Tokyo Institute of Technology

About: Tokyo Institute of Technology is a education organization based out in Tokyo, Tôkyô, Japan. It is known for research contribution in the topics: Thin film & Catalysis. The organization has 46775 authors who have published 101656 publications receiving 2357893 citations. The organization is also known as: Tokyo Tech & Tokodai.

Concanamycin A, a powerful tool for characterization and estimation of contribution of perforin- and Fas-based lytic pathways in cell-mediated cytotoxicity.

Abstract: Perforin- and Fas-based cytolytic pathways are two major mechanisms of cell-mediated cytotoxicity. Recently, we have shown that an inhibitor of vacuolar type H+-ATPase, concanamycin A (CMA), inhibits perforin-based cytotoxic activity, mostly due to accelerated degradation of perforin by an increase in the pH of lytic granules. Here we show that CMA failed to inhibit the cytolytic activity of CD4+ CTL clone and perforin-deficient CD8+ CTL clone, which exclusively mediate Fas-based cytotoxicity, although CMA inhibited acidification and induced drastic vacuolation of cytoplasmic granules in these clones. In a wide range of alloantigen-specific CTL, a significant amount of the lysis of Con A blasts from normal mice and of Fas-positive tumor cells remained unaffected even in excess concentrations of CMA. However, CMA almost completely inhibited the lysis of Con A blasts from lpr mice and of Fas low expressing or negative tumor cells. Cytolysis by alloantigen-specific CD8+ CTL derived from gld mice was completely prevented by CMA. Furthermore, CMA-insensitive cytolysis exerted by CD8+ CTL clone was completely inhibitable by soluble Fas molecules. Thus, these data clearly indicate not only that CMA-insensitive cytolysis mediated by alloantigen-specific CTL is Fas dependent, but also that CMA is a selective inhibitor to block only the perforin-based killing pathway. In contrast, brefeldin A blocked the Fas-based cytotoxicity, but only marginally reduced the perforin-based cytotoxicity. Moreover, CMA and brefeldin A in combination completely abrogated all cytolytic activity of alloantigen-specific CTL. Taken together, these results reveal that CTL mainly exert perforin-based cytotoxicity and complementary Fas-based cytotoxicity, and that CMA is a powerful tool to clarify the contributions of the two distinct cytolytic pathways.

Navigating the Anthropocene: Improving Earth System Governance

Abstract: Science assessments indicate that human activities are moving several of Earth's sub-systems outside the range of natural variability typical for the previous 500,000 years ( 1 , 2 ). Human societies must now change course and steer away from critical tipping points in the Earth system that might lead to rapid and irreversible change ( 3 ). This requires fundamental reorientation and restructuring of national and international institutions toward more effective Earth system governance and planetary stewardship.

Finding community structure in mega-scale social networks: [extended abstract]

Abstract: Community analysis algorithm proposed by Clauset, Newman, and Moore (CNM algorithm) finds community structure in social networks. Unfortunately, CNM algorithm does not scale well and its use is practically limited to networks whose sizes are up to 500,000 nodes. We show that this inefficiency is caused from merging communities in unbalanced manner and that a simple heuristics that attempts to merge community structures in a balanced manner can dramatically improve community structure analysis. The proposed techniques are tested using data sets obtained from existing social networking service that hosts 5.5 million users. We have tested three three variations of the heuristics. The fastest method processes a SNS friendship network with 1 million users in 5 minutes (70 times faster than CNM) and another friendship network with 4 million users in 35 minutes, respectively. Another one processes a network with 500,000 nodes in 50 minutes (7 times faster than CNM), finds community structures that has improved modularity, and scales to a network with 5.5 million.