Science, Technology and Medicine in East Asia: Policy, Practice, and Implications in a Global Context

Since the end of World War II, historical and contemporary developments in East Asian science, technology and medicine have received increasing scholarly attention partly due to historian of Japanese science James R. Bartholomew's career-long commitment to the field and his mentorship of a younger generation of scholars. This interdisciplinary conference proposes to examine the ways in which the sciences in East Asia – whether basic or applied, from technology to medicine—have shaped and been shaped historically, and are being transformed in the contemporary world by political, economic, institutional, social, and cultural forces, both regional and global.Association for Asian Studies North East Asia CouncilOhio State University. Office of International AffairsOhio State University. Department of HistoryOhio State University. Institute for Japanese StudiesOhio State University. College of Arts and HumanitiesEastern Kentucky University. Department of HistoryUtica College. Office of Institutional AdvancementOhio State University. Mershon Center for International Security StudiesEvent Web pag

Why Shashi?

oai:ojs.shashi.pitt.edu:article/1

The technologies of isolation: apocalypse and self in Kurosawa Kiyoshi's Kairo

In this investigation of the Japanese film Kairo, I contemplate how the horrors present in the film relate to the issue of self, by examining a number of interlocking motifs. These include thematic foci on disease and technology which are more intimately and inwardly focused that the film's conclusion first appears to suggest. The true horror here, I argue, is ontological: centred on the self and its divorcing from the exterior world, especially founded in an increased use of and reliance on communicative technologies. I contend that these concerns are manifested in Kairo by presenting the spread of technology as disease-like, infecting the city and the individuals who are isolated and imprisoned by their urban environment. Finally, I investigate the meanings of the apocalypse, expounding how it may be read as hopeful for the future rather than indicative of failure or doom

ISO 23494: Biotechnology - Provenance Information Model for Biological Specimen and Data

Exchange of research data and samples in biomedical research has become a common phenomenon demanding for their effective quality assessment. At the same time, several reports address reproducibility of research, where history of biological samples (acquisition, processing, transportation, storage, and retrieval) and data history (data generation and processing) defines their fitness for purpose, and hence their quality. The project aims at developing a comprehensive W3C PROV based provenance information standard intended for the biomedical research domain. The standard is being developed by the working group 5 ("data processing and integration") of the ISO (International Standardisation Organisation) technical committee 276 "biotechnology". The outcome of the project will be published in parts as international standards or technical specifications. The poster informs about the goals of the standardisation activity, presents the proposed structure of the standards, briefly describes its current state and outlines its future development and open issues

CK1ε Is Required for Breast Cancers Dependent on β-Catenin Activity

Background: Aberrant $\beta$-catenin signaling plays a key role in several cancer types, notably colon, liver and breast cancer. However approaches to modulate $\beta$-catenin activity for therapeutic purposes have proven elusive to date. Methodology: To uncover genetic dependencies in breast cancer cells that harbor active $\beta$-catenin signaling, we performed RNAi-based loss-of-function screens in breast cancer cell lines in which we had characterized $\beta$-catenin activity. Here we identify CSNK1E, the gene encoding casein kinase 1 epsilon (CK1$\varepsilon$) as required specifically for the proliferation of breast cancer cells with activated $\beta$-catenin and confirm its role as a positive regulator of $\beta$-catenin-driven transcription. Furthermore, we demonstrate that breast cancer cells that harbor activated $\beta$-catenin activity exhibit enhanced sensitivity to pharmacological blockade of Wnt/$\beta$-catenin signaling. We also find that expression of CK1$\varepsilon$ is able to promote oncogenic transformation of human cells in a $\beta$-catenin-dependent manner. Conclusions/Significance: These studies identify CK1$\varepsilon$ as a critical contributor to activated $\beta$-catenin signaling in cancer and suggest it may provide a potential therapeutic target for cancers that harbor active $\beta$-catenin. More generally, these observations delineate an approach that can be used to identify druggable synthetic lethal interactions with signaling pathways that are frequently activated in cancer but are difficult to target with the currently available small molecule inhibitors

RNA Sequencing of Pancreatic Circulating Tumour Cells Implicates WNT Signaling in Metastasis

