The exocyst is a conserved octameric complex that physically tethers a vesicle to the plasma membrane, prior to membrane fusion. It is important not only for secretion and membrane delivery but also, in mammalian cells, for cytokinesis, ciliogenesis, autophagy, tumorigenesis, and host defense. The combination of genome editing and advanced light microscopy of exocyst subunits in living cells has recently shown the complex to be much more dynamic than previously appreciated, and exposed how little we still know about its function (...) and regulation. (shrink)

Internet services, such as review sites, FAQ sites, online auction sites, online flea markets, and social networking services, are essential to our daily lives. Each Internet service aims to promote information exchange among people who share common interests, activities, or goods. Internet service providers aim to have users of their services actively communicate through their services. Without active interaction, the service falls into disuse. In this study, we consider that an Internet service has a network externality as its main feature, (...) and we model user behavior in the Internet service with network externality as a dynamic game. In particular, we model the diffusion process of users of an ISNE as an infinite-horizon extensive-form game of complete information in which: each user can choose whether or not to use the ISNE in her/his turn and the network effect of the ISNE depends on the history of each player’s actions. We then apply Markov perfect equilibrium to analyze how to increase the number of active users. We derive the necessary and sufficient condition under which the state in which every player is an active user is the unique Markov perfect equilibrium outcome. Moreover, we propose an incentive mechanism that enables the number of active users to increase steadily. (shrink)

The Millennium Development Goals were criticised for failing to address the issue of governance, and the associated notions of responsibility and accountability. The Sustainable Development Goals, we argue, need to recognise the structural constraints facing poor countries – the power imbalances in the global economic system that limit their ability to promote the prosperity and well-being of their people, as was clearly brought out by the Commission on Global Governance for Health, of which we were both members [Ottersen, O. P., (...) J. Dasgupta, C. Blouin, Paulo Buss, Virasakdi Chongsuvivatwong, Julio Frenk, Sakiko Fukuda-Parr, et al. 2014. “The Political Origins of Health Inequality: Prospects for Change.” Lancet 383: 630–667]. This article is divided into three parts. We begin by making the case for a global justice perspective which emphasises the responsibility – and hence also accountability – of international organisations and rule-making bodies. We next demonstrate the limitations of accountabi.. (shrink)

To become more broadly applicable, positions on AI ethics require perspectives from non-Western regions and cultures such as China and Japan. In this paper, we propose that the addition of the concept of harmony to the discussion on ethical AI would be highly beneficial due to its centrality in East Asian cultures and its applicability to the challenge of designing AI for social good. We first present a synopsis of different definitions of harmony in multiple contexts, such as music and (...) society, which reveals that the concept is, at its core, about well-balanced relationships and appropriate actions which give rise to order, balance, and aesthetically pleasing phenomena. The mediator for these well-balanced relationships isTaktwhich is an ability to act thoughtfully and sensibly according to the specific situation and to put things into proportion and order. We propose that the central challenge of building harmonizing AI is to make intelligent systems tactful and also to design and use them tactfully. For an AI system to become tactful, it needs to be able to have an advanced sensitivity to the specific contexts which it is in and their social and ethical implications and have the capability of approximately inferring the emotional and cognitive states of people with whom it is interacting. (shrink)

By unpacking some of the dichotomies inherent in the concepts of vulnerability and disability, the article problematises some of the current legal approaches to disability in Finland. It argues that where used to single out population groups or individuals due to their embodied characteristics, the vulnerability paradigm can be seen to create binaries both among the persons with disabilities, and between the “vulnerable” persons with disabilities and the perception of a rational, self-standing and autonomous human being. To mitigate such binaries, (...) the article explores an agency-centred discourse of vulnerability, one that recognises the co-existence of agency and vulnerability and sees agency as dynamic and responsive to the societal support structures that surround all of us. One of the central arguments of the article is that generalised approaches do, however, not suffice to make agency a reality for all persons with disabilities. Given the extensive diversity of intra-group variations between persons with disabilities, individualised solutions are needed for agency to be possible for all. To overcome objectification and de-agencification – and to enhance agency – this diversity of situations, needs and contexts of lived-in realities of individuals also needs to be expressly reflected in the legal language in addressing disability. (shrink)

