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We laser-ablated sub-wavelength structures (SWS) on 200 mm diameter birefringent sapphire disks to produce broadband anti-reflection coating (ARC). The disks were assembled into a stack of five plates making an achromatic half-wave plate (AHWP) suitable for operation between 40 and 140 GHz. We report on the SWS fabrication and transmission measurements of the stack at room temperature. From the measurements, we compute a band average transmission and modulation efficiency for nine spectral bands that correspond to the frequency coverage of the LiteBIRD Low-Frequency Telescope (LFT). We also assess the level of instrumental polarization the AHWP exhibits. We discuss paths for further development to minimize the instrumental polarization from the AHWP. This work is a development milestone toward the implementation of an AHWP for the LiteBIRD satellite.

Microwave kinetic inductance detector (MKID) is one of the candidates of focal plane detector for future satellite missions such as LiteBIRD. For the space use of MKIDs, the radiation tolerance is one of the challenges to be characterized prior to the launch. Aluminum (Al) MKIDs with 50 nm thickness on silicon substrate and on sapphire substrate were irradiated with a proton beam of 160 MeV at the heavy ion medical accelerator in Chiba. The total water-equivalent absorbed dose was ∼ 10 krad which should simulate the worst radiation absorption of 5 years observation at the Lagrange point L2. We measured characteristics of these MKIDs before and after the irradiation. We found no significant changes on resonator quality factor, responsivity, and recombination time of quasi-particles. The change on electrical noise equivalent power was also evaluated, and no significant increase was found at the noise level of O ( 10 - 18 )  W/ Hz .

We present the development of a frequency-domain multiplexing readout of kinetic inductance detectors (KIDs) for pulse signals with a self-trigger system. The KIDs consist of an array of superconducting resonators that have different resonant frequencies individually, allowing us to read out multiple channels in the frequency domain with a single wire using a microwave-frequency comb. The energy deposited to the resonators break Cooper pairs, changing the kinetic inductance and, hence, the amplitude and the phase of the probing microwaves. For some applications such as X-ray detections, the deposited energy is detected as a pulse signal shaped by the time constants of the quasiparticle lifetime, the resonator quality factor, and the ballistic phonon lifetime in the substrate, ranging from microseconds to milliseconds. A readout system commonly used converts the frequency-domain data to the time-domain data. For the short pulse signals, the data rate may exceed the data transfer bandwidth, as the short time constant pulses require us to have a high sampling rate. In order to overcome this circumstance, we have developed a KID readout system that contains a self-trigger system to extract relevant signal data and reduces the total data rate with a commercial off-the-shelf FPGA board. We have demonstrated that the system can read out pulse signals of 15 resonators simultaneously with about 10 Hz event rate by irradiating α particles from 241 Am to the silicon substrate on whose surface aluminum KID resonators are formed.

We present a status of the development of microwave kinetic inductance detectors (MKIDs) for a detection of athermal phonons in a substrate. The energy deposited in the substrate is converted to athermal phonons. Athermal phonons arriving at the surface can break Cooper pairs in the MKIDs which are formed as a thin superconducting metal layer in the substrate surface. By counting the number of Cooper pairs broken and measuring the phonon arrival times, we can measure the amount of deposited energy and its position. MKIDs are suitable for the frequency-domain multiplexing readout, which enables us to readout hundreds of pixels simultaneously and, hence, to detect athermal phonons with a large detection efficiency. We fabricated MKIDs with a combination of aluminum and niobium on a silicon substrate, and then irradiated it with α particles from an 241 Am source. We detected phonons and made a rough estimation of the phonon propagation velocity of 1.1–1.3 km/s. We found that a thin insulator layer can block the phonon propagation from the substrate to the thin metal layer.

