Screening the Pathogen Box for Identification of New Chemical Agents with Anti-Fasciola hepatica Activity

Fascioliasis is an infectious parasitic disease distributed globally and caused by the liver fluke Fasciola hepatica or F. gigantica. This neglected tropical disease affects both animals and humans, and it represents a latent public health problem due to the significant economic losses related to its effects on animal husbandry. For decades, triclabendazole has been the unique anti-Fasciola drug that can effectively treat this disease. However, triclabendazole resistance in fascioliasis has more recently been reported around the world, and thus, the discovery of novel drugs is an urgent need. The aim of this study was to investigate the fasciocidal properties of 400 compounds contained in the Pathogen Box. The first stage of the screening was carried out by measuring the fasciocidal activity on metacercariae at a concentration of 33 mu M each compound (the standard dose). Subsequently, the activities of the most active compounds (n = 33) at their 50% inhibitory concentration (IC50) values against metacercariae were assayed, and the results showed that 13 compounds had IC(50)s of 50%. Four hit compounds were selected on the basis of their predicted nontoxic properties, and the IC50 values obtained for adult worms were <10 mu M; thus, these compounds represented the best fasciocidal compounds tested here. A cytotoxicity assay on four types of cell lines demonstrated that three compounds were nontoxic at their most active concentration. In conclusion, three hit compounds identified in this proof-of-concept study are potential candidates in the discovery of new fasciocidal drugs. Further studies are warranted

Speculative Vectorization for Superscalar Processors

Traditional vector architectures have been shown to be very effective in executing regular codes in which the compiler can detect data-level parallelism, i.e. repeating the same computation over different elements in the same code-level data structure.A skilled programmer can easily create efficient vector code from regular applications. Unfortunately, this vectorization can be difficult if applications are not regular or if the programmer does not have an exact knowledge of the underlying architecture. The compiler has a partial knowledge of the program (i.e. it has a limited knowledge of the values of the variables). Because of this, it generates code that is safe for any possible scenario according to its knowledge, and thus, it may lose significant opportunities to exploit SIMD parallelism. In addition to this, we have the problem of legacy codes that have been compiled for former versions of the ISA with no SIMD extensions, which are therefore not able to exploit new SIMD extensions incorporated into newer ISA versions.In this dissertation, we will describe a mechanism that is able to detect and exploit DLP at runtime by speculatively creating vector instructions for prefetching and precomputing data for future instances of their scalar counterparts. This process will be called Speculative Dynamic Vectorization.A more in-depth study of this technique reveals a very positive characteristic: the mechanism can easily be tailored to alleviate the main drawbacks of current superscalar processors, particularly branch mispredictions and the memory gap. In this dissertation, we will describe how to rearrange the basic Speculative Dynamic Vectorization mechanism to alleviate the branch misprediction penalty based on reusing control-flow independent instructions. The memory gap problem will be addressed with a set of mechanisms that exploit the stall cycles due to L2 misses in order to virtually enlarge the instruction window.Finally, more refinements of the basic Speculative Dynamic Vectorization mechanism will be presented to improve its performance at a reasonable cost.Los procesadores vectoriales han demostrado ser muy eficientes ejecutando códigos regulares en los que el compilador ha detectado Paralelismo a Nivel de Datos. Este paralelismo consiste en repetir los mismos cálculos en diferentes elementos de la misma estructura de alto nivel.Un programador avanzado puede crear código vectorial eficiente para aplicaciones regulares. Por desgracia, esta vectorización puede llegar a ser compleja en aplicaciones regulares o si el programador no tiene suficiente conocimiento de la arquitectura sobre la que se va a ejecutar la aplicación.El compilador tiene un conocimiento parcial del programa. Debido a esto, genera código que se puede ejecutar sin problemas en cualquier escenario según su conocimiento y, por tanto, puede perder oportunidades de explotar el paralelismo SIMD (Single Instruction Multiple Data). Además, existe el problema de los códigos de legado que han sido compilados con versiones anteriores del juego de instrucciones que no disponían de instrucciones SIMD lo cual hace que no se pueda explotar las extensiones SIMD de las nuevas versiones de los juegos de instrucciones.En esta tesis se presentará un mecanismo capaz de detectar y explotar, en tiempo de ejecución, el paralelismo a nivel de datos mediante la creación especulativa de instrucciones vectoriales que prebusquen y precomputen valores para futuras instancias de instrucciones escalares. Este proceso se llamará Vectorización Dinámica Especulativa.Un estudio más profundo de esta técnica conducirá a una conclusión muy importante: este mecanismo puede ser fácilmente modificado para aliviar algunos de los problemas más importantes de los procesadores superescalares. Estos problemas son: los fallos de predicción de saltos y el gap entre procesador y memoria. En esta tesis describiremos como modificar el mecanismo básico de Vectorización Dinámica Especulativa para reducir la penalización de rendimiento producida por los fallos de predicción de saltos mediante el reuso de datos de instrucciones independientes de control. Además, se presentará un conjunto de técnicas que explotan los ciclos de bloqueo del procesador debidos a un fallo en la cache de segundo nivel mediante un agrandamiento virtual de la ventana de instrucciones. Esto reducirá la penalización del problema del gap entre procesador y memoria.Finalmente, se presentarán refinamientos del mecanismo básico de Vectorización Dinámica Especulativa enfocados a mejorar el rendimiento de éste a un bajo coste

