Malaria vaccine: roadblocks and possible solutions

Malaria remains the most prevalent and devastating parasitic disease worldwide. Vaccination is considered to be an approach that will complement other strategies for prevention and control of the disease in the future. In the last 10 years, intense studies aimed at the development of a malaria vaccine have provided important knowledge of the nature of the host immunological mechanisms of protection and their respective target antigens. It became well established that protective immune responses can be generated against the distinct stages of Plasmodium. However, in general, protective immune responses are directed at stage-specific antigens. The elucidation of the primary structure of these antigens made possible the generation of synthetic and recombinant proteins that are being extensively used in experimental immunizations against the infection. Today, several epitopes of limited polymorphism have been described and protective immunity can be generated by immunization with them. These epitopes are being tested as primary candidates for a subunit vaccine against malaria. Here we critically review the major roadblocks for the development of a malaria vaccine and provide some insight on how these problems are being solved

Malaria vaccine: roadblocks and possible solutions

Malaria remains the most prevalent and devastating parasitic disease worldwide. Vaccination is considered to be an approach that will complement other strategies for prevention and control of the disease in the future. In the last 10 years, intense studies aimed at the development of a malaria vaccine have provided important knowledge of the nature of the host immunological mechanisms of protection and their respective target antigens. It became well established that protective immune responses can be generated against the distinct stages of Plasmodium. However, in general, protective immune responses are directed at stage-specific antigens. The elucidation of the primary structure of these antigens made possible the generation of synthetic and recombinant proteins that are being extensively used in experimental immunizations against the infection. Today, several epitopes of limited polymorphism have been described and protective immunity can be generated by immunization with them. These epitopes are being tested as primary candidates for a subunit vaccine against malaria. Here we critically review the major roadblocks for the development of a malaria vaccine and provide some insight on how these problems are being solved.

Roadblocks to Teaching English as a Foreign Language in a Climate of Accelerated Curricular Change

This paper examines the global "English craze," in which non-Englishspeaking countries, especially in Asia, East Asia, and the Middle East, are engaged in a concerted push to get the language taught more widely and at increasingly lower grade levels. The goal of this paper is to document how this phenomenon has impacted teachers of English as a Foreign Language and how they can try to alleviate these problems.

Prospective motion correction of 3D echo-planar imaging data for functional MRI using optical tracking.

We evaluated the performance of an optical camera based prospective motion correction (PMC) system in improving the quality of 3D echo-planar imaging functional MRI data. An optical camera and external marker were used to dynamically track the head movement of subjects during fMRI scanning. PMC was performed by using the motion information to dynamically update the sequence's RF excitation and gradient waveforms such that the field-of-view was realigned to match the subject's head movement. Task-free fMRI experiments on five healthy volunteers followed a 2×2×3 factorial design with the following factors: PMC on or off; 3.0mm or 1.5mm isotropic resolution; and no, slow, or fast head movements. Visual and motor fMRI experiments were additionally performed on one of the volunteers at 1.5mm resolution comparing PMC on vs PMC off for no and slow head movements. Metrics were developed to quantify the amount of motion as it occurred relative to k-space data acquisition. The motion quantification metric collapsed the very rich camera tracking data into one scalar value for each image volume that was strongly predictive of motion-induced artifacts. The PMC system did not introduce extraneous artifacts for the no motion conditions and improved the time series temporal signal-to-noise by 30% to 40% for all combinations of low/high resolution and slow/fast head movement relative to the standard acquisition with no prospective correction. The numbers of activated voxels (p<0.001, uncorrected) in both task-based experiments were comparable for the no motion cases and increased by 78% and 330%, respectively, for PMC on versus PMC off in the slow motion cases. The PMC system is a robust solution to decrease the motion sensitivity of multi-shot 3D EPI sequences and thereby overcome one of the main roadblocks to their widespread use in fMRI studies.

