Computational KIR copy number discovery reveals interaction between inhibitory receptor burden and survival.

Natural killer (NK) cells have increasingly become a target of interest for immunotherapies. NK cells express killer immunoglobulin-like receptors (KIRs), which play a vital role in immune response to tumors by detecting cellular abnormalities. The genomic region encoding the 16 KIR genes displays high polymorphic variability in human populations, making it difficult to resolve individual genotypes based on next generation sequencing data. As a result, the impact of polymorphic KIR variation on cancer phenotypes has been understudied. Currently, labor-intensive, experimental techniques are used to determine an individual's KIR gene copy number profile. Here, we develop an algorithm to determine the germline copy number of KIR genes from whole exome sequencing data and apply it to a cohort of nearly 5000 cancer patients. We use a k-mer based approach to capture sequences unique to specific genes, count their occurrences in the set of reads derived from an individual and compare the individual's k-mer distribution to that of the population. Copy number results demonstrate high concordance with population copy number expectations. Our method reveals that the burden of inhibitory KIR genes is associated with survival in two tumor types, highlighting the potential importance of KIR variation in understanding tumor development and response to immunotherapy

VIS: the visible imager for Euclid

Euclid-VIS is a large format visible imager for the ESA Euclid space mission in their Cosmic Vision program, scheduled for launch in 2019. Together with the near infrared imaging within the NISP instrument it forms the basis of the weak lensing measurements of Euclid. VIS will image in a single r+i+z band from 550-900 nm over a field of view of ~0.5 deg2. By combining 4 exposures with a total of 2240 sec, VIS will reach to V=24.5 (10{\sigma}) for sources with extent ~0.3 arcsec. The image sampling is 0.1 arcsec. VIS will provide deep imaging with a tightly controlled and stable point spread function (PSF) over a wide survey area of 15000 deg2 to measure the cosmic shear from nearly 1.5 billion galaxies to high levels of accuracy, from which the cosmological parameters will be measured. In addition, VIS will also provide a legacy imaging dataset with an unprecedented combination of spatial resolution, depth and area covering most of the extra-Galactic sky. Here we will present the results of the study carried out by the Euclid Consortium during the Euclid Definition phase.Comment: 10 pages, 6 figure

The Next Generation Transit Survey—Prototyping Phase

We present the prototype telescope for the Next Generation Transit Survey, which was built in the UK in 2008/2009 and tested on La Palma in the Canary Islands in 2010. The goals for the prototype system were severalfold: to determine the level of systematic noise in an NGTS-like system; demonstrate that we can perform photometry at the (sub) millimagnitude level on transit timescales across a wide-field; show that it is possible to detect transiting super-Earth and Neptune-sized exoplanets and prove the technical feasibility of the proposed planet survey. We tested the system for around 100 nights and met each of the goals above. Several key areas for improvement were highlighted during the prototyping phase. They have been subsequently addressed in the final NGTS facility, which was recently commissioned at ESO Cerro Paranal, Chile

ESPRESSO: The next European exoplanet hunter

The acronym ESPRESSO stems for Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations; this instrument will be the next VLT high resolution spectrograph. The spectrograph will be installed at the Combined-Coud\'e Laboratory of the VLT and linked to the four 8.2 m Unit Telescopes (UT) through four optical Coud\'e trains. ESPRESSO will combine efficiency and extreme spectroscopic precision. ESPRESSO is foreseen to achieve a gain of two magnitudes with respect to its predecessor HARPS, and to improve the instrumental radial-velocity precision to reach the 10 cm/s level. It can be operated either with a single UT or with up to four UTs, enabling an additional gain in the latter mode. The incoherent combination of four telescopes and the extreme precision requirements called for many innovative design solutions while ensuring the technical heritage of the successful HARPS experience. ESPRESSO will allow to explore new frontiers in most domains of astrophysics that require precision and sensitivity. The main scientific drivers are the search and characterization of rocky exoplanets in the habitable zone of quiet, nearby G to M-dwarfs and the analysis of the variability of fundamental physical constants. The project passed the final design review in May 2013 and entered the manufacturing phase. ESPRESSO will be installed at the Paranal Observatory in 2016 and its operation is planned to start by the end of the same year.Comment: 12 pages, figures included, accepted for publication in Astron. Nach

