High‐molecular‐weight hyaluronan acts as a ligand of the tumor‐suppressive Hippo signal, whereas degradation of hyaluronan from a high‐molecular‐weight form to a low‐molecular‐weight forms by hyaluronidase 2 inhibits Hippo signal activation and thereby activates the pro‐oncogenic transcriptional coactivator yes‐associated protein (YAP), which creates a cancer‐predisposing microenvironment and drives neoplastic transformation of cells through both cell‐autonomous and non‐cell‐autonomous mechanisms. In fact, accumulation of low‐molecular‐weight hyaluronan in tissue stroma is observed in many types of cancers. Since inhibition of YAP activity suppresses tumor growth (...) in vivo, pharmacological intervention of the Hippo‐YAP signal is an attractive approach for future drug development. In this review, pharmacological intervention of excessive hyaluronan degradation as a novel approach for inhibition of the Hippo‐YAP signal is also discussed. Development of hyaluronidase inhibitors may provide novel therapeutic strategies for human malignant tumors. (shrink)

Hibakusha are “witnesses” of the atomic bombings, not just in a standard sense but also in the instrumental sense. For medical and scientific experts, hibakusha are biological resources of unparalleled scientific value. Over the past seventy years, the hibakusha bodies have narrated what it means to be exposed to radiation. In this paper, I explore studies at the Atomic Bomb Casualty Commission that examined hibakusha bodies as sites where risk could be read. I focus on a period from the mid-1950s (...) to 1975, during which new methods, practices, and technologies allowed ABCC scientists to investigate chromosomes as a way to study radiation exposure and human risk. By focusing on chromosomal aberrations, ABCC scientists connected their work directly to the emerging infrastructure for radiobiology at the time. ABCC administrators actively sought out such prestige, especially given their relationship with the Atomic Energy Commission. The shift in approach would also alleviate some public relations problems with which the institution was struggling. Launching a cytogenetics program required some older practices that had assumed American privilege and dominance to be abandoned. Eventually, the decision to let chromosomes speak of radiation exposure brought about fundamental changes in ABCC, which came to symbolize the model for future studies at the organization, especially as ABCC was transitioning to a US-Japan binational organization. More broadly, this case highlights the intricate scientific negotiation of radiation risk where uncertainties necessarily prevail. (shrink)

数理論理学の基本となる命題・述語論理から、チューリング機械・形式手法・ブール代数といった「少し先」の内容までを丁寧に解説。.

In his paper “Non-human moral status: problems with phenomenal consciousness,” Joshua Shepherd emphasized an objectivist understanding of welfare to establish the moral status of non-human entities...

The largest transcriptome reported so far comprises 60,770 mouse full‐length cDNA clones, and is an effective reference data set for comparative transcriptomics. The number of mouse cDNAs identified greatly exceeds the number of genes predicted from the sequenced human and mouse genomes. This is largely because of extensive alternative splicing and the presence of many non‐coding RNAs (ncRNAs), which are difficult to predict from genomic sequences. Notably, ncRNAs are a major component of the transcriptomes of higher organisms, and many sense–antisense (...) pairs have been identified. The ncRNAs function in a range of regulatory mechanisms for gene expression and other biological processes. They might also have contributed to the increased functional diversification of genomes during evolution. In this review, we discuss aspects of the transcriptome of various organisms in relation to the mouse data, in order to shed light on the regulatory mechanisms and physiological significance of these abundant RNAs. BioEssays 26:833–843, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The notion of the unconscious resulted in a reversal of optics concerning the evidence of consciousness, and the split which Freud created in the analysis of mental activities elicited many reactio...

