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The relationship between radio jet and black hole Radio jets from active galactic nuclei, such as the nearby galaxy M87, are thought to be powered by the accretion of material into a supermassive black hole. The relative position of this 'central engine' and the bright radio core that marks the base of the jet remain the subject of much speculation. New observations of M87 at six frequencies have been used to determine the position of the radio core to an accuracy of ∼ 20 microarcseconds. The data reveal that the central engine is located close to the radio core, within a distance of 14–23 Schwarzschild radii at 43 GHz. Powerful radio jets from active galactic nuclei are thought to be powered by the accretion of material onto the supermassive black hole (the ‘central engine’) 1 , 2 . M87 is one of the closest examples of this phenomenon, and the structure of its jet has been probed on a scale of about 100 Schwarzschild radii ( R s , the radius of the event horizon) 3 . However, the location of the central black hole relative to the jet base (a bright compact radio ‘core’) remains elusive 4 , 5 . Observations of other jets indicate that the central engines are located about 10 4 –10 6 R s upstream from the radio core 6 , 7 , 8 , 9 . Here we report radio observations of M87 at six frequencies that allow us to achieve a positional accuracy of about 20 microarcseconds. As the jet base becomes more transparent at higher frequencies, the multifrequency position measurements of the radio core enable us to determine the upstream end of the jet. The data reveal that the central engine of M87 is located within 14–23 R s of the radio core at 43 GHz. This implies that the site of material infall onto the black hole and the eventual origin of the jet reside in the bright compact region seen on the image at 43 GHz.

Perilymphatic fistula is defined as an abnormal communication between the perilymph-filled space and the middle ear, or cranial spaces. The manifestations include a broad spectrum of neuro-otological symptoms such as hearing loss, vertigo/dizziness, disequilibrium, aural fullness, tinnitus, and cognitive dysfunction. By sealing the fistula, perilymphatic fistula is a surgically correctable disease. Also, appropriate recognition and treatment of perilymphatic fistula can improve a patient's condition and hence the quality of life. However, the difficulty in making a definitive diagnosis due to the lack of an appropriate biomarker to detect perilymph leakage has caused a long-standing debate regarding its management. We have reported a clinical test for the diagnosis of perilymphatic fistula by detecting a perilymph specific protein, Cochlin-tomoprotein, as a diagnostic marker using a western blot. The aim of this study is to establish an ELISA-based human Cochlin-tomoprotein detection test and to evaluate its diagnostic accuracy in clinical subjects. The results of ELISA showed good dilution reproducibility. The mean concentration was 49.7±9.4 of 10 perilymph samples. The ROC curve in differentiating the perilymph leakage condition from the normal middle ear was significant (P < 0.001) with an area under the curve (AUC) of 0.918 (95% CI 0.824-0.100). We defined the diagnostic criteria as follows: CTP<0.4 negative; 0.4≦CTP<0.8 intermediate; 0.8≦CTP(ng/ml) positive in the clinical usage of the hCTP ELISA, and sensitivity and specificity were 86.4% and 100%, respectively. We further tested the expression specificity of the Cochlin-tomoprotein by testing blood and CSF samples. The concentration was below the detection limit (0.2 ng/ml) in 38 of the 40 blood, and 14 of the 19 CSF samples. We report the accuracy of this test for the diagnosis of perilymphatic fistula. Using ELISA, we can improve the throughput of the test. Furthermore, it is useful for a large-scale study to characterize the clinical picture and delineate the management of this medical condition.

We report on recent technical developments in the front- and back-ends for the four 20 m radio telescopes of the Japanese Very-Long-Baseline Interferometry (VLBI) project, VLBI Exploration of Radio Astrometry (VERA). We present a brief overview of a dual-circular polarization receiving and ultrawideband (16 Giga bit s−1) recording systems that were installed on each of the four telescopes operating at 22 and 43 GHz bands. The wider-band capability improves the sensitivity of VLBI observations for continuum emission, and the dual-polarization capability enables the study of magnetic fields in relativistic jets ejected from supermassive black holes in active galactic nuclei and in sites of star formation and around evolved stars.We present the linear polarization intensity maps of extragalactic sources at 22 and 43 GHz obtained from the most recent test observations to show the state of the art of the VERA polarimetric observations. At the end of this article, given the realization of VLBI polarimetry with VERA, we describe the future prospects for scientific aims and further technical developments.