Background Primary Sjogren syndrome (SS) is an autoimmune exocrinopathy. Mucin are present on apical surfaces of all healthy wet surface epithelia of human body and on the glands of simple secretory epithelial tissue. The major and minor salivary glands express the membrane-bound mucin, MUC1. Tn and sialyl-Tn antigens are tumor-associated carbohydrate antigens expressed on mucins in epithelial cancers. Alteration of glycoproteins is related with various immunoreactions. The study of sugar chains in autoimmune diseases is intriguing, however, there have been few reports on abnormalities of sugar chains, especially in the pathogenesis of SS. The functions of Tn and sialyl-Tn antigens, MUC1 expressed in human salivary gland is unknown. Objectives The carbohydrate chains represented by mucins are expressed by a variety of normal and malignant secretory epithelial cells and induce a variety of immunoreactions. The purpose of this study is to investigate the existence and bioactivity of tumor-associated carbohydrate antigens in SS. Methods A total of eleven patients (females) with primary SS (mean (SD) age = 52.4 (13.5) years) were enrolled. Saliva was collected by the gum test. Labial salivary gland biopsies were obtained in 11 patients. We examined the expression of Tn, sialyl Tn antigens, and MUC1 in salivary glands tissues from SS patients by immunohistochemistry. In addition, saliva from SS patients was subjected to gel filtration on Sepharose 6B and collected the fractions including mucins. The tumor necrosis factor (TNF)-α and prostaglandin E2 (PGE2) production by mucin in human peripheral blood monocytes (PBMC) were also investigated using ELISA. Results We found that Tn and sialyl Tn antigens, MUC-1 were strongly expressed in mucous acinar cells and infiltrating mononuclear cells on the labial salivary gland (p<0.001) (Image A). Western blotting and a dot blot analysis revealed that saliva fractions include these mucins. Saliva fractions can stimulate the production of TNF-α (Image B) and PGE2 (Image C) in human PBMC. Image/graph Conclusions We revealed that Tn and sialyl Tn antigens typical malignancy-associated mucins, MUC-1 expressed in SS salivary glands. We found an aberrantly glycosylated mucin from saliva in patients with SS, which can produce TNF-α and PGE2 in human PBMC. This finding suggests that the mucins exhibiting with abnormal glycosylation may be in part responsible for salivary glands inflammation, leading to the salivary glands destruction in the pathogenesis of SS. References Reduced sulfation of muc5b is linked to xerostomia in patients with Sjögren syndrome. Alliende C, et, al. Ann Rheum Dis. 2008 Oct;67(10):1480-7. Expression of Tn and sialyl Tn antigens in synovial tissues in rheumatoid arthritis. Ishino H, et, al. Clin Exp Rheumatol. 2010 Mar-Apr;28(2):246-9. Disclosure of Interest H. Ishino Grant/research support from: Grants-in-Aid for Scientific Research, M. Kohno: None Declared, N. Kajitani: None Declared, A. Yamamoto: None Declared, T. Seno: None Declared, K. Murakami: None Declared, W. Fujii: None Declared, H. Nagahara: None Declared, H. Nakada: None Declared, Y. Kawahito: None Declared

LiteBIRD is a next-generation satellite mission to measure the polarization of the cosmic microwave background (CMB) radiation. On large angular scales the B-mode polarization of the CMB carries the imprint of primordial gravitational waves, and its precise measurement would provide a powerful probe of the epoch of inflation. The goal of LiteBIRD is to achieve a measurement of the characterizing tensor to scalar ratio r to an uncertainty of δ r = 0.001 . In order to achieve this goal we will employ a kilo-pixel superconducting detector array on a cryogenically cooled sub-Kelvin focal plane with an optical system at a temperature of 4 K. We are currently considering two detector array options; transition edge sensor (TES) bolometers and microwave kinetic inductance detectors. In this paper we give an overview of LiteBIRD and describe a TES-based polarimeter designed to achieve the target sensitivity of 2  μ K arcmin over the frequency range 50–320 GHz.

The satellite LiteBIRD (Light satellite for the studies of B-mode polarization and Inflation from cosmic background Radiation Detection) is being designed to detect the B-mode polarization of the cosmic microwave background radiation. LiteBIRD will carry about 2,000 detectors for measurements in five bands (60, 80, 100, 150, and 220 GHz). Microwave kinetic inductance detectors (MKIDs) that can be multiplexed in a single readout line are suitable for the large focal plane detector array. We develop an MKID readout system for LiteBIRD to monitor the amplitude, phase, and resonant frequency of each MKID resonator simultaneously and follow movements of the resonant frequency caused by changes in the input radiation intensity. This mechanism enables us to have a larger dynamic range for the MKIDs, compared with a system that monitors the amplitude and phase on the resonant frequency. We also propose an MKID having a half-wavelength resonator. This MKID transmits the resonant microwave signal from one feedline to another. It can offer clear microwaves passing through the resonators, even if the coupling and internal quality factors are mismatched. With this MKID, our readout system can track resonance frequency changes much more easily. We present the status of the readout system development and demonstrate the performance with the half-wavelength MKID.

Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of hydrogen inhalation in patients with ulcerative colitis. Methods: In this randomised, double-blind, placebo-controlled trial, 10 active patients with ulcerative colitis (aged ≥20 years; Lichtiger’s clinical activity index, 3–10; and Mayo endoscopic subscores ≥1) participated, and they were assigned to either a hydrogen or air inhalation group (hydrogen and placebo groups, respectively). All patients inhaled gas for 4 h every day for 8 weeks. Subsequently, we performed clinical indices and microbiota analyses using the metagenomic sequencing of stool samples before and after inhalation. Results: There was significant difference in the sum of the Mayo endoscopic subscores before and after inhalation in the clinical assessment indices. The hydrogen group showed higher α-diversity (p = 0.19), and the variation in β-diversity was markedly different, compared to the placebo group, in intestinal microbiota analysis (p = 0.02). Functional gene analysis revealed 115 significant genetic changes in the hydrogen group following treatment. No inhalation-related adverse events were observed. Conclusions: Hydrogen inhalation appeared to improve intestinal microbiota diversity; however, no clear therapeutic effect on ulcerative colitis was observed. Further studies are needed, and hydrogen inhalation may possibly lead to a logical solution combined with microbiome therapy, such as faecal microbiota transplantation, with fewer adverse events.

Background Myeloid-derived suppressor cells (MDSCs) are of myeloid origin and are able to suppress T cell responses. MDSCs are characterized by the co-expression of the myeloid differentiation antigens Gr-1 and CD11b in mice (1). MDSCs in cancer have been studied in detail and are known to play roles in tumor associated immune suppression. However, the roles of MDSCs in autoimmune disease remain controversial and little is known about MDSCs in autoimmune arthritis. Objectives We investigate the roles of MDSCs in autoimmune arthritis using collagen-induced arthritis (CIA) mouse models. Methods We determined the number of Gr-1+ CD11b+ MDSCs in the spleens of CIA mice by flow cytometry. Next, we isolated MDSCs from CIA mice by magnetic cell sorting and cultured with CD4+ T cells to analyze the functions of MDSCs. We investigated the proliferation of CD4+ T cells by CFSE dye dilution assay and estimated cytokine levels produced by CD4+ T cells using ELISA. Furthermore, we investigated CD4+ T cell differentiation into Th17 cells by flow cytometry. Finally, we performed adoptive transfer of MDSCs into CIA mice and investigated the severity of arthritis. Results MDSCs significantly accumulated in the spleens of mice with CIA when arthritis severity peaked. These MDSCs inhibited CD4+ T cell proliferation and differentiation into Th17 cells. Moreover, MDSCs inhibited the production of IFNγ, IL-2, TNFα, and IL-6 by CD4+ T cells in vitro, whereas they promoted the production of IL-10. Adoptive transfer of MDSCs reduced both clinical (Image A) and histological arthritis scores (Image B) in vivo, which was accompanied by a decrease in the number of CD4+ T cells and Th17 cells in the draining lymph nodes. Image/graph Conclusions MDSCs in CIA suppress the progression of CIA by inhibiting the pro-inflammatory immune response of CD4+ T cells. These observations suggest that MDSCs play crucial roles in the regulation of autoimmune arthritis, which could be exploited in new cell-based therapies for human rheumatoid arthritis (RA). References Gabrilovich, D. I., and S. Nagaraj. 2009. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9: 162-174. Disclosure of Interest None Declared

Background: In Japan, vascular dementia (VD) has been responsible for the majority of all dementia cases in both epidemiological and neuropathological studies. Recently, however, several epidemiological investigations have shown that the rate of VD has decreased and senile dementia of the Alzheimer type (SDAT) is now the major cause of dementia, though few neuropathological investigations show that the majority of dementia is SDAT. Objective: The purpose of the study was to clarify the rates of dementia types in Japanese nursing home residents and to compare the ratio of SDAT to VD in the first and second halves of the study. Methods: One hundred and twenty-two demented nursing home residents (48 men and 74 women) were evaluated neuropathologically over a period of 17 years in Shimane prefecture, Japan. All subjects died between 1976 and 1992. The average age at death was 81.4 ± 9.4 years for men, 85.0 ± 7.2 for women and 83.6 ± 8.3 for total samples. Results: In classifying dementia type, SDAT accounted for 34% (41 cases); VD 35% (42); mixed dementia 11% (14); and ‘other’ dementia 20% (25) of all samples. Comparison of the first 9-year period with the second 8-year period revealed the ratio of SDAT to VD tended to increase (from 0.83 to 1.15). This increasing tendency was found both in men (from 0.53 to 0.7) and in women (from 1.13 to 1.44). These tendencies, however, were not statistically significant. Conclusion: There was no change statistically in the ratio of SDAT to VD between the first half of the study and the second half. However, there was an increasing tendency of the ratio in our study.