Human brain organoids are three-dimensional masses of tissues derived from human stem cells that partially recapitulate the characteristics of the human brain. They have promising applications in many fields, from basic research to applied medicine. However, ethical concerns have been raised regarding the use of human brain organoids. These concerns primarily relate to the possibility that brain organoids may become conscious in the future. This possibility is associated with uncertainties about whether and in what sense brain organoids could have consciousness (...) and what the moral significance of that would be. These uncertainties raise further concerns regarding consent from stem cell donors who may not be sufficiently informed to provide valid consent to the use of their donated cells in human brain organoid research. Furthermore, the possibility of harm to the brain organoids raises question about the scope of the donor’s autonomy in consenting to research involving these entities. Donor consent does not establish the reasonableness of the risk and harms to the organoids, which ethical oversight must ensure by establishing some measures to mitigate them. To address these concerns, we provide three proposals for the consent procedure for human brain organoid research. First, it is vital to obtain project-specific consent rather than broad consent. Second, donors should be assured that appropriate measures will be taken to protect human brain organoids during research. Lastly, these assurances should be fulfilled through the implementation of precautionary measures. These proposals aim to enhance the ethical framework surrounding human brain organoid research. (shrink)

We investigated the key anatomical structures mediating interhemispheric integration during the perception of apparent motion across the retinal midline. Previous studies of commissurotomized patients suggest that subcortical structures mediate interhemispheric transmission but the specific regions involved remain unclear. Here, we exploit interindividual variations in the propensity of normal subjects to perceive horizontal motion, in relation to vertical motion. We characterize these differences psychophysically using a Dynamic Dot Quartet (an ambiguous stimulus that induces illusory motion). We then tested for correlations between (...) a tendency to perceive horizontal motion and fractional anisotropy (FA) (from structural diffusion tensor imaging), over subjects. FA is an indirect measure of the orientation and integrity of white matter tracts. Subjects who found it easy to perceive horizontal motion showed significantly higher FA values in the pulvinar. Furthermore, fiber tracking from an independently identified (subject-specific) visual motion area converged on the pulvinar nucleus. These results suggest that the pulvinar is an anatomical hub and may play a central role in interhemispheric integration. (shrink)

Neuronal activities have recently been reported to exhibit power-law scaling behavior. However, it has not been demonstrated that the power-law component can play an important role in human perceptual functions. Here, we demonstrate that the power spectrum of magnetoencephalograph recordings of brain activity varies in coordination with perception of subthreshold visual stimuli. We observed that perceptual performance could be better explained by modulation of the power-law component than by modulation of the peak power in particular narrow frequency ranges. The results (...) suggest that the brain operates in a state of self-organized criticality, modulating the power spectral exponent of its activity to optimize its internal state for response to external stimuli. (shrink)

We investigated how the structure of the brain network relates to the stability of perceptual alternation in binocular rivalry. Historically, binocular rivalry has provided important new insights to our understandings in neuroscience. Although various relationships between the local regions of the human brain structure and perceptual switching phenomena have been shown in previous researches, the global organization of the human brain structural network relating to this phenomenon has not yet been addressed. To approach this issue, we reconstructed fiber-tract bundles using (...) diffusion tensor imaging and then evaluated the correlations between the speeds of perceptual alternation and fractional anisotropy (FA) values in each fiber-tract bundle integrating among 84 brain regions. The resulting comparison revealed that the distribution of the global organization of the structural brain network showed positive or negative correlations between the speeds of perceptual alternation and the FA values. First, the connections between the subcortical regions stably were negatively correlated. Second, the connections between the cortical regions mainly showed positive correlations. Third, almost all other cortical connections that showed negative correlations were located in one central cluster of the subcortical connections. This contrast between the contribution of the cortical regions to destabilization and the contribution of the subcortical regions to stabilization of perceptual alternation provides important information as to how the global architecture of the brain structural network supports the phenomenon of binocular rivalry. (shrink)

The brain is a very complex structure. Over the past several decades, many studies have aimed to understand how various non-uniform variables relate to each other. The current study compared the whole-brain network organization and global spatial distribution of cell densities in the monkey brain. Wide comparisons between 27 graph theoretical measures and cell densities revealed that only participation coefficients (PCs) significantly correlated with cell densities. Interestingly, PCs did not show a significant correlation with spatial coordinates. Furthermore, the significance of (...) the correlation between cell densities and spatial coordinates disappeared only with the removal of the visual module, while the significance of the correlation between cell densities and PCs disappeared with the removal of any one module. Taken together, these results suggested the presence of a combinatorial effect of modular architectures in the network organization related to the non-uniformity of cell densities additional to the spatially monotonic change. (shrink)

