Aerodynamic engineering of a pulmonary prime-pull vaccine against Tuberculosis

Tuberculosis (TB) remains the infectious disease with the highest mortality alongside HIV. Despite the existence of the Bacillus Calmette-Guerin (BCG) vaccine there is an unmet need for an effective vaccine against pulmonary TB, the most common form of TB. Traditional vaccines were based on live-attenuated organisms, but nowadays the development of subunit vaccines is attracting the attention of researches largely as a result of the improved safety profile. However, many subunit vaccines lack potent immunogenicity, therefore the inclusion of an adjuvant within the subunit vaccine formulation may be required.;Due to the optimal biological properties of the lipids, liposomes are extensively studied as delivery systems along with polymer-based particulate systems such as the well-known poly(lactic-co-glycolic acid) family (PLGA). The cationic liposomal adjuvant formulation (CAF) 01, which is based on the cationic surfactant dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator trehalose 6,6'-dibehenate (TDB) from Mycobacterium tuberculosis, has previously been shown to be a strong adjuvant system against several diseases such as TB. CAF01 is commonly prepared by the thin film method which has several drawbacks including scale-up and reproducibility.;In contrast, controllable technologies such as microfluidics have advantages in material preparation such as uniform flow and mixing, high efficiency, continuous operation, easy control and low cost. Therefore, initial studies were focused towards method optimisation of CAF01 through microfluidics, followed by in vivo evaluation of the optimised formulation (biodistribution and immunisation studies). The second part of the thesis was based in the formulation PLGA nano- and microparticles using microfluidics and the double emulsion method respectively.;All formulations were characterised according to their size, polydispersity and surface charge as empty particulate systems and incorporating either ovalbumin (OVA) as a model antigen or the vaccine candidate Ag85B-ESAT6-Rv2660c (H56). Selected PLGA particles were formulated as dry powders for inhalation and for the delivery of the H56 tuberculosis antigen into the deep lungs (alveoli). In vitro deposition within the lungs was evaluated using a Pharmacopoeia approved airway simulator, while cell viability, particle uptake and antigen processing was assessed in three macrophages cell lines.;Finally, a prime-pull vaccine approach for protection against pulmonary TB was investigated. An immunisation protocol consisting of parenteral (subcutaneous) priming with the TB vaccine candidate H56 alongside CAF01 followed by respiratory mucosal boosting of the H56 within PLGA nano- and micropaticles was carried out in order to elucidate if intranasal administration of the H56 antigen produces the desired immunological responses for the protection against pulmonary TB.;The immune responses generated indicate the retention of the immunogenicity of the antigen encapsulated within a lyophilised PLGA delivery system, demonstrating the successful scale independent manufacture of polymer based delivery systems encapsulating antigens for inhalation/aerolisation delivery to the lung mucosa.Tuberculosis (TB) remains the infectious disease with the highest mortality alongside HIV. Despite the existence of the Bacillus Calmette-Guerin (BCG) vaccine there is an unmet need for an effective vaccine against pulmonary TB, the most common form of TB. Traditional vaccines were based on live-attenuated organisms, but nowadays the development of subunit vaccines is attracting the attention of researches largely as a result of the improved safety profile. However, many subunit vaccines lack potent immunogenicity, therefore the inclusion of an adjuvant within the subunit vaccine formulation may be required.;Due to the optimal biological properties of the lipids, liposomes are extensively studied as delivery systems along with polymer-based particulate systems such as the well-known poly(lactic-co-glycolic acid) family (PLGA). The cationic liposomal adjuvant formulation (CAF) 01, which is based on the cationic surfactant dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator trehalose 6,6'-dibehenate (TDB) from Mycobacterium tuberculosis, has previously been shown to be a strong adjuvant system against several diseases such as TB. CAF01 is commonly prepared by the thin film method which has several drawbacks including scale-up and reproducibility.;In contrast, controllable technologies such as microfluidics have advantages in material preparation such as uniform flow and mixing, high efficiency, continuous operation, easy control and low cost. Therefore, initial studies were focused towards method optimisation of CAF01 through microfluidics, followed by in vivo evaluation of the optimised formulation (biodistribution and immunisation studies). The second part of the thesis was based in the formulation PLGA nano- and microparticles using microfluidics and the double emulsion method respectively.;All formulations were characterised according to their size, polydispersity and surface charge as empty particulate systems and incorporating either ovalbumin (OVA) as a model antigen or the vaccine candidate Ag85B-ESAT6-Rv2660c (H56). Selected PLGA particles were formulated as dry powders for inhalation and for the delivery of the H56 tuberculosis antigen into the deep lungs (alveoli). In vitro deposition within the lungs was evaluated using a Pharmacopoeia approved airway simulator, while cell viability, particle uptake and antigen processing was assessed in three macrophages cell lines.;Finally, a prime-pull vaccine approach for protection against pulmonary TB was investigated. An immunisation protocol consisting of parenteral (subcutaneous) priming with the TB vaccine candidate H56 alongside CAF01 followed by respiratory mucosal boosting of the H56 within PLGA nano- and micropaticles was carried out in order to elucidate if intranasal administration of the H56 antigen produces the desired immunological responses for the protection against pulmonary TB.;The immune responses generated indicate the retention of the immunogenicity of the antigen encapsulated within a lyophilised PLGA delivery system, demonstrating the successful scale independent manufacture of polymer based delivery systems encapsulating antigens for inhalation/aerolisation delivery to the lung mucosa