Circulating tumour cells (CTCs) shed into blood from primary cancers include putative precursors that initiate distal metastases. While these cells are extraordinarily rare, they may identify cellular pathways contributing to the blood-borne dissemination of cancer. Here, we adapted a microfluidic device for efficient capture of CTCs from an endogenous mouse pancreatic cancer model and subjected CTCs to single molecule RNA sequencing, identifying Wnt2 as a candidate gene enriched in CTCs. Expression of Wnt2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. This effect is correlated with fibronectin upregulation and suppressed by inhibition of Map3k7 (Tak1) kinase. In humans, formation of non-adherent tumour spheres by pancreatic cancer cells is associated with upregulation of multiple Wnt genes, and pancreatic CTCs revealed enrichment for Wnt signaling in 5 of 11 cases. Thus, molecular analysis of CTCs may identify candidate therapeutic targets to prevent the distal spread of cancer

Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging

Hematopoietic stem cells (HSCs) residing in the bone marrow (BM) accumulate during aging but are functionally impaired. However, the role of HSC-intrinsic and -extrinsic aging mechanisms remains debated. Megakaryocytes promote quiescence of neighboring HSCs. Nonetheless, whether megakaryocyte-HSC interactions change during pathological/natural aging is unclear. Premature aging in Hutchinson-Gilford progeria syndrome recapitulates physiological aging features, but whether these arise from altered stem or niche cells is unknown. Here, we show that the BM microenvironment promotes myelopoiesis in premature/physiological aging. During physiological aging, HSC-supporting niches decrease near bone but expand further from bone. Increased BM noradrenergic innervation promotes β2-adrenergic-receptor(AR)-interleukin-6-dependent megakaryopoiesis. Reduced β3-AR-Nos1 activity correlates with decreased endosteal niches and megakaryocyte apposition to sinusoids. However, chronic treatment of progeroid mice with β3-AR agonist decreases premature myeloid and HSC expansion and restores the proximal association of HSCs to megakaryocytes. Therefore, normal/premature aging of BM niches promotes myeloid expansion and can be improved by targeting the microenvironment.Y.-H.O. received fellowships from Alborada Scholar-ship (University of Cambridge), Trinity-Henry Barlow Scholarship (Universityof Cambridge), and R.O.C. Government Scholarship to Study Abroad (GSSA). A.G.G. received fellowships from the Ramon Areces Foundationand the LaCaixa Foundation. C.K. was supported by Marie Curie Career Inte-gration (H2020-MSCA-IF-2015-70841). S.M.-F. was supported by Red TerCel (ISCIII-Spanish Cell Therapy Network). V.A. is supported by grants from theSpanish Ministerio de Economıa,Industria y Competitividad (MEIC) with co-funding from the Fondo Europeo de Desarrollo Regional (FEDER, ‘‘Una manerade hacer Europa’’) (SAF2016-79490-R), the Instituto de Salud Carlos III (AC16/00091 and AC17/00067), the Fundacio Marato TV3 (122/C/2015), and the Progeria Research Foundation (Established Investigator Award 2014–52). TheCNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovacion y Universidades (MCIU), and the Pro CNIC Foundation,and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work wassupported by core support grants from the Wellcome Trust and the MRC to theCambridge Stem Cell Institute, MEIC (SAF-2011-30308), Ramon y Cajal Program Grant (RYC-2009-04703), ConSEPOC-Comunidad de Madrid (S2010/BMD-2542), National Health Service Blood and Transplant (United Kingdom), European Union’s Horizon 2020 research (ERC-2014-CoG-64765 and MarieCurie Career Integration grant FP7-PEOPLE-2011-RG-294096), and a Programme Foundation Award from Cancer Research UK to S.M.-F., who wasalso supported in part by an International Early Career Scientist grant fromthe Howard Hughes Medical Institute.S

Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging.

