Development of super broadband interferometer in FIR

We are developing the super broad band interferometer by applying the Fourier Transform Spectrometer(FTS) to aperture synthesis system in mm and sub-mm bands. We have constructed a compact system based on the Martin and Puplett type Fourier Transform spectrometer (MP-FT). We call this equipment Multi-Fourier Transform interferometer (MuFT). The band width of the system can be extended as large as one wants contrary to the severely limited band width of the usual interferometer due to the speed of the AD converter. The direct detectors, e.g. bolometer, SIS video detector, can be used as the focal plane detectors. This type of detectors have a great advantage in FIR band since they are free from the quantum limit of the noise which limits the sensitivity of the heterodyne detectors used in the usual interferometers. Further, the direct detectors are able to make a large format array contrary to the heterodyne detectors for which construction of a large format array is practically difficult. These three characteristics make one be possible to develop high sensitive super broad band FIR interferometer with wide field of view. In the laboratory experiments, we have succeeded in measuring the spectroscopically resolved 2D image of the source in 150GHz-900GHz band. The future application of this technique to the observations from the space could open new interesting possibilities in FIR astronomy.Comment: 9 pages, presented at the Glasgow SPIE conference "Optical, Infrared, and Millimeter Space Telescopes", to appear in Proc. SPIE, vol. #5487-20

Differential functions of G protein and Baz–aPKC signaling pathways in Drosophila neuroblast asymmetric division

Drosophila melanogaster neuroblasts (NBs) undergo asymmetric divisions during which cell-fate determinants localize asymmetrically, mitotic spindles orient along the apical–basal axis, and unequal-sized daughter cells appear. We identified here the first Drosophila mutant in the Gγ1 subunit of heterotrimeric G protein, which produces Gγ1 lacking its membrane anchor site and exhibits phenotypes identical to those of Gβ13F, including abnormal spindle asymmetry and spindle orientation in NB divisions. This mutant fails to bind Gβ13F to the membrane, indicating an essential role of cortical Gγ1–Gβ13F signaling in asymmetric divisions. In Gγ1 and Gβ13F mutant NBs, Pins–Gαi, which normally localize in the apical cortex, no longer distribute asymmetrically. However, the other apical components, Bazooka–atypical PKC–Par6–Inscuteable, still remain polarized and responsible for asymmetric Miranda localization, suggesting their dominant role in localizing cell-fate determinants. Further analysis of Gβγ and other mutants indicates a predominant role of Partner of Inscuteable–Gαi in spindle orientation. We thus suggest that the two apical signaling pathways have overlapping but different roles in asymmetric NB division

Automated bone marrow analysis using the CD4000 automated haematology analyser

At present, bone marrow analysis is performed microscopically, but is time consuming and labour intensive. No automated methods have been successfully applied to classification of bone marrows cells because automated blood cell analysers have been incapable of identifying erythroblasts. The present study was designed to evaluate automated analysis of bone marrow aspirates with the CELL-DYN 4000 (CD4000) haematology analyser, which enables automated determination of erythroblast counts in both the normal mode (haemolytic time; 11.5s) and the resistant RBC mode (34.0s). The percentages of subpopulations including lymphocytes, neutrophils and erythroblasts were obtained with the CD4000, and as a reference, differential counts by microscopic observation of May–Grünwald–Giesa-stained films of bone marrow aspirates were performed (n=98). Significant correlations (P < 0.01) between the results obtained with the two methods were observed for total nucleated cell count and lymphocytes, neutrophils, erythroblasts and myeloid/erythroid (M/E) ratio. However, there were biases in the average percentages of erythroblasts, lymphocytes and M/E ratio obtained using the normal mode with the CD4000 toward values lower than those obtained with the microscopic method. Using the RBC resistant mode with the CD4000, the average percentages of erythroblasts, lymphocytes and M/E ratio approximated those obtained with the microscopic method. In conclusion, the CD4000 in resistant RBC mode is more useful for analysis of bone marrow aspirates than is the normal mode, because the former better approximates the M/E ratio than the latter

Comparative proteomic analysis of Salmonella enterica serovar Typhimurium ppGpp-deficient mutant to identify a novel virulence protein required for intracellular survival in macrophages

