Unconventional T cell targets for cancer immunotherapy

Most studies on the immunotherapeutic potential of T cells have focused on CD8 and CD4 T cells that recognize peptide antigens (Ag) presented by polymorphic major histocompatibility complex (MHC) class I and MHC class II molecules, respectively. However, unconventional T cells, which interact with MHC class Ib and MHC-I like molecules, are also implicated in tumor immunity, although their role therein is unclear. These include unconventional T cells targeting MHC class Ib molecules such as HLA-E and its murine ortholog Qa-1b, natural killer T (NKT) cells, mucosal associated invariant T (MAIT) cells, and γδ T cells. Here, we review the current understanding of the roles of these unconventional T cells in tumor immunity and discuss why further studies into the immunotherapeutic potential of these cells is warrante

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation

The evolution of the dust and gas content in galaxies

We use deep Herschel observations taken with both PACS and SPIRE imaging cameras to estimate the dust mass of a sample of galaxies extracted from the GOODS-S, GOODS-N and the COSMOS fields. We divide the redshift–stellar mass (M star )–star formation rate (SFR) parameter space into small bins and investigate average properties over this grid. In the first part of the work we investigate the scaling relations between dust mass, stellar mass and SFR out to z = 2.5. No clear evolution of the dust mass with redshift is observed at a given SFR and stellar mass. We find a tight correlation between the SFR and the dust mass, which, under reasonable assumptions, is likely a consequence of the Schmidt-Kennicutt (S-K) relation. The previously observed correlation between the stellar content and the dust content flattens or sometimes disappears when considering galaxies with the same SFR. Our finding suggests that most of the correlation between dust mass and stellar mass obtained by previous studies is likely a consequence of the correlation between the dust mass and the SFR combined with the main sequence, i.e., the tight relation observed between the stellar mass and the SFR and followed by the majority of star-forming galaxies. We then investigate the gas content as inferred from dust mass measurements. We convert the dust mass into gas mass by assuming that the dust-to-gas ratio scales linearly with the gas metallicity (as supported by many observations). For normal star-forming galaxies (on the main sequence) the inferred relation between the SFR and the gas mass (integrated S-K relation) broadly agrees with the results of previous studies based on CO measurements, despite the completely different approaches. We observe that all galaxies in the sample follow, within uncertainties, the same S-K relation. However, when investigated in redshift intervals, the S-K relation shows a moderate, but significant redshift evolution. The bulk of the galaxy population at z ∼ 2 converts gas into stars with an efficiency (star formation efficiency, SFE = SFR/M gas , equal to the inverse of the depletion time) about 5 times higher than at z ∼ 0. However, it is not clear what fraction of such variation of the SFE is due to an intrinsic redshift evolution and what fraction is simply a consequence of high-z galaxies having, on average, higher SFR, combined with thesuper-linear slope of the S-K relation (whileother studies finda linear slope). We confirm that the gas fraction (f gas = M gas /(M gas + M star )) decreases with stellar mass and increases with the SFR. We observe no evolution with redshift once M star and SFR are fixed. We explain these trends by introducing a universal relation between gas fraction, stellar mass and SFR that does not evolve with redshift, at least out to z ∼ 2.5. Galaxies move across this relation as their gas content evolves across the cosmic epochs. We use the 3D fundamental f gas –M star –SFR relation, along with the evolution of the main sequence with redshift, to estimate the evolution of the gas fraction in the average population of galaxies as a function of redshift and as a function of stellar mass: we find that M star > ∼ 10 11 M ? galaxies show the strongest evolution at z > ∼ 1.3 and a flatter trend at lower redshift, while f gas decreases more regularly over the entire redshift range probed in M star < ∼ 10 11 Mo galaxies, in agreement with a downsizing scenario

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Legacy ExtraGalactic UV Survey with the Hubble Space Telescope: Stellar Cluster Catalogs and First Insights into Cluster Formation and Evolution in NGC 628

We report the large effort that is producing comprehensive high-level young star cluster (YSC) catalogs for a significant fraction of galaxies observed with the Legacy ExtraGalactic UV Survey (LEGUS) Hubble treasury program. We present the methodology developed to extract cluster positions, verify their genuine nature, produce multiband photometry (from NUV to NIR), and derive their physical properties via spectral energy distribution fitting analyses. We use the nearby spiral galaxy NGC 628 as a test case for demonstrating the impact that LEGUS will have on our understanding of the formation and evolution of YSCs and compact stellar associations within their host galaxy. Our analysis of the cluster luminosity function from the UV to the NIR finds a steepening at the bright end and at all wavelengths suggesting a dearth of luminous clusters. The cluster mass function of NGC 628 is consistent with a power-law distribution of slopes and a truncation of a few times 105. After their formation, YSCs and compact associations follow different evolutionary paths. YSCs survive for a longer time frame, confirming their being potentially bound systems. Associations disappear on timescales comparable to hierarchically organized star-forming regions, suggesting that they are expanding systems. We find mass-independent cluster disruption in the inner region of NGC 628, while in the outer part of the galaxy there is little or no disruption. We observe faster disruption rates for low mass (≤104) clusters, suggesting that a mass-dependent component is necessary to fully describe the YSC disruption process in NGC 628

