categoría de los espacios implicativos monádicos. También obtenemos una representación topológica para las álgebras -implicativas de Lukasiewicz trivalentes. Describimos a toda álgebra -implicativa de Lukasiewicz trivalente como la unión de una familia única de filtros implicativos de una cierta álgebra de Lukasiewicz trivalente. Introducimos la noción de espacio topológico implicativo 3-valuado, y probamos que existe una equivalencia dual entre la categoría de los mismos y las álgebras -implicativas de Lukasiewicz trivalentes. Como aplicación describimos el espacio implicativo 3-valuado del álgebra -implicativa de Lukasiewicz trivalente libre. / This thesis is divided into two parts. The first part is devoted to the study of the variety MMV of monadic MV-algebras and its implicative subreducts. First, we show that MMV is generated by its finite members and we characterize the indecomposable members using the monadic Boolean algebra of their complemented elements. We describe the fragment of the lattice of subvarieties that is con-tained in V([0,1]k), for each positive integer k, and we give an axiomatization of these subvarieties. We also study simple subvarieties that are not contained in V([0, 1]k) for any k.Our second objective is to extend Mundici`s functor �� to the category of monadic MV-algebras. More pre-cisely, we define monadic l-groups and we establish a natural equivalence between the category of monadic MV-al-gebras and the category of monadic l-groups with strong unit. We give some applications. We study the lattice of congruences of a monadic l-group G and we prove that this lattice is isomorphic to the lattice of monadic l-ideals and also to the lattice of l-ideals of 9G. We prove that every monadic l-group is a subdirect product of a family of monadic l-groups {Gi: i E I}such that every EGi is a chain. We devote a chapter to the study of the class of {O,-A,1}-subreducts of monadic MV-algebras. We prove that this class is an equational class and we introduce a set of equations that describe this variety. We characterize the subdirectly irreducible members and the lattice of con-gruences of every algebra. We describe the subvarieties of width k. In the last chapter of this part, we study the class of {-,A,1}-subreducts of monadic MV-algebras. We introduce the equations that characterize this class and we prove that this class is a variety. We characterize the subdirect irreducibles members and the lattice of con-gruences of every algebra. We describe completely the lattice of subvarieties and we give a equational basis for every proper subvariety. The second part of this thesis is devoted to getting topological representations for certain implication algebras. First, we extend the topological representation for implication algebras to a topological representation for monadic implication algebras. Every monadic implication algebra is represented as a union of a unique family of monadic filters of a suitable monadic Boolean algebra. Inspired by this representation, we introduce the notion of a monadic implication space, and we prove a dual equivalence between the category of monadic implication algebras and the category of monadic implication spaces. We also obtain a topological represen-tation for three-valued Lukasiewicz -implication alge-bras. Every Lukasiewicz -implication algebras is repre-sented as a union of a unique family of implication filters of a suitable three-valued Lukasiewicz algebras. Inspired in this representation, we introduce the notion of topological three-valued implication space, and we prove a dual equivalence. As an application, we describe the space of free three-valued Lukasiewicz -implication algebras.

Medium-voltage (MV) motor drives have found widespread applications in various heavy industries, such as in the oil and gas sectors, production plants, and process industries. Conventional cascaded H-bridge (CHB) multilevel inverters dominate the medium-voltage industrial drives domain due to their modularity, scalability, and reliability. The most prevalent CHB topology in the drive industry is based on the diodes-front-end (DFE) rectifier, which greatly limits the industrial application of the conventional CHB drives where the ability of handling regeneration is required. The main objective of this thesis is to develop a low-cost, high performance, reliable regenerative CHB drive. The thesis is concentrating on reducing the grid-tied filter size, shrinking the DC-link capacitors, improving the system’s performance and reliability through advanced control techniques. First, to reduce the number of passive filter components, a new sideband harmonic active filtering strategy based on the carrier-shifting method is proposed for regenerative CHB drives. This proposed approach extends the carrier shifted PWM method for regenerative CHB drives to further reduce the required passive filter size significantly and thus improves the overall size, cost, and efficiency while complying with IEEE Std 519-2014 grid standard. Second, a novel voltage ripple controller is proposed to reduce the dc-link capacitance in the three-phase regenerative CHB drive without adding extra measurements. Third, to achieve a faster dynamic response and the multi-objective performance during the control of CHB drives, a novel high-performance predictive control with long prediction horizons is proposed to improve the control performance of the CHB multilevel inverters. The formulation of the proposed high-performance finite control set model predictive control (FCS-MPC) is explained in detail and analyzed to reduce the real-time computation burden. Last, when a fault is detected in the regenerative CHB drive system, the reliability and fault-tolerant ability are considered as the main issues. To improve the drive system reliability, a non-symmetrical selective harmonic elimination (SHE) formulation is proposed to extend the output voltage range with a good harmonic profile under post-fault conditions. Experimental validation of the proposed algorithms is presented for the operation of a scaled-down seven-level regenerative CHB drive system. These proposed techniques make the regenerative CHB drive a promising solution for future medium-voltage regenerative drive applications in terms of cost, performance, and reliability. / Thesis / Doctor of Philosophy (PhD)