The HI Bias during the Epoch of Reionization

The neutral hydrogen (HI) and its 21 cm line are promising probes to the reionization process of the intergalactic medium (IGM). To use this probe effectively, it is imperative to have a good understanding on how the neutral hydrogen traces the underlying matter distribution. Here we study this problem using semi-numerical modeling by combining the HI in the IGM and the HI from halos during the epoch of reionization (EoR), and investigate the evolution and the scale-dependence of the neutral fraction bias as well as the 21 cm line bias. We find that the neutral fraction bias on large scales is negative during reionization, and its absolute value on large scales increases during the early stage of reionization and then decreases during the late stage. During the late stage of reionization, there is a transition scale at which the HI bias transits from negative on large scales to positive on small scales, and this scale increases as the reionization proceeds to the end.Comment: 11 pages, 11 figures, MNRAS accepte

14-3-3 σ Expression Effects G2/M Response to Oxygen and Correlates with Ovarian Cancer Metastasis

In vitro cell culture experiments with primary cells have reported that cell proliferation is retarded in the presence of ambient compared to physiological O₂ levels. Cancer is primarily a disease of aberrant cell proliferation, therefore, studying cancer cells grown under ambient O₂ may be undesirable. To understand better the impact of O₂ on the propagation of cancer cells in vitro, we compared the growth potential of a panel of ovarian cancer cell lines under ambient (21%) or physiological (3%) O₂.Our observations demonstrate that similar to primary cells, many cancer cells maintain an inherent sensitivity to O₂, but some display insensitivity to changes in O₂ concentration. Further analysis revealed an association between defective G2/M cell cycle transition regulation and O₂ insensitivity resultant from overexpression of 14-3-3 σ. Targeting 14-3-3 σ overexpression with RNAi restored O₂ sensitivity in these cell lines. Additionally, we found that metastatic ovarian tumors frequently overexpress 14-3-3 σ, which in conjunction with phosphorylated RB, results in poor prognosis.Cancer cells show differential proliferative sensitivity to changes in O₂ concentration. Although a direct link between O₂ insensitivity and metastasis was not determined, this investigation showed that an O₂ insensitive phenotype in cancer cells to correlate with metastatic tumor progression

Searching for the earliest galaxies in the 21 cm forest

We use a model developed by Xu et al. (2010) to compute the 21 cm line absorption signatures imprinted by star-forming dwarf galaxies (DGs) and starless minihalos (MHs). The method, based on a statistical comparison of the equivalent width (W_\nu) distribution and flux correlation function, allows us to derive a simple selection criteria for candidate DGs at very high (z >= 8) redshift. We find that ~ 18% of the total number of DGs along a line of sight to a target radio source (GRB or quasar) can be identified by the condition W_\nu < 0; these objects correspond to the high-mass tail of the DG distribution at high redshift, and are embedded in large HII regions. The criterion W_\nu > 0.37 kHz instead selects ~ 11% of MHs. Selected candidate DGs could later be re-observed in the near-IR by the JWST with high efficiency, thus providing a direct probe of the most likely reionization sources.Comment: 8 pages, 3 figures. Accepted for publication in Science in China Series

Negative Elongation Factor Controls Energy Homeostasis in Cardiomyocytes

SummaryNegative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation (FAO) and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptor α (PPARα), a master regulator of energy metabolism in the myocardium. Mechanistically, NELF helps stabilize the transcription initiation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPARα-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Topologically-protected refraction of robust kink states in valley photonic crystals

Recently discovered valley photonic crystals (VPCs) mimic many of the unusual properties of two-dimensional gapped valleytronic materials such as bilayer graphene or MoS2. Of the utmost interest to optical communications is their ability to support topologically protected chiral edge (kink) states at the internal domain wall between two VPCs with spectrally overlapping bandgap zones and opposite half-integer valley-Chern indices. We experimentally demonstrate the robustness of the kink states in VPCs that support degenerate transverse-electric-like (TE) and transverse-magnetic-like (TM) topological phases, thus enabling polarization multiplexing in a single topological waveguide. The propagation direction of the kink states is locked to the valleys of the reverse Brave lattice and, therefore, cannot be reversed in the absence of inter-valley scattering. At the intersection between the internal domain wall and the external edge separating the VPCs from free space, the kink states are shown to exhibit >97% out-coupling efficiency into directional free-space beams. This constitutes the first experimental demonstration of meron-like valley-projected topological phases with half-integer valley-Chern indices.Comment: 19 pages, 4 figure

