8,437 research outputs found

    The Stellar Masses and Star Formation Histories of Galaxies at z ≈ 6: Constraints from Spitzer Observations in the Great Observatories Origins Deep Survey

    Get PDF
    Using the deep Spitzer Infrared Array Camera (IRAC) observations of the Great Observatories Origins Deep Survey (GOODS), we study the stellar masses and star formation histories of galaxies at z approx 6 based on the i_(775)-band dropout sample selected from the GOODS fields. In total, we derive stellar masses for 53 i_(775)-band dropouts that have robust IRAC detections. These galaxies have typical stellar masses of ~10^(10) M_⊙ and typical ages of a couple of hundred million years, consistent with earlier results based on a smaller sample of z ≈ 6 galaxies. The existence of such massive galaxies at z ≈ 6 can be explained by at least one set of N-body simulations of the hierarchical paradigm. We also study 79 i_(775)-band dropouts that are invisible in the IRAC data and find that they are typically less massive by a factor of 10. These galaxies are much bluer than those detected by the IRAC, indicating that their luminosities are dominated by stellar populations with ages ≾ 40 Myr. Based on our mass estimates, we derive a lower limit to the global stellar mass density at z ≈ 6, which is 1.1-6.7 × 10^6 M_⊙ Mpc^(-3). The prospect of detecting the progenitors of the most massive galaxies at yet higher redshifts is explored. We also investigate the implication of our results for reionization and find that the progenitors of the galaxies comparable to those in our sample, even in the most optimized (probably unrealistic) scenario, cannot sustain the reionization for a period longer than ~2 Myr. Thus most of the photons required for reionization must have been provided by other sources, such as the progenitors of the dwarf galaxies that are far below our current detection capability

    BMP-2 and TGF-β3 do not prevent spontaneous degeneration in rabbit disc explants but induce ossification of the annulus fibrosus

    Get PDF
    Introduction: Different approaches for disc regeneration are currently under investigation. Beside gene therapy and tissue engineering techniques, the application of growth and differentiation factors own promising potential. Studies using reduced intervertebral disc models, such as cell or tissue fragment cultures, have limited validity and show controversial results depending on the employed experimental model. Therefore, the goal of the current study was to investigate the effect of BMP-2 and TGF-β3 on intervertebral disc degeneration using an in vitro full-organ disc/endplate culture system. Materials and methods: Intervertebral rabbit disc explants were cultured in the presence of 1μg/ml BMP-2 or TGF-β3 for 21days in DMEM/F12 media. Nucleus and annulus were analyzed for gene expression of collagen type I and II (Col I/II), aggrecan, collagenases (MMP-1/MMP-13) with RT-qPCR, histological changes with bone and proteoglycan-specific staining (von Kossa, toluidine blue) and differences in cellularity (DNA) and proteoglycan content (alcian blue binding assay). Results: The results demonstrate that disc proteoglycan concentration decreased with time in the TGF-β3 and BMP-2 groups. In the annulus fibrosus (AF), TGF-β3 and BMP-2 resulted in an up-regulation of Col I and type II, and of aggrecan gene expression. In contrast, MMP genes were inhibited. In the nucleus, the growth factors decreased gene expression of aggrecan and spontaneous Col I up-regulation was inhibited by TGF-β3, whereas expression of Col II was decreased with BMP-2. There was no effect on expression of MMP-1 and MMP-13 for most sampling points. However, TGF-β3 and BMP-2 induced ossification of the AF was demonstrated by histology. Conclusion: It can be concluded that both growth factors, at the tested concentrations, may not be suitable to regenerate the whole intervertebral disc organ but they are interesting candidates for being injected alone or in combination into a painful intervertebral disc to induce osseous fusion (spondylodesis

    The fractional chromatic number of triangle-free subcubic graphs

    Get PDF
    Heckman and Thomas conjectured that the fractional chromatic number of any triangle-free subcubic graph is at most 14/5. Improving on estimates of Hatami and Zhu and of Lu and Peng, we prove that the fractional chromatic number of any triangle-free subcubic graph is at most 32/11 (which is roughly 2.909)