Who expects what from whom? : a gender based study on expectations and secondary school administration

This study is about expectations and aspirations of secondary school teachers. It is an investigation of why some teachers aspire to become administrators and why some teachers do not. My research compares expectations and existing attltudes regarding aspirations toward administration which are held by three distinct groups within the secondary school system: 1) principals/vice-principals, 2) aspiring teachers, and 3) non-aspiring teachers. This study questions why, in the late 60's, secondary school administration is still predominated by men. The conclusions and recommendations were based on interviews with thirty men and women in the Hamilton Secondary School System. In addltion, Mr. Keith Rielly, Superintendent of Operations, made valuable contributions to my work. The interviews revealed experiences and percept ions of men and women in di scourse about f amil y re lat i onshi ps, educational choices and perceived internal and external barriers which inhiblted or enhanced their decision to aspire to secondary school administration. Candidates spoke about their personal and professional Hves wlth respect to encouragement, perceived images of an administrator, netWOrking and the effect of marriage and children on their careers. Historically, women have not accepted the challenge of administration and It would appear as if this is still the case today. My research suggests that women are under-represented in secondary school administration because of internal and external barriers which discourage many women from aspiring. I conclude that many of women's internal barrlers are reinforced by external roadblocks which prevent women from aspiring to secondory school administration. Thus. many women who do not envision a future in educational administration establish priorities outside the general realm of education. I recommend that males and females recognize that women make valuable contributions to educational theory and design based on their experiences which may be "differene from mole experiences. but just as significant. Mole and female representation in secondary school administration represents a balance between attitudes and behaviours which can not be accomplished when an administrative offlce is dominated by on all ma1e or all female staff.

Rôle de la topoisomérase I dans la stabilité du génome chez Escherichia coli

Les topoisomérases (topos) de type IA jouent un rôle primordial dans le maintien et l’organisation du génome. Cependant, les mécanismes par lesquels elles contrôlent cette stabilité génomique sont encore à approfondir. Chez E. coli, les deux principales topoisomérases de type IA sont la topo I (codée par le gène topA) et la topo III (codée par le gène topB). Il a déjà été montré que les cellules dépourvues des topos I et III formaient de très longs filaments dans lesquels les chromosomes ne sont pas bien séparés. Comme ces défauts de ségrégation des chromosomes sont corrigés par l’inactivation de la protéine RecA qui est responsable de la recombinaison homologue, il a été émis comme hypothèse que les topoisomérases de type IA avaient un rôle dans la résolution des intermédiaires de recombinaison afin de permettre la séparation des chromosomes. D’autre part, des études réalisées dans notre laboratoire démontrent que le rôle majeur de la topoisomérase I est d’empêcher la formation des R-loops durant la transcription, surtout au niveau des opérons rrn. Ces R-loops on été récemment identifiés comme des obstacles majeurs à l’avancement des fourches de réplication, ce qui peut provoquer une instabilité génomique. Nous avons des évidences génétiques montrant qu’il en serait de même chez nos mutants topA. Tout récemment, des études ont montré le rôle majeur de certaines hélicases dans le soutien aux fourches de réplication bloquées, mais aussi une aide afin de supprimer les R-loops. Chez E. coli, ces hélicases ont été identifiées et sont DinG, Rep et UvrD. Ces hélicases jouent un rôle dans la suppression de certains obstacles à la réplication. Le but de ce projet était de vérifier l’implication de ces hélicases chez le mutant topA en utilisant une approche génétique. Étonnamment, nos résultats montrent que la délétion de certains de ces gènes d’hélicases a pour effet de corriger plutôt que d’exacerber des phénotypes du mutants topA qui sont liés à la croissance et à la morphologie des nucléoides et des cellules. Ces résultats sont interprétés à la lumière de nouvelles fonctions attribuées aux topoisomérases de types IA dans la stabilité du génome.

