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

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

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

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

Effects of ranolazine on astrocytes and neurons in primary culture

Ranolazine (Rn) is an antianginal agent used for the treatment of chronic angina pectoris when angina is not adequately controlled by other drugs. Rn also acts in the central nervous system and it has been proposed for the treatment of pain and epileptic disorders. Under the hypothesis that ranolazine could act as a neuroprotective drug, we studied its effects on astrocytes and neurons in primary culture. We incubated rat astrocytes and neurons in primary cultures for 24 hours with Rn (10−7, 10−6 and 10−5 M). Cell viability and proliferation were measured using trypan blue exclusion assay, MTT conversion assay and LDH release assay. Apoptosis was determined by Caspase 3 activity assay. The effects of Rn on proinflammatory mediators IL-β and TNF-α was determined by ELISA technique, and protein expression levels of Smac/Diablo, PPAR-γ, Mn-SOD and Cu/Zn-SOD by western blot technique. In cultured astrocytes, Rn significantly increased cell viability and proliferation at any concentration tested, and decreased LDH leakage, Smac/Diablo expression and Caspase 3 activity indicating less cell death. Rn also increased anti-inflammatory PPAR-γ protein expression and reduced pro-inflammatory proteins IL-1 β and TNFα levels. Furthermore, antioxidant proteins Cu/Zn-SOD and Mn-SOD significantly increased after Rn addition in cultured astrocytes. Conversely, Rn did not exert any effect on cultured neurons. In conclusion, Rn could act as a neuroprotective drug in the central nervous system by promoting astrocyte viability, preventing necrosis and apoptosis, inhibiting inflammatory phenomena and inducing anti-inflammatory and antioxidant agents

Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy.

Dendritic cells (DCs) are antigen-presenting myeloid cells that regulate T cell activation, trafficking and function. Monocyte-derived DCs pulsed with tumor antigens have been tested extensively for therapeutic vaccination in cancer, with mixed clinical results. Here, we present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 and FLT3L. Cytokine-armed DCPs differentiated into conventional type-I DCs (cDC1) and suppressed tumor growth, including melanoma and autochthonous liver models, without the need for antigen loading or myeloablative host conditioning. Tumor response involved synergy between IL-12 and FLT3L and was associated with natural killer and T cell infiltration and activation, M1-like macrophage programming and ischemic tumor necrosis. Antitumor immunity was dependent on endogenous cDC1 expansion and interferon-γ signaling but did not require CD8 <sup>+</sup> T cell cytotoxicity. Cytokine-armed DCPs synergized effectively with anti-GD2 chimeric-antigen receptor (CAR) T cells in eradicating intracranial gliomas in mice, illustrating their potential in combination therapies

Engineered CD4 TCR T cells with conserved high-affinity TCRs targeting NY-ESO-1 for advanced cellular therapies in cancer.

While cancer immunotherapy has primarily focused on CD8 T cells, CD4 T cells are increasingly recognized for their role in antitumor immunity. The HLA-DRB3*02:02 allele is found in 50% of Caucasians. In this study, we screened HLA-DRB3*02:02 patients with melanoma for tumor-specific CD4 T cells and identified robust New York esophageal squamous cell carcinoma 1 (NY-ESO-1) <sub>123-137</sub> /HLA-DRB3*02:02 CD4 T cell activity in both peripheral blood and tumor tissue. By analyzing NY-ESO-1 <sub>123-137</sub> /HLA-DRB3*02:02-restricted CD4 T cell clones, we uncovered an unexpectedly high cytotoxicity, strong T helper 1 polarization, and recurrent αβ T cell receptor (TCRαβ) usage across patients and anatomical sites. These responses were also present in other NY-ESO-1-expressing cancers. TCRs from these clones, when transduced into primary CD4 T cells, showed direct antitumor efficacy both in vitro and in vivo. Our findings suggest that these TCRs are promising for adoptive T cell transfer therapy, enabling broader targeting of NY-ESO-1-expressing adult and pediatric cancers in clinical settings

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