[EN] The present PhD thesis aims at the development of a one-dimensional solver capable of solving single- and two-phase flow fluid systems. The novelty of this project lies in the use of an open source CFD platform, called OpenFOAM, as a development framework for the new tool. For the new solver development, the conservation equations based on Navier- Stokes (three-dimensional system) have been analyzed and reduced to one dimension. For the two-phase simulations, the Two Fluid Model method was used as base. In addition, a series of empirical models have been selected as closing equations of the system. The final solver includes a series of requirements that reinforce their capabilities. Among them, the use of a second mesh that represents the solid and takes into account the heat transmitted to the fluid by conduction through a solid, stands out. On the other hand, the possible transfer of mass between phases in twophase fluids has been taken into account. Similarly, a subcooled boiling model has been implemented which takes into account the possible generation of vapor near the wall while the bulk is kept below saturation temperature. Finally, this paper presents the verification and validation of the solver. The verification has been carried out mainly with the system code TRACE, whose validation has been demonstrated in numerous works and its use is very extended in the scientific community. For the validation, we have the results of two experimental cases that allow us to demonstrate the physical validity of the new application developed. The use of this platform allows for a much more direct coupling between one- and three-dimensional domains, obtaining a better optimization of the calculation. / [ES] El presente trabajo de doctorado tiene por objetivo el desarrollo de un solver unidimensional capaz de resolver sistemas de fluidos monofásicos y bifásicos. La novedad de este proyecto reside en el uso de una plataforma CFD de código abierto, llamada OpenFOAM, como marco para el desarrollo de la nueva herramienta. Para el desarrollo del nuevo solver, se han analizado las ecuaciones de conservación basadas en Navier-Stokes (tridimensionales) y se han reducido a una dimensión. Para la parte bifásica del solver, se utiliza el método Two Fluid Model. Además, se han incluido todos los modelos empíricos necesarios como ecuaciones de cierre del sistema. El solver final incluye una serie de requerimientos que refuerzan sus capacidades. Entre ellas, destacan, por un lado, el uso de una segunda malla que represente el sólido y tenga en cuenta el calor transmitido al fluido por conducción a través de un sólido. Por otro lado, se ha tenido en cuenta la posible transferencia de masa entre fases en fluidos bifásicos. Igualmente, se ha implementado un modelo de ebullición subenfriada que tiene en cuenta la posible generación de vapor cerca de la pared mientras el centro del fluido se mantiene por debajo de la temperatura de saturación. Finalmente, este trabajo presenta la verificación y validación del solver. La verificación se ha realizado principalmente con el código de sistema TRACE. Para la validación, se cuenta con los resultados de dos casos experimentales que permiten demostrar la validez física de la nueva aplicación desarrollada. La implementación del nuevo solver en esta plataforma abierta permite un futuro acoplamiento mucho más directo entre mallas unidimensionales y tridimensionales, obteniendo una mayor optimización del cálculo. / [CA] El present treball de doctorat té per objectiu el desenvolupament d'un nou solver unidimensional capaç de solucionar sistemes amb fluids monofàsics i bifàsics. La novetat d'aquest projecte resideix en l'ús d'una plataforma CFD de codi obert, anomenada OpenFOAM com a marc de desenvolupament de la nova eina. Per al desenvolupament del nou solver, s'han analitzat les equacions de conservació basades en Navier-Stokes (tridimensionals) i s'han reduït a una dimensió. Per a la part bifàsica del solver s'utilitza el mètode Two Fluid Model. A més, s'han inclòs tots els models empírics necessaris com a equacions de tancament del sistema. El solver final inclou una sèrie de requeriments que reforcen les seues capacitats. Entre elles, destaquen, d'una banda, l'ús d'una segona malla que represente el sòlid i es tinga en compte la calor transmesa al fluid per conducció a través d'un sòlid. D'altra banda, s'ha tingut en compte la possible transferència de massa entre fases en fluids bifàsics. Igualment, s'ha implementat un model d'ebullició subrefredada que té en compte la possible generació de vapor prop de la paret mentre el centre del fluid es manté per davall de la temperatura de saturació. Finalment, aquest treball presenta la verificació i validació del solver. La verificació s'ha realitzat principalment amb el codi de sistema TRACE, la validació del qual s'ha demostrat en nombrosos treballs i el seu ús està molt estés en la comunitat científica. Per a la validació, es compta amb els resultats de dos casos experimentals que permeten demostrar la validesa física de la nova aplicació desenvolupada. L'ús d'esta plataforma permiteix un futur acoblament més directe, entre elements unidimensionals i tridimensionals, obtenint una major optimització del càlcul. / Gómez-Zarzuela Quel, C. (2020). Development and assessment of a one-dimensional CFD solver for boiling flows in bubbly regimes [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/148368 / TESIS

