Kidnapping Politics in East Asia

Introduction: History is filled with political abductions, incidents in which individuals are kidnapped and held hostage by hostile groups or states to gain leverage or legitimacy for their cause.1 Such episodes have been used since antiquity to highlight the failure of rulers to perform their single-most important function-- protecting citizens from harm. Consequently, kidnappings have opened up deep political chasms and often have been used by political actors to identify enemies, distill collective fears, clarify national deficiencies, redefine frontiers, and mobilize social movements. They have long figured in justifications for both aggression and conciliation with neighbors. Some political actors have capitalized on captivity to frame and highlight national weakness and the fecklessness of leaders. Others have spun out accounts of heroism to demonstrate national strength and visionary leadership. Either way, the manipulation of the captivity passion for political ends often has been used to generate public sympathy to reorient national policies.Henry Luce FoundationChiang Ching-kuo Foundation for International Scholarly Exchang

Hugging and Hedging: Japanese Grand Strategy in the 21st Century

After decades of accepting US supremacy in Asia as the foundation of its foreign and security policies, finding the right distance between the U.S. and China is the most important strategic choice facing Japan today. “Getting it just right” with these two powers will require both military and economic readjustments. There is a great deal at stake in Tokyo’s recalculation. Japan, China, and the United States are, after all, the three largest economies in the world, together accounting for nearly 40% of global production. Each has a deep--and deepening--stake in the other two. The United States and Japan are China’s top two trade partners. The United States and China are Japan’s top two trade partners. And Japan and China are the top two U.S. trade partners outside of NAFTA. In security terms, the United States remains the world’s only hyper power, but China’s rapid (if opaque) military modernization is shifting regional dynamics. For its part, Japan annually spends over $50 billion on defense, no trivial sum despite its self-imposed cap on spending at 1% of GDP. Japan has an impressive navy and air force and has openly debated possessing strike cap abilities. Even the nuclear option reportedly has been discussed among members of the National Diet. In short, each of the three is a bona fide current or potential “great power”--viz., each has the ability to exert its economic, military, cultural, and diplomatic influence on a global scale in ways that could alter the regional and global balances

Japan’s Nuclear Hedge: Beyond "Allergy" and Breakout

This chapter examines the future of Japan’s hedged dependence on U.S. extended deterrence and encourages more imaginative thinking about potential outcomes and strategic implications as the second nuclear age unfolds

Research Collaboration in Japan

This paper was prepared for delivery at the annual meeting of the Association of Asian Studies, Boston, April 11, 1987. A preliminary version was delivered to the annual meeting of the American Association for the Advancement of Science, Chicago, February 16, 1987.Support for this research was provided by the Japan-MIT Endowment for International Energy Policy Studies under the auspices of the MIT Center for International Studies and with the cooperation of the MIT-Japan Science and Technology Program

Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

<p>Abstract</p> <p>Background</p> <p>Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL). However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential.</p> <p>Results</p> <p>Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel <it>in silico </it>and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation.</p> <p>Conclusions</p> <p>We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy <it>in vivo</it>.</p

CytoCensus, mapping cell identity and division in tissues and organs using machine learning.

A major challenge in cell and developmental biology is the automated identification and quantitation of cells in complex multilayered tissues. We developed CytoCensus: an easily deployed implementation of supervised machine learning that extends convenient 2D 'point-and-click' user training to 3D detection of cells in challenging datasets with ill-defined cell boundaries. In tests on such datasets, CytoCensus outperforms other freely available image analysis software in accuracy and speed of cell detection. We used CytoCensus to count stem cells and their progeny, and to quantify individual cell divisions from time-lapse movies of explanted Drosophila larval brains, comparing wild-type and mutant phenotypes. We further illustrate the general utility and future potential of CytoCensus by analysing the 3D organisation of multiple cell classes in Zebrafish retinal organoids and cell distributions in mouse embryos. CytoCensus opens the possibility of straightforward and robust automated analysis of developmental phenotypes in complex tissues

The Alzheimer’s Disease Risk Factor INPP5D Restricts Neuroprotective Microglial Responses in Amyloid Beta-Mediated Pathology

INTRODUCTION: Mutations in INPP5D, which encodes for the SH2-domain-containing inositol phosphatase SHIP-1, have recently been linked to an increased risk of developing late-onset Alzheimer\u27s disease. While INPP5D expression is almost exclusively restricted to microglia in the brain, little is known regarding how SHIP-1 affects neurobiology or neurodegenerative disease pathogenesis. METHODS: We generated and investigated 5xFAD Inpp5d RESULTS: SHIP-1 deletion in microglia led to substantially enhanced recruitment of microglia to Aβ plaques, altered microglial gene expression, and marked improvements in neuronal health. Further, SHIP-1 loss enhanced microglial plaque containment and Aβ engulfment when compared to microglia from Cre-negative 5xFAD Inpp5d DISCUSSION: These results define SHIP-1 as a pivotal regulator of microglial responses during Aβ-driven neurological disease and suggest that targeting SHIP-1 may offer a promising strategy to treat Alzheimer\u27s disease. HIGHLIGHTS: Inpp5d deficiency in microglia increases plaque-associated microglia numbers. Loss of Inpp5d induces activation and phagocytosis transcriptional pathways. Plaque encapsulation and engulfment by microglia are enhanced with Inpp5d deletion. Genetic ablation of Inpp5d protects against plaque-induced neuronal dystrophy