Hiroko Nakamura

Long-term ex vivo maintenance of testis tissues producing fertile sperm in a microfluidic device.

In contrast to cell cultures, particularly to cell lines, tissues or organs removed from the body cannot be maintained for long in any culture conditions. Although it is apparent that in vivo regional homeostasis is facilitated by the microvascular system, mimicking such a system ex vivo is difficult and has not been proved effective. Using the culture system of mouse spermatogenesis, we addressed this issue and devised a simple microfluidic device in which a porous membrane separates a tissue from the flowing medium, conceptually imitating the in vivo relationship between the microvascular flow and surrounding tissue. Testis tissues cultured in this device successfully maintained spermatogenesis for 6 months. The produced sperm were functional to generate healthy offspring with micro-insemination. In addition, the tissue kept producing testosterone and responded to stimulation by luteinizing hormone. These data suggest that the microfluidic device successfully created in vivo-like conditions, in which testis tissue maintained its physiologic functions and homeostasis. The present model of the device, therefore, would provide a valuable foundation of future improvement of culture conditions for various tissues and organs, and revolutionize the organ culture method as a whole.

Involvement of the Rabies Virus Phosphoprotein Gene in Neuroinvasiveness

ABSTRACT Rabies virus (RABV), which is transmitted via a bite wound caused by a rabid animal, infects peripheral nerves and then spreads to the central nervous system (CNS) before causing severe neurological symptoms and death in the infected individual. Despite the importance of this ability of the virus to spread from a peripheral site to the CNS (neuroinvasiveness) in the pathogenesis of rabies, little is known about the mechanism underlying the neuroinvasiveness of RABV. In this study, to obtain insights into the mechanism, we conducted comparative analysis of two fixed RABV strains, Nishigahara and the derivative strain Ni-CE, which cause lethal and asymptomatic infections, respectively, in mice after intramuscular inoculation. Examination of a series of chimeric viruses harboring the respective genes from Nishigahara in the genetic background of Ni-CE revealed that the Nishigahara phosphoprotein (P) gene plays a major role in the neuroinvasiveness by mediating infection of peripheral nerves. The results obtained from both in vivo and in vitro experiments strongly suggested that the Nishigahara P gene, but not the Ni-CE P gene, is important for stable viral replication in muscle cells. Further investigation based on the previous finding that RABV phosphoprotein counteracts the host interferon (IFN) system demonstrated that the Nishigahara P gene, but not the Ni-CE P gene, functions to suppress expression of the beta interferon (IFN-β) gene (Ifn-β) and IFN-stimulated genes in muscle cells. In conclusion, we provide the first data strongly suggesting that RABV phosphoprotein assists viral replication in muscle cells by counteracting the host IFN system and, consequently, enhances infection of peripheral nerves.

Citation lag analysis in supply chain research

Interdisciplinary research is expected to contribute to industrial and economic development. However, due to expansion of knowledge and the fragmentation of research fields, knowledge dissemination among different research fields is rare and we need a methodology for measuring such dissemination and promoting it. In this paper, we introduce a citation lag analysis of inter- and intra-clusters extracted by citation network analysis as a new indicator to represent the speed of knowledge diffusion in subfields of a research field. A case study was performed within supply chain research to investigate knowledge integration among its subfields. Based on the analysis, we discuss knowledge structure and reciprocal influence of subfields in supply chain research. This study contributes to offering a new approach for analyzing and understanding the development of boundary spanning research.

On-Chip Single Embryo Coculture With Microporous-Membrane-Supported Endometrial Cells

In vitro culture (IVC) of the mammalian embryo is an essential technique in reproductive technology and other related life science disciplines. Although embryos are usually cultured in groups, a single embryo culture has been highly desired for IVC to investigate developmental processes. In this study, we proposed and developed the first single embryo coculture device, which allows making an array of a single embryo coculture with endometrial cells by controlling the culture environment in a microfluidic device. To realize this concept, we investigated three key issues: selection of a culture medium for the embryo coculture with endometrial cells using a mouse embryo and endometrial cells, evaluation of an on-microporous-membrane coculture of endometrial cells and an embryo to control the polarization of endometrial cells on the membrane, and evaluation of the coculture of endometrial cells and the embryo in the microfluidic device. We successfully obtained an array of a single coculture of embryo with endometrial cells in a microfluidic device. This concept will open and enhance the management of an individual embryo for assisted reproductive technology, livestock breeding, and fundamental stage research by further development.

