Дисертації з теми "Potentiales vecteur"
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1
Bahouli, Bassem. "Caracterisations de champs de matrices, potentiels matrices et applications aux operateurs traces." Thesis, Pau, 2021. http://www.theses.fr/2021PAUU3053.
Анотація:
Plusieurs auteurs ont utilisé les champs de contraintes pour résoudre l'équation d’équilibre de la mécanique des milieux continus. Airy (1863) a résolu le cas bidimensionnel, Maxwell (1870) et Morera (1892) ont étudié le cas tridimensionnel. Les solutions obtenues sont des cas particuliers de celles de Beltrami (1892). Gurtin a donné un exemple de solutions ne satisfaisant pas la représentation S = CurlCurlA de Beltrami, ce qui signifie que la représentation précédente est incomplète. De plus, il a montré que si l’ouvert est régulier, alors elle est complète dans l’espace des champs réguliers de contraintes auto-équilibrés.Dans cette thèse intitulée ”Caractérisations de champs de matrices, potentiels matrices et applications aux opérateurs traces”, on s’intéresse à diverses caractérisations de champs de vecteurs, de champs de matrices et spécialement au résultat de Gurtin dans le cas où l’ouvert et les champs de contraintes ne sont pas réguliers.Cette thèse est décomposée en cinq chapitres. Le premier chapitre expose la problématique de recherche traitée dans cette thèse. Il présente également l’origine du sujet de recherche. Dans le deuxième chapitre, on étudie l’opérateur et en particulier l’existence de potentiels vecteurs dans différents cadres fonctionnels.Dans les chapitres 3 et 4, on va montrer quelques versions de la complétude de la représentation de Beltrami et en déduire des décompositions de Helmholtz pour les champs de matrices.Le dernier chapitre est consacré à l’étude de l’image de différents opérateurs traces de fonctions W 2,p (Ω), W 3,p (Ω) lorsque Ω est un ouvert borné de R 2 lipschitzien. L’ingrédient essentiel est donné par la fonction d’Airy ou par la représentation de BeltramiMany authors have used stress fields to solve the equilibrium equation of continuum me- chanics. Airy (1863) solved the two-dimensional case, Maxwell (1870) and Morera (1892) solved the three-dimensional case. The above solutions are special cases of those of Beltrami (1892). Gurtin gave an example of solutions that do not have Beltrami’s S = CurlCurlA representation. He showed that if the domain Ω is regular, then this representation is complete in the class of regular stress fields which are self-equilibrated.My thesis title is ”Characterizations of matrix fields, potential matrices and applications to trace operators”. In this work, we are interested by showing many characterizations ofvector fields, of matrix fields and especially by generalizing the result of Gurtin in the case when the open set and the stress fields are not regular.This thesis consists of five chapters. The first chapter presents the research problem ad- dressed in this thesis. It also presents the origin of the subject of research.In the second chapter, we study the operator . In particular, the existence of potential vectors in different functional frameworks.In Chapters 3 and 4, we will show some versions of Beltrami’s completeness and we deduce some Helmholtz decomopsitions for symmetric matrix fields.The last chapter is devoted to the study of the image of different trace operators of functions W 2,p (Ω), W 3,p (Ω) when Ω is a bounded open of R 2 with Lipschitz boundary. The essential ingredient is given by the Airy’s function or by the Beltrami representation
2
Miot, Elliott. "Potential of the mosquito Aedes malayensis as an arbovirus vector in South East Asia." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS548.
Анотація:
De nombreux virus transmis par les arthropodes (arbovirus), tels que ceux de la dengue (DENV) et de la fièvre jaune (YFV), circulaient à l’origine dans des cycles selvatiques et ont émergé chez l’Homme via des moustiques « bridge vectors » qui connectent les cycles de transmission selvatiques et humains. Ces « bridge vectors » peuvent aussi par transfert inverse établir de nouveaux cycles selvatiques. Cette thèse a évalué le potentiel de vecteur d’arbovirus d’un moustique répandu en Asie du sud-est, Aedes malayensis. Nous avons identifié Ae. malayensis pour la première fois au Laos lors de captures de moustiques dans une forêt de la réserve de Nakai Nam Theun. En utilisant des pièges à appâts humains sur le terrain, nous avons observé qu’Ae. malayensis pouvait piquer l’Homme et donc potentiellement agir comme « bridge vector ». En laboratoire, cette population selvatique d’Ae. malayensis a montré une faible compétence vectorielle relative pour DENV et YFV, et une absence d’attraction détectable pour l’odeur humaine. Cependant, des tests de compétence vectorielle et de pièges à appâts humains ont révélé qu’une population péri-domestique d’Ae. malayensis à Singapour était compétente pour YFV et entrait en contact avec l’Homme. Au final, ce travail de doctorat a souligné l’importance de ne pas négliger les vecteurs secondaires dans l’évaluation du risque d’émergence des arbovirusMany emerging arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and yellow fever virus (YFV) originated in sylvatic cycles and have emerged among humans through spillover transmission by mosquito species that ‘bridge’ sylvatic and human transmission cycles. These bridge vectors can also mediate ‘spillback’ transmission of arboviruses from humans into novel sylvatic cycles. This PhD focused on Aedes malayensis, a mosquito species widely distributed in South East Asia, to assess its potential as an arbovirus vector. We identified Ae. malayensis for the first time in Laos during mosquito surveys conducted in a forested area of the Nakai Nam Theun National Protected Area (NNT NPA). Using field-based human-baited traps, we found that Ae. malayensis engaged in human-biting behavior and therefore could act as bridge vector in the NNT NPA. In laboratory conditions, this sylvatic population of Ae. malayensis displayed a relatively low vector competence for DENV and YFV and a lack of detectable attraction to human odor. However, vector competence assays and a human-baited trap survey showed that a peridomestic Ae. malayensis population in Singapore was competent for YFV and engaged in contact with humans. Overall, this PhD work highlighted that ancillary vectors should not be overlooked to fully assess the risk of arbovirus emergence
3
Murray, Douglas R. "Vector potentials in bose-einstein condensates." Thesis, University of Strathclyde, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501825.
4
El-Damanawi, Khatab El-Sayed Khatab. "Studies in vector potential theory." Thesis, City University London, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238698.
5
Vrettea, Christine. "Relativistic scattering theory with a vector potential." Thesis, Keele University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268335.
6
Nedjadi, Youcef. "Elektroweak tests of the relativistic nuclear scalar-vector model." Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.236201.
7
Martin, Stuart. "The potential of a novel Adenovirus vector for vaccination." Thesis, University of Warwick, 2010. http://wrap.warwick.ac.uk/34601/.
Анотація:
Adenoviruses (Ads) have many attractive characteristics for use as agents of genebased vaccines and therapies. The most frequently used Ad vectors in preclinical research are based on Ad5. However, in the clinical setting Ad5 vectors have severe limitations. About 90% of the population have neutralising antibodies against Ad5 and infection requires expression of the viral receptor CAR, which is not present on important cell types. Previous data from this laboratory suggested that the species D adenovirus, Ad19a, may overcome some of these limitations. Most relevant for vaccination is its high efficiency of infection of human dendritic cells (DCs), the most important antigen presenting cells. This highly effective DC targeting was retained in Ad19aGFP vectors. To investigate the potential of Ad19a vectors for vaccination further, two transgenes, the nucleocapsid gene from pneumovirus of mice (PVM-N), and a HIV polyprotein cassette (HIVA), were inserted into replication-deficient Ad5 and Ad19a vectors using recombineering. rAd19aPVM and rAd19aHIVA expressed a significantly higher amount of transgene compared with their Ad5 homologues. Encouraging results were obtained when the ability of rAd5PVM and rAd19aPVM to protect mice from lethal PVM challenge was examined using various prime/boost vaccinations. A dose of 106 pfu of rAd19aPVM, but not rAd5PVM, provided protection. rAd5PVM did, however, protect mice at the same dose when combined with rAd19aPVM in a heterologous prime boost schedule. Vaccination-induced IgG responses to PVM-N did not correlate with protection, implicating cell-mediated immune responses in protection. Utilising rAd19aGFP, evidence is also provided that Ad19a may use CD46 and to some extent CAR as a receptor on CHO cells, expanding our knowledge of the basic biology of this virus.
8
Westmoreland, Patrick Riley. "Recombinant Adeno-associated Viral Vector Design Influences Genotoxic Potential." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1514462220056427.
9
Santamaría, Domínguez Cristina. "Aedes albopictus as a potential vector of arboviruses in Catalonia." Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/669636.
Анотація:
El mosquit tigre, Ae. albopictus, es troba àmpliament establert en regions tropicals, subtropicals
i templa des, on són un vector per l’arbovirus com chikungunya i dengue. Els brots que s’han
produït dels dos virus a Europa durant l’última dècada, han posat de manifest el risc de transmissió
d’arbovirus en zones on estan establerts els mosquits Ae. albopictus. Per determinar el risc que es
produeixi un brot a Catalunya, investiguem la competència vectorial d’una població espanyola
de mosquits Ae. albopictus per a tots dos virus en experiments de laboratori.
En aquest estudi, es va avaluar la susceptibilitat del mosquit Ae. albopictus al virus chikungunya
utilitzant diferents variables: dues dosis virals de diferents concentracions (alta i baixa), dues soques
(S27 i ITA) simulant les condicions ambientals de les estacions d’estiu i tardor de Catalunya.
Es van comparar els resultats obtinguts amb la informació existent sobre altres poblacions
europees d’ Ae. albopictus (Capítol III). Es va avaluar la patogènesi del chikungunya en ratolins
amb deficiència en el receptor d’interferó alfa/beta (IFN-α/β R-/-) Per estudiar la infecció del
chikungunya, als ratolins se’ls va inocular subcutàniament amb tres dosis (baixa, mitja i alta ) de
dues soques (S27, ITA) (Capítol IV). Per avaluar la transmissió del chikungunya, emprem un
model de ratolí (IFN-α/β R-/-) i un assaig in vitro (Capítol V). Per determinar la persistència
del virus chikungunya en la natura en les regions temperades, es va avaluar la susceptibilitat de
les larves de mosquit al virus mitjançant una suspensió viral i de cadàvers de mosquits infectats.
