SLC19A1 transports immunoreactive cyclic dinucleotides.

The accumulation of DNA in the cytosol serves as a key immunostimulatory signal associated with infections, cancer and genomic damage1,2. Cytosolic DNA triggers immune responses by activating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway3. The binding of DNA to cGAS activates its enzymatic activity, leading to the synthesis of a second messenger, cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP)4-7. This cyclic dinucleotide (CDN) activates STING8, which in turn activates the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), promoting the transcription of genes encoding type I interferons and other cytokines and mediators that stimulate a broader immune response. Exogenous 2'3'-cGAMP produced by malignant cells9 and other CDNs, including those produced by bacteria10-12 and synthetic CDNs used in cancer immunotherapy13,14, must traverse the cell membrane to activate STING in target cells. How these charged CDNs pass through the lipid bilayer is unknown. Here we used a genome-wide CRISPR-interference screen to identify the reduced folate carrier SLC19A1, a folate-organic phosphate antiporter, as the major transporter of CDNs. Depleting SLC19A1 in human cells inhibits CDN uptake and functional responses, and overexpressing SLC19A1 increases both uptake and functional responses. In human cell lines and primary cells ex vivo, CDN uptake is inhibited by folates as well as two medications approved for treatment of inflammatory diseases, sulfasalazine and the antifolate methotrexate. The identification of SLC19A1 as the major transporter of CDNs into cells has implications for the immunotherapeutic treatment of cancer13, host responsiveness to CDN-producing pathogenic microorganisms11 and-potentially-for some inflammatory diseases

The Classification of Periodic Light Curves from non-survey optimized observational data through Automated Extraction of Phase-based Visual Features

We implement two hidden-layer feedforward networks to classify 3011 variable star light curves. These light curves are generated from a reduction of non-survey optimized observational images gathered by wide-field cameras mounted on the Liverpool Telescope. We extract 16 features found to be highly informative in previous studies but achieve only 19.82% accuracy on a 30% test set, 5.56% above a random model. Noise and sampling defects present in these light curves poison these features primarily by reducing our Periodogram period match rate to fewer than 5%. We propose using an automated visual feature extraction technique by transforming the phase-folded light curves into image based representations. This eliminates much of the noise and the missing phase data, due to sampling defects, should have a less destructive effect on these shape features as they still remain at least partially present. We produced a set of scaled images with pixels turned either on or off based on a threshold of data points in each pixel defined as at minimum one fifth of those of the most populated pixel for each light curve. Training on the same feedforward network, we achieve 29.13% accuracy, a 13.16% improvement over a random model and we also show this technique scales with an improvement to 33.51% accuracy by increasing the number of hidden layer neurons. We concede that this improvement is not yet sufficient to allow these light curves to be used for automated classification and in conclusion we discuss a new pipeline currently being developed that simultaneously incorporates period estimation and classification. This method is inspired by approximating the manual methods employed by astronomers

GRAPE: Genetic Routine for Astronomical Period Estimation

Period estimation is an important task in the classification of many variable astrophysical objects. Here we present GRAPE: A Genetic Routine for Astronomical Period Estimation, a genetic algorithm optimised for the processing of survey data with spurious and aliased artefacts. It uses a Bayesian Generalised Lomb-Scargle (BGLS) fitness function designed for use with the Skycam survey conducted at the Liverpool Telescope. We construct a set of simulated light curves using both regular survey cadence and the unique Skycam variable cadence with four types of signal: sinusoidal, sawtooth, symmetric eclipsing binary and eccentric eclipsing binary. We apply GRAPE and a frequency spectrum BGLS periodogram to the light curves and show that the performance of GRAPE is superior to the frequency spectrum for any signal well modelled by the fitness function. This is due to treating the parameter space as a continuous variable.We also show that the Skycam sampling is sufficient to correctly estimate the period of over 90% of the sinusoidal shape light curves relative to the more standard regular cadence.We note that GRAPE has a computational overhead which makes it slower on light curves with low numbers of observations and faster with higher numbers of observations and discuss the potential optimisations used to speedup the runtime. Finally, we analyse the period dependence and baseline importance of the performance of both methods and propose improvements which will extend this method to the detection of quasi-periodic signals

The Diagnostic Potential of Transition Region Lines under-going Transient Ionization in Dynamic Events

We discuss the diagnostic potential of high cadence ultraviolet spectral data when transient ionization is considered. For this we use high cadence UV spectra taken during the impulsive phase of a solar flares (observed with instruments on-board the Solar Maximum Mission) which showed excellent correspondence with hard X-ray pulses. The ionization fraction of the transition region ion O V and in particular the contribution function for the O V 1371A line are computed within the Atomic Data and Analysis Structure, which is a collection of fundamental and derived atomic data and codes which manipulate them. Due to transient ionization, the O V 1371A line is enhanced in the first fraction of a second with the peak in the line contribution function occurring initially at a higher electron temperature than in ionization equilibrium. The rise time and enhancement factor depend mostly on the electron density. The fractional increase in the O V 1371A emissivity due to transient ionization can reach a factor of 2--4 and can explain the fast response in the line flux of transition regions ions during the impulsive phase of flares solely as a result of transient ionization. This technique can be used to diagnostic the electron temperature and density of solar flares observed with the forth-coming Interface Region Imaging Spectrograph.Comment: 18 pages, 6 figure

A Dynamic, Modular Intelligent-Agent framework for Astronomical Light Curve Analysis and Classification