The capacity of visual working memory (VWM) refers to the amount of visual information that can be maintained in mind at once, readily accessible for ongoing tasks. In healthy young adults, the capacity limit of VWM corresponds to about three simple objects. While some researchers argued that VWM capacity becomes adult-like in early years of life, others claimed that the capacity of VWM continues to develop beyond middle childhood. Here we assessed whether VWM capacity reaches adult levels in adolescence. Using (...) an adaptation of the visual change detection task, we measured visual working memory capacity estimates in 13 year-olds, 16-year-olds, and young adults. We tested whether the capacity estimates observed in early or later years of adolescence were comparable to the estimates obtained from adults. Our results demonstrated that the capacity of VWM continues to develop throughout adolescence, not reaching adult levels even in 16 year-olds. These findings suggest that VWM capacity displays a prolonged development, similar to the protracted trajectories observed in various other aspects of cognition. (shrink)

Many functional glycoproteins are expressed on the lymphocyte cell surface. Some of them carry O-linked oligosaccharides (O-glycans), which are conjugated through serine or threonine residues. During various biological processes, including T-cell activation, a tetrasaccharide on the T-cell surface is dramatically converted to a branched hexasaccharide, called core2 O-glycan. The same structural change in O-glycans is also found on the lymphocytes from patients with immunodeficiency conditions such as Wiskott-Aldrich syndrome and AIDS. Several studies revealing the roles of core2 O-glycans in immune (...) responses show that this is a biologically significant change. In particular, core2 O-glycans expressed on the cell surface reduce cell–cell interactions, thereby regulating immune responses. Furthermore, core2 O-glycan is a key backbone structure in forming selectin ligands. Thus, O-linked oligosaccharides, in particular those containing core2 branches, play vital roles in immune responses and may play dual roles in certain situations. This review will summarize the results obtained from various studies investigating the roles of O-glycans in immunological processes. BioEssays 23:46–53, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Many functional glycoproteins are expressed on the lymphocyte cell surface. Some of them carry O-linked oligosaccharides (O-glycans), which are conjugated through serine or threonine residues. During various biological processes, including T-cell activation, a tetrasaccharide on the T-cell surface is dramatically converted to a branched hexasaccharide, called core2 O-glycan. The same structural change in O-glycans is also found on the lymphocytes from patients with immunodeficiency conditions such as Wiskott-Aldrich syndrome and AIDS. Several studies revealing the roles of core2 O-glycans in immune (...) responses show that this is a biologically significant change. In particular, core2 O-glycans expressed on the cell surface reduce cell–cell interactions, thereby regulating immune responses. Furthermore, core2 O-glycan is a key backbone structure in forming selectin ligands. Thus, O-linked oligosaccharides, in particular those containing core2 branches, play vital roles in immune responses and may play dual roles in certain situations. This review will summarize the results obtained from various studies investigating the roles of O-glycans in immunological processes. BioEssays 23:46–53, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Children’s intentions should be respected. Parents are the key persons involved in decision-making related to their children. In Japan, the appropriate ages and standards for a child’s consent and assent, approval, and decision-making are not clearly defined, which makes the process of obtaining consent and assent for clinical research complex. The purpose of this paper is as follows: to understand the attitudes and motives of parents concerning children’s participation in medical research and the factors influencing their decision-making. We also sought (...) to clarify who has the right to be involved in decisions regarding children’s participation in research. A semi-structured Internet survey on parents’ opinions and attitudes and preferences concerning medical research involvement was conducted. Children were divided into three age groups (6–10-year-olds, 11–14-year-olds, and 15–18-year-olds), with three illness severity categories. Possible correlations between the number of children, children’s ages, parents’ educational levels, and parents’ attitudes were examined. Among the participants, 42.3% recognized the term “informed consent.” The proportion of participants who understood “informed consent” increased with educational level. Four out of five participants did not know, or had not heard of, the term “informed assent.” Furthermore, the percentage of those who understood the term “informed assent” increased with academic level. Participants generally believed in prioritizing parents’ opinions over children’s, and that parents and children would ideally reach a joint decision. Although many parents favored collaborative decision-making, they also wanted their own will reflected in the decision and felt they should receive important information before their children do. Decision-making was affected by the condition’s severity and prognosis. This indicates that most Japanese parents believe that their children have the right to know their disease name and treatment; nonetheless, they should be protected. Parents’ values and judgments regarding medical intervention involving their children varied. Children’s ability to consent to treatment and research believed to be in their best interests should be assessed appropriately. They should be permitted to provide consent or assent, and their views should be respected. Involving children in decision-making fosters more open communication and transparency between medical professionals, parents, and children. (shrink)

