Molecular determinants of IBDV pathogenesis and modulation of the host innate response

Viruses are known to interact with the innate immune pathways and, in some cases, strains that differ in virulence are known to interact with these pathways in different ways. This thesis aimed to directly compare IBDV strains of differing virulence to determine key interactions with the innate immune response that may contribute to disease outcome. Infection of chicken B cells with the very virulent s UK661 strain, suppressed type I IFN responses compared to both infection with the cell-adapted IBDV strain, D78 in primary bursal cells, and infection with the classical strain, F52/70 in DT40 cells. Birds infected with UK661 also had down-regulated type I IFN and pro-inflammatory responses in the bursa of Fabricius (BF), compared to infection with F52/70. No difference in the peak virus titres was detected in the BF or spleen, although UK661 reached higher titres in the caecal tonsils than F52/70. Increased type I IFN production following F52/70 infection coincided with a reduced mortality in these birds, indicating a protective role of this immune response. The UK661 VP4 protein was found to suppress IFNβ production in vitro compared to the F52/70 VP4, which instead suppressed Mx1 production, indicating that the IBDV VP4 from different strains impairs either IFN production or signalling pathways. Upon knocking out the protease function of UK661 VP4, IFNβ production remained suppressed, and multiple amino acids are likely responsible for the different phenotype between strains. This work demonstrates that UK661 and F52/70 have strain-specific differences in their interactions with the innate immune response, mediated by the VP4 protein, therefore differences in this protein between strains may contribute to virulence. This information could be useful in the development of recombinant rationally designed live attenuated IBDV vaccines, by generating a vvIBDV backbone containing a VP4 from a classical or cell-adapted strain, as a vaccine candidate.Open Acces

Science Pipelines for the Square Kilometre Array

The Square Kilometre Array (SKA) will be both the largest radio telescope ever constructed and the largest Big Data project in the known Universe. The first phase of the project will generate on the order of 5 zettabytes of data per year. A critical task for the SKA will be its ability to process data for science, which will need to be conducted by science pipelines. Together with polarization data from the LOFAR Multifrequency Snapshot Sky Survey (MSSS), we have been developing a realistic SKA-like science pipeline that can handle the large data volumes generated by LOFAR at 150 MHz. The pipeline uses task-based parallelism to image, detect sources, and perform Faraday Tomography across the entire LOFAR sky. The project thereby provides a unique opportunity to contribute to the technological development of the SKA telescope, while simultaneously enabling cutting-edge scientific results. In this paper, we provide an update on current efforts to develop a science pipeline that can enable tight constraints on the magnetised large-scale structure of the Universe.Comment: Published in Galaxies, as part of a Special Issue on The Power of Faraday Tomograph

Effect of gain and phase errors on SKA1-low imaging quality from 50-600 MHz

Simulations of SKA1-low were performed to estimate the noise level in images produced by the telescope over a frequency range 50-600 MHz, which extends the 50-350 MHz range of the current baseline design. The root-mean-square (RMS) deviation between images produced by an ideal, error-free SKA1-low and those produced by SKA1-low with varying levels of uncorrelated gain and phase errors was simulated. The residual in-field and sidelobe noise levels were assessed. It was found that the RMS deviations decreased as the frequency increased. The residual sidelobe noise decreased by a factor of ~5 from 50 to 100 MHz, and continued to decrease at higher frequencies, attributable to wider strong sidelobes and brighter sources at lower frequencies. The thermal noise limit is found to range between ~10 - 0.3 $\mu$Jy and is reached after ~100-100 000 hrs integration, depending on observation frequency, with the shortest integration time required at ~100 MHz.Comment: 23 pages, 11 figures Typo correcte