Així mateix, es va argumentar la contribució que tindria aquest mecanisme en la persistència del
virus chikungunya durant una epidèmia (Capítol VI). Finalment, es va avaluar la competència
vectorial dels mosquits Ae. albopictus enfront del virus del dengue utilitzant dues soques diferents
(serotip 1 i 2). Es van analitzar les taxes d’infecció, disseminació i transmissió del virus i es van
comparar aquests resultats amb els estudis existents de competència vectorial per al virus del
dengue en poblacions europees de Ae. albopictus (Capítol VII).
Els resultats d’aquest estudi van mostrar que les condicions ambientals van exercir una influència
important en el temps de desenvolupament del mosquit, la supervivència de les larves i adults, així
com la quantitat de virus chikungunya ingerit. Es trobaren majors taxes d’infecció i disseminació
en l’estació de tardor respecte a la d’estiu, en consonància amb altres estudis sobre competència
vectorial per al chikungunya.
Trobem que Ae. albopictus va ser capaç de transmetre la soca emergent ITA (5%). Així mateix, es
RESUM
21
va observar que els ratolins amb deficiència en el receptor d’interferó alfa/beta van ser altament
susceptibles a la infecció pel virus chikungunya, el que es congruent amb els estudis existents.
No obstant això, no es va poder demostrar la transmissió transestadial del anomenat virus. Es
va trobar que la població analitzada d’ Ae. albopictus va ser susceptible a la infecció oral amb les
dues soques del virus del dengue, encara que només va ser capaç de transmetre la soca de serotip
1 (4,6%).
En resum, els resultats d’aquesta tesi demostren que la població d’ Ae. albopictus a Catalunya
és competent per als dos virus chikungunya i dengue. Aquest estudi confirma el potencial que
té com vector el mosquit Ae. albopictus per iniciar cicles de transmissió local dels virus del
chikungunya i del dengue en la regió Mediterrània.
Desitgem que les nostres aportacions puguin ajudar a tindre un coneixement més profund de la
competència vectorial del mosquit Ae. albopictus a Espanya.El mosquito tigre, Aedes albopictus, se encuentra ampliamente establecido en regiones tropicales, subtropicales y templadas, donde es un vector para arbovirus como chikungunya y dengue. Los brotes que se han producido de ambos virus en Europa durante la última década, han puesto de manifiesto el riego de transmisión de arbovirus en zonas donde estén establecidos los mosquitos Ae. albopictus. Para determinar el riesgo de que se produzca un brote en Cataluña, investigamos la competencia vectorial de una población española de mosquitos Ae. albopictus para ambos virus en experimentos de laboratorio. En este estudio, se evaluó la susceptibilidad del mosquito Ae. albopictus al virus chikungunya usando diferentes variables: dos dosis virales de diferente concentración (alta y baja), dos cepas (S27, ITA) simulando las condiciones ambientales de las estaciones de verano y otoño de Cataluña. Se compararon los resultados obtenidos con la información existente sobre otras poblaciones europeas de Ae. albopictus (Capítulo III). Se evaluó la patogénesis del chikungunya en ratones con deficiencia en el receptor de interferón alfa/beta (IFN-α/β R-/-). Para estudiar la infección del chikungunya, a los ratones se les inoculó subcutáneamente con tres dosis (baja, media y alta) de dos cepas (S27, ITA) (Capítulo IV). Para evaluar la transmisión del chikungunya, empleamos un modelo de ratón (IFN-α/β R-/-) y un ensayo in vitro (Capítulo V). Para determinar la persistencia del virus chikungunya en la naturaleza en regiones templadas, se evaluó la susceptibilidad de las larvas de mosquito al virus a través de una suspensión viral y de cadáveres de mosquitos infectados. Asimismo, se argumentó la contribución que tendría este mecanismo en la persistencia de dicho virus durante una epidemia (Capítulo VI). Finalmente, se evaluó la competencia vectorial del mosquito Ae. albopictus frente al virus del dengue usando dos cepas diferentes (serotipos 1 y 2). Se analizaron las tasas infección, diseminación y transmisión del virus y se compararon dichos resultados con los estudios existentes de competencia vectorial para el virus del dengue en poblaciones europeas de Ae. albopictus (Capítulo VII). Los resultados de este estudio mostraron que las condiciones ambientales ejercieron una influencia importante en el tiempo de desarrollo del mosquito, la supervivencia de las larvas y adultos, así como la cantidad de virus chikungunya ingerido. Se encontraron mayores tasas de infección y diseminación en la estación de otoño respecto a la de verano, en acuerdo con otros estudios sobre competencia vectorial para el chikungunya. Encontramos que Ae. albopictus fue capaz de RESUMEN 19 transmitir la cepa emergente ITA (5%). Asimismo, se observó que los ratones con deficiencia en el receptor de interferon alfa/beta fueron altamente susceptibles a la infección por el virus chikungunya, lo que es congruente con los estudios ya existentes. Sin embargo, no se pudo demostrar la transmisión transestadial de dicho virus Se encontró que la población analizada de Ae. albopictus fue susceptible a la infección oral con ambas cepas del virus del dengue, aunque sólo fue capaz de transmitir la cepa de serotipo 1 (4,6%). En resumen, los resultados de esta tesis demostraron que la población de Ae. albopictus en Cataluña es competente para ambos virus, chikungunya y dengue. Este estudio confirma el potencial que tiene como vector el mosquito Ae. albopictus para iniciar ciclos de transmisión local de los virus del chikungunya y del dengue en la región Mediterránea. Esperamos que nuestras aportaciones puedan ayudar a tener un conocimiento más profundo de la competencia vectorial del mosquito Ae. albopictus en España.
The Asian tiger mosquito, Aedes albopictus, is widely established in tropical, subtropical, and temperate areas, where is considered a vector for arboviruses like chikungunya and dengue. In the last ten years, autochthonous outbreaks of chikungunya and dengue in Europe have highlighted the risk of arbovirus transmission in areas where Ae. albopictus mosquitoes have become established. To estimate the risk of transmission and spread of arboviruses in Catalonia, we investigate whether local mosquitoes are competent to Chikungunya and Dengue viruses (CHIKV and DENV). In this study, we assessed the susceptibility of a Spanish strain of Ae. albopictus for two CHIKV strains (S27 and ITA) at two viral doses (high and low) in environmental conditions mimicking the summer and autumn seasons in Catalonia. These results were compared with previously published data from other European Ae. albopictus populations (Chapter III). The pathogenesis of CHIKV was also investigated in mice deficient in the alpha/beta interferon receptor (IFN- α/β R-/-). In order to study CHIKV infection, the mice were injected subcutaneously with three different doses (low, medium and high) of two CHIKV strains (S27 and ITA) (Chapter IV). To evaluate CHIKV transmission, we employed a mouse model (IFN-α/β R-/-), and an in vitro assay (Chapter V). To evaluate the survival of CHIKV in nature in temperate areas, we assessed the susceptibility of larvae mosquitoes to CHIKV through viral suspension and infected carcasses mosquitoes. The potential contribution of this mechanism to the persistence of CHIKV in an epidemic settle was discussed (Chapter VI). Finally, we assessed the vector competence of a Spanish Ae. albopictus strain for two different DENV strains (serotype 1 and 2). Infection, dissemination, and transmission rates were assessed and compared with previous vector competence studies for DENV in European Ae. albopictus populations (Chapter VII). The present study found that environmental conditions had a significant effect on development time, larval and adult survival, biting rate and quantity of CHIKV ingested. As shown in previous studies of vector competence for CHIKV, cooler temperatures in the larval and adult stage enhanced CHIKV infection rate relative to warmer temperatures. We found that Ae. albopictus was capable of transmitting the emergent ITA strain (5 %). We also observed that mice lacking in the alpha/beta interferon (IFN-α/β -/-) were highly susceptible to CHIKV infection, in congruence with previously published studies. By contrast, we could not demonstrate transstadial ABSTRACT 17 transmission (passage of a pathogen from one instar to the next) of CHIKV. We found that the strain of Ae. albopictus tested was susceptible to oral infection with both DENV strains, although was able only to transmit DENV-1 (4.6%). In conclusion, the results of this dissertation demonstrated that the Spanish strain of Ae. albopictus tested was competent for CHIKV and DENV. This study confirms the potential of Ae. albopictus to start local transmission cycles in the Mediterranean region. We expect the findings of this study can improve our general understanding of vector competence of Ae. albopictus in Spain.
10
Zhou, Xiaoxian. "Improvements in field computation at high frequencies using vector potential." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309832.
11
Hatch, William Smith. "Plasma Velocity Vector Instrument for Small Satellites (PVVISS)." DigitalCommons@USU, 2016. https://digitalcommons.usu.edu/etd/5065.
Анотація:
Low-earth orbit (LEO) contains plasma which can impact satellite charging and radio frequency (RF) communications. Quantifying both the composition and movement of ions in LEO can improve efficiency of the forecasting models that predict the impact plasma will have on satellite communications and accuracy of global positioning satellite measurements.
Two instruments known as the Retarding Potential Analyzer (RPA) and the Ion Drift Meter (IDM) have been used in tandem to measure ionospheric properties including ion temperature, velocity, and density. These instruments are costly and occupy large areas on a spacecraft. In recent years, space mission budgets have diminished. This change has driven innovation towards creating new instruments which are compatible with smaller and cheaper satellites yet still yield measurements of comparable quality. This thesis presents the design of a new instrument that encompasses the functionality of both the RPA and IDM, known as the Plasma Velocity Vector Instrument for Small Satellites (PVVISS). PVVISS has compact form factor and low power requirements, making it a viable option for smaller, low cost nano-satellite sized missions. Missions utilizing the PVVISS sensor will allow increased exploration of the ionospheric impact on satellite communications.