We have developed a novel enzyme‐linked immunosorbent assay (ELISA) system for the detection of N‐ERC/mesothelin in the serum of mesothelioma patients and have begun to examine its clinical usefulness. N‐ERC/mesothelin is a 31‐kDa protein that forms the N‐terminal fragment of the full‐length 71‐kDa ERC/mesothelin protein, and is physiologically secreted into the blood of mesothelioma patients where it can be detected using our sandwich ELISA containing two antibodies (rabbit polyclonal anti‐ERC/mesothelin antibody‐282 and mouse monoclonal antibody 7E7). Our ELISA system has thus far detected much higher serum levels of N‐ERC/mesothelin in mesothelioma patients than in healthy controls or patients with other lung or pleural diseases. In conclusion, N‐ERC/mesothelin is a promising candidate tumor marker for mesothelioma. (Cancer Sci 2006; 97: 928–932)

We present here the East Asia to Italy Nearly Global VLBI (EATING VLBI) project. How this project started and the evolution of the international collaboration between Korean, Japanese, and Italian researchers to study compact sources with VLBI observations is reported. Problems related to the synchronization of the very different arrays and technical details of the telescopes involved are presented and discussed. The relatively high observation frequency (22 and 43 GHz) and the long baselines between Italy and East Asia produced high-resolution images. We present example images to demonstrate the typical performance of the EATING VLBI array. The results attracted international researchers and the collaboration is growing, now including Chinese and Russian stations. New in progress projects are discussed and future possibilities with a larger number of telescopes and a better frequency coverage are briefly discussed herein.

Mesothelioma is an aggressive cancer often caused by chronic asbestos exposure, and its prognosis is very poor despite the therapies currently used. Due to the long latency period between asbestos exposure and tumor development, the worldwide incidence will increase substantially in the next decades. Thus, novel effective therapies are warranted to improve the prognosis. The ERC/mesothelin gene (MSLN) is expressed in wide variety of human cancers, including mesotheliomas, and encodes a precursor protein cleaved by proteases to generate C‐ERC/mesothelin and N‐ERC/mesothelin. In this study, we investigated the antitumor activity of C‐ERC/mesothelin‐specific mouse monoclonal antibody, 22A31, against tumors derived from a human mesothelioma cell line, ACC‐MESO‐4, in a xenograft experimental model using female BALB/c athymic nude mice. Treatment with 22A31 did not inhibit cell proliferation of ACC‐MESO‐4 in vitro; however, therapeutic treatment with 22A31 drastically inhibited tumor growth in vivo. 22A31 induced antibody‐dependent cell‐mediated cytotoxicity by natural killer (NK) cells, but not macrophages, in vitro. Consistently, the F(ab′)2 fragment of 22A31 did not inhibit tumor growth in vivo, nor did it induce antibody‐dependent cell mediated cytotoxicity (ADCC) in vitro. Moreover, NK cell depletion diminished the antitumor effect of 22A31. Thus, 22A31 induced NK cell‐mediated ADCC and exerted antitumor activity in vivo. 22A31 could have potential as a therapeutic tool to treat C‐ERC/mesothelin‐expressing cancers including mesothelioma. (Cancer Sci 2010; 101: 969–974)

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease, which is usually diagnosed in an advanced stage. We have established transgenic rats carrying a mutated K-ras gene controlled by Cre/loxP activation. The animals develop PDA which is histopathologically similar to that in humans. Previously, we reported that serum levels of N-ERC/mesothelin were significantly higher in rats bearing PDA than in controls. In the present study, to determine whether serum levels of N-ERC/mesothelin correlated with tumor size, we measured N-ERC/mesothelin levels in rats bearing PDA. Increased serum levels of N-ERC/mesothelin correlated with increased tumor size. This result indicates an interrelationship between the serum level of N-ERC/mesothelin and tumor size. We next investigated the effect of chemotherapy on serum N-ERC/mesothelin levels. Rat pancreatic cancer cells were implanted subcutaneously into the flank of NOD-SCID mice. In the mice treated with 200 mg/kg gemcitabine, tumor weight and the serum level of N-ERC/mesothelin were significantly decreased compared to controls. These results suggest that serum N-ERC/mesothelin measurements might be useful for monitoring response to therapy.