The Effect of Foreground Mitigation Strategy on EoR Window Recovery

The removal of the Galactic and extragalactic foregrounds remains a major challenge for those wishing to make a detection of the Epoch of Reionization 21-cm signal. Multiple methods of modelling these foregrounds with varying levels of assumption have been trialled and shown promising recoveries on simulated data. Recently however there has been increased discussion of using the expected shape of the foregrounds in Fourier space to define an EoR window free of foreground contamination. By carrying out analysis within this window only, one can avoid the foregrounds and any statistical bias they might introduce by instead removing these foregrounds. In this paper we discuss the advantages and disadvantages of both foreground removal and foreground avoidance. We create a series of simulations with noise levels in line with both current and future experiments and compare the recovered statistical cosmological signal from foreground avoidance and a simplified, frequency independent foreground removal model. We find that while, for current generation experiments, foreground avoidance enables a better recovery at $k_{perp} > 0.6 \mathrm{Mpc}^{-1}$, foreground removal is able to recover significantly more signal at small $k_{los}$ for both current and future experiments. We also relax the assumption that the foregrounds are smooth by introducing a Gaussian random factor along the line-of-sight and then also spatially. We find that both methods perform well for foreground models with line-of-sight and spatial variations around $0.1\%$ however at levels larger than this foregrounds removal shows a greater signal recovery.Comment: 14 pages, 10 figures, accepted by MNRA

Genetic characterisation and phylogenetic analysis of bovine astroviruses and kobuviruses

Calf diarrhoea remains the most important cause of economic loss to both dairy and beef cattle industries worldwide, with approximately 50% of deaths among weaning calves resulting from diarrhoeal disease. Complex etiopathogenesis involving the infection of one or multiple pathogens, as well as other non-infectious factors such as the environment and nutrition, contributes to its devastating effects. Astroviruses (AstVs) and Kobuviruses (KoVs) are two single-stranded, positive-sense RNA viruses previously detected in healthy and diarrhoeic calves. AstV was identified in healthy and diarrhoeic calves in similar proportions, while KoV was predominantly associated with diarrhoeic individuals. In order to investigate the KoV strains found in diarrhoeic calves, the full genome of KoV from a diarrhoeic calf was sequenced. This KoV was then compared with the bovine U-1, porcine KoV and Aichi virus strains. Specifically-designed PCRs were used to target the full KoV genome of positive samples, and amplicons were cloned to allow the internal sequencing of one single KoV detected among possible mixed infections. Upon assembly of the genome sequences, some animals were found to be co-infected with multiple KoVs. The main region of diversity, the VP1 (capsid) region, was amplified from multiple samples to determine the diversity of KoV in Scotland. The genome sequenced in this study will be used to produce an infectious clone for future challenge studies to establish the potential role of bovine KoV in calf diarrhoea. Another aspect of the study was to explore the diversity and epidemiology of AstV in diarrhoeic and healthy calves by capsid gene analysis. As the AstV capsid protein is the major target of host antibody production, a serological test for AstV infection could then be developed. Following amplification of AstV capsid genes by PCR, phylogenetic analysis identified 4 lineages from which capsids from 2 of these lineages were successfully cloned ready for use in the baculovirus expression system. This information and the expression plasmids containing representative AstV capsid genes can then be used to develop serological tests for AstV, enabling estimation of the prevalence of AstV in the British cattle population

The magnetic field and geometry of the oblique shock in the jet of 3C 346

We investigate the brightest regions of the kpc-scale jet in the powerful radio galaxy 3C 346, using new optical HST ACS/F606W polarimetry together with Chandra X-ray data and 14.9 GHz and 22.5 GHz VLA radio polarimetry. The jet shows a close correspondence in optical and radio morphology, while the X-ray emission shows an 0.80 +/- 0.17 kpc offset from the optical and radio peak positions. Optical and radio polarimetry show the same apparent magnetic field position angle and fractional polarization at the brightest knot, where the jet undergoes a large kink of almost 70 degrees in the optical and radio images. The apparent field direction here is well-aligned with the new jet direction, as predicted by earlier work that suggested the kink was the result of an oblique shock. We have explored models of the polarization from oblique shocks to understand the geometry of the 3C 346 jet, and find that the upstream flow is likely to be highly relativistic (0.91 +0.05 / -0.07 c), where the plane of the shock front is inclined at an angle of 51 (+/- 11) degrees to the upstream flow which is at an angle 14 (+8 / -7) degrees to our line of sight. The actual deflection angle of the jet in this case is only 22 degrees.Comment: 11 pages, 5 figures. Accepted by MNRA

Sistema de Control Interno de la empresa “Lácteos Arasan” ubicada en la Comarca Llano Grande, Municipio de San Francisco de Cuapa, en el II semestre del 2015