12
KC, Prabhat. "3D Reconstruction of the Magnetic Vector Potential of Magnetic Nanoparticles Using Model Based Vector Field Electron Tomography." Research Showcase @ CMU, 2017. http://repository.cmu.edu/dissertations/935.
Анотація:
Lorentz TEM observations of magnetic nanoparticles contain information on the magnetic and electrostatic potentials of the sample. These potentials can be extracted from the electron wave phase shift by separating electrostatic and magnetic phase shifts, followed by 3D tomographic reconstructions. In past, Vector Field Electron Tomography (VFET) was utilized to perform the reconstruction. However, VFET is based on a conventional tomography method called filtered back-projection (FBP). Consequently, the VFET approach tends to produce inconsistencies that are prominent along the edges of the sample. We propose a model-based iterative reconstruction (MBIR) approach to improve the reconstruction of magnetic vector potential, A(r). In the case of scalar tomography, the MBIR method is known to yield better reconstructions than the conventional FBP approach, due to the fact that MBIR can incorporate prior knowledge about the system to be reconstructed. For the same reason, we seek to use the MBIR approach to optimize vector field tomographic reconstructions via incorporation of prior knowledge. We combine a forward model for image formation in TEM experiments with a prior model to formulate the tomographic problem as a maximum a posteriori probability estimation problem (MAP). The MAP cost function is minimized iteratively to deduce the vector potential. A detailed study of reconstructions from simulated as well as experimental data sets is provided to establish the superiority of the MBIR approach over the VFET approach.
13
Siegel, Lance Mitchell. "The Analysis of 3-Channel "Vector" Visual Evoked Potentials and Possible Neuroanatomical Correlates." VCU Scholars Compass, 1990. http://scholarscompass.vcu.edu/etd/5102.
Анотація:
he use of evoked potentials to evaluate the functional integrity of neuronal pathways has become a useful and accepted practice in clinical medicine. The use of visual evoked potentials for assisting in the diagnosis of such diseases as optic neuritis and multiple sclerosis is also well recognized. However, the visual evoked potential, unlike the auditory evoked potentials, lacks a well defined electrophysiological to neuroanatomical correlation; especially that of a significant non-cortical component. Currently, visual evoked potentials rely principally on the measurement of a cortical (occipital) positive peak of activity at 100ms (P100), recorded with a single channel electrode system, to evaluate pathway integrity. In this study, visual evoked potentials were recorded using a three-channel, orthogonal co-ordinate system which we have designated "vector" visual evoked potentials (VVEP). This method allows the generated evoked response to be plotted on a three dimensional co-ordinate system with respect to time. Through the use of pattern reversal of a checkerboard pattern, in full and hemi retinal field stimulation, reproducible activity both prior to and afier the P100 wave was demonstrated. In particular, activity found at approximately 55ms is believed to be generated from the Lateral Geniculate Body. Furthermore, because this method summarizes the activity of the entire brain for a given time, as opposed to the single channel recording, a great deal of information about the entire visual pathway can be suggested. Finally, anatomical correlates to discrete activities identified by this method can be made.
14
Frazier, Cameron. "Re-Active Vector Equilibrium: A Novel Method of Autonomous Vehicle Navigation using Artificial Potential Fields." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32270.
Анотація:
The use of potential field based navigation schemes in robotics has been limited by inherent local minima issues. Local minima traps, small passages, unstable motion, and targets positioned near objects all pose major concerns when using potential fields for local vehicle control. This work proposes a new algorithm, "Re-Active Vector Equilibrium" (RAVE) that mitigates many of these issues. The vehicle representation model is expanded to use multiple points subject to potential calculation and the addition of two forces, a velocity dependent "risk force" (F_rsk) and a velocity and direction dependent "tangential force" (F_tan). The vehicle representation model is also expanded from a single reactive point to a series of points that define the vehicle body, providing better and simpler vehicle control. This has the effect of simplifying the required calculations at the cost of increasing the calculation count. The risk force, F_rsk, allows for dynamic adaptation to the immediate environment by acting in opposition to the net obstacle force, and is inversely proportional to the vehicle speed. The tangential force, F_tan, encourages better wall-following behaviour and provides a biasing mechanism to resolve obstacle aligned with target local minima issues.
15
Ciupitu, Anne-Marie T. "Hsp70 in immunotherapy : a potential vector in cancer and viral vaccines /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4093-2/.
16
Shariat-Panahi, Ali Reza. "Modified hepatitis B surface antigen : potential as a liver-targeting vector." Thesis, University College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407081.
17
Bentley, Kirsten. "IBV : potential as a vaccine vector and identification of a novel subgenomic mRNA." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/54374/.
Анотація:
Using an IBV reverse genetics system a series of recombinant viruses were generated to investigate the potential for utilizing IBV as a vaccine vector. Through the replacement of non-essential regions of the IBV genome, with eGFP or hRluc, factors influencing the stability of recombinant viruses expressing heterologous genes were determined. Expression of heterologous proteins was possible from a variety of virus constructs. The stability of recombinant viruses varied depending on the genome location of the heterologous gene, with replacement of Gene 5 proving to be most stable following passage in cell culture. Stability was strongly influenced by the MOI at which viruses were passaged, with low MOIs resulting in increased stability. The replacement of Gene 5 with a heterologous virus gene may be a suitable target for development of a bivalent vaccine capable of protecting against IBV and a second avian viral disease. Analysis of recombinant IBV mRNA expression profiles led to an investigation into an uncharacterized RNA species, and its link to the IBV intergenic region. A novel subgenomic mRNA was identified associated with the intergenic region that was shown to be transcribed via a non-canonical transcription regulatory sequence. In contradiction to the current model of coronavirus transcription this mRNA has a transcription regulatory sequence derived mainly from the leader, and not the body, transcription regulatory sequence. The non-canonical sequence was shown to be responsible for reduced transcription levels of the intergenic region mRNA. This project proposes the presence of an additional IBV subgenomic mRNA, transcribed via a non-canonical mechanism, and encoding a novel 5th accessory protein of IBV and closely related gammacoronaviruses.
18
Bali, Aneesh Kumar. "Mechanism of entry for Herpesvirus saimiri : a potential viral vector for gene therapy." Thesis, University of Leeds, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424232.
19
Ferrouillat, Pauline. "Développement de formulations éléments finis 3D en potentiel vecteur magnétique : application aux machines asynchrones en mouvement." Thesis, Université Grenoble Alpes (ComUE), 2015. http://www.theses.fr/2015GREAT124/document.
Анотація:
Les machines électriques sont modélisées pour prédire leurs performances et optimiser leur rendement. Cette modélisation peut être faite par des simulations avec la méthode des éléments finis. En particulier, les machines asynchrones nécessitent des simulations 3D pour prendre en compte les courants de Foucault et les têtes de bobines. Dans le logiciel Flux®, des formulations 3D basées sur le potentiel scalaire magnétique sont utilisées avec succès depuis de nombreuses années. Néanmoins, des coupures mathématiques artificielles sont nécessaires, lorsque le domaine n'est pas simplement connexe.Afin de se libérer de ces contraintes de connexité, des formulations en potentiel vecteur magnétique ont été étudiées et développées. En 3D, leur mise en œuvre nécessite l'utilisation d'éléments finis d'arêtes afin de respecter la nature des champs. Avec les éléments d'arêtes, les formulations sont généralement résolues avec une condition de jauge pour les solveurs directs comme pour les solveurs itératifs. De nouvelles formulations en potentiel vecteur magnétique auto-jaugées ont été développées permettant la prise en compte des bobines maillées et des bobines non maillées. La prise en compte du mouvement est relativement simple à mettre en œuvre pour les formulations en potentiel scalaire magnétique avec l'interpolation nodale.Avec les éléments d'arête, l'interpolation est plus délicate. C'est pourquoi la méthode des éléments avec joints a été développée pour prendre en compte le mouvement dans un cas généralElectric machines are modeled in order to predict their performance and to optimize their output. This modeling can be done by simulation with the finite element method. In particular, induction machines require 3D simulation to take into account eddy currents and coils overhangs. In the Flux® software, 3D formulations based on magnetic scalar potential has been used with success for many years. Nevertheless, artificial mathematical cuts are necessary, when the domain is not simply connected.In order to avoid connection constraints, magnetic vector potential formulations have been studied and developed. In 3D, their implementation requires the use of edge elements to respect the nature of fields. With edge elements, formulations are generally solved with a gauge condition for direct solvers as well as for iterative solvers. New auto-gauged magnetic vector potential formulations have been developed to take into account meshed coils and non-meshed coils. Consideration of movement is relatively simple to implement for magnetic scalar potential formulations with nodal interpolation. With edge elements, the interpolation is more delicate. For this reason, the mortar method has been developed to take into account movement in a general case
20
Nordan, Robert Patrick Victor. "An Investigation of Potential Methods for Topology Preservation in Interactive Vector Tile Map Applications." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for bygg, anlegg og transport, 2012. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-18592.
Анотація:
Vector tiling is a new trend that the geospatial industry is likely to explore in coming years, bearing the promise of the advantages in clarity and interactivity afforded by vector data whilst also providing a cacheable and efficient solution akin to raster tiles. An important question is then to ascertain how one might ensure that topological metadata is preserved across tiles; i.e. how does one convey the fact that two lines on adjacent tiles are in fact part of the same road?This report aims to explore this question by assessing current vector tile solutions, and creating hypothetical solutions for a vector tile system that delivers tiles with topology preserved in line with the Simple Features Access Specification. Some of the most promising of these are selected for prototyping, and the prototypes are tested with regard to speed and functionality. Finally conclusions about suitable methods are drawn based on these tests. Furthermore, the suitability of using vector tiles for a Geographic Information System (GIS) application is discussed.
21
Schaffer, David L. Behrman Elizabeth. "The magnetic vector potential, Klein-Gordon equation and Klein's paradox in relativistic quantum mechanics." Diss., A link to full text of this thesis in SOAR, 2007. http://soar.wichita.edu/dspace/handle/10057/1170.