Hematopoietic stem cells (HSCs) residing in the bone marrow (BM) accumulate during aging but are functionally impaired. However, the role of HSC-intrinsic and -extrinsic aging mechanisms remains debated. Megakaryocytes promote quiescence of neighboring HSCs. Nonetheless, whether megakaryocyte-HSC interactions change during pathological/natural aging is unclear. Premature aging in Hutchinson-Gilford progeria syndrome recapitulates physiological aging features, but whether these arise from altered stem or niche cells is unknown. Here, we show that the BM microenvironment promotes myelopoiesis in premature/physiological aging. During physiological aging, HSC-supporting niches decrease near bone but expand further from bone. Increased BM noradrenergic innervation promotes β2-adrenergic-receptor(AR)-interleukin-6-dependent megakaryopoiesis. Reduced β3-AR-Nos1 activity correlates with decreased endosteal niches and megakaryocyte apposition to sinusoids. However, chronic treatment of progeroid mice with β3-AR agonist decreases premature myeloid and HSC expansion and restores the proximal association of HSCs to megakaryocytes. Therefore, normal/premature aging of BM niches promotes myeloid expansion and can be improved by targeting the microenvironment.We thank A.R. Green for advice and support; M. García-Fernández, C. Fielding, C. Kapeni, X. Langa, and other current and former members of the S.M.-F group for help and discussions; A. Barettino and A. Macías (CNIC), D. Pask, T. Hamilton, the Central Biomedical Services and Cambridge NIHR BRC Cell Phenotyping Hub for technical assistance; H. Jolin and A.N.J. McZenzie (MRC Laboratory of Molecular Biology, Cambridge, UK) for help with milliplex analyses. Y.-H.O. received fellowships from Alborada Scholarship (University of Cambridge), Trinity-Henry Barlow Scholarship (University of Cambridge) and R.O.C. Government Scholarship to Study Abroad (GSSA) A.G.G. received fellowships from Ramón Areces and LaCaixa Foundations. C.K. was supported by Marie Curie Career Integration grant H2020-MSCA-IF-2015-70841. S.M.F., by Red TerCel (ISCIII-Spanish Cell Therapy Network). VA is supported by grants from the Spanish Ministerio de Economía, Industria y Competitividad (MEIC) with cofunding from the Fondo Europeo de Desarrollo Regional (FEDER, “Una manera de hacer Europa”) (SAF2016-79490-R), the Instituto de Salud Carlos III (AC16/00091), the Fundació Marató TV3 (122/C/2015), and the Progeria Research Foundation (Established Investigator Award 2014–52). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). This work was supported by core support grants from the Wellcome Trust and the MRC to the Cambridge Stem Cell Institute, the Spanish Ministry of Economy and Competitiveness (SAF-2011-30308), Ramón y Cajal Program grant RYC-2009-04703, ConSEPOC-Comunidad de Madrid S2010/BMD-2542, National 427 Health Service Blood and Transplant (United Kingdom), European Union’s Horizon 428 2020 research (ERC-2014-CoG-64765 and Marie Curie Career Integration grant FP7- 429 PEOPLE-2011-RG-294096) and a Programme Foundation Award from Cancer Research 430 UK to S.M.-F., who was also supported in part by an International Early Career Scientist 431 grant of the Howard Hughes Medical Institute

Uphold the nuclear weapons test moratorium

The Trump administration is considering renewing nuclear weapons testing (1), a move that could increase the risk of another nuclear arms race as well as an inadvertent or intentional nuclear war. Following in the long tradition of scientists opposing nuclear weapons due to their harmful effects on both humanity and the planet (2), we ask the U.S. government to desist from plans to conduct nuclear tests. During the Cold War, the United States conducted 1030 nuclear weapons tests, more than all other nuclear-armed nations combined (3). In 1996, the United States signed the Comprehensive Nuclear Test Ban Treaty (CTBT), agreeing not to conduct a nuclear weapons test of any yield (4). The United States has not yet ratified the CTBT but did spearhead the 2016 adoption of UN Security Council Resolution 2310, which calls upon all countries to uphold the object and purpose of the CTBT by not conducting nuclear tests (5). Eight of the nine nuclear-armed states, including the five permanent members of the UN Security Council, have observed a moratorium on nuclear testing since 1998 (3, 4). The ninth, North Korea, responding to international pressure, stopped testing warhead detonations (as opposed to missile flights) in 2017 (6). If the United States ratified the CTBT, joining the 168 countries who have already done so (4), there is a good chance that the other holdout countries would ratify the treaty as well (7)