DAMP-Inducing Adjuvant and PAMP Adjuvants Parallelly Enhance Protective Type-2 and Type-1 Immune Responses to Influenza Split Vaccination

Recently, it was reported that 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD), a common pharmaceutical additive, can act as a vaccine adjuvant to enhance protective type-2 immunogenicity to co-administered seasonal influenza split vaccine by inducing host-derived damage-associated molecular patterns (DAMPs). However, like most other DAMP-inducing adjuvants such as aluminum hydroxide (Alum), HP-β-CyD may not be sufficient for the induction of protective type-1 (cellular) immune responses, thereby leaving room for improvement. Here, we demonstrate that a combination of HP-β-CyD with a humanized TLR9 agonist, K3 CpG-ODN, a potent pathogen-associated molecular pattern (PAMP), enhanced the protective efficacy of the co-administered influenza split vaccine by inducing antigen-specific type-2 and type-1 immune responses, respectively. Moreover, substantial antigen-specific IgE induction by HP-β-CyD, which can cause an allergic response to immunized antigen was completely suppressed by the addition of K3 CpG-ODN. Furthermore, HP-β-CyD- and K3 CpG-ODN-adjuvanted influenza split vaccination protected the mice against lethal challenge with high doses of heterologous influenza virus, which could not be protected against by single adjuvant vaccines. Further experiments using gene deficient mice revealed the unique immunological mechanism of action in vivo, where type-2 and type-1 immune responses enhanced by the combined adjuvants were dependent on TBK1 and TLR9, respectively, indicating their parallel signaling pathways. Finally, the analysis of immune responses in the draining lymph node suggested that HP-β-CyD promotes the uptake of K3 CpG-ODN by plasmacytoid dendritic cells and B cells, which may contributes to the activation of these cells and enhanced production of IgG2c. Taken together, the results above may offer potential clinical applications for the combination of DAMP-inducing adjuvant and PAMP adjuvant to improve vaccine immunogenicity and efficacy by enhancing both type-2 and type-1 immune responses in a parallel manner

The Structure of Pre-transitional Protoplanetary Disks I: Radiative Transfer Modeling of the Disk+Cavity in the PDS 70 system

Through detailed radiative transfer modeling, we present a disk+cavity model to simultaneously explain both the SED and Subaru H-band polarized light imaging for the pre-transitional protoplanetary disk PDS 70. Particularly, we are able to match not only the radial dependence, but also the absolute scale, of the surface brightness of the scattered light. Our disk model has a cavity 65 AU in radius, which is heavily depleted of sub-micron-sized dust grains, and a small residual inner disk which produces a weak but still optically thick NIR excess in the SED. To explain the contrast of the cavity edge in the Subaru image, a factor of ~1000 depletion for the sub-micron-sized dust inside the cavity is required. The total dust mass of the disk may be on the order of 1e-4 M_sun, only weakly constrained due to the lack of long wavelength observations and the uncertainties in the dust model. The scale height of the sub-micron-sized dust is ~6 AU at the cavity edge, and the cavity wall is optically thick in the vertical direction at H-band. PDS 70 is not a member of the class of (pre-)transitional disks identified by Dong et al. (2012), whose members only show evidence of the cavity in the millimeter-sized dust but not the sub-micron-sized dust in resolved images. The two classes of (pre-)transitional disks may form through different mechanisms, or they may just be at different evolution stages in the disk clearing process.Comment: 28 pages (single column), 7 figures, 1 table, ApJ accepte

Direct Imaging of Fine Structures in Giant Planet Forming Regions of the Protoplanetary Disk around AB Aurigae

We report high-resolution 1.6 \micron polarized intensity ($PI$) images of the circumstellar disk around the Herbig Ae star AB Aur at a radial distance of 22 AU ($0."15$) up to 554 AU (3.$"$85), which have been obtained by the high-contrast instrument HiCIAO with the dual-beam polarimetry. We revealed complicated and asymmetrical structures in the inner part ($\lesssim$140 AU) of the disk, while confirming the previously reported outer ($r$ $\gtrsim$200 AU) spiral structure. We have imaged a double ring structure at $\sim$40 and $\sim$100 AU and a ring-like gap between the two. We found a significant discrepancy of inclination angles between two rings, which may indicate that the disk of AB Aur is warped. Furthermore, we found seven dips (the typical size is $\sim$45 AU or less) within two rings as well as three prominent $PI$ peaks at $\sim$40 AU. The observed structures, including a bumpy double ring, a ring-like gap, and a warped disk in the innermost regions, provide essential information for understanding the formation mechanism of recently detected wide-orbit ($r$ $>$20 AU) planets.Comment: 12 pages, 3 figure

Search for Outer Massive Bodies around Transiting Planetary Systems: Candidates of Faint Stellar Companions around HAT-P-7

We present results of direct imaging observations for HAT-P-7 taken with the Subaru HiCIAO and the Calar Alto AstraLux. Since the close-in transiting planet HAT-P-7b was reported to have a highly tilted orbit, massive bodies such as giant planets, brown dwarfs, or a binary star are expected to exist in the outer region of this system. We show that there are indeed two candidates for distant faint stellar companions around HAT-P-7. We discuss possible roles played by such companions on the orbital evolution of HAT-P-7b. We conclude that as there is a third body in the system as reported by Winn et al. (2009, ApJL, 763, L99), the Kozai migration is less likely while planet-planet scattering is possible.Comment: 8 pages, 3 figures, 2 tables, PASJ in pres

