The use of insect cells to identify potent and selective inhibitors of the replication of the Dengue and Chikungunya viruses and unravel their molecular mechanism of action

Dengue and Chikungunya viruses cause the most important arthropod-borne viral infections for humans. These viruses are predominant in tropical and subtropical regions. In addition, these viruses are predominant in tropical and subtropical regions. Dengue mortality rate is around 1.2 to 3.5% and deaths due to chikungunya fever are around 1 in 1000; however, half of chikungunya-infected patients evolve into a chronic state that can persist for months up to years. There are no antiviral drugs available for DENV and CHIKV treatment and prevention. Moreover, vector control strategies have failed so far. Thus, the development of potent inhibitors for a broad spectrum of RNA viruses is urgently needed. We established and characterized a new embryonic insect cell line from Culex quinquefasciatus mosquito. Also we established the flaviviruses and alphavirus replication, both in C6/36 and Lulo insect cell lines, as well as in Vero cell line. In addition we carried out a reference compound library and reference panel of assays and data for DENV, which provides a benchmark for further studies. During this study, a panel of 9 antiviral molecules, with proven in vitro anti-dengue virus activity and that act at different stages of the DENV life cycle, was selected. Finally, Favipiravir or T-705, was identified as inhibitor in vitro and in vivo of alphaviruses and the mutation K291R in nsP4, which is responsible of the polymerase activity, was found as the mode of action in CHIKV. Interestingly, lysine in motif F1 is also highly conserved in positive-stranded RNA viruses and this might explain the broad spectrum of T-705 antiviral activity.

Sounds.

Diseñado para padres y cuidadores de niños en edad preescolar que buscan una forma sencilla de ayudarlos a desarrollar su aprendizaje a partir de los sonidos. También ofrece explicaciones y notas de los beneficios derivados de estas actividades.

Short vowel sounds.

Está indicado para los niños que están aprendiendo fonética. Se trata de hacer coincidir la letra de la solapa con el sonido vocal medio de la palabra, y de que aprendan a distinguir este mismo sonido pronunciando los profesores muy despacio las palabras, o mediante, la alternancia de consonante/vocal/consonante en la palabra. Los conocimientos y habilidades fónicos se pueden desarrollar con toda la clase, en grupos, o individualmente.

Initial letter sounds.

Está indicado para los niños que están empezando a aprender fonética. Se trata de hacer coincidir la letra de la solapa con el sonido que le corresponde y, de oír el sonido inicial de cada palabra. Los conocimientos y habilidades fónicos se pueden desarrollar con toda la clase, en grupos, o individualmente. También hay más actividades, así como una guía de pronunciación al final del libro.

End sounds.

Indicado para los niños que están aprendiendo fonética y ya pueden entender el sonido inicial de las palabras. Se trata de distinguir qué letra o letras de la solapa coinciden con un sonido, y,ayudar a los alumnos a que escuchen con atención los sonidos finales de cada palabra. Los conocimientos y habilidades fónicos se pueden desarrollar con toda la clase, en grupo, o individualmente.

Sounds poems.

Esta selección de poesía se ha elegido para que coincida con temas de interés para el grupo de edad: sonidos. Aunque los poemas son completamente independientes de otras historias, pueden ser introducidos junto con libros de cuentos. Destinado a escuelas infantiles, puede utilizarse para el trabajo curricular transversal, así como para la enseñanza de la lectura y el disfrute de la poesía, ritmo y rima. Desarrolla en los niños habilidades fonológicas y el conocimiento de la rima y los introduce en la poesía desde las primeras etapas de la lectura. Ofrece orientación para hablar y escuchar, con especial atención a la lectura en voz alta.

Jungle sounds.

Una pantera, un hipopótamo, un cocodrilo, un oso, un tigre y una serpiente emiten unos sonidos como feroces criaturas de la jungla provocados por pequeños animales, del tipo de: un mono, un gato, un pato, unos ratones.

Letters, sounds, and rhymes. Photocopy masters book 2 : stages 4-9.

Ayuda a desarrollar en los niños las habilidades para la lectura y la ortografía, a conocer los fonemas vocales y a distinguir entre fonema y grafema. Todo esto con el apoyo fónico de las historias, de esta misma serie, contadas para las etapas escolares de la cuatro a la seis y de la siete a la nueve. Cumple con los requisitos del plan de estudios del Reino Unido, y, en particular, con la Estrategia nacional de alfabetización (National Literacy Strategy).

Letters, sounds, and rhymes from starter stage. Teacher's guide.

Comprende una serie de materiales que satisfacen las demandas de aprendizaje de lectura y escritura de los niños dentro de un plan de estudios diseñados además conforme a unos principios: textos estructurados, de agradable y enriquecedora lectura. Para ello, tiene textos de ficción y no ficción, para edades de 4 a 7 años y, que pueden ser utilizados para la lectura compartida, para trabajo en grupo y para lectura independiente.