An impinging type solar receiver has been designed for potential applications in a future Brayton Solar Dish System. The EuroDish system is employed as the collector, and an externally fired micro gas turbine (EFMGT) has been chosen as the power conversion unit. In order to reduce the risks caused by the quartz glass window, which is widely used in traditional air receiver designs, a cylinder cavity absorber without a quartz window has been adopted. Additionally, an impinging design has been chosen as the heat exchange system due to its high heat transfer coefficient compared to other single-phase heat exchange mechanisms. This thesis work introduces the design of an solar air receiver without a glass window, which features jet impingement to maximize the heat transfer rate. A detailed study of the thermal performance of the designed solar receiver has been conducted using numerical tools from the ANSYS FLUENT package. Concerning receiver performance, an overall thermal efficiency of 72.9% is attained and an output air temperature of 1100 K can be achieved, according to the numerical results. The total thermal power output is 38.05 kW, enough to satisfy the input requirements of the targeted micro gas turbine. A preliminary design layout is presented and potential optimization approaches for future enhancement of the receiver are proposed, regarding local thermal stress and pressure loss reduction. This thesis project also introduces a ray-thermal coupled numerical design method, which combines ray tracing techniques (using FRED®), with thermal performance analysis (using ANSYS Workbench).

Pathogens such as <i>Listeria</i>, <i>Shigella</i>, <i>Brucella</i>, <i>Salmonella</i>, <i>Mycobacterium tuberculosis</i> and <i>methicillin-resistant Staphylococcus aureus</i> (MRSA) can traverse into mammalian cells, such as phagocytic macrophages. Once inside, these bacteria can survive and reproduce, causing chronic infections. It is of utmost importance to develop novel antibiotics with broad spectrum activity to control these deadly bacteria. Broad spectrum activity will allow for targeting of pathogens with different structures and cell membrane components.<div>This work focuses on the synthesis of a dual antibiotic agent, composed of a cationic amphiphilic polyproline helix (CAPH) possessing cell penetrating and nonmembrane lytic antimicrobial capabilities (P14LRR), and a derivative of the polymyxin B (PMX) antibacterial peptide. This dual antibiotic conjugate was created to be a tool to potentially clear intracellular pathogenic bacteria. Overall, the reduction of the disulfide bond linking the two antibiotics within the reducing environment of cells would release the individual antimicrobial agents, and could have improved cell membrane penetration and intracellular synergistic activity. Herein, the synthesis of the dual antibiotic agent, P14LRR-PMX, is discussed. </div>

Many children under the age of 5 die each year of invasive pneumococcal disease. Childhood vaccination against this disease reduces morbidity and mortality. Despite the introduction of a pneumococcal conjugate vaccine (PCV13) in a central African country in 2011, all provinces have not yet been vaccinated. The purpose of this quantitative quasi-experimental study was to determine whether there was an association between the introduction of PCV13 and new cases of pneumococcal disease in 2 provinces in central Africa. The sample size for the study was 380. The theoretical framework for this study was the epidemic model supported by the concept of herd immunity. Key research questions examined the incidence of pneumococcal disease in children by age, gender, and province. The independent variables were age, gender, province, and introduction of PCV13. The dependent variable was incidence of invasive pneumococcal disease. The research questions were evaluated using chi-square test of independence and logistic regression. The results of the study indicated that vaccination with PCV13 significantly reduced incident cases of invasive pneumococcal diseases (aOR 0.333, 95% CI 0.628-0.177, p = 0.001). However, this association was not significant for age (aOR 0.574, 95% CI 1.186-0.278, p = .134), and there were no significant gender differences (aOR 1.047, 95% CI 1.929-0.569, p = 0.882). Positive social change may result by enabling the protection of more children in the central Africa country provinces that have not yet adopted using PCV13 and by introducing the vaccine in other African countries.