This article reports an interesting link between the psychophysical property of intentional control of perceptual switching and the underlying neural activities. First, we revealed that the timing of perceptual switching for a dynamical dot quartet can be controlled by the observers' intention, without eye movement. However, there is a clear limitation to this control, such that each animation frame of the stimulus must be presented for a sufficiently long time length; in other words, the frequency of the stimulus alternation must (...) be sufficiently slow for the control. The typical stimulus onset asynchrony for a 50% level of success was about 275 ms for an average of 10 observers. On the basis of psychophysical property, we designed three experiments for investigating the neural process with a magnetoencephalography. They revealed that: (1) a peak component occurring about 300 ms after a reversal was stronger when the direction of perceived motion was switched intentionally than when it was not switched, and (2) neural components about 30–40 ms and 240–250 ms after the reversal of the stimulus animation were stronger when perception was altered intentionally than when it was switched unintentionally. The 300 ms component is consistent with a previous study about passive perceptual switching (Struber and Herrmann [2002]: Cogn Brain Res 14:370–382), but the intentional effect was seemed to be a different component from the well-known P300 component. (shrink)

Recently, there have been an increasing number of studies on the Buddhist monastic community as a whole and on individual Buddhist monks and nuns in Vinaya literature. However, we do not know much about how a local Buddhist monastic community was administered. In order to consider just an aspect of the administration in a local monastic community, I will in this paper investigate descriptions of agreements that local monastic communities or local Buddhist monks conclude in Vinaya texts belonging to the (...) sarv?stiv?dins. (shrink)

The notion of quasi-minimal structures was defined by B. Zil'ber as a natural generalization of minimal structures. Inspired by his work, we study here basic model theoretic properties of quasiminimal structures. Main result is the construction of ω-saturated quasi-minimal models under ω-stability assumption.

We study the following conjecture. Conjecture. Let T be an ω-stable theory with continuum many countable models. Then either i) T has continuum many complete extensions in L1(T), or ii) some complete extension of T in L1 has continuum many L1-types without parameters. By Shelah's proof of Vaught's conjecture for ω-stable theories, we know that there are seven types of ω-stable theory with continuum many countable models. We show that the conjecture is true for all but one of these seven (...) cases. In the last case we show the existence of continuum many L2-types. (shrink)

We study the following conjecture. Conjecture. Let $T$ be an $\omega$-stable theory with continuum many countable models. Then either i) $T$ has continuum many complete extensions in $L_1$, or ii) some complete extension of $T$ in $L_1$ has continuum many $L_1$-types without parameters. By Shelah's proof of Vaught's conjecture for $\omega$-stable theories, we know that there are seven types of $\omega$-stable theory with continuum many countable models. We show that the conjecture is true for all but one of these seven (...) cases. In the last case we show the existence of continuum many $L_2$-types. (shrink)

We show that is a quasi-minimal torsion-free divisible abelian group. After discussing the axiomatization of the theory of this structure, we present its ω-saturated quasi-minimal model.

In this paper, a system called Caretta that integrates personal and shared workspaces to support face-to-face collaboration is described. We use PDAs for individual users' personal workspaces that enable them to reflect on their own idea. A shared workspace has been implemented by using a multiple-input sensing board, which allows a group of users to simultaneously manipulate physical objects. In order to raise the level of awareness among users, we have used augmented reality technologies and created an immersive environment for (...) the users' shared workspace. Users of Caretta can discuss and negotiate with each other in the shared workspace, while they individually examine their ideas in their own personal workspaces. Therefore, Caretta allows users to participate in group activities interchangeably and seamlessly by using both these workspaces. Caretta can be used for several types of group activities. In this paper, it is used for supporting a group of users in urban planning tasks by allowing the users to actually construct a town on the shared space and evaluate the town through computer simulations. User studies to evaluate Caretta were conducted. Usage logs of Caretta, video analyses, and comments from users proved that each user could utilize personal and shared space interchangeably at their own pace and without being hindered by other users. (shrink)

We show that K-generic projective planes have Morley rank either two or infinity. We also show give a direct argument that such planes are not Desarguesian.

