Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23, selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type mice at the (...) same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated. (shrink)

The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the (...) development of the community-based Coronavirus Infectious Disease Ontology in early 2020. -/- As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment. -/- CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications. (shrink)

We hypothesize that aspects of animal multicellularity originated before the divergence of metazoans from fungi and social amoebae. Polarized epithelial tissues are a defining feature of metazoans and contribute to the diversity of animal body plans. The recent finding of a polarized epithelium in the non‐metazoan social amoeba Dictyostelium discoideum demonstrates that epithelial tissue is not a unique feature of metazoans, and challenges the traditional paradigm that multicellularity evolved independently in social amoebae and metazoans. An alternative view, presented here, is (...) that the common ancestor of social amoebae, fungi, and animals spent a portion of its life cycle in a multicellular state and possessed molecular machinery necessary for forming an epithelial tissue. Some descendants of this ancestor retained multicellularity, while others reverted to unicellularity. This hypothesis makes testable predictions regarding tissue organization in close relatives of metazoans and provides a novel conceptual framework for studies of early animal evolution.Editor's suggested further reading in BioEssays Searching for Eve: Basal metazoans and the evolution of multicellular complexity Abstract. (shrink)

Exploring what theologians at the University of Paris in the thirteenth century understood about the boundary between humans and animals, this book demonstrates the great variety of ways in which they held similarity and difference in productive tension. Analysing key theological works, Ian P. Wei presents extended close readings of William of Auvergne, the Summa Halensis, Bonaventure, Albert the Great and Thomas Aquinas. These scholars found it useful to consider animals and humans together, especially with regard to animal knowledge (...) and behaviour, when discussing issues including creation, the fall, divine providence, the heavens, angels and demons, virtues and passions. While they frequently stressed that animals had been created for use by humans, and sometimes treated them as tools employed by God to shape human behaviour, animals were also analytical tools for the theologians themselves. This study thus reveals how animals became a crucial resource for generating knowledge of God and the whole of creation. (shrink)

مداخلة مترجمة عن الفرنسية للفيلسوف الفرنسي جيل دولوز.

Emotion recognition is an important part of building an intelligent human-computer interaction system and plays an important role in human-computer interaction. Often, people express their feelings through a variety of symbols, such as words and facial expressions. A business ecosystem is an economic community based on interacting organizations and individuals. Over time, they develop their capabilities and roles together and tend to develop themselves in the direction of one or more central enterprises. This paper aims to study a multimodal ER (...) method based on attention mechanism. It analyzes the current emotional state of consumers and the development direction of enterprises through multi-modal ER of human emotions and analysis of market trends, so as to provide the most appropriate response or plan. This paper firstly describes the related methods of multimodal ER and deep learning in detail, and briefly outlines the meaning of enterprise strategy in the business ecosystem. Then, two datasets, CMU-MOSI and CMU-MOSEI, are selected to design the scheme for multimodal ER based on self-attention mechanism. Through the comparative analysis of the accuracy of single-modal and multi-modal ER, the self-attention mechanism is applied in the experiment. The experimental results show that the average recognition accuracy of happy under multimodal ER reaches 91.5%. (shrink)

The Gifford Lectures were established in 1885 at the universities of St Andrews, Glasgow, Aberdeen and Edinburgh to promote the discussion of 'Natural Theology in the widest sense of the term - in other words, the knowledge of God', and some of the world's most influential thinkers have delivered them. The 1901–2 lectures given in Edinburgh by American philosopher William James are considered by many to be the greatest in the series. The lectures were published in book form in (...) 1902 and have been reprinted many times. James, who was educated in the United States and Europe, and spent much of his career teaching philosophy at Harvard, was very influential in the development of modern psychology, and in these twenty lectures he explores the personal experience of religion. Some of the topics include religion and neurology, 'the sick soul', saintliness, and mysticism. (shrink)

This paper explores the cooperation mechanisms for the prisoner’s dilemma game, a canonical example for studying cooperation mechanisms, with Bayesian games. By the approach allowing simultaneous moves with the assumption that the players might be self-interested or norm-following, we establish four possible Bayesian game models, all of which are cooperation mechanisms for the prisoner’s dilemma game except for the model in which one of the two players must be self-interested.