El presente trabajo investigativo aborda aspectos generales de la empresa “Lácteos Arasan”, conceptos básicos, clasificación, importancia de los procesos de operación, políticas y el control interno en las empresas. Planteamiento del problema. Esta empresa es familiar se trabaja de manera imprevista solucionando problemas conforme se presentan, no cuenta con profesionales que oriente como debe de llevarse el funcionamiento dentro de esta, pues se tiene trabajando a familiares que tienen poco conocimiento en el manejo de la empresa; además por la confianza que representa ser parte de la familia, se omiten evaluaciones siendo que de manera intencional o no se puede caer en fraudes o irregularidades. Antecedentes Serrano & González (2011) “Diagnostico empresarial en la empresa Lácteos Las tucas, San Pedro de Lóvago, Chontales”. Se concluyó que la empresa no tenía redactada ni plasmada la misión, visión y objetivos de su negocio, lo cual la hace ser débil, debido a que sus trabajadores no saben identificarse en la empresa que laboran. Carrillo & Hurtado (2011-2013) “Diagnóstico a la empresa Lácteos La Esperanzas”. En este trabajo se concluyó que la empresa traza metas, pero no tiene formalizado el concepto de objetivos estratégicos, todo lo hace de manera informal. Justificación. El tema de investigación se consideró debido a que es indispensable para las empresas de este sector económico, un buen control interno hace posible que una empresa realice sus operaciones de manera eficiente y eficaz y poder llevar a cabo un adecuado control de su gestión, uso correcto de sus recursos humanos, financiero, tecnológico y material. El tema en estudio beneficiara principalmente a la empresa “Lácteos Arasan” puesto que necesita controlar y realizar sus operaciones de manera eficiente. Objetivo General. Determinar el sistema de control interno aplicado en la empresa “Lácteos Arasan” en la Comarca Llano Grande, Municipio de San Francisco de Cuapa, en el II semestre del año 2015. Objetivos Específicos. 1. Describir los procesos de operación de la empresa “Lácteos Arasan”. 2. Identificar los controles internos que se implementan en la empresa “Lácteos Arasan”. 3. Señalar las políticas y normativas que se aplican en la empresa “Lácteos Arasan”. 4. Proponer un sistema de control interno en la empresa Lácteos Arasan con la finalidad de que las actividades sean realizadas con mayor eficiencia y eficacia. Marco Teórico. 1. Aspectos generales del Municipio de San Francisco de Cuapa. 2. Aspectos Generales de “Lácteos Arasan”. 3. Conceptos básicos de los procesos de operación. 4. Definiciones de control interno, clasificación, componentes y métodos. 5. Políticas y normativas en una empresa. Diseño Metodológico. -Según el periodo de tiempo: Corte transversal, puesto que se recoge información en oportunidad única, se recolectan y analizan datos en un período de tiempo determinado. -Según la Profundidad u objeto: Descriptiva, trabaja sobre realidades de hecho y su característica fundamental es la de presentar una interpretación correcta. -Según la finalidad. De campo se apoya en información que provienen de entrevistas, la auxilia y mejora la información documental. -Según Carácter de la medida: Cualitativa, se centra principalmente en aspectos observables y analíticos. -Población: 10 -Instrumento: Entrevista Conclusiones. 1. La empresa elabora planes de trabajo, aunque no existe formalmente definido un departamento de planificación. 2. La mayoría de los empleados conoce la misión, visión, objetivos, valores y el organigrama de la empresa, sin embargo, estos están desactualizados. 3. No existe un sistema de control interno aplicado formalmente a la empresa, sin embargo, si hay presencia de algunos controles tanto financieros como administrativos, pero estos se mantienen desactualizados. 4. La empresa no posee políticas a lo interno, como empresa no se logra saber qué dirección tomar en caso de que exista cualquier tipo de conflicto con alguno de los agentes que les rodean (proveedores, clientes, trabajadores); sin embargo, hay normativas y leyes por los que externamente son regidos y por las cuales tratan de guiarse. Recomendaciones 1. Aperturar un área de planificación, para que sean diseñados planes más efectivos. 2. Diseñar un sistema de control de costos el cual incluye el desarrollo de modelos, normas y procedimientos adecuados para suministrar la información relacionada con los costos de producción de la empresa. 3. Elaborar manuales de funciones y procedimientos donde se definan todas las normas, sistemas, instrucciones las cuales deben de apegarse los trabajadores; estos manuales deben de ser elaborados de manera clara precisa y concreta. 4. políticas de venta, mercadeo, crédito, selección de personal, y políticas de uso de los activos fijos reflejarlas por escrito, ya sea en manuales, instrucciones o comunicaciones internas