Genetic crossing experiments were performed between tuberous sclerosis‐2 (Tsc2) KO and expressed in renal carcinoma (Erc) KO mice to analyze the function of the Erc/mesothelin gene in renal carcinogenesis. We found the number and size of renal tumors were significantly less in Tsc2+/−;Erc−/− mice than in Tsc2+/−;Erc+/+ and Tsc2+/−;Erc+/− mice. Tumors from Tsc2+/−;Erc−/− mice exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen (Ki67) and TUNEL analysis, respectively. Adhesion to collagen‐coated plates in vitro was enhanced in Erc‐restored cells and decreased in Erc‐suppressed cells with siRNA. Tumor formation by Tsc2‐deficient cells in nude mice was remarkably suppressed by stable knockdown of Erc with shRNA. Western blot analysis showed that the phosphorylation of focal adhesion kinase, Akt and signal transducer and activator of transcription protein 3 were weaker in Erc‐deficient/suppressed cells compared with Erc‐expressed cells. These results indicate that deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 KO mice and inhibits the phosphorylation of several kinases of cell adhesion mechanism. This suggests that Erc/mesothelin may have an important role in the promotion and/or maintenance of carcinogenesis by influencing cell‐substrate adhesion via the integrin‐related signal pathway. (Cancer Sci 2011; 102: 720–727)

Mesothelioma is a type of malignant tumor that most commonly arises from the pleural or peritoneal membrane and is usually associated with previous exposure to asbestos. In humans, ERC/mesothelin is expressed on the normal mesothelium and in some cancers such as mesothelioma or ovarian carcinoma. Recently, several enzyme‐linked immunosorbent assay (ELISA) systems for ERC/mesothelin have been developed, the reported usefulness of which has been assessed and demonstrated as a diagnostic tool. However, the basic roles or physiological functions of, and relationship between, ERC/mesothelin and asbestos exposure–mediated carcinogenesis remain to be resolved. In order to elucidate the precise mechanism, animal models of mesothelioma are desperately needed. In this study, we consider the development of a novel specific ELISA system for not only rat N‐ERC/mesothelin but also C‐ERC/mesothelin, and the first data on the presence of rat ERC/mesothelin in the body fluids of rat malignant mesothelioma–bearing nude mice. The transplanted mice have revealed the higher concentrations of rat N‐ERC/mesothelin in the blood and ascites than C‐ERC/mesothelin. We hope these novel ELISA systems are useful in the rat model system to clarify the mechanism of asbestos‐induced carcinogenesis and to develop new effective drugs for mesothelioma. (Cancer Sci 2008; 99: 666–670)

The nearby radio galaxy M87 offers a unique opportunity to explore the connections between the central supermassive black hole and relativistic jets. Previous studies of the inner region of M87 revealed a wide opening angle for the jet originating near the black hole 1 – 4 . The Event Horizon Telescope resolved the central radio source and found an asymmetric ring structure consistent with expectations from general relativity 5 . With a baseline of 17 years of observations, there was a shift in the jet’s transverse position, possibly arising from an 8- to 10-year quasi-periodicity 3 . However, the origin of this sideways shift remains unclear. Here we report an analysis of radio observations over 22 years that suggests a period of about 11 years for the variation in the position angle of the jet. We infer that we are seeing a spinning black hole that induces the Lense–Thirring precession of a misaligned accretion disk. Similar jet precession may commonly occur in other active galactic nuclei but has been challenging to detect owing to the small magnitude and long period of the variation. This study analyses radio observations of the jet in galaxy M87, from which the existence of a spinning black hole that induces Lense–Thirring precession of a misaligned accretion disk is inferred.