Primordial Non-Gaussianity and Analytical Formula for Minkowski Functionals of the Cosmic Microwave Background and Large-scale Structure

We derive analytical formulae for the Minkowski Functions of the cosmic microwave background (CMB) and large-scale structure (LSS) from primordial non-Gaussianity. These formulae enable us to estimate a non-linear coupling parameter, f_NL, directly from the CMB and LSS data without relying on numerical simulations of non-Gaussian primordial fluctuations. One can use these formulae to estimate statistical errors on f_NL from Gaussian realizations, which are much faster to generate than non-Gaussian ones, fully taking into account the cosmic/sampling variance, beam smearing, survey mask, etc. We show that the CMB data from the Wilkinson Microwave Anisotropy Probe should be sensitive to |f_NL|\simeq 40 at the 68% confidence level. The Planck data should be sensitive to |f_NL|\simeq 20. As for the LSS data, the late-time non-Gaussianity arising from gravitational instability and galaxy biasing makes it more challenging to detect primordial non-Gaussianity at low redshifts. The late-time effects obscure the primordial signals at small spatial scales. High-redshift galaxy surveys at z>2 covering \sim 10Gpc^3 volume would be required for the LSS data to detect |f_NL|\simeq 100. Minkowski Functionals are nicely complementary to the bispectrum because the Minkowski Functionals are defined in real space and the bispectrum is defined in Fourier space. This property makes the Minksowski Functionals a useful tool in the presence of real-world issues such as anisotropic noise, foreground and survey masks. Our formalism can be extended to scale-dependent f_NL easily.Comment: 16 pages, 5 figures, accepted for publication in ApJ (Vol. 653, 2006

Three-Dimensional Genus Statistics of Galaxies in the SDSS Early Data Release

We present the first analysis of three-dimensional genus statistics for the SDSS EDR galaxy sample. Due to the complicated survey volume and the selection function, analytic predictions of the genus statistics for this sample are not feasible, therefore we construct extensive mock catalogs from N-body simulations in order to compare the observed data with model predictions. This comparison allows us to evaluate the effects of a variety of observational systematics on the estimated genus for the SDSS sample, including the shape of the survey volume, the redshift distortion effect, and the radial selection function due to the magnitude limit. The observed genus for the SDSS EDR galaxy sample is consistent with that predicted by simulations of a $\Lambda$-dominated spatially-flat cold dark matter model. Standard ($\Omega_0=1$) cold dark matter model predictions do not match the observations. We discuss how future SDSS galaxy samples will yield improved estimates of the genus.Comment: 20 pages, 10 figures, accepted for publication in PASJ (Vol.54, No.5, 2002

Limits on Isocurvature Perturbations from Non-Gaussianity in WMAP Temperature Anisotropies

We study the effect of primordial isocurvature perturbations on non-Gaussian properties of CMB temperature anisotropies. We consider generic forms of the non-linearity of isocurvature perturbations which can be applied to a wide range of theoretical models. We derive analytical expressions for the bispectrum and the Minkowski Functionals for CMB temperature fluctuations to describe the non-Gaussianity from isocurvature perturbations. We find that the isocurvature non-Gaussianity in the quadratic isocurvature model, where the isocurvature perturbation S is written as a quadratic function of the Gaussian variable sigma, S=sigma^2-, can give the same signal-to-noise as f_NL=30 even if we impose the current observational limit on the fraction of isocurvature perturbations contained in the primordial power spectrum alpha. We give constraints on isocurvature non-Gaussianity from Minkowski Functionals using WMAP 5-year data. We do not find a significant signal of the isocurvature non-Gaussianity. For the quadratic isocurvature model, we obtain a stringent upper limit on the isocurvature fraction alpha<0.070 (95% CL) for a scale invariant spectrum which is comparable to the limit obtained from the power spectrum.Comment: 13 pages, 5 figures, MNRAS accepte

Microarray analysis of promoter methylation in lung cancers

Aberrant DNA methylation is an important event in carcinogenesis. Of the various regions of a gene that can be methylated in cancers, the promoter is the most important for the regulation of gene expression. Here, we describe a microarray analysis of DNA methylation in the promoter regions of genes using a newly developed promoter-associated methylated DNA amplification DNA chip (PMAD). For each sample, methylated Hpa II-resistant DNA fragments and Msp I-cleaved (unmethylated + methylated) DNA fragments were amplified and labeled with Cy3 and Cy5 respectively, then hybridized to a microarray containing the promoters of 288 cancer-related genes. Signals from Hpa II-resistant (methylated) DNA (Cy3) were normalized to signals from Msp I-cleaved (unmethylated + methylated) DNA fragments (Cy5). Normalized signals from lung cancer cell lines were compared to signals from normal lung cells. About 10.9% of the cancer-related genes were hypermethylated in lung cancer cell lines. Notably, HIC1, IRF7, ASC, RIPK3, RASSF1A, FABP3, PRKCDBP, and PAX3 genes were hypermethylated in most lung cancer cell lines examined. The expression profiles of these genes correlated to the methylation profiles of the genes, indicating that the microarray analysis of DNA methylation in the promoter region of the genes is convenient for epigenetic study. Further analysis of primary tumors indicated that the frequency of hypermethylation was high for ASC (82%) and PAX3 (86%) in all tumor types, and high for RIPK3 in small cell carcinoma (57%). This demonstrates that our PMAD method is effective at finding epigenetic changes during cancer

