285 research outputs found

    Weak lensing minima and peaks: Cosmological constraints and the impact of baryons

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    We present a novel statistic to extract cosmological information in weak lensing data: the lensing minima. We also investigate the effect of baryons on the cosmological constraints from peak and minimum counts. Using the \texttt{MassiveNuS} simulations, we find that lensing minima are sensitive to non-Gaussian cosmological information and are complementary to the lensing power spectrum and peak counts. For an LSST-like survey, we obtain 95%95\% credible intervals from a combination of lensing minima and peaks that are significantly stronger than from the power spectrum alone, by 44%44\%, 11%11\%, and 63%63\% for the neutrino mass sum mν\sum m_\nu, matter density Ωm\Omega_m, and amplitude of fluctuation AsA_s, respectively. We explore the effect of baryonic processes on lensing minima and peaks using the hydrodynamical simulations \texttt{BAHAMAS} and \texttt{Osato15}. We find that ignoring baryonic effects would lead to strong (4σ\approx 4 \sigma) biases in inferences from peak counts, but negligible (0.5σ\approx 0.5 \sigma) for minimum counts, suggesting lensing minima are a potentially more robust tool against baryonic effects. Finally, we demonstrate that the biases can in principle be mitigated without significantly degrading cosmological constraints when we model and marginalize the baryonic effects.UK Science and Technology Facilities Council (grant number ST/N000927/1)

    Grafting Neural Stem and Progenitor Cells Into the Hippocampus of Juvenile, Irradiated Mice Normalizes Behavior Deficits

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    The pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus of the hippocampus is reduced by ionizing radiation. This explains, at least partly, the learning deficits observed in patients after radiotherapy, particularly in pediatric cases. An 8 Gy single irradiation dose was delivered to the whole brains of postnatal day 9 (P9) C57BL/6 mice, and BrdU-labeled, syngeneic NSPCs (1.0 × 105 cells/injection) were grafted into each hippocampus on P21. Three months later, behavior tests were performed. Irradiation impaired novelty-induced exploration, place learning, reversal learning, and sugar preference, and it altered the movement pattern. Grafting of NSPCs ameliorated or even normalized the observed deficits. Less than 4% of grafted cells survived and were found in the dentate gyrus 5 months later. The irradiation-induced loss of endogenous, undifferentiated NSPCs in the dentate gyrus was completely restored by grafted NSPCs in the dorsal, but not the ventral, blade. The grafted NSPCs did not exert appreciable effects on the endogenous NSPCs; however, more than half of the grafted NSPCs differentiated. These results point to novel strategies aimed at ameliorating the debilitating late effects of cranial radiotherapy, particularly in children

    The Hyper Suprime-Cam SSP Survey: Overview and Survey Design

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    Hyper Suprime-Cam (HSC) is a wide-field imaging camera on the prime focus of the 8.2m Subaru telescope on the summit of Maunakea in Hawaii. A team of scientists from Japan, Taiwan and Princeton University is using HSC to carry out a 300-night multi-band imaging survey of the high-latitude sky. The survey includes three layers: the Wide layer will cover 1400 deg2^2 in five broad bands (grizygrizy), with a 5σ5\,\sigma point-source depth of r26r \approx 26. The Deep layer covers a total of 26~deg2^2 in four fields, going roughly a magnitude fainter, while the UltraDeep layer goes almost a magnitude fainter still in two pointings of HSC (a total of 3.5 deg2^2). Here we describe the instrument, the science goals of the survey, and the survey strategy and data processing. This paper serves as an introduction to a special issue of the Publications of the Astronomical Society of Japan, which includes a large number of technical and scientific papers describing results from the early phases of this survey.Comment: 14 pages, 7 figures, 5 tables. Corrected for a typo in the coordinates of HSC-Wide spring equatorial field in Table

    Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

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    Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

    Integrative analysis of RUNX1 downstream pathways and target genes

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    Background: The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML). The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. Results: Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1) cell lines with RUNX1 mutations from FPD-AML patients, 2) over-expression of RUNX1 and CBF[Beta], and 3) Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes) significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBF[Beta]. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. Conclusion: This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease progression in both familial and sporadic leukemia as well as therapeutic implications

    Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana

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    We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ~32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene

    Lysine acetyltransferase Tip60 is required for hematopoietic stem cell maintenance.

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    Hematopoietic stem cells (HSCs) have the potential to replenish the blood system for the lifetime of the organism. Their 2 defining properties, self-renewal and differentiation, are tightly regulated by the epigenetic machineries. Using conditional gene-knockout models, we demonstrated a critical requirement of lysine acetyltransferase 5 (Kat5, also known as Tip60) for murine HSC maintenance in both the embryonic and adult stages, which depends on its acetyltransferase activity. Genome-wide chromatin and transcriptome profiling in murine hematopoietic stem and progenitor cells revealed that Tip60 colocalizes with c-Myc and that Tip60 deletion suppress the expression of Myc target genes, which are associated with critical biological processes for HSC maintenance, cell cycling, and DNA repair. Notably, acetylated H2A.Z (acH2A.Z) was enriched at the Tip60-bound active chromatin, and Tip60 deletion induced a robust reduction in the acH2A.Z/H2A.Z ratio. These results uncover a critical epigenetic regulatory layer for HSC maintenance, at least in part through Tip60-dependent H2A.Z acetylation to activate Myc target genes.Cancer Research UK, Wellcome Trust, National Institutes of Health, Singapore state fundin

    HSC Year 1 cosmology results with the minimal bias method: HSC×\timesBOSS galaxy-galaxy weak lensing and BOSS galaxy clustering

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    We present cosmological parameter constraints from a blinded joint analysis of galaxy-galaxy weak lensing, Δ ⁣Σ(R)\Delta\!\Sigma(R), and projected correlation function, wp(R)w_\mathrm{p}(R), measured from the first-year HSC (HSC-Y1) data and SDSS spectroscopic galaxies over 0.15<z<0.70.15<z<0.7. We use luminosity-limited samples as lens samples for Δ ⁣Σ\Delta\!\Sigma and as large-scale structure tracers for wpw_\mathrm{p} in three redshift bins, and use the HSC-Y1 galaxy catalog to define a secure sample of source galaxies at zph>0.75z_\mathrm{ph}>0.75 for the Δ ⁣Σ\Delta\!\Sigma measurements, selected based on their photometric redshifts. For theoretical template, we use the "minimal bias" model for the cosmological clustering observables for the flat Λ\LambdaCDM cosmological model. We compare the model predictions with the measurements in each redshift bin on large scales, R>12R>12 and 8 h1Mpc8~h^{-1}\mathrm{Mpc} for Δ ⁣Σ(R)\Delta\!\Sigma(R) and wp(R)w_\mathrm{p}(R), respectively, where the perturbation theory-inspired model is valid. When we employ weak priors on cosmological parameters, without CMB information, we find S8=0.9360.086+0.092S_8=0.936^{+0.092}_{-0.086}, σ8=0.850.11+0.16\sigma_8=0.85^{+0.16}_{-0.11}, and Ωm=0.2830.035+0.12\Omega_\mathrm{m}=0.283^{+0.12}_{-0.035} for the flat Λ\LambdaCDM model. Although the central value of S8S_8 appears to be larger than those inferred from other cosmological experiments, we find that the difference is consistent with expected differences due to sample variance, and our results are consistent with the other results to within the statistical uncertainties. (abriged)Comment: 24 pages, 19 figures, 4 tables, to be submitted to Phys. Rev.
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