We introduce meraxes, a new, purpose-built semi-analytic galaxy formation model designed for studying galaxy growth during reionization. meraxes is the first model of its type to include a temporally ...and spatially coupled treatment of reionization and is built upon a custom (100 Mpc)3
N-body simulation with high temporal and mass resolution, allowing us to resolve the galaxy and star formation physics relevant to early galaxy formation. Our fiducial model with supernova feedback reproduces the observed optical depth to electron scattering and evolution of the galaxy stellar mass function between z = 5 and 7, predicting that a broad range of halo masses contribute to reionization. Using a constant escape fraction and global recombination rate, our model is unable to simultaneously match the observed ionizing emissivity at z ≲ 6. However, the use of an evolving escape fraction of 0.05–0.1 at z ∼ 6, increasing towards higher redshift, is able to satisfy these three constraints. We also demonstrate that photoionization suppression of low-mass galaxy formation during reionization has only a small effect on the ionization history of the intergalactic medium. This lack of ‘self-regulation’ arises due to the already efficient quenching of star formation by supernova feedback. It is only in models with gas supply-limited star formation that reionization feedback is effective at regulating galaxy growth. We similarly find that reionization has only a small effect on the stellar mass function, with no observationally detectable imprint at M
* > 107.5 M⊙. However, patchy reionization has significant effects on individual galaxy masses, with variations of factors of 2–3 at z = 5 that correlate with environment.
Nine questions on energy decomposition analysis Andrés, Juan; Ayers, Paul W.; Boto, Roberto A. ...
Journal of computational chemistry,
October 5, 2019, Letnik:
40, Številka:
26
Journal Article
Abstract
Motivated by recent measurements of the number density of faint AGN at high redshift, we investigate the contribution of quasars to reionization by tracking the growth of central ...supermassive black holes in an update of the Meraxes semi-analytic model. The model is calibrated against the observed stellar mass function at z ∼ 0.6–7, the black hole mass function at z ≲ 0.5, the global ionizing emissivity at z ∼ 2–5 and the Thomson scattering optical depth. The model reproduces a Magorrian relation in agreement with observations at z < 0.5 and predicts a decreasing black hole mass towards higher redshifts at fixed total stellar mass. With the implementation of an opening angle of 80 deg for quasar radiation, corresponding to an observable fraction of ∼23.4 per cent due to obscuration by dust, the model is able to reproduce the observed quasar luminosity function at z ∼ 0.6–6. The stellar light from galaxies hosting faint active galactic nucleus (AGN) contributes a significant or dominant fraction of the UV flux. At high redshift, the model is consistent with the bright end quasar luminosity function and suggests that the recent faint z ∼ 4 AGN sample compiled by Giallongo et al. (2015) includes a significant fraction of stellar light. Direct application of this luminosity function to the calculation of AGN ionizing emissivity consequently overestimates the number of ionizing photons produced by quasars by a factor of 3 at z ∼ 6. We conclude that quasars are unlikely to make a significant contribution to reionization.
We present the Dark-ages Reionization and Galaxy formation Observables from Numerical Simulations (DRAGONS) programme and Tiamat, the collisionless N-body simulation programme upon which DRAGONS is ...built. The primary trait distinguishing Tiamat from other large simulation programme is its density of outputs at high redshift (100 from z = 35 to z = 5; roughly one every 10 Myr) enabling the construction of very accurate merger trees at an epoch when galaxy formation is rapid and mergers extremely frequent. We find that the friends-of-friends halo mass function agrees well with the prediction of Watson et al. at high masses, but deviates at low masses, perhaps due to our use of a different halo finder or perhaps indicating a break from 'universal' behaviour. We then analyse the dynamical evolution of galaxies during the Epoch of Reionization finding that only a small fraction (~20 per cent) of galactic haloes are relaxed. We illustrate this using standard relaxation metrics to establish two dynamical recovery time-scales: (i) haloes need ~1.5 dynamical times following formation, and (ii) ~2 dynamical times following a major (3:1) or minor (10:1) merger to be relaxed. This is remarkably consistent across a wide mass range. Lastly, we use a phase-space halo finder to illustrate that major mergers drive long-lived massive phase-space structures which take many dynamical times to dissipate. This can yield significant differences in the inferred mass build-up of galactic haloes and we suggest that care must be taken to ensure a physically meaningful match between the galaxy formation physics of semi-analytic models and the halo finders supplying their input.