本书从现代美育理论研究入手、评论著名美学人物、提出把“完美功利主义”作为中国美学现代传统的想法、并对这种现代传统进行阐述。.

本书研究了西方科学哲学中的八个主要问题,即:认知意义的判断标准、归纳与验证、科学说明模型及其问题、科学的发展模式、科学划界、科学实在论、科学与价值、社会科学哲学。.

Liberal thinkers of the eighteenth and nineteenth centuries were alert to the political costs and human cruelties involved in European colonialism, but they also thought that European expansion held out progressive possibilities. In Progress, Pluralism, and Politics David Williams examines the colonial and anti-colonial arguments of Adam Smith, Immanuel Kant, Jeremy Bentham, and L.T. Hobhouse. Williams locates their ambivalent attitude towards European conquest and colonial rule in a set of tensions between the impact of colonialism on European states, the possibilities (...) of progress in distant and diverse places, and the relationship between universalism and cultural pluralism. In so doing he reveals some of the central ambiguities that characterize the ways that liberal thought has dealt with the reality of an illiberal world. Of particular importance are appeals to various forms of universal history, attempts to mediate between the claims of identity and the reality of difference, and the different ways of thinking about the achievement of liberal goods in other places. Pointing to key elements in still ongoing debates within liberal states about how they should relate to illiberal places, Progress, Pluralism, and Politics enriches the discussion on political thought and the relationship between liberalism and colonialism. (shrink)

In fourteen scholarly yet delightfully readable essays, Ober solves some ancient mysteries and reveals the secret kinks and passions of famous and obscure historical figures.

In this foundational work in contemporary political theory, William Connolly makes a distinctive contribution to our understanding of the relationship between ...

Since 2004, Nanyan Cao and some other scholars have implicitly or explicitly claimed that engineering ethics in China is importantly different from engineering ethics in the United States. The evidence for that claim relies on examination of official documents or certain large features of Chinese society. Though neither is an uncommon approach to studying engineering ethics in China, neither actually studies engineering practice in China. This article does—or at least gets much closer. The authors have asked almost two hundred Chinese (...) engineers about what they do and why they do it. The responses suggest that Chinese engineers, or at least those surveyed, think about engineering ethics much as American engineers do. The responses also suggest that much more empirical work needs to be done before we can claim to understand either the similarities or differences between engineering ethics in China and engineering ethics in “the West.”. (shrink)

This research examines wearable, fashionable interaction design to mediate the narrative and semiotic concepts found in technology and fashion. We discuss the principles of design anthropology using Taiwan proverbs to transmit the “people-situation-reason-object” method and analyze five case studies that provide new approaches for designers engaged in future industry. Design anthropology attempts to engage physiological and psychological design through technological function, meaning formation, and fashion aesthetics to achieve cognition between people and the environment. The wearable, fashionable interaction displays characteristics of (...) narrative and semantics transmitted through craft culture as well as collective, cheerful, and creative performance. It is a confident and innovative attempt, which bears a joyful and fundamental interface. This study takes two directions, with cultural thinking serving as the basis to establish a set of traditional craft designs and interactive objects that assist designers in using the senses to inform and initiate new lifestyle values. (shrink)

This research examines wearable, fashionable interaction design to mediate the narrative and semiotic concepts found in technology and fashion. We discuss the principles of design anthropology using Taiwan proverbs to transmit the “people-situation-reason-object” method and analyze five case studies that provide new approaches for designers engaged in future industry. Design anthropology attempts to engage physiological and psychological design through technological function, meaning formation, and fashion aesthetics to achieve cognition between people and the environment. The wearable, fashionable interaction displays characteristics of (...) narrative and semantics transmitted through craft culture as well as collective, cheerful, and creative performance. It is a confident and innovative attempt, which bears a joyful and fundamental interface. This study takes two directions, with cultural thinking serving as the basis to establish a set of traditional craft designs and interactive objects that assist designers in using the senses to inform and initiate new lifestyle values. (shrink)

