Chemorepulsion by blood S1P regulates osteoclast precursor mobilization and bone remodeling in vivo

Chemotaxis and chemorepulsion of osteoclast precursors depends on S1P concentrations and expression of the receptors S1PR1 and S1PR2, which act to regulate osteoclast precursor localization

A Tunable Lyot Filter at Prime Focus: a Method for Tracing Supercluster Scales at z ~ 1

Tunable narrow-band, emission-line surveys have begun to show the ease with which star forming galaxies can be identified in restricted redshift intervals to z ~ 5 with a 4m class telescope. These surveys have been carried out with imaging systems at the Cassegrain or Nasmyth focus and are therefore restricted to fields smaller than 10 arcmin. We now show that tunable narrowband imaging is possible over a 30 arcmin field with a high-performance Lyot filter placed directly in front of a CCD mosaic at the prime focus. Our design is intended for the f/3.3 prime focus of the AAT 3.9m, although similar devices can be envisaged for the Subaru 8m (f/2), Palomar 5m (f/3.4), VISTA 4m (f/6), Mayall 4m (f/2.6) or CFHT 3.6m (f/4). A modified Wynne doublet ensures sub-arcsecond performance over the field. In combination with the new Wide-Field Imaging 8K x 8K mosaic (WFI) at the AAT, the overall throughput (35%) of the system to unpolarised light is expected to be comparable to the TAURUS Tunable Filter (TTF). Unlike the TTF, the field is fully monochromatic and the instrumental profile has much better wing suppression. For targetted surveys of emission-line sources at z ~ 1, a low-resolution (R ~ 150 at 550nm) Lyot filter on a 4m telescope is expected to be comparable or superior to current instruments on 8-10m class telescopes. We demonstrate that the 30 arcmin field is well matched to superclusters at these redshifts such that large-scale structure should be directly observable.Comment: Astrophysical Journal, accepted. 53 pages, 16 figures, aaste

Insulated gate and surface passivation structures for GaN-based power transistors

Recent years have witnessed GaN-based devices delivering their promise of unprecedented power and frequency levels and demonstrating their capability as an able replacement for Si-based devices. High-electron-mobility transistors (HEMTs), a key representative architecture of GaN-based devices, are well-suited for high-power and high frequency device applications, owing to highly desirable III-nitride physical properties. However, these devices are still hounded by issues not previously encountered in their more established Si- and GaAs-based devices counterparts. Metal–insulator–semiconductor (MIS) structures are usually employed with varying degrees of success in sidestepping the major problematic issues such as excessive leakage current and current instability. While different insulator materials have been applied to GaN-based transistors, the properties of insulator/III-N interfaces are still not fully understood. This is mainly due to the difficulty of characterizing insulator/AlGaN interfaces in a MIS HEMT because of the two resulting interfaces: insulator/AlGaN and AlGaN/GaN, making the potential modulation rather complicated. Although there have been many reports of low interface-trap densities in HEMT MIS capacitors, several papers have incorrectly evaluated their capacitance–voltage (C–V) characteristics. A HEMT MIS structure typically shows a 2-step C–V behavior. However, several groups reported C–V curves without the characteristic step at the forward bias regime, which is likely to the high-density states at the insulator/AlGaN interface impeding the potential control of the AlGaN surface by the gate bias. In this review paper, first we describe critical issues and problems including leakage current, current collapse and threshold voltage instability in AlGaN/GaN HEMTs. Then we present interface properties, focusing on interface states, of GaN MIS systems using oxides, nitrides and high-κ dielectrics. Next, the properties of a variety of AlGaN/GaN MIS structures as well as different characterization methods, including our own photo-assisted C–V technique, essential for understanding and developing successful surface passivation and interface control schemes, are given in the subsequent section. Finally we highlight the important progress in GaN MIS interfaces that have recently pushed the frontier of nitride-based device technology

PEARLS: Near-infrared Photometry in the JWST North Ecliptic Pole Time Domain Field * * Partly based on observations taken with the MMT, a joint facility operated by the University of Arizona and the Smithsonian Institution.

We present near-infrared (NIR) ground-based Y, J, H, and K imaging obtained in the James Webb Space Telescope (JWST) North Ecliptic Pole Time Domain Field (NEP TDF) using the MMT-Magellan Infrared Imager and Spectrometer on the MMT. These new observations cover a field of approximately 230 arcmin2 in Y, H, and K, and 313 arcmin2 in J. Using Monte Carlo simulations, we estimate a 1σ depth relative to the background sky of (Y, J, H, K) = (23.80, 23.53, 23.13, 23.28) in AB magnitudes for point sources at a 95% completeness level. These observations are part of the ground-based effort to characterize this region of the sky, supplementing space-based data obtained with Chandra, NuSTAR, XMM, AstroSat, Hubble Space Telescope, and JWST. This paper describes the observations and reduction of the NIR imaging and combines these NIR data with archival imaging in the visible, obtained with the Subaru Hyper-Suprime-Cam, to produce a merged catalog of 57,501 sources. The new observations reported here, plus the corresponding multiwavelength catalog, will provide a baseline for time-domain studies of bright sources in the NEP TDF

PEARLS: Near Infrared Photometry in the JWST North Ecliptic Pole Time Domain Field