Gene expression atlases have transformed our understanding of the development, composition and function of human tissues. New technologies promise improved cellular or molecular resolution, and have ...led to the identification of new cell types, or better defined cell states. But as new technologies emerge, information derived on old platforms becomes obsolete. We demonstrate that it is possible to combine a large number of different profiling experiments summarised from dozens of laboratories and representing hundreds of donors, to create an integrated molecular map of human tissue. As an example, we combine 850 samples from 38 platforms to build an integrated atlas of human blood cells. We achieve robust and unbiased cell type clustering using a variance partitioning method, selecting genes with low platform bias relative to biological variation. Other than an initial rescaling, no other transformation to the primary data is applied through batch correction or renormalisation. Additional data, including single-cell datasets, can be projected for comparison, classification and annotation. The resulting atlas provides a multi-scaled approach to visualise and analyse the relationships between sets of genes and blood cell lineages, including the maturation and activation of leukocytes in vivo and in vitro. In allowing for data integration across hundreds of studies, we address a key reproduciblity challenge which is faced by any new technology. This allows us to draw on the deep phenotypes and functional annotations that accompany traditional profiling methods, and provide important context to the high cellular resolution of single cell profiling. Here, we have implemented the blood atlas in the open access Stemformatics.org platform, drawing on its extensive collection of curated transcriptome data. The method is simple, scalable and amenable for rapid deployment in other biological systems or computational workflows.
Abstract
Stemformatics is an established gene expression data portal containing over 420 public gene expression datasets derived from microarray, RNA sequencing and single cell profiling ...technologies. Developed for the stem cell community, it has a major focus on pluripotency, tissue stem cells, and staged differentiation. Stemformatics includes curated ‘collections’ of data relevant to cell reprogramming, as well as hematopoiesis and leukaemia. Rather than simply rehosting datasets as they appear in public repositories, Stemformatics uses a stringent set of quality control metrics and its own pipelines to process handpicked datasets from raw files. This means that about 30% of datasets processed by Stemformatics fail the quality control metrics and never make it to the portal, ensuring that Stemformatics data are of high quality and have been processed in a consistent manner. Stemformatics provides easy-to-use and intuitive tools for biologists to visually explore the data, including interactive gene expression profiles, principal component analysis plots and hierarchical clusters, among others. The addition of tools that facilitate cross-dataset comparisons provides users with snapshots of gene expression in multiple cell and tissues, assisting the identification of cell-type restricted genes, or potential housekeeping genes. Stemformatics is freely available at stemformatics.org.
Dendritic cells (DCs) are functionally diverse and are present in most adult tissues, but deep understanding of human DC biology is hampered by relatively small numbers of these in circulation and ...their short lifespan in human tissues. We built a transcriptional atlas of human DCs by combining samples from 14 expression profiling studies derived from 10 laboratories. We identified significant gene expression variation of DC subset-defining markers across tissue type and upon viral or bacterial stimulation. We further highlight critical gaps between in vitro-derived DC subsets and their in vivo counterparts and provide evidence that monocytes or cord blood progenitor in vitro-differentiated DCs fail to capture the repertoire of primary DC subsets or behaviors. In constructing a reference DC atlas, we provide an important resource for the community wishing to identify and annotate tissue-specific DC subsets from single-cell datasets, or benchmark new in vitro models of DC biology.