Анотація:
Thesis (M.S.)--Wichita State University, College of Liberal Arts and Sciences, Dept. of Physics."May 2007." Title from PDF title page (viewed on Dec. 29, 2007). Thesis adviser: Elizabeth Behrman. Includes bibliographic references (leaves 84-86).
22
Gianotti, Rebecca L. (Rebecca Louise). "The potential for environmental management to contribute to malaria vector control in western Niger." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/43914.
Анотація:
Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2008.Includes bibliographical references (leaves 88-93).
This thesis investigated the potential for environmental management techniques to contribute to malaria vector control in Niger, with a case study on Banizoumbou village in western Niger. Numerical modeling was used to simulate habitat modifications in the form of leveling a topographic depression, ploughing the land surface to enhance infiltration and providing barriers to surface runoff on hillslopes. The hydrologic model described by Bomblies et al. (2008) was used for the modeling investigation, calibrated using environmental observations obtained in Banizoumbou for the years 2005, 2006 and 2007. The modeling investigation showed that leveling of topographic depressions could reduce the persistence time of a pool to less than the time needed for establishment of mosquito breeding, approximately 7 days. Increasing the surface soil permeability by ploughing also reduced the persistence time of the pool but was not as effective as leveling. Therefore leveling is the recommended intervention for pools of a small to intermediate size, while ploughing would be recommended for large pools where leveling would require too much work to implement. Interception of hillslope runoff using a barrier was demonstrated to be the most effective way to prevent a pool from becoming breeding habitat. However, this method has the most risk of creating unintended downstream impacts and therefore must be used with extreme caution. A field trial was also undertaken during July to September 2007 in Banizoumbou to investigate the efficacy of neem seeds as a larvicide and to reduce adult emergence from breeding pools.
(cont.) The neem field trial showed that twice-weekly applications of neem seed powder to known breeding habitats of Anopheles larvae in 2007 resulted in 49% fewer adult female Anopheles gambiae s.L mosquitoes in Banizoumbou compared with previous captures under similar environmental conditions and with similar habitat characteristics in 2005 and 2006. The results of the neem field trial suggest that neem seeds could provide an appropriate, sustainable larvicide for the malaria vector An. gambiae s.I. in the Sahel region of Niger and adjacent areas having similar environmental characteristics and vector dynamics.
by Rebecca L. Gianotti.
S.M.
23
Mansuripur, M. "Comment on Jackson's analysis of electric charge quantization due to interaction with Dirac's magnetic monopole." ELSEVIER SCIENCE BV, 2016. http://hdl.handle.net/10150/622958.
Анотація:
In J.D. Jackson's Classical Electrodynamics textbook, the analysis of Dirac's charge quantization condition in the presence of a magnetic monopole has a mathematical omission and an all-too-brief physical argument that might mislead some students. This paper presents a detailed derivation of Jackson's main result, explains the significance of the missing term, and highlights the close connection between Jackson's findings and Dirac's original argument. (C) 2016 Sharif University of Technology. All rights reserved.
24
Premachandra, W. T. S. Dammini. "Biology, population dynamics, vector potential and management of Ceratothripoides claratris on tomato in central Thailand." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=974373826.
25
Retief, Liezl. "Molecular detection and characterisation of potentially zoonotic bacteria in bathyergids from the Western Cape Province." Diss., University of Pretoria, 2017. http://hdl.handle.net/2263/67139.
Анотація:
Globally emphasis has been given to identify emerging and re-emerging pathogens. Rapid urban
expansion creates a problem which is two-fold. Firstly, increasing slum living conditions due to
inadequate rate of infrastructure development results in an increased reliance on natural resources,
including the capture and consumption of surrounding wildlife to subsist, thereby facilitating the transfer
of emergent zoonotic pathogens. Secondly, through activities such as pollution or alien species
introductions, the rapid transformation of once pristine environments, alters natural systems, potentially
exposing these environments to new bacterial pathogens. Therefore, the main aim of this study was to
assess overlooked bacterial species harboured by four host species (Bathyergus suillus, Georychus
capensis, Cryptomys hottentotus hottentotus and Fukomys damarensis) belonging to the subterranean
rodent family Bathyergidae, which inhabit an environment well-suited for an array of bacterial species,
and which varied in their exposure to human settlements. Bacterial prevalence and diversity was initially
evaluated using broad-range PCR techniques in combination with nucleotide sequencing. This revealed
high levels of bacterial prevalence (82.91%) and mixed infections (22.60%) in bathyergid species. Two
bacterial groups, the Bacillus cereus complex (a group of soil-dwelling bacterial strains with pathogenic
potential with an overall prevalence of 8.55%) and haemotropic Mycoplasma strains (vector-borne
bacterial strains of zoonotic potential with an overall prevalence of 1.28%) were subsequently selected for
further genetic analysis with genus and species-specific PCRs. Bacillus molecular screening and
phylogenetic analyses was achieved by targeting four gene regions with seven published primer assays
and two novel PCR assays. This enabled identification of two B. cereus complex strains in bathyergid
lungs and revealed an overall B. cereus complex prevalence of 17.95% for the 234 bathyergid lung
samples screened. Bacillus genome prevalence was significantly higher in B. suillus individuals (45.35%),
sampled in a peri-urban environment, compared to the other bathyergid species sampled from pristine
habitats (ranging from 0% - 4.44%). Anthropogenic activities in the area where B. suillus was sampled
could, at least partially, attribute to the perceived difference between urban and naturally sampled
bathyergid species, highlighting the role of B. suillus to act as both a reservoir of potentially zoonotic
pathogens and as a sentinel for anthropogenic soiling. Mycoplasma molecular screening using three
different PCR assays, all targeting the 16S rRNA gene region, confirmed an overall haemotropic
Mycoplasma prevalence of 24.13% in the 286 bathyergid organs (lung, spleen and liver) screened. A
significantly higher prevalence and diversity of haemotropic Mycoplasma strains was found in B. suillus
lungs (41.86%) compared to its naturally occurring relatives (ranging from 0%-36%). Phylogenetic analyses identified six novel haemotropic Mycoplasma strains, all grouping within a discrete
monophyletic cluster, sister to Mycoplasma coccoides, and comprising two well-supported sub-clusters.
The human introduction of commensal rodents harbouring Mycoplasma strains transferred through
cosmopolitan arthropod vectors to indigenous bathyergids, likely underlies the higher prevalence in urban
areas, although other biotic and abiotic factors affecting ectoparasite load also merit consideration. The
data generated by the current study indicate the need to identify largely overlooked and potentially
zoonotic bacterial pathogens in subterranean mammals and emphasises the importance of monitoring
anthropogenically-introduced, opportunistic pathogens and the threats they pose to vulnerable
communities and co-occurring, free-living animal speciesDissertation (MSc)--University of Pretoria, 2017.
Airports Company of South Africa (ACSA)
National Research Foundation (NRF)
Zoology and Entomology
MSc
Unrestricted
26
Golding, Nicholas. "Mapping and understanding the distributions of potential vector mosquitoes in the UK : new methods and applications." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:6ae52a0a-2aaa-42d6-a57a-e3879ad559d8.
Анотація:
A number of emerging vector-borne diseases have the potential to be transmitted in the UK by native mosquitoes. Human infection by some of these diseases requires the presence of communities of multiple vector mosquito species. Mitigating the risk posed by these diseases requires an understanding of the spatial distributions of the UK mosquito fauna. Little empirical data is available from which to determine the distributions of mosquito species in the UK. Identifying areas at risk from mosquito-borne disease therefore requires statistical modelling to investigate and predict mosquito distributions. This thesis investigates the distributions of potential vector mosquitoes in the UK at landscape to national scales. A number of new methodological approaches for species distri- bution modelling are developed. These methods are then used to map and understand the distributions of mosquito communities with the potential to transmit diseases to humans. Chapter 2 reports the establishment of substantial populations of the West Nile virus (WNV) vector mosquito Culex modestus in wetlands in southern England. This represents a drastic shift in the species’ known range and an increase in the risk of WNV transmission where Cx. modestus is present. Chapter 3 develops and applies a new species interaction distribution model which identifies fish and ditch shrimp of the genus Palaemonetes as predators which may restrict the distribution of the potential WNV vector community in these wetlands. Chapter 4 develops a number of methods to make robust predictions of the probability of presence of a species from presence-only data, by eliciting and applying estimates of the species’ prevalence. Chapter 5 introduces a new Bayesian species distribution modelling approach which outperforms existing methods and has number of useful features for dealing with poor- quality data. Chapter 6 applies methods developed in the previous two chapters to produce the first high-resolution distribution maps of potential vector mosquitoes in the UK. These maps identify several wetland areas where vector communities exist which could maintain WNV transmission in birds and transmit it to humans. This thesis makes significant contributions to our understanding of the distributions of UK mosquito species. It also provides methods for species distribution modelling which could be widely applied in ecology and epidemiology.
27
Rochon, Katreyn. "Vector Potential of Stable Flies (Stomoxys calcitrans) for the Transmission of Porcine Reproductive and Respiratory Syndrome Virus." NCSU, 2008. http://www.lib.ncsu.edu/theses/available/etd-11282008-160747/.
Анотація:
Porcine Reproductive and Respiratory Syndrome (PRRS) is a globally significant viral disease of swine. The link between outbreaks in separate farms within an area remains unclear despite biosecurity measures. We have investigated the vector potential of stable flies in the transmission of PRRSV under laboratory conditions. We first determined that blood seeking stable flies are attracted to pigs by olfactory cues. We determined stable flies could acquire the virus through a bloodmeal, and the amount of virus in the flies declined with time, indicating the virus does not replicate in fly digestive tissues. Transmission of the virus to naïve pigs failed in all attempts. The volume of blood contained in the closed mouthparts of the stable fly appears to be insufficient to deliver an infective dose of the virus. We further examined the fate of PRRS virus in the hemolymph of the flies following a midgut barrier bypass. Virus levels were up to 9,500 times greater in the hemolymph when compared to those detected in the digestive tract at the same time point. Further study to test the saliva of inoculated stable flies for presence of the virus is needed to determine if PRRS virus can enter and escape stable fly salivary glands. Although stable flies are unlikely vectors of PRRS virus between animals, they may play a role in virus dissemination by harboring the virus and contaminating the environment.
