Development of Atmospheric Monitoring System at Akeno Observatory for the Telescope Array Project

We have developed an atmospheric monitoring system for the Telescope Array experiment at Akeno Observatory. It consists of a Nd:YAG laser with an alt-azimuth shooting system and a small light receiver. This system is installed inside an air conditioned weather-proof dome. All parts, including the dome, laser, shooter, receiver, and optical devices are fully controlled by a personal computer utilizing the Linux operating system. It is now operated as a back-scattering LIDAR System. For the Telescope Array experiment, to estimate energy reliably and to obtain the correct shower development profile, the light transmittance in the atmosphere needs to be calibrated with high accuracy. Based on observational results using this monitoring system, we consider this LIDAR to be a very powerful technique for Telescope Array experiments. The details of this system and its atmospheric monitoring technique will be discussed.Comment: 24 pages, 13 figures(plus 3 gif files), Published in NIM-A Vol.488, August 200

Dopaminergic Differentiation of Human Embryonic Stem Cells on PA6-Derived Adipocytes.

Human embryonic stem cells (hESCs) are a promising source for cell replacement therapies. Parkinson's disease is one of the candidate diseases for the cell replacement therapy since the motor manifestations of the disease are associated with the loss of dopaminergic neurons in the substantia nigra pars compacta. Stromal cell-derived inducing activity (SDIA) is the most commonly used method for the dopaminergic differentiation of hESCs. This chapter describes a simple, reliable, and scalable dopaminergic induction method of hESCs using PA6-derived adipocytes. Coculturing hESCs with PA6-derived adipocytes markedly reduces the variable outcomes among experiments. Moreover, the colony differentiation step of this method can also be used for the dopaminergic induction of mouse embryonic stem cells and NTERA2 cells as well

Toll‐like receptor signalling induces the expression of serum amyloid A in epidermal keratinocytes and dermal fibroblasts

BACKGROUND: Toll-like receptors (TLRs) play critical roles in innate immune response by sensing pathogen- or damage-associated molecular patterns. Epidermal keratinocytes and dermal fibroblasts also produce proinflammatory cytokines and chemokines under stimulation with TLR ligands. Serum amyloid A (SAA) is an essential factor in the pathogenesis of secondary amyloidosis, and also has immunomodulatory functions. SAA are produced mainly by hepatocytes but also by a variety of cells, including immune cells, endothelial cells, synoviocytes, and epidermal keratinocytes. However, SAA expression in human dermal fibroblasts has not been shown to date. AIM: To investigate the effect of TLR ligands on SAA expression in epidermal keratinocytes and dermal fibroblasts. METHODS: We investigated whether TLR ligands induce the expression of SAA in normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) by real-time quantitative PCR and ELISA. The effect of SAA on its own expression in NHDFs was also studied. RESULTS: SAA expression was induced via nuclear factor-κB by TLR1/2, 3, 5 and 2/6 ligands in NHEKs. In NHDFs, TLR1/2 and TLR2/6 ligands increased SAA expression. SAA further induced its own expression via TLR1/2 and NF-κB in NHDFs, as previously reported for NHEKs. CONCLUSIONS: Our results provide new evidence that the skin's innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa

Cathelicidin antimicrobial peptide LL-37 augments interferon-beta expression and antiviral activity induced by double-stranded RNA in keratinocytes

Background Cathelicidin antimicrobial peptide LL-37 has the capacity to kill a wide range of microbes and to modify host immunity. Recently, our group observed that the activation of keratinocytes by LL-37 and DNA greatly increases interferon (IFN)-beta through Toll-like receptor (TLR) 9. However, the effect of LL-37 on the induction of IFN-beta through TLR3, a sensor of double-stranded (ds) RNA, in keratinocytes is not well known. Objectives To investigate whether LL-37 could affect TLR3 signalling and antiviral activity in normal human epidermal keratinocytes (NHEKs). Methods We investigated the production of IFN-beta in NHEKs stimulated with a TLR3 ligand, poly (I:C), in the presence of LL-37. To examine the effect of LL-37 and poly (I:C) on antiviral activity, a virus plaque assay using herpes simplex (HS) virus type-1 was carried out. The uptake of poly (I:C) conjugated with fluorescein isothiocyanate (FITC) into the keratinocytes was observed in the presence of LL-37. Immunostaining for TLR3 and LL-37 was performed using skin samples from HS. Results LL-37 and poly (I:C) synergistically induced the expression of IFN-beta in NHEKs. Furthermore, co-stimulation with LL-37 and poly (I:C) significantly decreased the viral plaque numbers compared with poly (I:C) or LL-37 alone. LL-37 enhanced the uptake of FITC-conjugated poly (I:C) into cells. Immunohistochemical analysis demonstrated that the expression of TLR3 and LL-37 is up-regulated in HS lesions. Conclusions Our findings suggest that LL-37 augments the antiviral activity induced by dsRNA in keratinocytes, which may contribute to the innate immune response to cutaneous viral infections such as HS

Nephron organoids derived from human pluripotent stem cells model kidney development and injury

Kidney cells and tissues derived from human pluripotent stem cells (hPSCs) would enable organ regeneration, disease modeling, and drug screening in vitro. We established an efficient, chemically defined protocol for differentiating hPSCs into multipotent nephron progenitor cells (NPCs) that can form nephron-like structures. By recapitulating metanephric kidney development in vitro, we generate SIX2+SALL1+WT1+PAX2+ NPCs with 90% efficiency within 9 days of differentiation. The NPCs possess the developmental potential of their in vivo counterparts and form PAX8+LHX1+ renal vesicles that self-pattern into nephron structures. In both 2D and 3D culture, NPCs form kidney organoids containing epithelial nephron-like structures expressing markers of podocytes, proximal tubules, loops of Henle, and distal tubules in an organized, continuous arrangement that resembles the nephron in vivo. We also show that this organoid culture system can be used to study mechanisms of human kidney development and toxicity

Homozygous CDA*3 is a major cause of life-threatening toxicities in gemcitabine-treated Japanese cancer patients

Among 242 Japanese pancreatic cancer patients, three patients (1.2%) encountered life-threatening toxicities, including myelosuppression, after gemcitabine-based chemotherapies. Two of them carried homozygous CDA*3 (CDA208G>A [Ala70Thr]), and showed extremely low plasma cytidine deaminase activity and gemcitabine clearance. Our results suggest that homozygous *3 is a major factor causing gemcitabine-mediated severe adverse reactions among the Japanese population