Multi-level perspectives with technology readiness measures for aviation innovation

Sustainability science requires the development of a theoretical framework to understand, analyze, and design innovation to solve social, economic, and environmental issues. This paper extends the framework of multi-level perspectives (MLP) by introducing a technology readiness level (TRL), and analyzes the innovation of the advanced turboprop (ATP) engine in the aviation industry, also known as a propfan or an open rotor engine, which is one of the most promising engine innovations expected to mitigate climate change. The concept of TRL was introduced to explain the mechanisms of ATP failure in the late 1980s as well as the transition of the geared turbofan (GTF). In this paper, we discuss why ATP and GTF faced different fates although both were developed under the same landscape in the aviation industry. We also discuss the different roles of the socio-technical regime, such as uneven and dynamic opportunity windows, technological readiness, niche stock, institutional support of export products, and the risk of a ‘launch’ customer, at different TRLs. As illustrated in this paper, MLP with TRL is expected to facilitate future interdisciplinary collaboration between social scientists and engineers, and also transdisciplinary expertise between academia and practitioners by supporting analysis and design of the industry’s transition toward a more environmentally friendly regime as well as its effective management.

The effect of patent family information in patent citation network analysis: a comparative case study in the drivetrain domain

Abstract Previous researchers of citation analysis often analyze patent data of a single authority because of the availability of the data and the simplicity of analysis. Patent analysis, on the other hand, is used not only for filing and litigation, but also for technology trend analysis. However, global technology trends cannot be understood only with the analysis of patent data issued by a single authority. In this paper, we propose the use of patents from multiple authorities and discuss the effect of bundling patent family information. We investigate the effect of patent families with cases from automobile drivetrain technology. Based on the results, we conclude that the use of multiple authorities’ patent data bundled with the patent family information can significantly improve the coverage and practicability of patent citation analysis.

Cancer Cell Analyses at the Single Cell-Level Using Electroactive Microwell Array Device.

Circulating tumor cells (CTCs), shed from primary tumors and disseminated into peripheral blood, are playing a major role in metastasis. Even after isolation of CTCs from blood, the target cells are mixed with a population of other cell types. Here, we propose a new method for analyses of cell mixture at the single-cell level using a microfluidic device that contains arrayed electroactive microwells. Dielectrophoretic (DEP) force, induced by the electrodes patterned on the bottom surface of the microwells, allows efficient trapping and stable positioning of single cells for high-throughput biochemical analyses. We demonstrated that various on-chip analyses including immunostaining, viability/apoptosis assay and fluorescent in situ hybridization (FISH) at the single-cell level could be conducted just by applying specific reagents for each assay. Our simple method should greatly help discrimination and analysis of rare cancer cells among a population of blood cells.

Shedding light on a neglected area: a new approach to knowledge creation

Awareness is needed of sustainability issues that are currently neglected but potentially important. A computer-based approach can highlight unconscious and neglected areas because it can structure vast amounts of knowledge. In this article, we propose a methodology to perceive unconscious areas of sustainability with the support of a computer-based approach, which creates a matrix, named the recognized-unrecognized matrix, which highlights both local and globally neglected problems. A case study is conducted to consider the potential contribution of the aviation industry to sustainability issues. We demonstrate that a citation network analysis is an effective methodology to chart the recognized-unrecognized matrix. We highlight issues of water use in the aviation industry by designing an innovative water and air circulation system, which significantly reduces water and fuel consumption on board airplane flights. We also suggest a new approach to integrating both explicit and tacit knowledge to enable knowledge creation.

Science and technology map analysis of a multi-disciplinary field -Case study of aerospace engineering-

Both the expansion of knowledge and the fragmentation of disciplines are causing delay in important development strategy decision in many promising industries. Policy makers and practitioners expect tools to structure the expanding knowledge and to roadmap for breakthroughs. In this paper, we approach this challenge with a citation network analysis to academic publications and patents. The case study is discussed within one of the most complex galaxy of disciplines, Aerospace Engineering (AE). The analysis is based both on academic papers of major AE journals and on patents classified to AE by International Patent Classification. We found the difference between knowledge structure of AE, an integrated multi-technology system and the results obtained from our previous studies in component technology fields. This study contributes toward developing the adaptability of our tool to roadmap for innovation.

Transition management of a risky technology: Case of small unmanned aerial vehicles

Taking the Technology Innovation System (TIS) of small Unmanned Aerial Vehicle (sUAV) in Japan as a case, we extend the TIS framework to understand and manage the transition of risky technologies. In Japan, the environment for sUAV was dramatically changed in 2015 due to an incident of sUAV at the official residence of the Prime Minister of Japan. In December 2015, while amendment of Civil Aeronautics Act (Act) to include sUAV in the scope took effect, the Public-Private council (Council) for improvement of the environment concerning to sUAV business was formed. This paper assumes the Council reflects the TIS of sUAV in Japan and analyses the discourse at the Council to understand the status of the sUAV TIS. Then we discuss how we can manage the transition.