El trabajo en equipo en el Proceso Administrativo y de Compras en OPL Carga de Bucaramanga

El proceso administrativo y de compras de OPL Carga tiene algunas falencias entre ellas: fallas en la Comunicación entre el personal operativo, no se realizan llamadas internas usando con frecuencia el email, produciendo la saturación de solicitudes las cuales terminan sin ser resueltas en cuanto a roles se refiere, no hay enfoque de procesos en vista que no se tiene claras las tareas de cada cargo, adicionalmente no hay claridad en los subprocesos, perjudicando el proceso con el aumento de costos, pérdida de tiempo, las responsabilidades de los funcionario no todas las veces se ejecutan en el tiempo asignado, el liderazgo compartido presenta ambigüedades. Objetivos: Definir el trabajo en equipo en el proceso administrativo y de compras en OPL carga de Bucaramanga. La investigación que a realizar es de tipo descriptivo, busca descubrir las falencias o características que permiten diseñar y desarrollar un modelo de solución para los problemas del equipo de OPL Carga S.A.S. Materiales y métodos: La investigación efectuada es de tipo descriptivo, el objetivo es definir el modelo del trabajo en equipo y describir las falencias en el proceso administrativo y de compras en OPL carga de Bucaramanga, que permitan obtener un diagnóstico integral que conlleve a la implementación de estrategias de solución. Resultados: Se identificaron las falencias en los siguientes aspectos: Variable comunicación, rendimiento, destrezas complementarias, propósito significativo y meta específicas de los funcionarios en OPL carga sección administrativa. Conclusiones: El modelo de trabajo en equipo que OPL aplica es jerárquico, en el que se ofrece estabilidad, seguridad, se toman decisiones en forma piramidal, mediante la planeación de tareas, la colaboración, igualdad y respeto por los miembros, trabajando en pro de la solución de problemas. Se construyó un plano conceptual que permitió exponer la interpretación que la estudiante tiene de las teorías, investigaciones y antecedentes válidos para la comprensión del problema investigado. Área comunicacional: Coordinar acciones tendientes para que los funcionarios respondan a tiempo los emails atenientes a su trabajo. Área condiciones de trabajo: Clarificar y diseñar las reglas de comportamiento al interior de los equipos de trabajo que redunden en el mejoramiento del mismo y la búsqueda de soluciones oportunas. Área metas específicas: Procurar mediante auditorías el cumplimiento de las metas y objetivos propuestos por cada equipo de trabajo.

Probiotics and prebiotics: prospects for public health and nutritional recommendations

Probiotics and prebiotics are useful interventions for improving human health through direct or indirect effects on the colonizing microbiota. However, translation of these research findings into nutritional recommendations and public health policy endorsements has not been achieved in a manner consistent with the strength of the evidence. More progress has been made with clinical recommendations. Conclusions include that beneficial cultures, including probiotics and live cultures in fermented foods, can contribute towards the health of the general population; prebiotics, in part due to their function as a special type of soluble fiber, can contribute to the health of the general population; and a number of challenges must be addressed in order to fully realize probiotic and prebiotic benefits, including the need for greater awareness of the accumulated evidence on probiotics and prebiotics among policy makers, strategies to cope with regulatory roadblocks to research, and high-quality human trials that address outstanding research questions in the field.

Design/Evaluation of A Methodology For Performance Optimization Of Indexable Carbide Inserts

In this project, two broad facets in the design of a methodology for performance optimization of indexable carbide inserts were examined. They were physical destructive testing and software simulation.For the physical testing, statistical research techniques were used for the design of the methodology. A five step method which began with Problem definition, through System identification, Statistical model formation, Data collection and Statistical analyses and results was indepthly elaborated upon. Set-up and execution of an experiment with a compression machine together with roadblocks and possible solution to curb road blocks to quality data collection were examined. 2k factorial design was illustrated and recommended for process improvement. Instances of first-order and second-order response surface analyses were encountered. In the case of curvature, test for curvature significance with center point analysis was recommended. Process optimization with method of steepest ascent and central composite design or process robustness studies of response surface analyses were also recommended.For the simulation test, AdvantEdge program was identified as the most used software for tool development. Challenges to the efficient application of this software were identified and possible solutions proposed. In conclusion, software simulation and physical testing were recommended to meet the objective of the project.

Liquidações extrajudiciais no mercado supervisionado pela SUSEP: impacto, dificuldades e oportunidades.

