1,777 research outputs found

    The VLT-UVES Survey for Molecular Hydrogen in High-Redshift Damped Lyman Ī± Systems: Physical Conditions in the Neutral Gas

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    We study the physical conditions in damped Lyman Ī± systems (DLAs), using a sample of 33 systems towards 26 quasi-stellar objects (QSOs) acquired for a recently completed survey of H2 by Ledoux, Petitjean & Srianand. We use the column densities of H2 in different rotational levels, together with those of C I, C I*, C I**, C II* and singly ionized atomic species to discuss the kinetic temperature, the density of hydrogen and the electronic density in the gas together with the ambient ultraviolet (UV) radiation field. Detailed comparisons are made between the observed properties in DLAs, the interstellar medium (ISM) of the Galaxy and the Large and Small Magellanic Clouds (LMCs and SMCs). The mean kinetic temperature of the gas corresponding to DLA subcomponents in which an H2 absorption line is detected, derived from the ortho-to-para ratio (OPR) (153 Ā± 78 K), is higher than that measured in the ISM (77 Ā± 17 K) and in Magellanic Clouds (82 Ā± 21 K). Typical pressure in these components (corresponding to T = 100ā€“300 K and nH = 10āˆ’200 cmāˆ’3), measured using C I fine-structure excitation, are higher than what is measured along ISM sightlines. This is consistent with the corresponding higher values for N(H2, J = 2)/N(H2, J = 0) seen in DLAs. From the column densities of the high-J rotational levels, we derive that the typical radiation field in the H2-bearing components is of the order of or slightly higher than the mean UV field in the Galactic ISM. Determination of electron density in the gas with H2 and C I shows that the ionization rate is similar to that of a cold neutral medium (CNM) in a moderate radiation field. This, together with the fact that we see H2 in 13ā€“20 per cent of the DLAs, can be used to conclude that DLAs at z \u3e 1.9 could contribute as much as 50 per cent star formation rate (SFR) density seen in Lyman break galaxies (LBGs). C II* absorption line is detected in all the components where H2 absorption line is seen. The excitation of C II in these systems is consistent with the physical parameters derived from the excitation of H2 and C I. We detect CII* in about 50 per cent of the DLAs and, therefore, in a considerable fraction of DLAs that do not show H2. In part of the later systems, physical conditions could be similar to that in the CNM gas of the Galaxy. However, the absence of C I absorption line and the presence of Al III absorption lines with a profile similar to the profiles of singly ionized species suggest an appreciable contribution from a warm neutral medium (WNM) and/or partially ionized gas. The absence of H2, for the level of metallicity and dust depletion seen in these systems, is consistent with low densities (i.e.nHā‰¤ 1 cmāˆ’3) for a radiation field similar to the mean Galactic UV field

    The anatomy of friendship:neuroanatomic homophily of the social brain among classroom friends

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    Homophily refers to the tendency to like similar others. Here, we ask if homophily extends to brain structure. Specifically: do children who like one another have more similar brain structures? We hypothesized that neuroanatomic similarity tied to friendship is most likely to pertain to brain regions that support social cognition. To test this hypothesis, we analyzed friendship network data from 1186 children in 49 classrooms. Within each classroom, we identified ā€œfriendship distanceā€ā€”mutual friends, friends-of-friends, and more distantly connected or unconnected children. In total, 125 children (mean age = 7.57 years, 65 females) also had good quality neuroanatomic magnetic resonance imaging scans from which we extracted properties of the ā€œsocial brain.ā€ We found that similarity of the social brain varied by friendship distance: mutual friends showed greater similarity in social brain networks compared with friends-of-friends (Ī²Ā = 0.65, t = 2.03, Pā€‰=ā€‰0.045) and even more remotely connected peers (Ī² =ā€‰0.77, tā€‰= 2.83, PĀ = 0.006); friends-of-friends did not differ from more distantly connected peers (Ī² =ā€‰āˆ’0.13, t = āˆ’0.53, Pā€‰=ā€‰0.6). We report that mutual friends have similar ā€œsocial brainā€ networks, adding a neuroanatomic dimension to the adage that ā€œbirds of a feather flock together.