<p>Abstract</p> <p>Background</p> <p>The global ppGpp-mediated stringent response in pathogenic bacteria plays an important role in the pathogenesis of bacterial infections. In <it>Salmonella enterica </it>serovar Typhimurium (<it>S</it>. Typhimurium), several genes, including virulence genes, are regulated by ppGpp when bacteria are under the stringent response. To understand the control of virulence genes by ppGpp in <it>S</it>. Typhimurium, agarose 2-dimensional electrophoresis (2-DE) combined with mass spectrometry was used and a comprehensive 2-DE reference map of amino acid-starved <it>S</it>. Typhimurium strain SH100, a derivative of ATCC 14028, was established.</p> <p>Results</p> <p>Of the 366 examined spots, 269 proteins were successfully identified. The comparative analysis of the wild-type and ppGpp⁰mutant strains revealed 55 proteins, the expression patterns of which were affected by ppGpp. Using a mouse infection model, we further identified a novel virulence-associated factor, STM3169, from the ppGpp-regulated and <it>Salmonella</it>-specific proteins. In addition, <it>Salmonella </it>strains carrying mutations in the gene encoding STM3169 showed growth defects and impaired growth within macrophage-like RAW264.7 cells. Furthermore, we found that expression of <it>stm3169 </it>was controlled by ppGpp and SsrB, a response regulator of the two-component system located on <it>Salmonella </it>pathogenicity island 2.</p> <p>Conclusions</p> <p>A proteomic approach using a 2-DE reference map can prove a powerful tool for analyzing virulence factors and the regulatory network involved in <it>Salmonella </it>pathogenesis. Our results also provide evidence of a global response mediated by ppGpp in <it>S. enterica</it>.</p

The nonlinear redshift space probability distribution function in models with local primordial non-Gaussianity

We use the ellipsoidal collapse approximation to investigate the nonlinear redshift space evolution of the density field with primordial non-Gaussianity of the local f_{nl}-type. We utilize the joint distribution of eigenvalues of the initial non-Gaussian shear field and evaluate the evolved redshift space probability distribution function (PDF). It is shown that, similar to the real space analysis, the underdense tail of the nonlinear redshift space PDF differs significantly from that for Gaussian initial conditions. We also derive the lowest order correction of the Kaiser's formulain the presence of a non-zero f_{nl}.Comment: Matched version accepted by MNRA

Very compact millimeter sizes for composite star-forming/AGN submillimeter galaxies

We report the study of far-IR sizes of submillimeter galaxies (SMGs) in relation to their dust-obscured star formation rate (SFR) and active galactic nuclei (AGN) presence, determined using mid-IR photometry. We determined the millimeter-wave ($\lambda_{\rm obs}=1100 \mu$m) sizes of 69 ALMA-identified SMGs, selected with $\geq10$$\sigma$ confidence on ALMA images ($F_{\rm 1100 \mu m}=1.7$--7.4 mJy). We found that all the SMGs are located above an avoidance region in the millimeter size-flux plane, as expected by the Eddington limit for star formation. In order to understand what drives the different millimeter-wave sizes in SMGs, we investigated the relation between millimeter-wave size and AGN fraction for 25 of our SMGs at $z=1$--3. We found that the SMGs for which the mid-IR emission is dominated by star formation or AGN have extended millimeter-sizes, with respective median $R_{\rm c,e} = 1.6^{+0.34}_{-0.21}$ and 1.5$^{+0.93}_{-0.24}$ kpc. Instead, the SMGs for which the mid-IR emission corresponds to star-forming/AGN composites have more compact millimeter-wave sizes, with median $R_{\rm c,e}=1.0^{+0.20}_{-0.20}$ kpc. The relation between millimeter-wave size and AGN fraction suggests that this size may be related to the evolutionary stage of the SMG. The very compact sizes for composite star-forming/AGN systems could be explained by supermassive black holes growing rapidly during the SMG coalescing, star-formation phase.Comment: 9 pages, 4 figures, 1 table. Accepted for publication in ApJ Lette

SXDF-ALMA 2 Arcmin^2 Deep Survey: Resolving and Characterizing the Infrared Extragalactic Background Light Down to 0.5 mJy