Cosmic Dawn and Epoch of Reionization Foreground Removal with the SKA

The exceptional sensitivity of the SKA will allow observations of the Cosmic Dawn and Epoch of Reionization (CD/EoR) in unprecedented detail, both spectrally and spatially. This wealth of information is buried under Galactic and extragalactic foregrounds, which must be removed accurately and precisely in order to reveal the cosmological signal. This problem has been addressed already for the previous generation of radio telescopes, but the application to SKA is different in many aspects. In this chapter we summarise the contributions to the field of foreground removal in the context of high redshift and high sensitivity 21-cm measurements. We use a state-of-the-art simulation of the SKA Phase 1 observations complete with cosmological signal, foregrounds and frequency-dependent instrumental effects to test both parametric and non-parametric foreground removal methods. We compare the recovered cosmological signal using several different statistics and explore one of the most exciting possibilities with the SKA --- imaging of the ionized bubbles. We find that with current methods it is possible to remove the foregrounds with great accuracy and to get impressive power spectra and images of the cosmological signal. The frequency-dependent PSF of the instrument complicates this recovery, so we resort to splitting the observation bandwidth into smaller segments, each of a common resolution. If the foregrounds are allowed a random variation from the smooth power law along the line of sight, methods exploiting the smoothness of foregrounds or a parametrization of their behaviour are challenged much more than non-parametric ones. However, we show that correction techniques can be implemented to restore the performances of parametric approaches, as long as the first-order approximation of a power law stands.Comment: Accepted for publication in the SKA Science Book 'Advancing Astrophysics with the Square Kilometre Array', to appear in 201

A GPU-based survey for millisecond radio transients using ARTEMIS

Astrophysical radio transients are excellent probes of extreme physical processes originating from compact sources within our Galaxy and beyond. Radio frequency signals emitted from these objects provide a means to study the intervening medium through which they travel. Next generation radio telescopes are designed to explore the vast unexplored parameter space of high time resolution astronomy, but require High Performance Computing (HPC) solutions to process the enormous volumes of data that are produced by these telescopes. We have developed a combined software /hardware solution (code named ARTEMIS) for real-time searches for millisecond radio transients, which uses GPU technology to remove interstellar dispersion and detect millisecond radio bursts from astronomical sources in real-time. Here we present an introduction to ARTEMIS. We give a brief overview of the software pipeline, then focus specifically on the intricacies of performing incoherent de-dispersion. We present results from two brute-force algorithms. The first is a GPU based algorithm, designed to exploit the L1 cache of the NVIDIA Fermi GPU. Our second algorithm is CPU based and exploits the new AVX units in Intel Sandy Bridge CPUs.Comment: 4 pages, 7 figures. To appear in the proceedings of ADASS XXI, ed. P.Ballester and D.Egret, ASP Conf. Se

The structure of the jet in 3C 15 from multi-band polarimetry

We investigate the structure of the kpc-scale jet in the nearby (z = 0.073) radio galaxy 3C 15, using new optical Hubble Space Telescope (HST) ACS/F606W polarimetry together with archival multi-band HST imaging, Chandra X-ray data and 8.4 GHz VLA radio polarimetry. The new data confirm that synchrotron radiation dominates in the optical. With matched beams, the jet is generally narrower in the optical than in the radio, suggesting a stratified flow. We examine a simple two-component model comprising a highly relativistic spine and lower-velocity sheath. This configuration is broadly consistent with polarization angle differences seen in the optical and radio data. The base of the jet is relatively brighter in the ultraviolet and X-ray than at lower energies, and the radio and optical polarization angles vary significantly as the jet brightens downstream. Further out, the X-ray intensity rises again and the apparent magnetic field becomes simpler, indicating a strong shock. Modelling the synchrotron spectrum of this brightest X-ray knot provides an estimate of its minimum internal pressure, and a comparison with the thermal pressure from X-ray emitting gas shows that the knot is overpressured and likely to be a temporary, expanding feature.Comment: 12 pages, 7 figures, accepted by MNRA