Imaging of a Transitional Disk Gap in Reflected Light: Indications of Planet Formation Around the Young Solar Analog LkCa 15

We present H- and Ks-band imaging data resolving the gap in the transitional disk around LkCa 15, revealing the surrounding nebulosity. We detect sharp elliptical contours delimiting the nebulosity on the inside as well as the outside, consistent with the shape, size, ellipticity, and orientation of starlight reflected from the far-side disk wall, whereas the near-side wall is shielded from view by the disk's optically thick bulk. We note that forward-scattering of starlight on the near-side disk surface could provide an alternate interpretation of the nebulosity. In either case, this discovery provides confirmation of the disk geometry that has been proposed to explain the spectral energy distributions (SED) of such systems, comprising an optically thick outer disk with an inner truncation radius of ~46 AU enclosing a largely evacuated gap. Our data show an offset of the nebulosity contours along the major axis, likely corresponding to a physical pericenter offset of the disk gap. This reinforces the leading theory that dynamical clearing by at least one orbiting body is the cause of the gap. Based on evolutionary models, our high-contrast imagery imposes an upper limit of 21 Jupiter masses on companions at separations outside of 0.1" and of 13 Jupiter masses outside of 0.2". Thus, we find that a planetary system around LkCa 15 is the most likely explanation for the disk architecture.Comment: 5 pages, 4 figures, accepted for publication in ApJ Letters. Minor change to Figure

New Techniques for High-Contrast Imaging with ADI: the ACORNS-ADI SEEDS Data Reduction Pipeline

We describe Algorithms for Calibration, Optimized Registration, and Nulling the Star in Angular Differential Imaging (ACORNS-ADI), a new, parallelized software package to reduce high-contrast imaging data, and its application to data from the SEEDS survey. We implement several new algorithms, including a method to register saturated images, a trimmed mean for combining an image sequence that reduces noise by up to ~20%, and a robust and computationally fast method to compute the sensitivity of a high-contrast observation everywhere on the field-of-view without introducing artificial sources. We also include a description of image processing steps to remove electronic artifacts specific to Hawaii2-RG detectors like the one used for SEEDS, and a detailed analysis of the Locally Optimized Combination of Images (LOCI) algorithm commonly used to reduce high-contrast imaging data. ACORNS-ADI is written in python. It is efficient and open-source, and includes several optional features which may improve performance on data from other instruments. ACORNS-ADI requires minimal modification to reduce data from instruments other than HiCIAO. It is freely available for download at www.github.com/t-brandt/acorns-adi under a BSD license.Comment: 15 pages, 9 figures, accepted to ApJ. Replaced with accepted version; mostly minor changes. Software update

Polarimetric Imaging of Large Cavity Structures in the Pre-transitional Protoplanetary Disk around PDS 70: Observations of the disk

We present high resolution H-band polarized intensity (PI; FWHM = 0."1: 14 AU) and L'-band imaging data (FWHM = 0."11: 15 AU) of the circumstellar disk around the weak-lined T Tauri star PDS 70 in Centaurus at a radial distance of 28 AU (0."2) up to 210 AU (1."5). In both images, a giant inner gap is clearly resolved for the first time, and the radius of the gap is ~70 AU. Our data show that the geometric center of the disk shifts by ~6 AU toward the minor axis. We confirm that the brown dwarf companion candidate to the north of PDS 70 is a background star based on its proper motion. As a result of SED fitting by Monte Carlo radiative transfer modeling, we infer the existence of an optically thick inner disk at a few AU. Combining our observations and modeling, we classify the disk of PDS 70 as a pre-transitional disk. Furthermore, based on the analysis of L'-band imaging data, we put an upper limit mass of companions at ~30 to ~50MJ within the gap. Taking account of the presence of the large and sharp gap, we suggest that the gap could be formed by dynamical interactions of sub-stellar companions or multiple unseen giant planets in the gap.Comment: accepted by APJ

Subaru Imaging of Asymmetric Features in a Transitional Disk in Upper Scorpius

We report high-resolution (0.07 arcsec) near-infrared polarized intensity images of the circumstellar disk around the star 2MASS J16042165-2130284 obtained with HiCIAO mounted on the Subaru 8.2 m telescope. We present our $H$-band data, which clearly exhibits a resolved, face-on disk with a large inner hole for the first time at infrared wavelengths. We detect the centrosymmetric polarization pattern in the circumstellar material as has been observed in other disks. Elliptical fitting gives the semimajor axis, semiminor axis, and position angle (P.A.) of the disk as 63 AU, 62 AU, and -14 $^{\circ}$, respectively. The disk is asymmetric, with one dip located at P.A.s of $\sim85^{\circ}$. Our observed disk size agrees well with a previous study of dust and CO emission at submillimeter wavelength with Submillimeter Array. Hence, the near-infrared light is interpreted as scattered light reflected from the inner edge of the disk. Our observations also detect an elongated arc (50 AU) extending over the disk inner hole. It emanates at the inner edge of the western side of the disk, extending inward first, then curving to the northeast. We discuss the possibility that the inner hole, the dip, and the arc that we have observed may be related to the existence of unseen bodies within the disk.Comment: 21 pages, 3 figures, published 2012 November 7 by ApJL, typo correcte