Vivid visual mental imagery in the absence of the primary visual cortex

The role of the primary visual cortex in visual mental imagery has provided significant debate in the imagery literature. Functional neuroimaging studies show considerable variation depending on task and technique. Patient studies can be difficult to interpret due to the diverse nature of cortical damage. The type of cortical damage in patient SBR is exceedingly rare as it is restricted to the gray matter of the calcarine sulcus. In this study, we show that in spite of his near-complete cortical blindness, SBR exhibits vivid visual mental imagery both behaviorally and when measured with functional magnetic resonance imaging. The pattern of cortical activation to visual mental imagery in SBR is indistinguishable from individual sighted subjects, in contrast to the visual perceptual responses, which are greatly attenuated

The Brightest Young Star Clusters in NGC 5253

67 pages; 11 figures; 7 tables. Accepted for publication in the Astrophysical JournalThe nearby dwarf starburst galaxy NGC5253 hosts a number of young, massive star clusters, the two youngest of which are centrally concentrated and surrounded by thermal radio emission (the `radio nebula'). To investigate the role of these clusters in the starburst energetics, we combine new and archival Hubble Space Telescope images of NGC5253 with wavelength coverage from 1500 Ang to 1.9 micron in 13 filters. These include H-alpha, P-beta, and P-alpha, and the imaging from the Hubble Treasury Program LEGUS (Legacy Extragalactic UV Survey). The extraordinarily well-sampled spectral energy distributions enable modeling with unprecedented accuracy the ages, masses, and extinctions of the 9 optically brightest clusters (M_V < -8.8) and the two young radio nebula clusters. The clusters have ages ~1-15 Myr and masses ~1x10^4 - 2.5x10^5 M_sun. The clusters' spatial location and ages indicate that star formation has become more concentrated towards the radio nebula over the last ~15 Myr. The most massive cluster is in the radio nebula; with a mass 2.5x10^5 M_sun and an age ~1 Myr, it is 2-4 times less massive and younger than previously estimated. It is within a dust cloud with A_V~50 mag, and shows a clear nearIR excess, likely from hot dust. The second radio nebula cluster is also ~1 Myr old, confirming the extreme youth of the starburst region. These two clusters account for about half of the ionizing photon rate in the radio nebula, and will eventually supply about 2/3 of the mechanical energy in present-day shocks. Additional sources are required to supply the remaining ionizing radiation, and may include very massive stars.Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with program # 13364. Support for program # 13364 was provided by NASA through a grant from the Space Telescope Science Institute. Based also on observations made with the NASA/ESA Hubble Space Telescope, and obtained from the Hubble Legacy Archive, which is a collaboration between the Space Telescope Science Institute (STScI/NASA), the Space Telescope European Coordinating Facility (ST-ECF/ESA) and the Canadian Astronomy Data Centre (CADC/NRC/CSA). This research has made use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. Part of this work was conducted while D.C. was a Raymond and Beverley Sackler Distinguished Visitor at the Institute of Astronomy, University of Cambridge (UK), and an Overseas Fellow at the Churchill College (Cambridge, UK). D.C. acknowledges the kind hospitality of both the Institute and the College. A.S.E. was supported by the Taiwan, R.O.C. Ministry of Science and Technology grant MoST 102-2119-M-001-MY3. M.F. acknowledges support by the Science and Technology Facilities Council [grant number ST/L00075X/1]. D.A.G. kindly acknowledges financial support by the German Research Foundation (DFG) through grant GO 1659/3-2. E.Z. acknowledges research funding from the Swedish Research Council (project 2011-5349)

ACCESS IV: The quenching of star formation in a cluster population of dusty S0s

We present an analysis of the mid-infrared (MIR) colours of 165 70um-detected galaxies in the Shapley supercluster core (SSC) at z=0.048 using panoramic Spitzer/MIPS 24 and 70um imaging. While the bulk of galaxies show f70/f24 colours typical of local star-forming galaxies, we identify a significant sub-population of 23 70micron-excess galaxies, whose MIR colours (f70/f24>25) are much redder and cannot be reproduced by any of the standard model infrared SEDs. These galaxies are found to be strongly concentrated towards the cores of the five clusters that make up the SSC, and also appear rare among local field galaxies, confirming them as a cluster-specific phenomenon. Their optical spectra and lack of significant UV emission imply little or no ongoing star formation, while fits to their panchromatic SEDs require the far-IR emission to come mostly from a diffuse dust component heated by the general interstellar radiation field rather than ongoing star formation. Most of these 70micron-excess galaxies are identified as ~L* S0s with smooth profiles. We find that almost every cluster galaxy in the process of star-formation quenching is already either an S0 or Sa, while we find no passive galaxies of class Sb or later. Hence the formation of passive early-type galaxies in cluster cores must involve the prior morphological transformation of late-type spirals into Sa/S0s, perhaps via pre-processing or the impact of cluster tidal fields, before a subsequent quenching of star formation once the lenticular encounters the dense environment of the cluster core. In the cases of many cluster S0s, this phase of star-formation quenching is characterised by an excess of 70um emission, indicating that the cold dust content is declining at a slower rate than star formation.Comment: 17 pages, 12 figures. Accepted for publication in MNRA

A network linking scene perception and spatial memory systems in posterior cerebral cortex

The neural systems supporting scene-perception and spatial-memory systems of the human brain are well-described. But how do these neural systems interact? Here, using fine-grained individual-subject fMRI, we report three cortical areas of the human brain, each lying immediately anterior to a region of the scene perception network in posterior cerebral cortex, that selectively activate when recalling familiar real-world locations. Despite their close proximity to the scene-perception areas, network analyses show that these regions constitute a distinct functional network that interfaces with spatial memory systems during naturalistic scene understanding. These “place-memory areas” offer a new framework for understanding how the brain implements memory-guided visual behaviors, including navigation