    Disease activity flares and pain flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae

    Get PDF
    © 2019 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: RA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities. Methods: People from the Early RA Network (ERAN) cohort were assessed annually up to 11 years after presentation (n = 719, 3703 person-years of follow up). Flare events were defined in 2 different ways that were analysed in parallel; DAS28 or Pain Flares. DAS28 Flares satisfied OMERACT flare criteria of increases in DAS28 since the previous assessment (≥1.2 points if active RA or ≥ 0.6 points if inactive RA). A ≥ 4.8-point worsening of SF36-Bodily Pain score defined Pain Flares. The first documented episode of each of DAS28 and Pain Flare in each person was analysed. Subgroups within DAS28 and Pain Flares were determined using Latent Class Analysis. Clinical course was compared between flare subgroups. Results: DAS28 (45%) and Pain Flares (52%) were each common but usually discordant, with 60% of participants in DAS28 Flare not concurrently in Pain Flare, and 64% of those in Pain Flare not concurrently in DAS28 Flare. Three discrete DAS28 Flare subgroups were identified. One was characterised by increases in tender/swollen joint counts (14.4%), a second by increases in symptoms (13.1%), and a third displayed lower flare severity (72.5%). Two discrete Pain Flare subgroups were identified. One occurred following low disease activity and symptoms (88.6%), and the other occurred on the background of ongoing active disease and pain (11.4%). Despite the observed differences between DAS28 and Pain Flares, each was associated with increased disability which persisted beyond the flare episode. Conclusion: Flares are both common and heterogeneous in people with RA. Furthermore our findings indicate that for some patients there is a discordance between inflammation and pain in flare events. This discrete flare subgroups might reflect different underlying inflammation and pain mechanisms. Treatments addressing different mechanisms might be required to reduce persistent disability after DAS28 and Pain Flares.Peer reviewedFinal Published versio

    Vertebral endplate trauma induces disc cell apoptosis and promotes organ degeneration in vitro

    Get PDF
    There is a major controversy whether spinal trauma with vertebral endplate fractures can result in post-traumatic disc degeneration. Intervertebral discs, which are adjacent to burst endplates, are frequently removed and an intercorporal spondylodesis is performed. In any case, the biological effects within the discs following endplate factures are poorly elucidated to date. The aim of our investigations was therefore to establish a novel disc/endplate trauma culture model to reproducibly induce endplate fractures and investigate concurrent disc changes in vitro. This model is based on a full-organ disc/endplate culture system, which has been validated by the authors before. Intervertebral disc/endplate specimens were isolated from Burgundy rabbits and cultured in standard media (DMEM/F12, 10%FCS). Burst endplate fractures were induced in half of the specimens with a custom-made fracture device and subsequently cultured for 9days. The biological effects such as necrotic or apoptotic cell death and the expression of pro-apoptotic genes and other genes involved in organ degeneration, e.g. matrix metalloproteinases (MMPs) were analyzed. Cell damage was assessed by quantification of the lactate dehydrogenase (LDH) activity in the supernatant. The expression of genes involved in the cellular apoptotic pathway (caspase3) and the pro-apoptotic proteins FasL and TNF-α were monitored. The results demonstrate that LDH levels increased significantly post trauma compared to the control and remained elevated for 3days. Furthermore, a constant up-regulation of the caspase3 gene in both disc compartments was present. The pro-apoptotic proteins FasL and TNF-α were up regulated predominantly in the nucleus whereas the MMP-1 and -13 transcripts (collagenases) were increased in both disc structures. From this study we can conclude that endplate burst fractures result in both necrotic and apoptotic cell death in nucleus and annulus tissue. Moreover, FasL and TNF-α expression by nucleus cells may lead to continued apoptosis induced by Fas- and TNF-α receptor bearing cells. In addition TNF-α over-expression has potentially deleterious effects on disc metabolism such as over-expression of matrix proteinases. Taken together, the short term biological response of the disc following endplate fracture exhibits characteristics, which may initiate the degeneration of the orga
    corecore