In experiments of games, players frequently make choices which are regarded as irrational in game theory. In papers of Khrennikov (Information Dynamics in Cognitive, Psychological and Anomalous Phenomena. Fundamental Theories of Physics, Kluwer Academic, Norwell, 2004; Fuzzy Sets Syst. 155:4–17, 2005; Biosystems 84:225–241, 2006; Found. Phys. 35(10):1655–1693, 2005; in QP-PQ Quantum Probability and White Noise Analysis, vol. XXIV, pp. 105–117, 2009), it was pointed out that statistics collected in such the experiments have “quantum-like” properties, which can not be explained in (...) classical probability theory. In this paper, we design a simple quantum-like model describing a decision-making process in a two-players game and try to explain a mechanism of the irrational behavior of players. Finally we discuss a mathematical frame of non-Kolmogorovian system in terms of liftings (Accardi and Ohya, in Appl. Math. Optim. 39:33–59, 1999). (shrink)

This paper addresses the conceptual as well as social origins of Mendeleev’s discovery of the periodic law and its reception by the chemical community by taking account of three factors: Mendeleev’s early research and its relevance to the discovery; his concepts of chemistry, especially that of the chemical elements; and the social context of the discovery and the reception in the chemical community. Mendeleev's clear distinction between abstract elements and simple bodies was a departure from Lavoisier’s famous definition of elements (...) as an endpoint of analysis and originated from his research in indefinite compounds. As a comparison, the paper also analyzes Lothar Meyer’s approach to the classification of the elements. Mendeleev’s new concept of chemical elements and the existence of an audience in the form of the newly established Russian Chemical Society, and his ``German connection'', helped Mendeleev in his discovery and its reception. (shrink)

In this paper, we outline how one might conduct a comprehensive ethical evaluation of human brain organoid transplantation in animals. Thus far, ethical concerns regarding this type of research have been assumed to be similar to those associated with other transplants of human cells in animals, and have therefore not received significant attention. The focus has been only on the welfare, moral status, or mental capacities of the host animal. However, the transplantation of human brain organoids introduces several new ethical (...) issues. Many of these are related to uncertainty regarding whether or not brain organoids might be conscious. While these concerns might not be immediately relevant, they warrant closer scrutiny. We discuss how various ethical issues are relevant to different stages of human brain organoid transplantation and can guide the ethical evaluation of research. Our examination would broaden the horizons of the debate on the transplantation of brain organoids. (shrink)

Transcriptional regulation is coupled with numerous intracellular signaling processes often mediated by second messengers. Now, growing evidence points to the importance of Ca2+, one of the most versatile second messengers, in activating or inhibiting gene transcription through actions frequently mediated by members of the EF‐hand superfamily of Ca2+‐binding proteins. Calmodulin and calcineurin, representative members of this EF‐hand superfamily, indirectly regulate transcription through phosphorylation/dephosphorylation of transcription factors in response to a Ca2+ increase in the cell. Recently, a novel EF‐hand Ca2+‐binding protein (...) called DREAM has been found to interact with regulatory sequences of DNA, thereby acting as a direct regulator of transcription. Finally, S100B, a dimeric EF‐hand Ca2+‐binding protein, interacts with the tumor suppressor p53 and controls its transcriptional activity. In light of the structural studies reported to date, this review provides an overview of the structural basis of EF‐hand Ca2+‐binding proteins linked with transcriptional regulation. BioEssays 24:625–636, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

A lifting is a map from the state of a system to that of a compound system, which was introduced in Accardi and Ohya (Appl. Math. Optim. 39:33–59, 1999). The lifting can be applied to various physical processes.In this paper, we defined a quantum mutual entropy by the lifting. The usual quantum mutual entropy satisfies the Shannon inequality (Ohya in IEEE Trans. Inf. Theory 29(5):770–774, 1983), but the mutual entropy defined through the lifting does not satisfy this inequality unless some (...) conditions hold. (shrink)

ホセ・ヨンパルト上智大学教授が西暦2000年(平成12年)3月をもって、目出度く古稀を迎えられることになった。教授は、1968年(昭和43年)以来、30年以上にわたって上智大学で法哲学を講じてこられた ほか、慶応義塾大学、中央大学、明治大学、専修大学、その他の大学でも非常勤講師として法哲学等を教えてこられ、その教え子は極めて多数にのぼっている。その中には、既に研究者として一人立ちし、各地の大学に奉職 して立派な仕事をしておられる教え子も少なくない。そうした教え子たちによる教授の古稀祝賀論集。.