Observation of unidirectional backscattering-immune topological electromagnetic states

One of the most striking phenomena in condensed-matter physics is the quantum Hall effect, which arises in two-dimensional electron systems subject to a large magnetic field applied perpendicular to the plane in which the electrons reside. In such circumstances, current is carried by electrons along the edges of the system, in so-called chiral edge states (CESs). These are states that, as a consequence of nontrivial topological properties of the bulk electronic band structure, have a unique directionality and are robust against scattering from disorder. Recently, it was theoretically predicted that electromagnetic analogues of such electronic edge states could be observed in photonic crystals, which are materials having refractive-index variations with a periodicity comparable to the wavelength of the light passing through them. Here we report the experimental realization and observation of such electromagnetic CESs in a magneto-optical photonic crystal fabricated in the microwave regime. We demonstrate that, like their electronic counterparts, electromagnetic CESs can travel in only one direction and are very robust against scattering from disorder; we find that even large metallic scatterers placed in the path of the propagating edge modes do not induce reflections. These modes may enable the production of new classes of electromagnetic device and experiments that would be impossible using conventional reciprocal photonic states alone. Furthermore, our experimental demonstration and study of photonic CESs provides strong support for the generalization and application of topological band theories to classical and bosonic systems, and may lead to the realization and observation of topological phenomena in a generally much more controlled and customizable fashion than is typically possible with electronic systems

Adaptive Response in Mice Exposed to 900 MHz Radiofrequency Fields: Primary DNA Damage

The phenomenon of adaptive response (AR) in animal and human cells exposed to ionizing radiation is well documented in scientific literature. We have examined whether such AR could be induced in mice exposed to non-ionizing radiofrequency fields (RF) used for wireless communications. Mice were pre-exposed to 900 MHz RF at 120 µW/cm2 power density for 4 hours/day for 1, 3, 5, 7 and 14 days and then subjected to an acute dose of 3 Gy γ-radiation. The primary DNA damage in the form of alkali labile base damage and single strand breaks in the DNA of peripheral blood leukocytes was determined using the alkaline comet assay. The results indicated that the extent of damage in mice which were pre-exposed to RF for 1 day and then subjected to γ-radiation was similar and not significantly different from those exposed to γ-radiation alone. However, mice which were pre-exposed to RF for 3, 5, 7 and 14 days showed progressively decreased damage and was significantly different from those exposed to γ-radiation alone. Thus, the data indicated that RF pre-exposure is capable of inducing AR and suggested that the pre-exposure for more than 4 hours for 1 day is necessary to elicit such AR

CMS: A web-based system for visualization and analysis of genome-wide methylation data of human cancers

DNA methylation of promoter CpG islands is associated with gene suppression, and its unique genome-wide profiles have been linked to tumor progression. Coupled with high-throughput sequencing technologies, it can now efficiently determine genome-wide methylation profiles in cancer cells. Also, experimental and computational technologies make it possible to find the functional relationship between cancer-specific methylation patterns and their clinicopathological parameters.Cancer methylome system (CMS) is a web-based database application designed for the visualization, comparison and statistical analysis of human cancer-specific DNA methylation. Methylation intensities were obtained from MBDCap-sequencing, pre-processed and stored in the database. 191 patient samples (169 tumor and 22 normal specimen) and 41 breast cancer cell-lines are deposited in the database, comprising about 6.6 billion uniquely mapped sequence reads. This provides comprehensive and genome-wide epigenetic portraits of human breast cancer and endometrial cancer to date. Two views are proposed for users to better understand methylation structure at the genomic level or systemic methylation alteration at the gene level. In addition, a variety of annotation tracks are provided to cover genomic information. CMS includes important analytic functions for interpretation of methylation data, such as the detection of differentially methylated regions, statistical calculation of global methylation intensities, multiple gene sets of biologically significant categories, interactivity with UCSC via custom-track data. We also present examples of discoveries utilizing the framework.CMS provides visualization and analytic functions for cancer methylome datasets. A comprehensive collection of datasets, a variety of embedded analytic functions and extensive applications with biological and translational significance make this system powerful and unique in cancer methylation research. CMS is freely accessible at: http://cbbiweb.uthscsa.edu/KMethylomes/