28
Layek, Buddhadev. "Evaluation of Hydrophobically Modified Low Molecular Weight Chitosan as a Potential Nonviral Vector for DND Vaccine Delivery." Diss., North Dakota State University, 2014. https://hdl.handle.net/10365/27555.
Анотація:
Gene therapy has great potential in disease prevention and treatment. The purpose of the proposed research was to advance the development of safe and effective nonviral polymeric vectors for targeted gene therapy and DNA vaccine delivery. A series of hydrophobically modified chitosan derivatives with increasing degrees of chain length, substitution, and hydrophobicity was synthesized via carbodiimide mediated coupling reaction. The chemical structure of the polymers was determined using proton nuclear magnetic resonance (1H NMR), fourier transform infrared (FTIR) spectroscopy, and elemental analysis. These polymers form micellar structures in aqueous environment and effectively condense plasmid DNA (pDNA) into nanoscale polyplexes. The acyl chain length, degree of substitution, and hydrophobicity of the substituent had great impact on the particle size, pDNA binding strength, in vitro pDNA release profile, cellular uptake, and in vitro gene transfection efficiency of the polymer/pDNA polyplexes. The hexanoic acid grafted chitosan [NAC-6(15)] and L-phenylalanine grafted chitosan (AGC-F) with a 15% degree of amino substitution demonstrated significantly (p < 0.05) higher gene transfection in HEK 293 cells, and their transfection efficiency surpassed the transfection capacity of FuGENE HD. The NAC-6(15) and AGC-F polymers were mannosylated to provide selective antigen presenting cell (APC) targeting, thereby facilitating cellular uptake to ultimately improve the overall immune response to the DNA vaccine. The chemical composition of the mannosylated copolymers was analyzed by 1H NMR spectroscopy. These polymers efficiently condense pDNA into nanosized polyplexes with net positive surface charges. The resultant polyplexes demonstrated excellent protection of the condensed pDNA from enzymatic degradation by deoxyribonuclease (DNase). The synthesized mannosylated polymers exhibited 7-fold greater cellular uptake than chitosan in RAW 264.7 cells, which express mannose receptors, mainly via the receptor-mediated endocytosis without affecting biocompatibility. The in vitro transfection efficiencies of mannosylated polymer/pDNA polyplexes were significantly (p < 0.05) higher than other polymers and FuGENE HD. An in vivo study in Balb/c mice using hepatitis B surface antigen encoding pDNA as a model DNA vaccine reflected good efficacy and biocompatibility of the delivery system. Therefore, hydrophobically modified mannosylated chitosan derivatives have the potential to be a safe and efficient APC targeting gene carrier for DNA vaccine delivery.National Institutes of Health (NIH)
Fraternal Order of Eagles
Pharmaceutical Sciences (NDSU)
North Dakota Experimental Program to Stimulate Competitive Research (NDEPSCoR)
29
Song, Xiaohui. "FPGA Implementation of a Support Vector Machine based Classification System and its Potential Application in Smart Grid." University of Toledo / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1376579033.
30
Costa, José Tarcisio. "Éléments finis stabilisés VMS appliqués aux modèles magnétohydrodynamiques (MHD) des plasmas de fusion." Thesis, Université Côte d'Azur (ComUE), 2016. http://www.theses.fr/2016AZUR4117/document.
Анотація:
L'objectif principal de cette thèse concerne la mise en oeuvre d'une méthoded'éléments finis stabilisés pour la simulation des plasmas de fusion. Pour cela,nous avons d'abord dérivé les modèles magnétohydrodynamiques depuis lemodèle cinétique. Les modèles MHD sont généralement utilisés pour simuler lesinstabilités macroscopiques des plasmas. Nous nous sommes concentrés sur lemodèles de la MHD complète. Ensuite, l'approche numérique est décrite dans lecadre de la stabilisation Variationelle Multi-Échelles (VMS). Cette stabilisationvient ajouter un terme à la formulation faible pour mimer les effets des échellesnon-résolues sur celles résolues. Si les effets de ces sous-échelles ne sont paspris en compte lorsque l'on traite des écoulements dominés par convection,comme dans le cadre des plasmas de fusion, le schéma numérique conduit àdes résultats non-physiques. Une étude détaillée de l'instabilité de « Kinkinterne » a été faite ainsi qu'une étude préliminaire des plasmas avec point-Xayant pour but la validation du schéma numérique développé iciThe main objective of this thesis concerns the implementation of a robuststabilized finite element method for simulating fusion plasmas. For that, we firstderive the magnetohydrodynamic models from the kinetic model. MHD modelsare generally used for macroscopic simulations of plasma instabilities. Weconcentrate ou efforts on the full MHD model. Next, the numerical approach isdescribed in the context of the Variational Multi-Scale (VMS) stabilization. Thisstabilization comes to add a term to the weak formulation to mimics the effectsof the unresolved scales over the coarse scales. If the effects of these subscalesare not taken into account when dealing with fluxes dominated byconvection, as it is the cases for fusion plasmas, the numerical scheme canlead to unphysical results. A detailed study of the resistive internal kinkinstability has been done as well as an introductory study of the so called Xpointplasmas in order to validate the numerical scheme developed here
31
Maximilian, Spiegelberg. "Exploring the potentials of a new perspective for a local approach: The Water-Energy-Food Nexus at the Dampalit Stream, the Philippines." Kyoto University, 2017. http://hdl.handle.net/2433/225950.
32
QUINONERO, JEROME. "Etude des potentialites des cellules macrogliales et endotheliales cerebrales comme vecteurs cellulaires de transfert de gene dans le systeme nerveux central par greffe intracerebrale." Paris 6, 1996. http://www.theses.fr/1996PA066347.
Анотація:
Les travaux que nous avons realises ont eu pour but de caracteriser les potentialites offertes par les cellules macrogliales (oligodendrocytes et astrocytes) d'une part, et surtout les cellules endotheliales cerebrales d'autre part, pour leur utilisation comme vecteur cellulaire de therapie genique du snc, apres greffe intracerebrale. Nous avons etudie dans un premier temps les capacites de survie, de migration et d'integration des cellules macrogliales dans un modele de xenogreffe intracerebrale obtenu par la greffe de fragments de corps calleux de lapin embryonnaire dans le cerveau de souriceaux nouveau-nes mutants de souche shiverer. Nous avons pu decrire, chez un meme animal, les voies de migration et de differenciation des astrocytes et des oligodendrocytes. Dans une seconde partie, dans la recherche de cibles cellulaires pour un transfert genique dans le cerveau, nous avons etudie les capacites de cellules endotheliales cerebrales immortalisees, greffees dans le cerveau de rat adulte, a survivre, migrer et s'integrer dans le parenchyme cerebral et/ou a la paroi des microvaisseaux de l'hote. L'introduction d'un transgene dans ces cellules, les genes lacz et ngf etant pris ici comme systemes modeles, devait permettre de developper une approche nouvelle de therapie genique du cerveau. Ce travail ouvre de nouvelles voies de recherche dans le domaine de la therapie genique cellulaire des troubles du snc. L'application la plus immediate de ce travail pourrait etre le traitement des modeles de tumeurs intracerebrales experimentales, par la greffe intra-tumorale ou l'injection systemique de cellules endotheliales cerebrales modifiees genetiquement pour exprimer des facteurs anti-tumoraux
33
Siu, Ka-yan Sky. "DDT as a malarial vector control method and its potential risks to human reproductive health and neonatal development." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B3847864X.
34
Siu, Ka-yan Sky, and 蕭加欣. "DDT as a malarial vector control method and its potential risks to human reproductive health and neonatal development." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B3972458X.
35
Wallace, David Brian. "An evaluation of the vaccine-vector potential of thymidine kinase-disrupted recombinants of lumpy skin disease virus (South African vaccine." Thesis, Pretoria : [s.n.], 2006. http://upetd.up.ac.za/thesis/available/etd-09062006-125038.
36
Ruiz, Joaquim, Gabriela M. Ulloa, Maria J. Pons, Fernando Vásquez-Achaya, Valle Mendoza Juana del, Cláudia Gomes, and Valle Luis J. del. "Molecular Detection of Bartonella bacilliformis in Lutzomyia maranonensis in Cajamarca, Peru: A New Potential Vector of Carrion’s Disease in Peru?" American Society of Tropical Medicine and Hygiene, 2018. http://hdl.handle.net/10757/624642.
Анотація:
El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado.Carrion's disease is a neglected, vector-borne illness that affects Colombia, Ecuador, and especially Peru. The phlebotomine sand flies Lutzomyia verrucarum and Lutzomyia peruensis are the main illness vectors described, although other species may be implicated in endemic areas such as some northern Peruvian regions, in which Carrion's disease vector has not been established. The aim of this study was to evaluate the presence of Bartonella bacilliformis DNA in Lutzomyia maranonensis from Cajamarca, northern Peru. This sand fly has not been defined as a vector yet. Centers for Disease Control and Prevention light traps were used to collect adult phlebotomine sand flies from 2007 to 2008 in the Cajamarca department. Female specimens were identified using morphological keys and were grouped into pools of five sand flies, taking into account district and sampling site (intradomicile or peridomicile). DNA was extracted, and then conventional and real-time polymerase chain reaction (RT-PCR) were performed to detect B. bacilliformis and subsequently confirmed by sequencing. A total of 383 specimens of L. maranonensis species were analyzed. Two of 76 pools were positive for B. bacilliformis by sequencing; all positives pools were from Querocotillo district. In addition, Mesorhizobium spp. were identified in two pools of sand flies, which is an α-proteobacteria phylogenetically very close to B. bacilliformis. This study presents molecular evidence that suggests L. maranonensis is naturally infected by B. bacilliformis in the Cajamarca department. Further research should determine if L. maranonensis is a vector and could transmit B. bacilliformis.
Revisión por pares
37
Shen, Yen-Ju. "An investigation into the Use of Lumpy Skin Disease Virus as a Vaccine Vector for a Potential HIV-1 vaccine." Doctoral thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/3180.
