Optimal Control Design for Multiterminal HVDC

This thesis proposes an optimal-control based design for distributed frequency control in multi-terminal high voltage direct current (MTDC) systems. The current power grid has become overstressed by rapid growth in the demand for electric power and penetration of renewable energy. To address these challenges, MTDC technology has been developed, which has the potential to increase the flexibility and reliability of power transmission in the grid. Several control strategies have been proposed to regulate the MTDC system and its interaction with connected AC systems. However, all the existing control strategies are based on proportional and integral (PI) control with predetermined controller structures. The objective of the thesis is to first determine if existing control structures are optimal, and if improved controller structures can be developed.The thesis proposes a general framework to determine the optimal structure for the control system in MTDC transmission through optimal feedback control. The proposed method is validated and demonstrated using an example of frequency control in a MTDC system connecting five AC areas

The role of the class III phosphoinositide 3-kinase VPS34 in regulatory T cells and activated CD8+ T cells

The class III PI3-kinase VPS34 is a mediator of endocytosis, trafficking of intracellular membranes and vesicles, and autophagy in various cell types. Given its central role in key cellbiological processes, we explored whether VPS34 is critical for immune cells by generating conditional knockout mice where exon 21 of Pik3c3 (the VPS34 gene) is deleted specifically in regulatory T (Treg) cells or activated CD8+ T cells, respectively. We found that mice with VPS34-deficient Treg cells died within 6 weeks of birth from an autoimmune lymphoproliferative disease, similar to mice lacking Treg cells. However, VPS34- deficient Treg cells developed normally and populated the peripheral lymphoid organs, demonstrating a critical role for VPS34 in Treg cell suppressive functions rather than survival. However, none of the known Treg cell suppressive mechanisms were impaired by the loss of VPS34. Nonetheless, VPS34-deficient Treg cells had a competitive disadvantage and impaired activation compared to VPS34-sufficient Treg cells, suggesting that VPS34 is required for Treg cells maturation or the survival of mature Treg cells. In an attempt to determine which cellular processes are affected by the loss of VPS34, we performed proteomic profiling, and while the results could not provide a definite clue about the mechanism leading to the observed phenotype in mice with VPS34-deficient Treg cells, they suggested that loss of VPS34 induces a state of heightened metabolic activity in Treg cells. Autophagy is critical for the formation of memory CD8+ T cells, while it is dispensable during the effector phase. Since VPS34 is required for the induction of autophagy, it was striking to observe that deletion of VPS34 in activated CD8+ T cells did not result in a phenotype similar to mice with autophagy (ATG7)-deficient CD8+ T cells. Rather, mice with VPS34-deficient, activated CD8+ T cells displayed reduced proportions of antigen-specific CD8+ T cells and reduced effector functions at the peak of expansion after infection with Listeria monocytogenes, while memory formation seemed intact. Results from in vitro data suggested that while proliferation was intact, the transition through the cell cycle was impaired in VPS34-deficient, activated CD8+ T cells.This project has received funding from the European Union’s Horizon 2020 Research and Innovation programme under the Marie Skłodowska-Curie grant agreement No 675392

Design of a Bio-Inspired 3D Orientation Coordinate System and Application in Robotised Tele-Sonography

International audienc

Scientific Preparations for Lunar Exploration with the European Lunar Lander

This paper discusses the scientific objectives for the ESA Lunar Lander Mission, which emphasise human exploration preparatory science and introduces the model scientific payload considered as part of the on-going mission studies, in advance of a formal instrument selection.Comment: Accepted for Publication in Planetary and Space Science 51 pages, 8 figures, 1 tabl

Errores de medicación en pediatría

Concerns regarding patient safety affect healthcare, and medication errors are the most frequent category of medical errors and linked with severe consequences. This study discusses epidemiologic characteristics of medication errors in pediatric patients and points out prevention strategies. Approximately 8% of the studies on the subject of medication errors identified in different national and international databases are distinctively related to the pediatric population. Children are vulnerable to medication errors due to intrinsic factors, such as proper anatomic and physiological characteristics; and due to extrinsic factors, with emphasis on the lack of public health politics and changes in the pharmaceutical industry to attend children's needs. The available evidences indicate, as imperative, the implementation of strategies to prevent medication errors, contributing to promote patient safety.La seguridad del paciente es un problema de salud pública y los errores con medicamentos son los más frecuentes y más graves. Este artículo describe características epidemiológicas de errores de medicación en áreas de atención pediátrica y algunas estrategias de prevención. Aproximadamente 8% de las investigaciones sobre errores de medicación identificadas en las bases de datos nacionales e internacionales se refieren específicamente a niños. Los niños tienen mayor vulnerabilidad a la ocurrencia de errores debidos a factores intrínsecos, con destaque para características anatómicas y fisiológicas, e extrínsecos, en particular con respecto a falta de políticas sanitarias y de la industria farmacéutica orientada a la atención de tales características. Evidencias muestran la necesidad de aplicar estrategias para prevenir errores de medicación, promoviendo la seguridad del paciente.A segurança do paciente constitui problema de saúde pública, e erros com medicamentos são os mais freqüentes e graves. O artigo apresenta características epidemiológicas dos erros de medicação em diferentes áreas de atendimento pediátrico, e aponta estratégias de prevenção. Aproximadamente 8% das pesquisas sobre erros de medicação identificadas em bases de dados nacionais e internacionais referem-se à população pediátrica. Crianças apresentam maior vulnerabilidade à ocorrência de erros devido a fatores intrínsecos, destacando-se características anatômicas e fisiológicas; e extrínsecos, relativos à falta de políticas de saúde e da indústria farmacêutica voltadas ao atendimento de tais especificidades. As evidências apontam para a necessidade de implementação de estratégias de prevenção de erros de medicação, contribuindo para promover a segurança do paciente.Universidade Federal de São Paulo (UNIFESP) Departamento de EnfermagemUNIFESP, Depto. de EnfermagemSciEL