    Memory CD8<sup>+</sup> T cells exhibit tissue imprinting and non-stable exposure-dependent reactivation characteristics following blood-stage Plasmodium berghei ANKA infections

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    Experimental cerebral malaria (ECM) is a severe complication of Plasmodium berghei ANKA (PbA) infection in mice, characterized by CD8(+) Tā€cell accumulation within the brain. Whilst the dynamics of CD8(+) Tā€cell activation and migration during extant primary PbA infection have been extensively researched, the fate of the parasiteā€specific CD8(+) T cells upon resolution of ECM is not understood. In this study, we show that memory OTā€I cells persist systemically within the spleen, lung and brain following recovery from ECM after primary PbAā€OVA infection. Whereas memory OTā€I cells within the spleen and lung exhibited canonical central memory (Tcm) and effector memory (Tem) phenotypes, respectively, memory OTā€I cells within the brain postā€PbAā€OVA infection displayed an enriched CD69(+)CD103(āˆ’) profile and expressed low levels of Tā€bet. OTā€I cells within the brain were excluded from shortā€term intravascular antibody labelling but were targeted effectively by longerā€term systemically administered antibodies. Thus, the memory OTā€I cells were extravascular within the brain postā€ECM but were potentially not resident memory cells. Importantly, whilst memory OTā€I cells exhibited strong reactivation during secondary PbAā€OVA infection, preventing activation of new primary effector T cells, they had dampened reactivation during a fourth PbAā€OVA infection. Overall, our results demonstrate that memory CD8(+) T cells are systemically distributed but exhibit a unique phenotype within the brain postā€ECM, and that their reactivation characteristics are shaped by infection history. Our results raise important questions regarding the role of distinct memory CD8(+) Tā€cell populations within the brain and other tissues during repeat Plasmodium infections

    ATR maintains chromosomal integrity during postnatal cerebellar neurogenesis and is required for medulloblastoma formation

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    Microcephaly and medulloblastoma may both result from mutations that compromise genomic stability. We report that ATR, which is mutated in the microcephalic disorder Seckel syndrome, sustains cerebellar growth by maintaining chromosomal integrity during postnatal neurogenesis. Atr deletion in cerebellar granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis and cerebellar hypoplasia in mice. Co-deletions of either p53 or Bax and Bak prevented apoptosis in Atr-deleted CGNPs, but failed to fully rescue cerebellar growth. ATR-deficient CGNPs had impaired cell cycle checkpoint function and continued to proliferate, accumulating chromosomal abnormalities. RNA-Seq demonstrated that the transcriptional response to ATR-deficient proliferation was highly p53 dependent and markedly attenuated by p53 co-deletion. Acute ATR inhibition in vivo by nanoparticle-formulated VE-822 reproduced the developmental disruptions seen with Atr deletion. Genetic deletion of Atr blocked tumorigenesis in medulloblastoma-prone SmoM2 mice. Our data show that p53-driven apoptosis and cell cycle arrest ā€“ and, in the absence of p53, non-apoptotic cell death ā€“ redundantly limit growth in ATR-deficient progenitors. These mechanisms may be exploited for treatment of CGNP-derived medulloblastoma using ATR inhibition

    Cloud System Evolution in the Trades (CSET): Following the Evolution of Boundary Layer Cloud Systems with the NSFNCAR GV

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    The Cloud System Evolution in the Trades (CSET) study was designed to describe and explain the evolution of the boundary layer aerosol, cloud, and thermodynamic structures along trajectories within the North Pacific trade winds. The study centered on seven round trips of the National Science FoundationNational Center for Atmospheric Research (NSFNCAR) Gulfstream V (GV) between Sacramento, California, and Kona, Hawaii, between 7 July and 9 August 2015. The CSET observing strategy was to sample aerosol, cloud, and boundary layer properties upwind from the transition zone over the North Pacific and to resample these areas two days later. Global Forecast System forecast trajectories were used to plan the outbound flight to Hawaii with updated forecast trajectories setting the return flight plan two days later. Two key elements of the CSET observing system were the newly developed High-Performance Instrumented Airborne Platform for Environmental Research (HIAPER) Cloud Radar (HCR) and the high-spectral-resolution lidar (HSRL). Together they provided unprecedented characterizations of aerosol, cloud, and precipitation structures that were combined with in situ measurements of aerosol, cloud, precipitation, and turbulence properties. The cloud systems sampled included solid stratocumulus infused with smoke from Canadian wildfires, mesoscale cloudprecipitation complexes, and patches of shallow cumuli in very clean environments. Ultraclean layers observed frequently near the top of the boundary layer were often associated with shallow, optically thin, layered veil clouds. The extensive aerosol, cloud, drizzle, and boundary layer sampling made over open areas of the northeast Pacific along 2-day trajectories during CSET will be an invaluable resource for modeling studies of boundary layer cloud system evolution and its governing physical processes

    Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A

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    Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota. However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive. We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting. We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA. Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities. Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA. These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses

    Phase II Study of a Non-Platinumā€“Containing Doublet of Paclitaxel and Pemetrexed with Bevacizumab as Initial Therapy for Patients with Advanced Lung Adenocarcinomas

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    Many patients with lung cancers cannot receive platinum-containing regimens due to co-morbid medical conditions. We designed the PPB regimen of paclitaxel, pemetrexed, and bevacizumab to maintain or improve outcomes while averting the unique toxicities of platinum-based chemotherapies
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