Cambios en la composición de la captura y de la captura accesoria y en diversidad específica en una pesquería con nasas camaroneras semi-flotantes en tres ecosistemas insulares del Atlántico oriental sujetos a distinta presión antrópica

Composition and bycatch of semi-floating shrimp-trap fisheries (SSTF) were compared among areas with different levels of anthropogenic alteration of marine ecosystems. The three areas selected were Madeira, the Canary Islands and Cape Verde. Mean species richness and diversity of the SSTF did not show significant differences among areas. The dominant species in catches of the SSTF for all regions studied was the main target species, Plesionika edwardsii, which accounted for 96.0% of the catch in Cape Verde, 75.8% in Madeira and 59.1% in the Canary Islands. Targeted pandalid shrimps accounted for more than 96.8% of total catches for all areas combined. Numbers of non-target species caught were 18 (Madeira), 14 (Canary Islands) and 16 (Cape Verde), of which 13 (Madeira), 8 (Canary Islands) and 11 (Cape Verde) were always discarded. Bycatch accounted for 0.5% (Madeira), 0.7% (Canary Islands) and 3.1% (Cape Verde) in numbers. Shark species accounted for 0.11% of all individuals caught. A total of 5 species in Madeira, 6 in the Canary Islands and 4 in Cape Verde, accounting for 0.2% to 0.8% of total catches, were not landed due to the small size of individuals or low numbers of individuals caught (self-consumption). The present results suggest that the selectivity of traps for the main target species, P. edwardsii, in SSTF changes due to changes in species dominance, which are probably linked to the degree of human fishing exploitation of the marine ecosystems in each area.Se comparó la composición de las capturas y la captura accesoria de la pesquería de camarones con nasas semi-flotantes (SSTF) entre áreas con diferentes niveles de alteración de sus ecosistemas marinos por la acción humana. Se seleccionaron tres áreas: Madeira, Canarias y Cabo Verde. La riqueza de especies y la diversidad de la pesquería no mostraron diferencias significativas entre áreas. La especie dominante en las capturas de la SSTF fue la principal especie objetivo, Plesionika edwardsii, en las tres regiones estudiadas, variando desde 96.0% (Cabo Verde) hasta 59.1% (Canarias), con 75.8% en Madeira. Los camarones pandálidos objetivo de la pesca representaron más del 96.8% de la captura total en el conjunto de las tres áreas. El número de especies no-objetivo capturadas fue 18 (Madeira), 14 (Canarias) y 16 (Cabo Verde), de las cuales siempre fueron descartadas 13 especies en Madeira, 8 en Canarias y 11 en Cabo Verde. El porcentaje de individuos (en número) de las capturas accesorias en relación con las capturas totales representó el 0.5% en Madeira, 0.7% en Canarias y 3.1% en Cabo Verde. Las especies de tiburones representaron solo el 0.11% de los individuos capturados. Cinco especies en Madeira, seis en Canarias y cuatro en Cabo Verde representaron entre 0.2 y 0.8% del total de las capturas no desembarcadas debido a su pequeño tamaño o al bajo número de individuos capturados (auto consumo). Los resultados obtenidos sugieren que las nasas de la SSTF cambian sus características de selectividad con respecto a la especie objetivo principal, P. edwardsii, debido a cambios relativos entre las especies dominantes, lo que probablemente está relacionado con la explotación pesquera de los ecosistemas marinos en cada área