This essay develops an inferential account of model explanation, based on Mauricio Suárez’s inferential conception of scientific representation and Alisa Bokulich’s counterfactual account of model explanation. It is suggested that the fact that a scientific model can explain is essentially linked to how a modeler uses an established model to make various inferences about the target system on the basis of results derived from the model. The inference practice is understood as a two-step activity, with the first step involving making (...) counterfactual statements about the model itself and the second step involving making hypothetical statements transferring over claims derived from the model onto the target. To illustrate how this two-step activity proceeds, an agent-based simulation model is discussed. (shrink)

In this paper, we propose an empirically based Monte Carlo bus-network model as a test bed to simulate intervention strategies to overcome the inefficiencies of bus bunching. The EMB model is an agent-based model which utilizes the positional and temporal data of the buses obtained from the Global Positioning System to constitute a set of empirical velocity distributions of the buses and a set of exponential distributions of interarrival time of passengers at the bus stops. Monte Carlo sampling is then (...) performed on these two derived probability distributions to yield the stochastic dynamics of both the buses’ motion and passengers’ arrival. Our EMB model is generic and can be applied to any real-world bus network system. In particular, we have validated the model against the Nanyang Technological University’s Shuttle Bus System by demonstrating its accuracy in capturing the bunching dynamics of the shuttle buses. Furthermore, we have analyzed the efficacy of three intervention strategies: holding, no-boarding, and centralized-pulsing, against bus bunching by incorporating the rule set of these strategies into the model. Under the scenario where the buses have the same velocity, we found that all three strategies improve both the waiting and travelling times of the commuters. However, when the buses have different velocities, only the centralized-pulsing scheme consistently outperforms the control scenario where the buses periodically bunch together. (shrink)

Tu (Chinese history and philosophy, Harvard U.) offers a panoramic view of the core values of Confucian intellectual thought that have kept it vital for more than two millennia, and underlie the recent resurgence in eastern Asia. Of interest to students of either China or religion and ethics. Paper edition (unseen), $14.95. Annotation copyright by Book News, Inc., Portland, OR.

This paper examines Aristotle’s vocabulary of pain, that is the differences and relations of the concepts of pain expressed by synonyms in the same semantic field. It investigates what is particularly Aristotelian in the selection of the pain-words in comparison with earlier authors and specifies the special semantic scope of each word-cluster. The result not only aims to pin down the exact way these terms converge with and diverge from each other, but also serves as a basis for further understanding (...) Aristotle’s philosophical conception of pain. (shrink)

The spread of epidemics, especially COVID-19, is having a significant impact on the world. If an epidemic is not properly controlled at the beginning, it is likely to spread rapidly and widely through the coexistence relationship between natural and social systems. A university community is a special, micro-self-organized social system that is densely populated. However, university authorities in such an environment seem to be less cautious in the defence of an epidemic. Currently, there is almost no quantitative research on epidemic (...) spreading and response strategies in universities. In this paper, a case study of a university community is considered for a simulation of an infection evolving after an epidemic outbreak based on the method of system dynamics of the three stages. The results show the following: By improving the speed of the initial emergency response, the total number of patients can be effectively controlled. A quarantine policy helps to slow down the evolution of infection. The higher the isolation ratio, the higher the cost; therefore, the isolation ratio should be optimized. It is important to make emergency plans for controlling epidemic spreading and carry out emergency drills and assessments regularly. According to the results of this study, we suggest an emergency management framework for public health events in university communities. (shrink)