Immune checkpoint blockade (ICB) can produce durable responses against cancer. We and others have found that a subset of patients experiences paradoxical rapid cancer progression during ...immunotherapy. It is poorly understood how tumors can accelerate their progression during ICB. In some preclinical models, ICB causes hyperprogressive disease (HPD). While immune exclusion drives resistance to ICB, counterintuitively, patients with HPD and complete response (CR) following ICB manifest comparable levels of tumor-infiltrating CD8+ T cells and interferon γ (IFNγ) gene signature. Interestingly, patients with HPD but not CR exhibit elevated tumoral fibroblast growth factor 2 (FGF2) and β-catenin signaling. In animal models, T cell-derived IFNγ promotes tumor FGF2 signaling, thereby suppressing PKM2 activity and decreasing NAD+, resulting in reduction of SIRT1-mediated β-catenin deacetylation and enhanced β-catenin acetylation, consequently reprograming tumor stemness. Targeting the IFNγ-PKM2-β-catenin axis prevents HPD in preclinical models. Thus, the crosstalk of core immunogenic, metabolic, and oncogenic pathways via the IFNγ-PKM2-β-catenin cascade underlies ICB-associated HPD.
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•Hyperprogressive disease (HPD) occurs during immunotherapy•HPD is associated with high levels of IFNγ, FGF2, and β-catenin signaling•CD8+ T cell derived IFNγ promotes HPD via rewiring cancer oncometabolic pathways•High IFNγ-FGF2-β-catenin signature is a potential biomarker and target for HPD
Li et al. uncover crosstalk between core immunogenic, metabolic, and oncogenic pathways in cancer cells during immunotherapy, which enables hyperprogressive disease (HPD) in preclinical models and correlates with immunotherapy-associated HPD in patients with cancer.
We use the Dark-ages, Reionization And Galaxy formation Observables from Numerical Simulations (DRAGONS) framework to investigate the effect of galaxy formation physics on the morphology and ...statistics of ionized hydrogen (H ii) regions during the Epoch of Reioinization (EoR). DRAGONS self-consistently couples a semi-analytic galaxy formation model with the inhomogeneous ionizing UV background, and can therefore be used to study the dependence of morphology and statistics of reionization on feedback phenomena of the ionizing source galaxy population. Changes in galaxy formation physics modify the sizes of H ii regions and the amplitude and shape of 21-cm power spectra. Of the galaxy physics investigated, we find that supernova feedback plays the most important role in reionization, with H ii regions up to ≈20 per cent smaller and a fractional difference in the amplitude of power spectra of up to ≈17 per cent at fixed ionized fraction in the absence of this feedback. We compare our galaxy formation-based reionization models with past calculations that assume constant stellar-to-halo mass ratios and find that with the correct choice of minimum halo mass, such models can mimic the predicted reionization morphology. Reionization morphology at fixed neutral fraction is therefore not uniquely determined by the details of galaxy formation, but is sensitive to the mass of the haloes hosting the bulk of the ionizing sources. Simple EoR parametrizations are therefore accurate predictors of reionization statistics. However, a complete understanding of reionization using future 21-cm observations will require interpretation with realistic galaxy formation models, in combination with other observations.
Evidence for the effectiveness of serious games (SGs) and their various features is inconsistent in the motor rehabilitation field, which makes evidence based development of SGs a rare practice.
To ...investigate the effectiveness of SGs in motor rehabilitation for upper limb and movement/balance and to test the potential moderating role of SGs features like feedback, activities, characters and background.
We ran a meta-analysis including 61 studies reporting randomized controlled trials (RCTs), controlled trials (CTs) or case series designs in which at least one intervention for motor rehabilitation included the use of SGs as standalone or in combination.
There was an overall moderate effect of SGs on motor indices, d = 0.59, 95% CI, 0.48, 0.71, p < 0.001. Regarding the game features, only two out of 17 moderators were statistically different in terms of effect sizes: type of activity (combination of group with individual activities had the highest effects), and realism of the scenario (fantasy scenarios had the highest effects).
While we showed that SGs are more effective in improving motor upper limb and movement/balance functions compared to conventional rehabilitation, there were no consistent differences between various game features in their contribution to effects. Further research should systematically investigate SGs features that might have added value in improving effectiveness.
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