Neromarketing : Neuromarketing aplicado a las ventas

Actualmente se ha podido evidenciar como ha surgido el interés por aplicar la neurología para estudiar el comportamiento del consumidor y como este reacciona a diferentes estímulos de marketing, esto se remonta al estudio del cerebro humano y todo acerca de los gustos y preferencias que intervienen en la elección de algún producto o servicio determinado. El Neuromarketing forma parte de un mecanismo esencial en el proceso de las ventas, ya que actualmente influye la parte emocional al momento de adquirir un producto o servicio. Es por ello que en el siguiente trabajo monográfico hemos tratado de explicar la importancia fundamental del Neuromarketing aplicado a la venta de bienes y servicios, así como su rol esencial en el crecimiento económico de los sectores comerciales, industriales y agropecuarios del país. También se realiza un estudio sobre los conocimientos esenciales sobre las ventas que requiere un vendedor conocer y aplicar, así como los diferentes técnicas de ventas. Se plantea en el presente trabajo monográfico la aplicación del Neuromarketing en las diversas actividades relacionadas con las ventas. Hemos también explicado como gracias a los procesos psicológicos y al estudio de la conducta de los consumidores se puede influir en el proceso de toma de decisiones, todo con el fin de satisfacer sus deseos y necesidades

Projeto Teachers´Aids on Creating Content for Learning Environments

Recensão de recurso digita

First total synthesis of (+)-Neplanocin B

(+)-Neplanocin B ((+)-5), the unnatural isomer of a minor component of the neplanocin family of antibiotics was enantioselectively synthesized starting from D-ribono-1,4-lactone. This synthetic strategy employed (+)-9-[(1R, 2R, 5S)-5-Benzyloxy-3-(benzyloxy)methyl-2-hydroxycyclopent-3-en-1-yl]-6-chloropurine (compound 7) as an advanced synthetic intermediate.Fil: Comin, Maria Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Pellegrinet, Silvina Carla. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Rodriguez, Juan Bautista. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentin

Habitat policies, “villas” and city: Current trends and possible futures (Buenos Aires, Argentina)

El artículo presenta una serie de reflexiones y propuestas a partir del análisis de las políticas dirigidas a la urbanización de asentamientos precarios (villas) y otras de integración en la trama urbana formal consolidada, a través del impulso de la producción autogestionaria del hábitat (Ley 341) en la ciudad de Buenos Aires. La metodología se basa en una estrategia cuali-cuantitativa que integra fuentes primarias (entrevistas semiestructuradas con diversos actores, encuesta de elaboración propia con inquilinos de villas, observaciones en campo) y secundarias (base documental de noticias, fuentes censales, documentos de organismos públicos, planos y cartografías), elaboradas como parte de una línea de investigación longitudinal que dirijo en el área de estudios urbanos del Instituto de Investigaciones Gino Germani de la Universidad de Buenos Aires . Argumenta que no serán posibles políticas de integración urbanística y social de los barrios precarios e informales sin intervenir, simultáneamente, escalando políticas e instrumentos para que los mismos sectores de bajos ingresos puedan habitar en la trama urbana consolidada, sin ser excluidos por sus posiciones de mercado.This article presents a series of reflections and proposals that involve public policies focused on the re-development of slums (villas) and their urban integration through self-managed processes of habitat production (law n° 341) in the city of Buenos Aires. The methodology makes use of a qualitative-quantitative strategy that integrates both primary sources (semi-structured interviews with different actors, surveys with tenants of villas, field observations), and secondary sources (news-clippings, census sources, of-ficial documents, plans and maps), elaborated as part of a longitudinal research line that I coordinate in the field on Urban Studies of the Instituto de Investigaciones Gino Germani on the Universidad de Buenos Aires. My main argument is that policies aimed at the social and urban integration of precarious and informal settlements cannot be successful unless they be simultaneously paired with instruments that integrate the low-income population with the consolidated urban system to prevent their exclusion as a result of their positions in the marketFil: Rodriguez, Maria Carla. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; Argentin