We present a multi-wavelength analysis of five submillimeter sources (S_1.1mm = 0.54-2.02 mJy) that were detected during our 1.1-mm-deep continuum survey in the SXDF-UDS-CANDELS field (2 arcmin^2, 1sigma = 0.055 mJy beam^-1) using the Atacama Large Millimeter/submillimeter Array (ALMA). The two brightest sources correspond to a known single-dish (AzTEC) selected bright submillimeter galaxy (SMG), whereas the remaining three are faint SMGs newly uncovered by ALMA. If we exclude the two brightest sources, the contribution of the ALMA-detected faint SMGs to the infrared extragalactic background light is estimated to be ~ 4.1^{+5.4}_{-3.0} Jy deg^{-2}, which corresponds to ~ 16^{+22}_{-12}% of the infrared extragalactic background light. This suggests that their contribution to the infrared extragalactic background light is as large as that of bright SMGs. We identified multi-wavelength counterparts of the five ALMA sources. One of the sources (SXDF-ALMA3) is extremely faint in the optical to near-infrared region despite its infrared luminosity (L_IR ~ 1e12 L_sun or SFR ~ 100 M_sun yr^{-1}). By fitting the spectral energy distributions (SEDs) at the optical-to-near-infrared wavelengths of the remaining four ALMA sources, we obtained the photometric redshifts (z_photo) and stellar masses (M_*): z_photo ~ 1.3-2.5, M_* ~ (3.5-9.5)e10 M_sun. We also derived their star formation rates (SFRs) and specific SFRs (sSFRs) as ~ 30-200 M_sun yr^{-1} and ~ 0.8-2 Gyr^{-1}, respectively. These values imply that they are main-sequence star-forming galaxies.Comment: PASJ accepted, 15 pages, 6 figures, 2 table

iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD). Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ), a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development

Nuclear Quadrupole Resonance Frequency in Multi-Layered Cuprates

The 63Cu nuclear quadrupole resonance (NQR) frequency, nu_q, in the multi-layered cuprates is calculated in the cluster model by the exact diagonalization method. The charge imbalance between the outer CuO_2 plane (OP) with apical oxygen (OA) and the inner plane (IP) without OA in three-layered Tl2223 is estimated by comparing our results with the experimental nu_q. In Tl-based cuprates with more than three layers, we predict a large enhancement of the splitting of nu_q between OP and IP by taking into account the reduction of bond length between Cu and OA and a resulting enhancement of the charge transfer energy. Our results show that the NQR frequency is a useful quantity to estimate the charge imbalance in the multi-layered cuprates.Comment: 4 pages, 5 figure

Compact starbursts in z~3-6 submillimeter galaxies revealed by ALMA

We report the source size distribution, as measured by ALMA millimetric continuum imaging, of a sample of 13 AzTEC-selected submillimeter galaxies (SMGs) at z_photo ~ 3-6. Their infrared luminosities and star-formation rates (SFR) are L_IR ~ 2-6 x 10^12 L_sun and ~ 200-600 M_sun yr-1, respectively. The size of z ~ 3-6 SMGs ranges from 0".10 to 0".38 with a median of 0".20+0".03-0".05 (FWHM), corresponding to a median circularized effective radius (Rc,e) of 0.67+0.13-0.14 kpc, comparable to the typical size of the stellar component measured in compact quiescent galaxies at z ~ 2 (cQGs) --- R ~ 1 kpc. The median surface SFR density of our z ~ 3-6 SMGs is 100+42-26 M_sun yr-1 kpc-2, comparable to that seen in local merger-driven (U)LIRGsrather than in extended disk galaxies at low and high redshifts. The discovery of compact starbursts in z >~ 3 SMGs strongly supports a massive galaxy formation scenario wherein z ~ 3-6 SMGs evolve into the compact stellar components of z ~ 2 cQGs. These cQGs are then thought to evolve into the most massive ellipticals in the local Universe, mostly via dry mergers. Our results thus suggest that z >~ 3 SMGs are the likely progenitors of massive local ellipticals, via cQGs, meaning that we can now trace the evolutionary path of the most massive galaxies over a period encompassing ~ 90% of the age of the Universe.Comment: 12 pages, 10 figures, accepted to the Astrophysical Journal part