38
Rahimi, Khameneh Shabnam. "Assessment of Retroviruses as Potential Vectors for the Cell Delivery of Prions." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23472.
Анотація:
Transmissible spongiform encephalopathies (TSEs) or prion diseases are a class of fatal brain disorders better known as Creutzfeldt-Jacob Disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep, and chronic wasting disease (CWD) in deer and elk. The infectious agent responsible for these diseases is a misfolded prion protein capable of catalyzing a conformational change in normal cellular prion proteins (PrPC) into aberrant disease-causing structural isoforms (PrPSc). Although the etiological agent for TSEs has clearly been defined as PrPSc, there are important gaps in our understanding of how these proteins target and invade brain tissue. It remains to be established how ingested PrPSc ultimately reach the brain and also to understand why these tissues are particularly targeted, notwithstanding that several other tissues highly express prion proteins. Certain viruses, retroviruses in particular, efficiently hijack host proteins and can carry these proteins with them when they are released from a cell. Several lines of evidence have shown that prions and retroviruses can interact and associate at various stages of the retroviral replication cycle. Of special interest is that most retroviruses can cross the blood-brain barrier and could therefore deliver host-derived proteins to neuronal cells. In view of these observations, this thesis investigates whether retroviruses can act as vectors to capture prions from an infected cell and deliver them to a susceptible target cell.
In this work, I have cloned human and mouse prion cDNAs from PBMCs and the murine cell line NIH 3T3. Either a FLAG epitope tag or the eGFP reporter protein cDNA was inserted into a region of the prion cDNA that is predicted to be amenable to such genetic insertions without affecting protein folding or expression. I then confirmed using both fluorescent and confocal microscopy and that the recombinant proteins had a similar cell distribution to the endogenous prion protein. Using Western blot analysis, I then showed that endogenous and overexpressed prion proteins can be detected in co-transfected cells producing HIV and murine leukemia virus (MLV) retroviral particles. Finally, I went on to show that prions are also present at high levels in HIV and MLV retroviral particles released from these cells.
This work constitutes the first step in determining whether retroviruses can act as vectors for prion dissemination. Establishing a strong and clear association between retroviruses, pathogenic prions and prion disease would provide the rationale for preventive measures to be taken directly against retroviruses in order to protect humans and animals that have been newly exposed to PrPSc-infected products or those who are genetically predisposed to develop prion diseases. Anti-retroviral drugs could also be potentially used to delay disease progression and reduce prion transmission in human and animal tissues. The availability of such a treatment would constitute a significant advancement because there is currently no cure or treatment for prion diseases.
39
White, Elaine Joanna. "Evaluation of receptor-mediated gene transfer using an integrin-targeting vector as a potential form of therapy for lysosomal storage diseases." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340643.
40
Hellsing, Edvin, and Joel Klingberg. "It’s a Match: Predicting Potential Buyers of Commercial Real Estate Using Machine Learning." Thesis, Uppsala universitet, Institutionen för informatik och media, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-445229.
Анотація:
This thesis has explored the development and potential effects of an intelligent decision support system (IDSS) to predict potential buyers for commercial real estate property. The overarching need for an IDSS of this type has been identified exists due to information overload, which the IDSS aims to reduce. By shortening the time needed to process data, time can be allocated to make sense of the environment with colleagues. The system architecture explored consisted of clustering commercial real estate buyers into groups based on their characteristics, and training a prediction model on historical transaction data from the Swedish market from the cadastral and land registration authority. The prediction model was trained to predict which out of the cluster groups most likely will buy a given property. For the clustering, three different clustering algorithms were used and evaluated, one density based, one centroid based and one hierarchical based. The best performing clustering model was the centroid based (K-means). For the predictions, three supervised Machine learning algorithms were used and evaluated. The different algorithms used were Naive Bayes, Random Forests and Support Vector Machines. The model based on Random Forests performed the best, with an accuracy of 99.9%.Denna uppsats har undersökt utvecklingen av och potentiella effekter med ett intelligent beslutsstödssystem (IDSS) för att prediktera potentiella köpare av kommersiella fastigheter. Det övergripande behovet av ett sådant system har identifierats existerar på grund av informtaionsöverflöd, vilket systemet avser att reducera. Genom att förkorta bearbetningstiden av data kan tid allokeras till att skapa förståelse av omvärlden med kollegor. Systemarkitekturen som undersöktes bestod av att gruppera köpare av kommersiella fastigheter i kluster baserat på deras köparegenskaper, och sedan träna en prediktionsmodell på historiska transkationsdata från den svenska fastighetsmarknaden från Lantmäteriet. Prediktionsmodellen tränades på att prediktera vilken av grupperna som mest sannolikt kommer köpa en given fastighet. Tre olika klusteralgoritmer användes och utvärderades för grupperingen, en densitetsbaserad, en centroidbaserad och en hierarkiskt baserad. Den som presterade bäst var var den centroidbaserade (K-means). Tre övervakade maskininlärningsalgoritmer användes och utvärderades för prediktionerna. Dessa var Naive Bayes, Random Forests och Support Vector Machines. Modellen baserad p ̊a Random Forests presterade bäst, med en noggrannhet om 99,9%.
41
Varouchas, Dimitris. "Study of the Higgs boson discovery potential, produced by the vector boson fusion with the ATLAS detector and commissioning of calorimetric transverse missing energy." Paris 11, 2009. http://www.theses.fr/2009PA112217.
Анотація:
Le but de cette thèse est d'évaluer le potentiel de découverte par le détecteur ATLAS au LHC du boson de Higgs du MS. Le mode de production étudié est défini par la fusion de bosons vecteurs (VBF) suivie de la désintégration en une paire de leptons τ (H->τ). C'est l'un des canaux de découverte les plus prometteurs pour un boson de Higgs de basse masse, qui est favorisé par les mesures de précision dans le secteur électro-faible. La topologie caractéristique de VBF, qui est constituée des deux jets vers l'avant du détecteur et des produits de désintégration de boson de Higgs dans la région centrale, fournit une signature unique permettant la suppression du bruit de fond. En outre, puisque le VBF est un processus purement électro-faible, aucune activité de QCD n'est prévue et donc aucun jet central n'est attendu. Ceci permet l'application de la coupure de «central jet veto» pour encore réduire le bruit de fond. Une analyse basée sur des coupures a été utilisée, se concentrant sur l'optimisation de la coupure de «central jet veto». L'objectif principal était d'étudier le potentiel de découverte du boson de Higgs avec ATLAS,sous une luminosité intégrée de 30 fb-1 dans la gamme de masse mH=(115,140) GeV pour une énergie au centre de la masse of 14 TeV. Après l'application des coupures, un excès au-dessus de 5ƒb-1 de signal significance a été est trouvé pour la gamme de masse mH=(115,125). Pour le canal H->ττ, la résolution de l'énergie transverse manquante (ETmiss ) est importante puisqu'elle affecte directement la résolution sur la masse du boson de Higgs. Cela a été la motivation initiale pour réaliser et présenter dans cette thèse une étude de «commissioning» calorimétrique basée sur les quantités ETmiss , plus particulièrement sur la contribution du bruit de l' électronique, mesurée dans des événements cosmiques. Un comportement gaussien de bruit dans tous les calorimètres de l'argon liquide a été trouvé, tandis qu'un comportement non-gaussien dans une partie du calorimètre a tuile scintillante du a un bruit cohérent, a été observé. Pour ce dernier, un nouveau modèle de bruit a été examiné utilisant une paramétrisation de double gaussienne ayant pour résultat une description plus réalisteThe subject of this thesis is the evaluation of the discovery potential of the ATLAS detector at the LHC for the SM Higgs boson in vector boson fusion (VBF) production and a subsequent decay into a τ-lepton pair (H->ττ). This is one of the most promising discovery channels in the low mass range, which is the mass range favored from precision measurements of the electroweak interaction. The characteristic VBF topology, which consists of two jets in the forward regions of the detector and the Higgs boson decay products in the central region, provides a unique signature allowing the suppression of background. In addition, since VBF is a purely electroweak process, no QCD activity is expected and thus no central jets are expected. This allows the central jet veto cut application to further reject background processes. A cut-oriented analysis was used, focusing on the central jet veto cut optimization. The main objective was to investigate the Higgs boson ATLAS discovery potential with an integrated luminosity of 30 fb-1 in the mass range mH=(115,140) GeV, for an LHC energy at the center of mass of 14 TeV. After the application of all cuts, an excess above 5σ of signal signifcance was found for the mass range mH=(115,125). In H->ττ decay channel, transverse missing energy (ETmiss) resolution is of high importance since it affects directly the resolution of the Higgs boson mass. This was the initial motivation for performing and presenting in this thesis a calorimetric commissioning study based on ETmiss quantities, focused on the electronics noise ETmiss contribution, measured with cosmics data of the period fall 2008. A Gaussian behavior of noise in all liquid argon calorimeters was found, whereas a region of non-Gaussian tails in scintillating tile calorimeter due to a coherent noise, was high-lighted. For the latter, a new noise model was tested using a double Gaussian parameterization resulting in a more realistic description
42
Ustuntepe, Bulent. "A Novel Two-parameter Modulation And Neutral Point Potential Control Method For The Three-level Neutral Point Clamped Inverter." Master's thesis, METU, 2005. http://etd.lib.metu.edu.tr/upload/12606928/index.pdf.
Анотація:
In this thesis, the neutral point potential drift/fluctuation of the three-level neutral
point clamped inverter is analyzed and a novel control algorithm, the two-parameter
PWM method is proposed to confine the neutral point potential variation to a very
small range. The two-parameter PWM method provides superior neutral point
potential control performance even with small DC bus capacitors. The method is
based on PWM pulse pattern modification and requires no additional hardware.
Detailed analytical models of the neutral point current and potential as a function of
the modulation parameters are established and the neutral point potential behavior is
thoroughly investigated. Based on the study, the deficiency of the known methods is
illustrated and the two-parameter PWM method is developed and its superior
performance demonstrated. The performance of the two-parameter PWM method is
verified by means of computer simulations utilizing both the per-PWM-cycle
average model and the detailed model of the inverter. The results are supported by
laboratory experiments involving both an R-L load and an induction motor drive.