Contemplating one’s own death is a core aspect in the history of Western philosophy. In the modern era, existential philosophy has inherited this tradition and established unique discussions on the concept of “_my_ death,” resting on the premise that this concept is unapproachable via scientific inquiry. Conversely, biological research is essentially conducted within the scope of life phenomena, with death being referred to in the sense of lifespan; thus, death is not among its inherent themes, which automatically excludes the concept (...) of _my_ death from its scope. To establish a dialogue between the two fields, this study questions the widely held premise that _my_ death is unrelated to science and is best examined by philosophy. I consider the movement between continuity and discontinuity as foundational to scientific development, and integrate it with the relationship between the unknown and known. Furthermore, I extend this to the concepts of consciousness and body, and subsequently clarify and define the unknown divisions. Finally, I examine the kinds of unknowns that science confronts to interpret philosophically how an aspect of reproductive theory has unwittingly revealed a completely new dimension of life: _my_ death. Overall, I argue that _my_ death is an essential point of contact between philosophy and biology that reveals the scholarly significance of the unknown. (shrink)

The inositol phosphate metabolism network has been found to be much more complex than previously thought, as more and more inositol phosphates and their metabolizing enzymes have been discovered. Some of the inositol phosphates have been shown to have biological activities, but little is known about their signal transduction mechanisms except for that of inositol 1,4,5‐trisphosphate. The recent discovery, however, of a number of binding proteins for inositol high polyphosphate [inositol 1,3,4,5‐tetrakisphosphate (IP4), inositol 1,3,4,5,6‐pentakisphosphate, or inositol hexakisphosphate] enables us to (...) speculate on the physiological function of these compounds. In this article we focus on two major issues: (1) the roles of inositol high polyphosphates in vesicular trafficking, especially exocytosis, and (2) pleckstrin homology domaincontaining IP4 binding proteins involved in the Ras signaling pathway. (shrink)

We clarify the significance of quasiprobability in quantum mechanics that is relevant in describing physical quantities associated with a transition process. Our basic quantity is Aharonov’s weak value, from which the QP can be defined up to a certain ambiguity parameterized by a complex number. Unlike the conventional probability, the QP allows us to treat two noncommuting observables consistently, and this is utilized to embed the QP in Bohmian mechanics such that its equivalence to quantum mechanics becomes more transparent. We (...) also show that, with the help of the QP, Bohmian mechanics can be recognized as an ontological model with a certain type of contextuality. (shrink)

_An Inquiry into the Good_ represented the foundation of Nishida’s philosophy—reflecting both his deep study of Zen Buddhism and his thorough analysis of Western philosophy—and established its author as the foremost Japanese philosopher of this century. In this important new translation, two scholars—one Japanese and one American—have worked together to present a lucid and accurate rendition of Nishida’s ideas. "The translators do an admirable job of adhering to the cadence of the original while avoiding unidiomatic, verbatim constructions."—John C. (...) Maraldo, _Philosophy East and West_ __ __ "More accurate and critical than the first translation into English of Nishida's earliest book.... An important addition to library collections of twentieth-century philosophy, Japanese intellectual history, and contemporary Buddhist thought."—_Choice_ "A welcome new translation of a work by probably the most original and influential of modern Japanese philosophers."—Hidé Ishiguro, _Times Literary Supplement_ "Undoubtedly the most important work for anyone in the West interested in understanding modern Japanese thought. This work premiered Japanese philosophy as modern but has also shown unusual staying power. In the late twentieth century Japanese thinkers, both religious and secular, insist on its importance and relevance."—William R. La Fleur, University of Pennsylvania. (shrink)

In the near future, our life will normally be surrounded with fairly complicated artifacts, enabled by the autonomous robot and brain–machine interface technologies. In this paper, we argue that what we call the responsibility flaw problem and the inappropriate use problem need to be overcome in order for us to benefit from complicated artifacts. In order to solve these problems, we propose an approach to endowing artifacts with an ability of socially communicating with other agents based on the artifact-as-a-half-mirror metaphor. (...) The idea is to have future artifacts behave according to the hybrid intention composed of the owner’s intention and the social rules. We outline the approach and discuss its feasibility together with preliminary work. (shrink)