A new perspective on Copper Age technology, economy and settlement: grinding tools at the Valencina mega‑site

Activity patterns at large prehistoric sites are often difficult to interpret, as they frequently combine productive, domestic and funerary components. Valencina, the largest of the Copper Age mega-sites in Iberia, has proved particularly challenging in this regard. Macrolithic tool assemblages have been generally neglected in these debates but can provide specific insight into the nature and patterning of activities. In this study, 185 grinding tools from seven separate excavations across this 450 ha mega-site were subjected to multiple lines of analysis including quantification, morphology, raw material, use-wear and depositional context. A surprising feature of this assemblage is the high degree of fragmentation, with more than half of the items representing less than 25% of the original artefact and only a small minority of them (< 10%) complete. The absence of intact quernstones is particularly striking. The results indicate a ritualization of deposition at Valencina, and throw new light on the interpretation of this complex site. Furthermore, they emphasize the central role that grinding technology should play in future discussion of European prehistoric mega-sites

BACILOSCOPIA EN SINTOMÁTICOS RESPIRATORIOS EN UN CENTRO MATERNO INFANTIL EN LIMA, PERÚ

Se determino la incidencia, de tuberculosis pulmonar frotis positivo (TBP-FP) entre pacientes sintomático respiratorio (SR) en el Centro Materno Infantil ”Canto Grande” – Lima, Perú. Se analizaron muestras de esputo de 1263 pacientes SR mediante baciloscopia con la técnica de Ziehl-Neelsen, entre los meses de enero y junio del 2001. Se diagnosticaron 128 (10.1%) casos de TBP-FP, 69 (54.0%) fueron hombres y 59 (46.0%) mujeres; el grupo etáreo más afectado fue de 15 a 44 años con 109 (87.9%) casos. De los 128 casos de TBP-FP, 48 (37.5%) presentaron carga bacilar (+), 39 (30.5%) con carga bacilar (++) y 41 (32.0%) con carga bacilar (+++); 88 (68.8%) casos fueron positivos a la primera evaluación baciloscópica y 30 (23.4%) en la segunda evaluación. Se concluye que el diagnóstico de TBP-FP es independiente del género de los pacientes y la población económicamente activa es la más afectada. La obtención de la primera muestra de esputo en el momento en que se identifica al SR es fundamental para el diagnóstico. Estos resultados nos permite afirmar la confiabilidad de la técnica de baciloscopia utilizada en el presente estudio contribuyendo así a la epidemiología de la Tuberculosis en el Perú.Palabras clave: baciloscopia, sintomático respiratorio, tuberculosisbacilloscopy, respiratory symptomatic, tuberculosi

Trichomonas vaginalis Infection and Associated Risk Factors in a Socially-Marginalized Female Population in Coastal Peru

Objective. The epidemiology of Trichomonas vaginalis infection among sexually active socially-marginalized women in three urban, coastal Peruvian cities was examined in order to quantify the prevalence of trichomonas infection and identify associated risk factors. Methods. We conducted a cross-sectional, venue-based study of women from socially-marginalized populations in three coastal Peruvian cities. Results. Among the 319 women enrolled, the overall prevalence of trichomonal infection was 9.1% (95% CI, 5.9%–12.3%). The mean age was 26.3 years, and 35.5% reported having had unprotected intercourse with nonprimary partners and 19.8% reported two or more sex partners in the last three months. Trichomonal infection was associated with increased number of sex partners (PR 2.5, 95% CI 1.4–4.6) and unprotected sex with nonprimary partner in the last three months (PR 2.3, 95% CI 1.1–4.9). Conclusions. A moderately high prevalence of trichomonal infection was found among women in our study. Trichomonal infection was associated with unprotected sex and multiple sex partners. Efforts to control the continued spread of trichomonal infection are warranted