Different Modes of Retrovirus Restriction by Human APOBEC3A and APOBEC3G In Vivo

The apolipoprotein B editing complex 3 (A3) cytidine deaminases are among the most highly evolutionarily selected retroviral restriction factors, both in terms of gene copy number and sequence diversity. Primate genomes encode seven A3 genes, and while A3F and 3G are widely recognized as important in the restriction of HIV, the role of the other genes, particularly A3A, is not as clear. Indeed, since human cells can express multiple A3 genes, and because of the lack of an experimentally tractable model, it is difficult to dissect the individual contribution of each gene to virus restriction in vivo. To overcome this problem, we generated human A3A and A3G transgenic mice on a mouse A3 knockout background. Using these mice, we demonstrate that both A3A and A3G restrict infection by murine retroviruses but by different mechanisms: A3G was packaged into virions and caused extensive deamination of the retrovirus genomes while A3A was not packaged and instead restricted infection when expressed in target cells. Additionally, we show that a murine leukemia virus engineered to express HIV Vif overcame the A3G-mediated restriction, thereby creating a novel model for studying the interaction between these proteins. We have thus developed an in vivo system for understanding how human A3 proteins use different modes of restriction, as well as a means for testing therapies that disrupt HIV Vif-A3G interactions.United States. Public Health Service (Grant R01-AI-085015)United States. Public Health Service (Grant T32-CA115299 )United States. Public Health Service (Grant F32-AI100512

Integración de las ciencias básicas a través de las guías de trabajos prácticos en una currícula innovada

En medicina como en otras disciplinas, los modelos innovadores de educación han demostrado que la apropiación de la situación problemática por parte de los estudiantes mejora la práctica en la búsqueda del conocimiento para aplicarlo a situaciones concretas. Estas nuevas formas de aprendizaje rompen la secuencia de enseñar-aprender-aplicar para traer una nueva estrategia: frente a una situación confusa, aprender a buscar las claves para avanzar en la solución de los conflictos. Las  Guías de Trabajos Prácticos adoptadas en la Carrera de Medicina de la Universidad Nacional de La Matanza, traen algunos cambios respecto de las guías tradicionales para cumplir con este objetivo articulador entre ciencia básica – ciencia aplicada. Estos elementos son: mapas conceptuales (que funcionan como guía orientadora y establecen un circuito que el estudiante recorrerá en el aprendizaje de cada unidad, organizando el conocimiento de manera escalar, de lo más general a las particularidades), guía de preguntas o lectura dirigida (que trabajan también sobre conceptos generales profundizando el grado de complejidad en las mismas) y casos clínicos y ejercicios tomados por lo general de la práctica real y cotidiana. Habitualmente provenimos de un sistema educativo donde se nos enseñaba que el aprendizaje de los contenidos era esencial y primario y que de esta enseñanza se derivaba la posibilidad de aprender y aplicar lo aprendido en contextos de problema. En esta nueva forma de trabajo, los estudiantes emprenden el camino de la búsqueda de soluciones a medida para cada situación problemática, es decir, tomando lo que necesitan de las ciencias básicas. Para esto se diseñaron estas guías que permiten funcionar como tutores escritos, sin reemplazar la presencia del docente guía en el aula. Palabras clave: guías de trabajos prácticos; currícula integrada; innovación; articulación  básico; aplicado; mapa conceptual Integration of basic sciences through guides of practical work in a new curriculum This paper describes and analyzes the didactic use of Guides of Practical Work (including conceptual maps, reading guides and analysis of clinical cases) in Medicine Courses at the Universidad Nacional de La Matanza (Argentina). These Guides are conceived as “written tutors” performing a  didactic articulation between Basic and Applied Sciences, since they demand from the students an integral approach to a real life problematic situation given as an exercise. Keywords: practical work guide; basic and applied sciences; innovative curriculum; conceptual map

Lack of phosphatidylinositol 3-kinase VPS34 in regulatory T cells leads to a fatal lymphoproliferative disorder without affecting their development

Regulatory T (Treg) cells are essential for the maintenance of immunological tolerance, yet the molecular components required for their maintenance and effector functions remain incompletely defined. Inactivation of VPS34 in Treg cells led to an early, lethal phenotype, with massive effector T cell activation and inflammation, like mice lacking Treg cells completely. However, VPS34-deficient Treg cells developed normally, populated the peripheral lymphoid organs and effectively supressed conventional T cells in vitro. Our data suggest that VPS34 is required for the maintaining normal numbers of mature Treg. Functionally, we observed that lack of VPS34 activity impairs cargo processing upon transendocytosis, that defective autophagy may contribute to, but is not sufficient to explain this lethal phenotype, and that loss of VPS34 activity induces a state of heightened metabolic activity that may interfere with metabolic networks required for maintenance or suppressive functions of Treg cells