Large-Scale Anisotropic Correlation Function of SDSS Luminous Red Galaxies

We study the large-scale anisotropic two-point correlation function using 46,760 luminous red galaxies at redshifts 0.16 -- 0.47 from the Sloan Digital Sky Survey. We measure the correlation function as a function of separations parallel and perpendicular to the line-of-sight in order to take account of anisotropy of the large-scale structure in redshift space. We find a slight signal of baryonic features in the anisotropic correlation function, i.e., a ``baryon ridge'' which corresponds to a baryon acoustic peak in the spherically averaged correlation function which has already been reported using the same sample. The baryon ridge has primarily a spherical structure with a known radius in comoving coordinates. It enables us to divide the redshift distortion effects into dynamical and geometrical components and provides further constraints on cosmological parameters, including the dark energy equation-of-state. With an assumption of a flat $\Lambda$ cosmology, we find the best-fit values of $\Omega_{\rm m} = 0.218^{+0.047}_{-0.037}$ and $\Omega_{\rm b} = 0.047^{+0.016}_{-0.016}$ (68% C.L.) when we use the overall shape of the anisotropic correlation function of 40 including a scale of baryon acoustic oscillations. When an additional assumption $\Omega_{\rm b}h^2=0.024$ is adopted, we obtain $\Omega_{\rm DE}=0.770^{+0.051}_{-0.040}$ and $w=-0.93^{+0.45}_{-0.35}$. These constraints are estimated only from our data of the anisotropic correlation function, and they agree quite well with values both from the cosmic microwave background (CMB) anisotropies and from other complementary statistics using the LRG sample. With the CMB prior from the 3 year WMAP results, we give stronger constraints on those parameters.Comment: 11 pages, 9 figures, 1 table, typo corrected, references added with respect to published versio

Using galaxy-galaxy weak lensing measurements to correct the Finger-of-God

For decades, cosmologists have been using galaxies to trace the large-scale distribution of matter. At present, the largest source of systematic uncertainty in this analysis is the challenge of modeling the complex relationship between galaxy redshift and the distribution of dark matter. If all galaxies sat in the centers of halos, there would be minimal Finger-of-God (FoG) effects and a simple relationship between the galaxy and matter distributions. However, many galaxies, even some of the luminous red galaxies (LRGs), do not lie in the centers of halos. Because the galaxy-galaxy lensing is also sensitive to the off-centered galaxies, we show that we can use the lensing measurements to determine the amplitude of this effect and to determine the expected amplitude of FoG effects. We develop an approach for using the lensing data to model how the FoG suppresses the power spectrum amplitudes and show that the current data implies a 30% suppression at wavenumber k=0.2h/Mpc. Our analysis implies that it is important to complement a spectroscopic survey with an imaging survey with sufficient depth and wide field coverage. Joint imaging and spectroscopic surveys allow a robust, unbiased use of the power spectrum amplitude information: it improves the marginalized error of growth rate fg=dln D/dln a by up to a factor of 2 over a wide range of redshifts z<1.4. We also find that the dark energy equation-of-state parameter, w0, and the neutrino mass, fnu, can be unbiasedly constrained by combining the lensing information, with an improvement of 10--25% compared to a spectroscopic survey without lensing calibration.Comment: 26 pages, 13 figures, accepted for publication in MNRA

Impact on cell to plasma ratio of miR-92a in patients with acute leukemia: in vivo assessment of cell to plasma ratio of miR-92a

<p>Abstract</p> <p>Background</p> <p>Plasma microRNA (miRNA) has become a promising biomarker for detecting cancer; however, it remains uncertain whether miRNA expression levels in plasma reflect those in tumor cells. Our aim was to determine the biological relevance of miR-92a, which has been implicated as an oncomiR in both plasma and leukemia cells in patients with acute leukemia and to evaluate whether it could be a novel biomarker for monitoring these patients.</p> <p>Results</p> <p>We quantified the expression level of miR-92a in both cells and plasma by reverse transcription polymerase chain reaction in 91 patients with acute leukemia. We also determined miR-92a expression levels in peripheral blood mononuclear cells (PBMNC) from normal controls. We compared miR-92a expression in plasma with its expression in leukemia cells. Synthetic anti-miR-92a inhibitor was transfected into Raji and OM9;22 cells, and apoptosis was assessed. For in vivo assessment, 6-week-old female nude mice were injected with U937 cells, and miR-92a expression in plasma and tumors was measured. The level of miR-92a expression in fresh leukemia cells was highly variable compared with PBMNC, but significantly lower compared with CD34-positive cells obtained from healthy volunteers. We also noticed that miR-92a was preferentially expressed in acute lymphoblastic leukemia (ALL) cells in comparison with acute myeloid leukemia (AML) cells. More specifically, cellular miR-92a expression was significantly increased in a subset of ALL cells, and ALL patients with overexpressed miR-92a had poor prognoses. The anti-miR-92a inhibitor-treated Raji and OM9;22 cells revealed an increase of apoptotic cells. Notably, the cell to plasma ratio of miR-92a expression was significantly higher in both AML and ALL cells compared with PBMNC from healthy volunteers. In tumor-bearing mice, the plasma miR-92a level was significantly decreased in accordance with tumor growth, while tumor tissue was strongly positive for miR-92a.</p> <p>Conclusions</p> <p>The miR-92a expression in leukemia cells could be a prognostic factor in ALL patients. The inverse correlation of miR-92a expression between cells and plasma and the cell to plasma ratio may be important to understanding the clinical and biological relevance of miR-92a in acute leukemia.</p

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target