43
Mendoza, Alonzo Jennifer Lorena. "Predicting the Clinical Outcome in Patients with Traumatic Brain Injury using Clinical Pathway Scores." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4544.
Анотація:
The Polytrauma/TBI Rehabilitation Center (PRC) of the Veterans Affairs Hospital (VAH) treats patients with Traumatic Brain Injury (TBI). These patients have major motor and cognitive disabilities. Most of the patients stay in the hospital for many months without major improvements. This suggests that patients, family and the VAH could benefit if healthcare provider had a way to better assess or "predict" patients' progression. The individual progress of patients over time is assessed using a pre-defined multi-component performance measure Functional Independence Measures (FIM) at admission and discharge, and a semi-quantitative documentation parameter Clinical Pathway (CP) at weekly intervals. This work uses already de-identified and transformed data to explore developing a clinical outcome predictive model for patients with TBI, as early as possible. The clinical outcome is measured as percentage of recovery using CP scores. The results of this research will allow healthcare providers to improve the current resource management (e.g. staff, equipment, space) through setting goals for each patient, as well as to provide the family more accurate and timely information about the status and needs of the patient.
44
Barbu, Andreea Roxana. "In vitro Studies of β-cell Death and Survival. Modulation by Adenoviral Vectors and Bcl-2 Overexpression". Doctoral thesis, Uppsala universitet, Institutionen för medicinsk cellbiologi, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3973.
Анотація:
Type 1 diabetes is a multifactorial disease resulting from the selective destruction of insulin-producing β-cells within the pancreatic islets of Langerhans. The mechanisms of β-cell death are not fully understood but cytokines are important mediators of this process. In the present study we found that the combination of IL-1β, TNF-α and IFN-γ induced a nitric oxide-dependent disruption of the mitochondrial membrane potential in rat insulin-producing RINm5F-cells, which seems to be a necessary event for both RINm5F-cell apoptosis and necrosis. The antiapoptotic protein Bcl-2 was able to prevent cellular death in RINm5F cells, most probably by counteracting the mitochondrial permeability transition. These results pointed out the potential of such antiapoptotic genes as gene therapy tools, to allow enhanced resistance against autoimmune destruction of β-cells in type 1 diabetes. For this purpose we used a progesterone-antagonist (RU 486)-inducible gene transfer system to achieve an efficient and controlled Bcl-2 overexpression in primary rat β-cells. However, in our experience, prolonged in vitro culture revealed adenoviral-induced islet cell necrosis, a process that was not prevented by Bcl-2 overexpression. Moreover, we observed that specific adenoviral genotypes correlate with differential induction of necrosis in both human and rat pancreatic islet cells. Although human islet cells showed an increased resistance in terms of viral concentrations required for the induction of cell-toxicity, our results showed that they were unable to build up an efficient antiviral response following infection and that their survival was dependent on the exogenous addition of α-interferon. In conclusion, adenoviral techniques for overexpression of antiapoptotic proteins in insulin-producing cells may provide useful tools against β-cell directed autoimmune destruction. However, understanding the specific interactions of the viral gene products with cellular proteins and how they are involved in β-cell death regulation is fundamental for an efficient and safe application of gene therapy approaches to type 1 diabetes.
45
Pereira, Aldo Gomes. "Um estudo histórico da evolução do conceito de potencial vetor no eletromagnetismo clássico." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-09062009-115922/.
Анотація:
Atualmente o potencial vetor é geralmente tratado no eletromagnetismo clássico como um artifício para o cálculo dos campos elétricos e magnéticos sem um significado claro. No entanto, quando foi proposto na metade do século XIX, ele possuía um significado físico claro e desempenhava um papel central para Faraday, Maxwell e outros físicos britânicos. Um dos objetivos deste trabalho é entender como se deu esta mudança na interpretação do conceito de potencial vetor. Para isto foi realizado um estudo histórico analisando as diferentes interpretações para este conceito partindo dos trabalhos de Faraday sobre indução eletromagnética, onde propôs o conceito de estado eletrotônico. Analisamos as contribuições de William Thomson que fortemente inspiraram Maxwell a sugerir diferentes interpretações para o conceito em trabalhos publicados ao longo de cerca de duas décadas até a publicação do Treatise on Electricity and Magnestism em 1873. No final do século XIX a interpretação dada por Maxwell ao conceito de potencial vetor começou a ser questionada por vários físicos. Uma das questões envolvidas neste processo foi a realidade das grandezas físicas. Nomes como Heaviside, Hertz e outros defendiam que as grandezas dotadas de realidade física na teoria eletromagnética eram os campos elétrico e magnético e não o potencial vetor. Com essa nova visão desenvolveram uma nova teoria eletromagnética próxima da que conhecemos atualmente. No entanto, este processo não foi linear e aceito acriticamente. Ao longo do século XX foram publicados trabalhos propondo uma interpretação física para o potencial vetor, ainda no contexto clássico. O estudo histórico aqui desenvolvido priorizou a abordagem desenvolvida na Grã-BretanhaCurrently the vector potential generally is considered in the classical electromagnetic theory as an artifice for the calculation of the electric and magnetic fields and without a clear physical meaning. However, when it was proposed in the mid-nineteenth century, it used to have a clear physical meaning and played a central role for Faraday, Maxwell and other British physicists. One of the goals of this dissertation is to understand how the meanings attributed to the vector potential changed along years. In order to answer to this question, we developed a historical study analyzing the different interpretations for this concept starting with the works of Faraday on electromagnetic induction, where he introduced the concept of electrotonic state. We analyzed the contributions of William Thomson that inspired strongly Maxwell to suggest different interpretations for the concept in works published along the next two decades until the publication of the Treatise on Electricity and Magnestism in 1873. In the end of the nineteenth century Maxwells interpretations for the vector potential began to be questioned by several physicists. One of the issues involved in this questioning was the reality of the physical quantities. People as Heaviside, Hertz and others defended that electric and magnetic fields, not the vector potential, were quantities endowed with physical reality. With this new approach they developed a new electromagnetic theory closer to the currently accepted. Nevertheless, this process was not linear and uncritically accepted. Throughout the twentieth century papers and books were published defending a physical interpretation for the vector potential considering a classical context for the electromagnetic theory. The historical study developed here focused the developments in Great-Britain although some mentions to Continental physics are made
46
Hosie, Louise Christine. "Characterisation of CMV CD8+T-cell memory-inflation to immediate early HLA-C restricted targets and the potential of CMV as a vaccine vector for cancer therapy." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7410/.
Анотація:
CMV CD8+T-cell memory-inflation can occupy up to 50% of the total CD8+ T cell pool. Studies using an MHC class I immunevasion-deleted strain revealed novel peptide-epitopes across the virus genome both in-frame and translated in a non-canonical manner. This study functionally and phenotypically characterised CD8+T-cells responding to these CMV-derived epitopes with age. They were found to be frequent component of the in vivo repertoire dedicated towards HCMV during latency. A HLA-Cw*0702-restricted immunodominant CD8+T-cell response that accumulated within elderly donors was identified to reach 32% of the total CD8+T-cell pool producing IFN-γ/TNF-α. Subsequently, HLA-Cw*0702-restricted memory-inflation was observed to a further two peptides dominating the CD8+T-cell memory compartment. HLA-Cw*0702 CD8+T-cells demonstrated a TEMRA phenotype - CD45RA+/CD27-/CD28-/CCR7-/perforinhigh/granzymeBhigh - and represented promising candidates for inclusion in HSCT adoptive immunotherapies. Consequently, the global HCMV-specific CD8+T-cell response is being vastly underestimated by restricting studies to; in-frame translation products, HLA-A/-B-restricted peptide-epitopes and utilising WT-strains to characterise novel CD8+T-cell targets. Lastly, understanding why particular HCMV antigens induce inflationary CD8+T-cells will facilitate harnessing HCMV as a cancer therapy. In an attempt to direct HCMV-mediated inflationary responses towards malignancies, a HCMV-based vaccine vector expressing the NYESO1 CTAg was generated. Preliminary results indicate the immunogenicity of such a vaccine in vitro.
47
Rogasch, Eva [Verfasser], Helge [Akademischer Betreuer] Kampen, Helge [Gutachter] Kampen, and Günter [Gutachter] Schaub. "Diversity, ecology and vector potential of mosquito populations (Diptera: Culicidae) in two differentially structured zoological gardens in Germany / Eva Rogasch ; Gutachter: Helge Kampen, Günter Schaub ; Betreuer: Helge Kampen." Greifswald : Universität Greifswald, 2019. http://d-nb.info/1197232621/34.
48
Rogasch, Eva Verfasser], Helge [Akademischer Betreuer] Kampen, Helge [Gutachter] Kampen, and Günter A. [Gutachter] [Schaub. "Diversity, ecology and vector potential of mosquito populations (Diptera: Culicidae) in two differentially structured zoological gardens in Germany / Eva Rogasch ; Gutachter: Helge Kampen, Günter Schaub ; Betreuer: Helge Kampen." Greifswald : Universität Greifswald, 2019. http://d-nb.info/1197232621/34.
49
Rogasch, Eva Verfasser], Helge [Akademischer Betreuer] [Kampen, Helge Gutachter] Kampen, and Günter A. [Gutachter] [Schaub. "Diversity, ecology and vector potential of mosquito populations (Diptera: Culicidae) in two differentially structured zoological gardens in Germany / Eva Rogasch ; Gutachter: Helge Kampen, Günter Schaub ; Betreuer: Helge Kampen." Greifswald : Universität Greifswald, 2019. http://nbn-resolving.de/urn:nbn:de:gbv:9-opus-32630.
50
Costa, Verdera Helena. "Towards the development of a gene therapy for Pompe disease : Characterization of the immune phenotype in Pompe disease and comparison of the therapeutic potential of gene therapy with the current standard of care." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS516.