O problema de pesquisa neste trabalho é a averiguação da eficiência e eficácia do processo de liquidação extrajudicial de seguradoras, companhias de capitalização e de previdência aberta sob o comando da SUSEP, autarquia que regula e supervisiona estes mercados. Historicamente os processos de liquidação na SUSEP têm demorado em média mais de onze anos e ao final a maioria das liquidações encerra-se por autofalência, revelando baixa eficácia e eficiência do processo. Disto decorre nosso objetivo central de pesquisa que é descobrir os fatores que contribuem para esse quadro negativo e fazer recomendações de melhorias, a partir do estudo das leis, normativos e procedimentos aplicáveis e de entrevistas de profundidade com supervisores e pesquisa eletrônica com os liquidantes. Ao final, recomendamos medidas objetivas, que emergiram da análise e do próprio trabalho de pesquisa, as quais vemos como capazes de eliminar os maiores obstáculos que impedem melhores resultados nos processos de liquidação da SUSEP.

A contextualização e a interdisplinaridade no ensino de Química: uma analise de livros didáticos ACIDO-BASE e das propostas pedagógicas realizadas pelos docentes diante da temática

Nowadays, chemistry contents taught in high school continue to be presented in a fragmented and decontextualized manner by the teachers and the textbooks. Even though it is known that contextualization and interdisciplinary exchange play an important role in the process of Chemistry teaching/learning. Therefore, the present study aims at enlightening the importance of these methodological foundations in the learning of chemistry. The data acquisition about the subject Contextualization and Interdisciplinary Exchange involved in Chemistry Teaching was developed through bibliographical researches on chemistry textbooks, which focused on the analysis of the topics acid and base , since it is a theme studied throughout all three years of high school. The present study also developed questionnaires which were applied to analyze to what extent chemistry teachers are working in a contextualized and interdisciplinary manner throughout the process of Chemistry teaching/learning. The results obtained in the researches show that a contextualized and interdisciplinary teaching contributes to a more meaningful acquisition of chemistry knowledge, in a dynamic and interactive way, but there are still many roadblocks towards the achievement of this kind of Chemistry teaching/learning process

Mechanistic study of the effects of 8-oxo-7,8-dihydroguanine (8-oxoG) on reporter gene expression in mammalian cells

DNA damage causes replication errors, leading to genetic instability or cell death. Besides that, many types of DNA base modifications have been shown to interfere with transcriptional elongation if they are located in the transcribed DNA strand of active genes, acting as roadblocks for RNA polymerases. It is widely assumed that transcription blockage by endogenous DNA damage is responsible for the early cell senescence in organs and accelerated ageing observed in individuals with compromised nucleotide excision repair.rnThe aims of this work were to design new experimental systems for testing transcription blocking potentials of DNA base modifications in an individual gene and to apply these test systems to the investigation of the effects of a frequent endogenously generated base modification, namely 8-oxo-7,8-hydroxyguanine (8-oxoG), on the gene transcription in cells. Several experimental strategies were employed for this purpose. First, I constructed an episomal vector encoding for a short-lived EGFP-ODC fusion protein and measured expression of the reporter gene in permanently transfected clonal cell lines exposed to DNA damaging agents. Second, the expression of plasmid-borne EGFP gene damaged with photosensitisers to obtain one or several oxidative purine modifications per plasmid molecule was determined in transiently transfected human and mouse host cells in an approach known as “host cell reactivation”. As a prerequisite for these experiments, a robust method of precise quantitative measurement of the EGFP gene expression in transiently transfected cells by flow cytometry was developed and validated. Third, I elaborated a very efficient procedure for insertion of synthetic oligonucleotides carrying 8-oxoG into plasmid DNA, avoiding any unwanted base damage and strand breaks. The consequences of 8-oxoG placed in defined positions in opposing DNA strands of the EGFP gene for transcription were measured by host cell reactivation in cells with functional 8-oxoguanine DNA glycosylase (OGG1) gene and in OGG1 null cells.rnThe results obtained in Ogg1-/- cells demonstrated that unrepaired 8-oxoG, even if situated in the transcribed DNA strand, does not have any negative effect on the reporter gene transcription. On the other hand, as few as one 8-oxoG was sufficient to cause a significant decrease of the gene expression in OGG1-proficient cell lines, i.e. in the presence of base excision repair. For two analysed positions of 8-oxoG in the plasmid DNA, the inhibition of gene transcription by the base modification correlated with the efficiency of its excision by purified OGG1 protein under cell-free conditions. Based on these findings, it has to be concluded that the observed decrease of transcription is mediated by excision of the base modification by OGG1 and probably caused by the repair-induced single-strand breaks. The mechanism of transcription inhibition by 8-oxoG is therefore clearly distinct from stalling of elongating RNA polymerase II complexes at the modified base.