I propose a dynamic causal approach to characterizing the notion of a mechanism. Levy and Bechtel, among others, have pointed out several critical limitations of the new mechanical philosophy, and pointed in a new direction to extend this philosophy. Nevertheless, they have not fully fleshed out what that extended philosophy would look like. Based on a closer look at neuroscientific practice, I propose that a mechanism is a dynamic causal system that involves various components interacting, typically nonlinearly, with one another (...) to produce a phenomenon of interest. (shrink)

Michael Weisberg’s account of scientific models concentrates on the ways in which models are similar to their targets. He intends not merely to explain what similarity consists in, but also to capture similarity judgments made by scientists. In order to scrutinize whether his account fulfills this goal, I outline one common way in which scientists judge whether a model is similar enough to its target, namely maximum likelihood estimation method. Then I consider whether Weisberg’s account could capture the judgments involved (...) in this practice. I argue that his account fails for three reasons. First, his account is simply too abstract to capture what is going on in MLE. Second, it implies an atomistic conception of similarity, while MLE operates in a holistic manner. Third, Weisberg’s atomistic conception of similarity can be traced back to a problematic set-theoretic approach to the structure of models. Finally, I tentatively suggest how these problems might be solved by a holistic approach in which models and targets are compared in a non-set-theoretic fashion. (shrink)

Introduction: the advance of governmentality -- Foucault, power, and governmentality: introduction; what is governmentality?; beyond the microphysics of power?; from theory of the state to genealogy of the state; history of the art of government; pastoral power; raison d'état; liberal governmentality; five propositions on foucault and governmentality -- Governmentality 3.4.7.: introduction; governmentality after Foucault; governmentality and the political sciences; some problems in governmentality -- Foucault effect redux? some notes on international governmentality studies: constellation; a few preliminary observations; problems and debates (...) in international governmentality studies -- Reconnecting governmentality and genealogy: introduction; genealogy and governmentality; pluralizing genealogy; practicing genealogy; lines of descent: the family tree of power?; counter-memory and re-serialization; the retrieval of forgotten struggles and subjugated knowledges -- Conclusion: encountering governmentality: governmentality as a new cartography of power; from mapping to encountering; governmentality and politics. (shrink)

Polger and Shapiro argue that their official recipe, a criterion for judging when the phenomenon of multiple realization exists, renders MR less widespread than its proponents have assumed. I argue that, although Polger and Shapiro’s criterion is a useful contribution, they arrive at their conclusion too hastily. Contrary to Polger and Shapiro, I claim that the phenomenon of multiple realization in the biological world, judged by their criterion, is not as scarce as they suggest. To show this, an updated official (...) recipe, namely a multiple mechanistic realization thesis, integrating Polger and Shapiro’s criterion with a compositional conception of realization, is developed. Then, three examples of varied kinds are examined, showing that cases of MR are not so hard to find in the biological world. (shrink)

Research on knowledge hiding has largely focused on its antecedents while overlooking its consequences. Drawing on moral cleansing theory, we adopt a “perpetrator-centric view” and posit that employees who engage in playing dumb and evasive hiding–two specific knowledge hiding behaviors that involve deception–will subsequently perform more organizational citizenship behavior directed toward individuals (OCB-I) because they perceive a loss of moral credits following their moral transgression. Further, we propose that the indirect effects are contingent on perpetrators’ moral identity internalization. We tested (...) our hypotheses using a time-lagged research design with a sample of 362 respondents from a large pharmaceutical group company. Consistent with our hypotheses, we found that employees who engaged in playing dumb and evasive hiding subsequently exhibited more OCB-I as they perceived a loss of moral credits, whereas employees who engaged in rationalized hiding did not. In addition, the positive relationships between playing dumb and evasive hiding with perceived loss of moral credits were stronger when perpetrators had high moral identity internalization, as were the indirect effects of playing dumb and evasive hiding on OCB-I via perceived loss of moral credits. Our research contributes to the understanding of when and how engaging in knowledge hiding affects perpetrators and their compensatory behaviors toward coworkers. (shrink)