In this Letter we report the discovery of TeV gamma-ray emission from a supernova remnant made with the CANGAROO 3.8 m telescope. TeV gamma rays were detected at the sky position and extension coincident with the northeast rim of shell-type supernova remnant (SNR) SN 1006 (Type Ia). SN 1006 has been a most likely candidate for an extended TeV gamma-ray source, since the clear synchrotron X-ray emission from the rims was recently observed by ASCA (Koyama et al.), which is strong evidence for the existence of very high energy (up to hundreds of TeV) electrons in the SNR. The observed TeV gamma-ray flux was (2.4 ‫ע‬ 0.0.7 [systematic]) # 10 3.0 ‫ע‬ 0.9 (4.6 ‫ע‬ 0.6 ‫ע‬ 1.4) # 10 1.7 ‫ע‬ 0.5 from the 1996 and 1997 observations, respectively. Also, we set an upper limit on the TeV gamma-ray emission from the southwest rim, which is estimated to be cm Ϫ2 s Ϫ1 (≥ TeV, 95% confidence level) Ϫ12

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The strong barrier function of the blood–brain barrier (BBB) protects the central nervous system (CNS) from xenobiotic substances, while the expression of selective transporters controls the transportation of nutrients between the blood and brain. As a result, the delivery of drugs to the CNS and prediction of the ability of specific drugs to penetrate the BBB can be difficult. Although in vivo pharmacokinetic analysis using rodents is a commonly used method for predicting human BBB permeability, novel in vitro BBB models, such as Transwell models, have been developed recently. Induced pluripotent stem cells (iPSCs) have the potential to differentiate into various types of cells, and protocols for the differentiation of iPSCs to generate brain microvascular endothelial cells (BMECs) have been reported. The use of iPSCs makes it easy to scale-up iPSC-derived BMECs (iBMECs) and enables production of BBB disease models by using iPSCs from multiple donors with disease, which are advantageous properties compared with models that utilize primary BMECs (pBMECs). There has been little research on the value of iBMECs for predicting BBB permeability. This study focused on the similarity of iBMECs to pBMECs and investigated the ability of iPSC-BBB models (monoculture and coculture) to predict in vivo human BBB permeability using iBMECs. iBMECs express BMEC markers (e.g., VE-cadherin and claudin-5) and influx/efflux transporters (e.g., Glut-1, SLC7A5, CD220, P-gp, ABCG2, and MRP-1) and exhibit high barrier function (transendothelial electrical resistance, >1000 Ω × cm2) as well as similar transporter expression profiles to pBMECs. We determined that the efflux activity using P-glycoprotein (P-gp) transporter is not sufficient in iBMECs, while in drug permeability tests, iPSC-derived BBB models showed a higher correlation with in vivo human BBB permeability compared with a rat BBB model and the Caco-2 model. In a comparison between monoculture and coculture models, the coculture BBB model showed higher efflux activity for compounds with low CNS permeability (e.g., verapamil and thioridazine). In conclusion, iPSC-BBB models make it possible to predict BBB permeability, and employing coculturing can improve iPSC-BBB function.

A new imaging atmospheric Cherenkov telescope with a light-weight re ector has been constructed. Light, robust, and durable mirror facets of containing CFRP (Carbon Fiber Reinforced Plastic) laminates were developed for the telescope. The re ector has a parabolic shape (f/1.1) with a 30 m 2 surface area which consists of sixty spherical mirror facets. The image size of each mirror facet is 0 .08 (FWHM) on average. The attitude of each facet can be adjusted by stepping motors. After Preprint submitted to Elsevier Preprint 26 May 2 0 0 0 the rst in situ adjustment, a point image of about 0 .14 (FWHM) over 3 degree eld-of-view was obtained. The e ect of gravitational load on the optical system was con rmed to be negligible at the focal plane. The telescope has been in operation with an energy threshold for gamma-rays of < 300 GeV since May 1999.

We collected several biofilm samples from Japanese rivers and established a reproducible multi-species biofilm model that can be analyzed in laboratories. Bacterial abundance at the generic level was highly similar between the planktonic and biofilm communities, whereas comparative metatranscriptomic analysis revealed many upregulated and downregulated genes in the biofilm. Many genes involved in iron-sulfur metabolism, stress response, and cell envelope function were upregulated; biofilm formation is mediated by an iron-dependent signaling mechanism and the signal is relayed to stress-responsive and cell envelope function genes. Flagella-related gene expression was regulated depending upon the growth phase, indicating different roles of flagella during the adherence, maturation, and dispersal steps of biofilm formation. Downregulation of DNA repair genes was observed, indicating that spontaneous mutation frequency would be elevated within the biofilm and that the biofilm is a cradle for generating novel genetic traits. Although the significance remains unclear, genes for rRNA methyltransferase, chromosome partitioning, aminoacyl-tRNA synthase, and cysteine, methionine, leucine, thiamine, nucleotide, and fatty acid metabolism were found to be differentially regulated. These results indicate that planktonic and biofilm communities are in different dynamic states. Studies on biofilm and sessile cells, which have received less attention, are important for understanding microbial ecology and for designing tailor-made anti-biofilm drugs.