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

VIS: the visible imager for Euclid

Euclid-VIS is the large format visible imager for the ESA Euclid space mission in their Cosmic Vision program, scheduled for launch in 2020. Together with the near infrared imaging within the NISP instrument, it forms the basis of the weak lensing measurements of Euclid. VIS will image in a single r+i+z band from 550-900 nm over a field of view of ~0.5 deg2. By combining 4 exposures with a total of 2260 sec, VIS will reach to V=24.5 (10σ) for sources with extent ~0.3 arcsec. The image sampling is 0.1 arcsec. VIS will provide deep imaging with a tightly controlled and stable point spread function (PSF) over a wide survey area of 15000 deg2 to measure the cosmic shear from nearly 1.5 billion galaxies to high levels of accuracy, from which the cosmological parameters will be measured. In addition, VIS will also provide a legacy dataset with an unprecedented combination of spatial resolution, depth and area covering most of the extra-Galactic sky. Here we will present the results of the study carried out by the Euclid Consortium during the period up to the Preliminary Design Review. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

The Next Generation Transit Survey (NGTS)

© 2017 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. We describe the Next Generation Transit Survey (NGTS), which is a ground-based project searching for transiting exoplanets orbiting bright stars. NGTS builds on the legacy of previous surveys, most notably WASP, and is designed to achieve higher photometric precision and hence find smaller planets than have previously been detected from the ground. It also operates in red light,maximizing sensitivity to late K and earlyMdwarf stars. The survey specifications call for photometric precision of 0.1 per cent in red light over an instantaneous field of view of 100 deg 2 , enabling the detection of Neptune-sized exoplanets around Sun-like stars and super-Earths around M dwarfs. The survey is carried out with a purpose-built facility at Cerro Paranal, Chile, which is the premier site of the European Southern Observatory (ESO). An array of twelve 20 cm f/2.8 telescopes fitted with back-illuminated deep-depletion CCD cameras is used to survey fields intensively at intermediateGalactic latitudes. The instrument is also ideally suited to ground-based photometric follow-up of exoplanet candidates from space telescopes such as TESS, Gaia and PLATO. We present observations that combine precise autoguiding and the superb observing conditions at Paranal to provide routine photometric precision of 0.1 per cent in 1 h for stars with I-band magnitudes brighter than 13. We describe the instrument and data analysis methods as well as the status of the survey, which achieved first light in 2015 and began full-survey operations in 2016. NGTS data will be made publicly available through the ESO archive

alphabeta T cell receptors as predictors of health and disease

The diversity of antigen receptors and the specificity it underlies are the hallmarks of the cellular arm of the adaptive immune system. T and B lymphocytes are indeed truly unique in their ability to generate receptors capable of recognizing virtually any pathogen. It has been known for several decades that T lymphocytes recognize short peptides derived from degraded proteins presented by major histocompatibility complex (MHC) molecules at the cell surface. Interaction between peptide-MHC (pMHC) and the T cell receptor (TCR) is central to both thymic selection and peripheral antigen recognition. It is widely assumed that TCR diversity is required, or at least highly desirable, to provide sufficient immune coverage. However, a number of immune responses are associated with the selection of predictable, narrow, or skewed repertoires and public TCR chains. Here, we summarize the current knowledge on the formation of the TCR repertoire and its maintenance in health and disease. We also outline the various molecular mechanisms that govern the composition of the pre-selection, naive and antigen-specific TCR repertoires. Finally, we suggest that with the development of high-throughput sequencing, common TCR \u27signatures\u27 raised against specific antigens could provide important diagnostic biomarkers and surrogate predictors of disease onset, progression and outcome