Анотація:
La maladie de Pompe est une maladie lysosomale causée par des mutations sur l'enzyme α-glucosidase acide (GAA), responsable de la dégradation du glycogène lysosomal. Le déficit en GAA provoque l'accumulation de glycogène dans de multiples tissus, conduisant à une maladie neuromusculaire complexe avec une morbidité et mortalité élevées. En plus des symptômes connus, nos études montrent que le déficit en GAA affecte l’activation et le fonctionnement des cellules immunitaires chez les patients et le modèle murin de la maladie de Pompe. En particulier, nous avons observé une suractivation des cellules T effectrices, ainsi qu’un défaut dans l’induction et la fonction des cellules T régulatrices (Tregs). De plus, les souris atteintes de la maladie de Pompe présentent de l’inflammation tissulaire précoce, ce qui pourrait contribuer à la physiopathologie de la maladie. Ces résultats pourraient ouvrir des nouvelles voies pour étudier des stratégies qui retardent la progression de la maladie. Dans une deuxième série d'expériences, nous montrons qu'une thérapie génique ciblée au foie avec un transgène GAA sécrétable conduit à une meilleure correction de la maladie dans un modèle murin immunodéficient de la maladie, par rapport au traitement enzymatique substitutif existant. Étant donné que les Treg jouent un rôle essentiel dans la thérapie génique ciblée au foie, en induisant une tolérance immunitaire vers les transgènes hépatiques, de futures études devront évaluer l'impact des altérations immunitaires associées à cette maladie sur l'efficacité de la thérapie géniquePompe disease is a lysosomal storage disease caused by mutations on the enzyme acid α-glucosidase (GAA), responsible for degrading lysosomal glycogen. GAA deficiency causes the accumulation of glycogen in multiple tissues, particularly in muscles and central nervous system, leading to a complex neuromuscular disease with high morbidity and mortality. In addition to the known symptoms, our studies in Pompe disease patients and mice show that GAA deficiency affects the activation and function of immune cells, particularly of T cells, leading to a higher activation of effector cells and impaired induction and suppressive function of regulatory T cells (Tregs). Moreover, Pompe disease mice present tissue inflammation at early stages of the disease, altogether suggesting that alterations in the immune system could contribute to the disease pathophysiology. These findings could open new venues to investigate strategies that delay the progression of the disease. In a second set of experiments we show that liver-directed gene therapy with a secretable GAA transgene results in superior disease rescue in an immunodefficient Pompe disease mouse model, when compared to the current enzyme replacement therapy. Because Tregs play an essential role in liver-directed gene therapy, by inducing immune tolerance towards hepatic transgenes, future studies will have to evaluate the potential impact of immune alterations associated to Pompe disease on the efficacy of liver-targeted gene transfer
La enfermedad de Pompe es una enfermedad lisosomal (lysosomal storage disease, LSD) causada por mutaciones en la enzima α-glucosidasa ácida (GAA), que hidroliza el glucógeno en glucosa en los lisosomas. La disfunción de esta enzima causa la acumulación de glucógeno en múltiples tejidos, principalmente en células musculares y neuronas. Como resultado, los pacientes desarrollan hipertrofia cardíaca, debilidad muscular, insuficiencia respiratoria, alteraciones cognitivas y muerte prematura por paro cardiorrespiratorio. Actualmente la enfermedad de Pompe se trata con terapia de reemplazo enzimático (Enzyme replacement therapy, ERT) con GAA recombinante humana (rhGAA). Este tratamiento ha demostrado corregir la patología cardíaca y extender la esperanza de vida de los pacientes. Sin embargo, la eficacia de la ERT en los músculos respiratorios y esqueléticos es parcial, y nula en el sistema nervioso central (SNC). Además, la proteína rhGAA es altamente inmunogénica, por lo que el tratamiento no es efectivo en ciertos pacientes. Otros inconvenientes son el elevado coste de la ERT y la necesidad de infusiones continuadas a lo largo de la vida del paciente. En este estudio mostramos que la terapia génica dirigida al hígado mediante vectores adeno-asociados (AAV) expresando una versión modificada de la GAA revierte de forma significativa la enfermedad a nivel de la musculatura esquelética y del SNC, en un modelo animal de la enfermedad de Pompe. Además, mostramos que este tratamiento es superior en eficacia al tratamiento estándar por ERT, incluso a dosis reducidas de vector AAV. Con tal de comprender mejor los mecanismos de acción de estos dos tratamientos, hemos llevado a cabo un estudio farmacocinético de los niveles de GAA en circulación y en múltiples tejidos en los dos casos. Dicho estudio muestra que niveles reducidos pero constantes de GAA en circulación proporcionados por el hígado permiten una mayor acumulación de GAA en los tejidos en comparación a la ERT, mejorando así la eficacia del tratamiento. Debido a que las reacciones inmunes contra el vector AAV y el transgén son un obstáculo importante en la aplicación clínica de la terapia génica, y a que alteraciones en los lisosomas han demostrado tener un impacto sobre el sistema inmune en diferentes modelos, también hemos estudiado el sistema inmune en el caso de la enfermedad de Pompe. Mediante estos estudios, hemos observado que la acumulación de glucógeno en los lisosomas de células inmunes está asociada a una mayor activación de estas células, tanto en pacientes como en ratones con enfermedad de Pompe, y particularmente en las células T. Además, ratones con enfermedad de Pompe presentan inflamación en los tejidos ya en las primeras etapas de la enfermedad. Por otra parte, mostramos que el mayor estado de activación de las células T podría deberse a alteraciones en el metabolismo de estas células, como resultado de las alteraciones lisosómicas. Finalmente, los ratones con enfermedad de Pompe presentan un defecto en la inducción de células T reguladoras Foxp3+ (Tregs), y estas células tienen un menor potencial inhibidor en comparación con Tregs de ratones sanos. Alteraciones en el sistema inmunitario podrían contribuir a la fisiopatología de la enfermedad. Por lo tanto, estos hallazgos podrían abrir nuevos caminos para investigar estrategias que retrasen la progresión de la enfermedad. Además, las Tregs juegan un papel esencial en la terapia génica dirigida al hígado, mediante la inducción de tolerancia inmune hacia transgenes expresados por hepatocitos. Por lo tanto, futuros estudios deberán evaluar el impacto de las alteraciones inmunitarias asociadas a la enfermedad de Pompe sobre la eficacia de la terapia génica
La malaltia de Pompe és una malaltia lisosomal (lysosomal storage disease, LSD) deguda a mutacions en l'enzim α-glucosidasa àcida (GAA), que hidrolitza el glicogen en glucosa als lisosomes. La disfunció d'aquest enzim causa l'acumulació de glicogen en múltiples teixits, principalment en cèl·lules musculars i neurones. Com a resultat, els pacients presenten hipertròfia cardíaca, debilitat muscular, insuficiència respiratòria, alteracions cognitives i mort prematura per aturada cardiorespiratòria. Actualment, la malaltia de Pompe és tractada amb teràpia de reemplaçament enzimàtic (Enzyme replacement therapy, ERT) amb GAA recombinant humana (rhGAA). Aquest tractament ha demostrat corregir la patologia cardíaca i estendre l'esperança de vida dels pacients. No obstant, l'eficàcia de l'ERT en els músculs respiratoris i esquelètics és parcial, i nul·la en el sistema nerviós central (SNC). A més, la proteïna rhGAA és altament immunogènica, de manera que el tractament no és efectiu en certs pacients. Altres inconvenients són l'elevat cost de l'ERT i la necessitat d'infusions continuades al llarg de la vida del pacient. En aquest estudi mostrem que la teràpia gènica dirigida al fetge mitjançant vectors adeno-associats (AAV) expressant una versió modificada de la GAA millora de forma significativa la malaltia a nivell de la musculatura esquelètica i del SNC, en un model animal de la malaltia de Pompe. A més, mostrem que aquest tractament és superior en eficàcia al tractament estàndard per ERT, fins i tot a dosis reduïdes de vector AAV. Per tal de comprendre millor els mecanismes d'acció d'aquests dos tractaments, hem dut a terme un estudi farmacocinètic dels nivells de GAA en circulació i en múltiples teixits en ambdós casos. Aquest estudi mostra que nivells reduïts però constants de GAA en circulació proporcionats pel fetge permeten una major acumulació de la GAA en els teixits en comparació a la ERT, millorant així l'eficàcia del tractament. Degut a que les reaccions immunes contra el vector AAV i el transgèn són un obstacle important en l'aplicació clínica de la teràpia gènica, i a que alteracions en els lisosomes han demostrat tenir un impacte sobre el sistema immune en differents models, també hem avaluat el sistema immune en el cas de la malaltia de Pompe. Mitjançant aquests estudis, hem observat que l'acumulació de glicogen en els lisosomes de les cèl·lules immunes està associada a una major activació d'aquestes cèl·lules en pacients i ratolins amb malaltia de Pompe, particularment en les cèl·lules T. A més, ratolins amb malaltia de Pompe presenten inflamació dels teixits ja en les primeres etapes de la malaltia. D’altra banda, hem observat que el major estat d'activació de les cèl·lules T podria ser degut a alteracions en el metabolisme d'aquestes cèl·lules, com a resultat de les alteracions lisosomals. Finalment, els ratolins amb malaltia de Pompe presenten un defecte en la inducció de cèl·lules T reguladores Foxp3+ (Tregs), i aquestes cèl·lules tenen un menor potencial inhibidor en comparació amb les Tregs de ratolins sans. Alteracions en el sistema immunitari podrien contribuir a la fisiopatologia de la malaltia. Per tant, aquestes observacions podrien obrir nous camins a l’hora d’investigar estratègies que retardin la progressió de la malaltia. A més, les Tregs juguen un paper essencial en la teràpia gènica dirigida al fetge, mitjançant la inducció de tolerància immune cap a transgens expressats per hepatòcits. Per tant, futurs estudis hauran d'avaluar l'impacte de les alteracions immunitàries associades a la malaltia de Pompe sobre l'eficàcia del tractament per teràpia gènica