Running in Heels: an Analysis of Advertisements By Female Senate Candidates

Female candidates have become more successful in the political arena, specifically in the United States Senate. Today, females make up twenty percent of the total Senate seats. Despite this increase, females are still underrepresented in Washington. As such, understanding the roadblocks to equality will help us achieve parity. In an attempt to understand various challenges that female senatorial candidates face, this project looks at a specific element of their campaign, TV advertisements. Assessing candidate advertisements will help us understand whether gender affects strategic campaign decisions. Specifically, this project investigates the relationship between candidate gender and casting and setting of TV advertisements. Does gender influence the makeup of political ad spots? In order to understand this relationship more completely, I employ both quantitative data and case study analysis for same-gender and mixed-gender primary and general election contests in 2004 and 2008. Ultimately, candidate gender has little to no effect on casting of senatorial advertisements across both election cycles. Despite this variation in casting, we observe consistent findings across three settings, the political setting, the home setting, and the neighborhood setting. In both 2004 and 2008, female candidates use smaller proportions of ad frames with the political setting in comparison to their male counterparts. Female candidates in both election cycles also employed greater proportions of ad frames with the home and neighborhood setting compared to male candidates. These discrepancies point to a distinction in advertisement strategy depending on gender of the candidate.

En los zapatos de otros : La construcción de subjetividad colectiva en un movimiento de trabadores desocupados

La consolidación del modelo neoliberal en la Argentina de los años noventa, generó un fuerte impacto en los sectores subalternos y en sus formas históricas de dar sentido. Al mismo tiempo se abrieron espacios de disputa por la construcción de sentido y de acción colectiva con posibilidad de resignificar experiencias históricas, tal como es el caso de los movimientos desocupados. Estas nuevas formas de organización y participación política con anclaje barrial, caracterizadas por acciones de protesta mediante la modalidad de cortes de ruta, fueron paulatinamente constituyéndose en espacios de disputa del orden social relevantes hasta la actualidad. A razón de esto último, la siguiente investigación propone un análisis sobre los aspectos subjetivos de experiencias colectivas de trabajo de militantes y participantes de base al interior del Movimiento de Trabajadores Desocupados Aníbal Verón Barrio Malvinas de la ciudad de La Plata, 2009. Fundamentalmente, busca analizar cómo se constituyen y relacionan ambas subjetividades a partir de sus experiencias de trabajo colectivas y cotidianas, con el propósito de entender el proceso de conformación de subjetividad colectiva. En tal dirección, recorre el universo de representaciones, imaginarios, visión de futuro y proyecto colectivo puesto en locución en las prácticas colectivas del movimiento de desocupados en estudio. La presente investigación busca dar cuenta de los elementos de mediación subjetiva puestos en juego en experiencias de trabajo colectivo a razón de considerar la centralidad de la demanda laboral en la conformación de los movimientos desocupados. De este modo, el análisis contempla el contexto de crisis y transformación de la Argentina neoliberal en las últimas década, permitiéndonos pensar no sólo la relación entre orden social, subjetividad y acción dentro de la perspectiva de un movimiento social en concreto sino, también, abriendo preguntas de interés para otros estudios abocados a la misma problemática