Modern time-domain astronomy is capable of collecting a staggeringly large amount of data on millions of objects in real time. This makes it almost impossible for objects to be identified manually. Therefore the production of methods and systems for the automated classification of time-domain astro-nomical objects is of great importance. The Liverpool Telescope has a number of wide-field image gathering instruments mounted upon its structure. These in-struments have been in operation since March 2009 gathering data of multi-degree sized areas of sky around the current field of view of the main telescope. Utilizing a Structured Query Language database established by a pre-processing operation upon the resultant images, which has identified millions of candidate variable stars with multiple time-varying magnitude observations, we applied a method designed to extract time-translation invariant features from the time-series light curves of each object for future input into a classification system. These efforts were met with limited success due to noise and uneven sampling within the time-series data. Additionally, finely surveying these light curves is a processing intensive task. Fortunately, these algorithms are capable of multi-threaded implementations based on available resources. Therefore we propose a new system designed to utilize multiple intelligent agents that distribute the data analysis across multiple machines whilst simultaneously a powerful intelligence service operates to constrain the light curves and eliminate false signals due to noise and local alias periods. This system will be highly scalable, capable of operating on a wide range of hardware whilst maintaining the production of ac-curate features based on the fitting of harmonic models to the light curves within the initial Structural Query Language database

Ionization state, excited populations and emission of impurities in dynamic finite density plasmas: I. The generalized collisional-radiative model for light elements

The paper presents an integrated view of the population structure and its role in establishing the ionization state of light elements in dynamic, finite density, laboratory and astrophysical plasmas. There are four main issues, the generalized collisional-radiative picture for metastables in dynamic plasmas with Maxwellian free electrons and its particularizing to light elements, the methods of bundling and projection for manipulating the population equations, the systematic production/use of state selective fundamental collision data in the metastable resolved picture to all levels for collisonal-radiative modelling and the delivery of appropriate derived coefficients for experiment analysis. The ions of carbon, oxygen and neon are used in illustration. The practical implementation of the methods described here is part of the ADAS Project

A new layout optimization technique for interferometric arrays, applied to the MWA

Antenna layout is an important design consideration for radio interferometers because it determines the quality of the snapshot point spread function (PSF, or array beam). This is particularly true for experiments targeting the 21 cm Epoch of Reionization signal as the quality of the foreground subtraction depends directly on the spatial dynamic range and thus the smoothness of the baseline distribution. Nearly all sites have constraints on where antennas can be placed---even at the remote Australian location of the MWA (Murchison Widefield Array) there are rock outcrops, flood zones, heritages areas, emergency runways and trees. These exclusion areas can introduce spatial structure into the baseline distribution that enhance the PSF sidelobes and reduce the angular dynamic range. In this paper we present a new method of constrained antenna placement that reduces the spatial structure in the baseline distribution. This method not only outperforms random placement algorithms that avoid exclusion zones, but surprisingly outperforms random placement algorithms without constraints to provide what we believe are the smoothest constrained baseline distributions developed to date. We use our new algorithm to determine antenna placements for the originally planned MWA, and present the antenna locations, baseline distribution, and snapshot PSF for this array choice.Comment: 12 pages, 6 figures, 1 table. Accepted for publication in MNRA

WSClean : an implementation of a fast, generic wide-field imager for radio astronomy

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2014 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.Astronomical widefield imaging of interferometric radio data is computationally expensive, especially for the large data volumes created by modern non-coplanar many-element arrays. We present a new widefield interferometric imager that uses the w-stacking algorithm and can make use of the w-snapshot algorithm. The performance dependencies of CASA's w-projection and our new imager are analysed and analytical functions are derived that describe the required computing cost for both imagers. On data from the Murchison Widefield Array, we find our new method to be an order of magnitude faster than w-projection, as well as being capable of full-sky imaging at full resolution and with correct polarisation correction. We predict the computing costs for several other arrays and estimate that our imager is a factor of 2-12 faster, depending on the array configuration. We estimate the computing cost for imaging the low-frequency Square-Kilometre Array observations to be 60 PetaFLOPS with current techniques. We find that combining w-stacking with the w-snapshot algorithm does not significantly improve computing requirements over pure w-stacking. The source code of our new imager is publicly released.Peer reviewedFinal Published versio

ADAS analysis of the differential emission measure structure of the inner solar corona. II. A study of the `quiet Sun' inhomogeneities from SOHO CDS-NIS spectra

We present a study of the differential emission measure (DEM) of a `quiet Sun' area observed in the extreme ultraviolet at normal incidence by the Coronal Diagnostic Spectrometer (CDS) on the SOHO spacecraft. The data used for this work were taken using the NISAT_S observing sequence. This takes the full wavelength ranges from both the NIS channels (308-381 Angtr. and 513-633 Angst.) with the 2 arcsec by 240 arcsec slit, which is the narrowest slit available, yielding the best spectral resolution. In this work we contrast the DEM from subregions of 2 by 80 arcsec$^2$ with that obtained from the mean spectrum of the whole raster (20 by 240 arcsec$^2$). We find that the DEM maintains essentially the same shape in the subregions, differing by a constant factor between 0.5 and 2 from the mean DEM, except in areas were the electron density is below $2 \times 10^7$ cm$^{-3}$ and downflow velocities of 50 km/s are found in the transition region. Such areas are likely to contain plasma departing from ionisation equilibrium, violating the basic assumptions underlying the DEM method. The comparison between lines of Li-like and Be-like ions may provide further evidence of departure from ionisation equilibrium. We find also that line intensities tend to be lower where velocities of the order of 30 km/s or higher are measured in transition region lines. The DEM analysis is also exploited to improve the line identification performed by Brooks et al (1999) and to investigate possible elemental abundance variations from region to region. We find that the plasma has composition close to photospheric in all the subregions examined.Comment: 18 pages, 9 figures, 7 tables. Table 5 is available only online. A copy of Table 5 can be found at http://webusers.ct.astro.it/acl/table5.dat. The ReadMe file is at http://webusers.ct.astro.it/acl/ReadMe. Accepted by Astronomy and Astrophysic