We present Near-Infrared (NIR) ground-based Y, J, H, and K imaging obtained in the James Webb Space Telescope North Ecliptic Pole Time Domain Field (TDF) using the MMT-Magellan Infrared Imager and Spectrometer (MMIRS) on the MMT.These new observations cover a field of approximately 230 arcmin^2 in Y, H, and K and 313 arcmin^2 in J. Using Monte Carlo simulations we estimate a 1 sigma depth relative to the background sky of (Y, J, H, K}) = (23.80, 23.53, 23.13, 23.28) in AB magnitudes for point sources at a 95% completeness level. These observations are part of the ground-based effort to characterize this region of the sky, supplementing space-based data obtained with Chandra, NuSTAR, XMM, AstroSat, HST, and JWST. This paper describes the observations and reduction of the NIR imaging and combines these NIR data with archival imaging in the visible, obtained with the Subaru Hyper-Suprime-Cam, to produce a merged catalog of 57,501 sources. The new observations reported here, plus the corresponding multi-wavelength catalog, will provide a baseline for time-domain studies of bright sources in the TDF.Comment: 23 pages, 10 figures. Accepted for publication in ApJS. Images and catalogs available at https://doi.org/10.5281/zenodo.7934393. Data description available under ancillary files and at the Zenodo site. Added a reference, fixed typos in metadat

Structural Relationships between Highly Conserved Elements and Genes in Vertebrate Genomes

Large numbers of sequence elements have been identified to be highly conserved among vertebrate genomes. These highly conserved elements (HCEs) are often located in or around genes that are involved in transcription regulation and early development. They have been shown to be involved in cis-regulatory activities through both in vivo and additional computational studies. We have investigated the structural relationships between such elements and genes in six vertebrate genomes human, mouse, rat, chicken, zebrafish and tetraodon and detected several thousand cases of conserved HCE-gene associations, and also cases of HCEs with no common target genes. A few examples underscore the potential significance of our findings about several individual genes. We found that the conserved association between HCE/HCEs and gene/genes are not restricted to elements by their absolute distance on the genome. Notably, long-range associations were identified and the molecular functions of the associated genes do not show any particular overrepresentation of the functional categories previously reported. HCEs in close proximity are found to be linked with different set of gene/genes. The results reflect the highly complex correlation between HCEs and their putative target genes

Novel Mouse Xenograft Models Reveal a Critical Role of CD4+ T Cells in the Proliferation of EBV-Infected T and NK Cells

Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients' PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rγnull strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Expression of the EBV nuclear antigen 1 (EBNA1), the latent membrane protein 1 (LMP1), and LMP2, but not EBNA2, in the engrafted cells is consistent with the latency II program of EBV gene expression known in CAEBV. High levels of human cytokines, including IL-8, IFN-γ, and RANTES, were detected in the peripheral blood of the model mice, mirroring hypercytokinemia characteristic to both CAEBV and EBV-HLH. Transplantation of individual immunophenotypic subsets isolated from patients' PBMC as well as that of various combinations of these subsets revealed a critical role of CD4+ T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4+ T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases

Integrative analysis of genomic, functional and protein interaction data predicts long-range enhancer-target gene interactions

Multicellular organismal development is controlled by a complex network of transcription factors, promoters and enhancers. Although reliable computational and experimental methods exist for enhancer detection, prediction of their target genes remains a major challenge. On the basis of available literature and ChIP-seq and ChIP-chip data for enhanceosome factor p300 and the transcriptional regulator Gli3, we found that genomic proximity and conserved synteny predict target genes with a relatively low recall of 12–27% within 2 Mb intervals centered at the enhancers. Here, we show that functional similarities between enhancer binding proteins and their transcriptional targets and proximity in the protein–protein interactome improve prediction of target genes. We used all four features to train random forest classifiers that predict target genes with a recall of 58% in 2 Mb intervals that may contain dozens of genes, representing a better than two-fold improvement over the performance of prediction based on single features alone. Genome-wide ChIP data is still relatively poorly understood, and it remains difficult to assign biological significance to binding events. Our study represents a first step in integrating various genomic features in order to elucidate the genomic network of long-range regulatory interactions

SynBlast: Assisting the analysis of conserved synteny information

<p>Abstract</p> <p>Motivation</p> <p>In the last years more than 20 vertebrate genomes have been sequenced, and the rate at which genomic DNA information becomes available is rapidly accelerating. Gene duplication and gene loss events inherently limit the accuracy of orthology detection based on sequence similarity alone. Fully automated methods for orthology annotation do exist but often fail to identify individual members in cases of large gene families, or to distinguish missing data from traceable gene losses. This situation can be improved in many cases by including conserved synteny information.</p> <p>Results</p> <p>Here we present the <monospace>SynBlast</monospace> pipeline that is designed to construct and evaluate local synteny information. <monospace>SynBlast</monospace> uses the genomic region around a focal reference gene to retrieve candidates for homologous regions from a collection of target genomes and ranks them in accord with the available evidence for homology. The pipeline is intended as a tool to aid high quality manual annotation in particular in those cases where automatic procedures fail. We demonstrate how <monospace>SynBlast</monospace> is applied to retrieving orthologous and paralogous clusters using the vertebrate <it>Hox </it>and <it>ParaHox </it>clusters as examples.</p> <p>Software</p> <p>The <monospace>SynBlast</monospace> package written in <monospace>Perl</monospace> is available under the GNU General Public License at <url>http://www.bioinf.uni-leipzig.de/Software/SynBlast/</url>.</p