京都大学 / 0048 / 新制・課程博士 / 博士(情報学) / 甲第17968号 / 情博第512号 / 新制||情||91(附属図書館) / 30798 / 京都大学大学院情報学研究科数理工学専攻 / (主査)教授 中村 佳正, 教授 西村 直志, 准教授 山下 信雄 / 学位規則第4条第1項該当 / Doctor of Informatics / Kyoto University / DFAM

Millions of people worldwide die of cancer every year. In the last decade, im- munotherapy offered new treatment options achieving long-lasting remissions in a number of patients. Several new immunotherapy-based drugs have been ap- proved by Food and Drug Administration. However, majority of patients either do not respond or soon relapse. Combination of therapies as well as exploring new immune checkpoints seems promising. This thesis focuses on the new immunotherapeutic target CD73. CD73 is membrane ectonucleotidase, widely expressed on the regulatory leukocytes and on cancer cells. The enzymatically active CD73 contributes to the tumour mi- croenvironment by production of immunosuppressive adenosine. This novel im- mune checkpoint is being intensively studied. This thesis aims on development of new approaches for targeting and inhibition of CD73. Soluble recombinant CD73 (rhCD73) was prepared in mammalian expression system and transfectants stably expressing membrane-bound CD73 were prepared as well. Inhibitors necessary for both of my goals have been designed based on published inhibitor of CD73. Development and evaluation of novel antibody mimetic for CD73 characteri- sation was done. The so-called iBody, HPMA polymer conjugate decorated with CD73 inhibitor for targeting, fluorophore for...

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The rise in antibiotic resistant strains of bacteria has led to the need for new methods of combatting bacterial infection. Since the surfaces of bacteria are covered in uniquely patterned capsular polysaccharides, vaccines targeting these polysaccharides have become a popular field of research for protection against pathogenic bacteria. Though licensed polysaccharide vaccines are commercially available, they lack the efficiency to protect patients that are immunocompromised or at high risk because they elicit T cell independent immune responses, resulting in low-affinity antibodies. To elicit a T cell dependent response and thereby recruit B cells that produce high-affinity antibodies, a vaccine was developed consisting of a short target oligosaccharide antigen of no more than four carbohydrate units, a virus-like particle that the antigen is conjugated to, and an NKT cell adjuvant that recruits T cell help. Previously the vaccine utilized in this work successfully elicited the T cell dependent adaptive immune response desired, and B cells were isolated producing high-affinity antibodies to our specific targets. The previous results were from using tetrasaccharide antigens for serotypes 14 and 3 of Streptococcus pneumonia (Sp). To further optimize this vaccine, disaccharides were tested as minimal epitopes for high-affinity antibody production to specific serotypes of Sp. Four disaccharides were synthesized for serotypes 3, 4, 7F, and 9v, one for each serotype. The synthesis of each disaccharide is described. These disaccharides were tested using the vaccine platform we developed. Reactive B cells were isolated producing high-affinity antibodies to the serotype 3 disaccharide antigen. For the other disaccharides only weak antibody responses were observed.

[pt] A importância de sistemas que monitorem continuamente as resposta dos consumidores à propaganda é notadamente reconhecida pela comunidade de pesquisa de mercado. A coleta sistemática deste tipo de informação é importante porque através desta, pode-se revisar campanhas anteriores, corrigir tendências detectadas em pré-testes e melhor orientar as tomadas de decisão nos setores de propaganda. O presente trabalho contém um modelo para tentar medir esta resposta baseada em Modelos Lineares Dinâmicos Generalizados. / [en] Analysis of consumer markets define and attempt to measure many variables in studies of the effectiveness of adversitising. The awareness in a consumer population of a particular advertising is one such quantity, the subject of the above-referenced studies. We define and give the implementation of model based in dynamic Generalised Linear Models which is used to measure this quantity.

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