Sounds like a good idea : using audio technology in the classroom.

La generación actual de estudiantes está familiarizada con medios tecnológicos del tipo: MP3, podcasts, descargas, redes sociales, teléfonos móviles, etc, por ello, el autor del texto considera que el profesorado debe conocer la tecnología audio y su uso para la enseñanza en clase. Así, a los docentes se les proporcionan consejos prácticos para la grabación, edición y mezcla de audio, sobre la elección de equipos, y se les muestra, también, que es un medio para involucrar a los alumnos, de primaria y de secundaria, en el aprendizaje y, también, para el desarrollo de otras habilidades necesarias para su vida fuera de la escuela.

Elizabeth Bishop’s sounds of sanity

In this article, I examine the implications of rewriting definitions of sanity and insanity through the use of noise, silence, and language,positioningElizabeth Bishop’s short story “In the Village” as a form of resistance against traditional readings of madness, logocentrism, and identity. I suggest that by writing her characters as undivided from the world of sound, Elizabeth Bishop’s story shifts understandings of insanity, which is often conceptualized through denials of agency, allowing her characters to escape in noises and hesitations in language and communication. “In the Village” avoids silencing the “insane” mother through her placement in a caesura of sound and silence. This article avoids a biographical reading of “In the Village,” which is often connected with her own mother’s “mental breakdown,” because Bishop’s writing would have been as much affected by her conscious awareness of her past as it was by the unconscious impulses and histories of writing in the West. Rather, I take into account Bishop’s own personal history as well as the repetitions that reflect a placement in a tradition appearing in the story itself. Using this particular lens, I believe a rereading of “In the Village” is in order, where the “mad mother” is not silenced by the oppressive social structures that control the insane,” but she instead finds escape in the multitudes of sounds that associate with her, erasing the power of language and opening a new world where agency exists in a scream or in a striking hammer.

Dichotic identification of complex sounds

This paper is a study of speech perception and related variables to better understand the psychoacoustics of speech.

Conditioning the chinchilla to novel sounds

This paper is a review of a study on chinchillas to test discrimination of sounds and related factors such as novelty, habituation and same-different discrimination.

The biometeorology of high-altitude insect layers.

Flight at high altitude is part of a migration strategy that maximises insect population displacement. This thesis represents the first substantial analysis of insect migration and layering in Europe. Vertical-looking entomological radar has revealed specific characteristics of high-altitude flight: in particular layering (where a large proportion of the migrating insects are concentrated in a narrow altitude band). The meteorological mechanisms underpinning the formation of these layers are the focus of this thesis. Aerial netting samples and radar data revealed four distinct periods of high-altitude insect migration: dawn, daytime, dusk, and night-time. The most frequently observed nocturnal profiles during the summertime were layers. It is hypothesised that nocturnal layers initiate at a critical altitude (200–500 m above ground level) and time (20:00–22:00 hours UTC). Case study analysis, statistical analysis, and a Lagrangian trajectory model showed that nocturnal insect layers probably result from the insects’ response to meteorological conditions. Temperature was the variable most correlated with nocturnal insect layer presence and intensity because insects are poikilothermic, and temperatures experienced during high-altitude migration in temperate climates are expected to be marginal for many insects’ flight. Hierarchical effects were detected such that other variables—specifically wind speed—were only correlated with insect layer presence and intensity once temperatures were warm. The trajectory model developed comprised: (i) insect flight characteristics; (ii) turbulent winds (which cause vertical spread of the layer); and (iii) mean wind speed, which normally leads to horizontal displacements of hundreds of kilometres in a single migratory flight. This thesis has revealed that there is considerable migratory activity over the UK in the summer months, and a range of fascinating phenomena can be observed (including layers). The UK has moved from one of the least studied to perhaps the best studied environments of aerial insect migration and layering in the world.

Layers of nocturnal insect migrants at high-altitude: the influence of atmospheric conditions on their formation

1 Radar studies of nocturnal insect migration have often found that the migrants tend to form well-defined horizontal layers at a particular altitude. 2 In previous short-term studies, nocturnal layers were usually observed to occur at the same altitude as certain meteorological features, most notably at the altitudes of temperature inversions or nocturnal wind jets. 3 Statistical analyses are presented of four years’ data that compared the presence, sharpness and duration of nocturnal layer profiles (observed using continuously-operating entomological radar) with meteorological variables at typical layer altitudes over the UK. 4 Analysis of these large datasets demonstrated that temperature was the foremost meteorological factor persistently associated with the presence and formation of longer-lasting and sharper layers of migrating insects over southern UK.