Selective protein degradation maintains cellular homeostasis, but this process is disrupted in many diseases. Targeted protein degradation (TPD) approaches, built upon existing cellular mechanisms, are promising methods for therapeutically regulating protein levels. Here, we review the diverse palette of tools that are now available for doing so throughout the gene expression pathway and in specific cellular compartments. These include methods for directly removing targeted proteins via the ubiquitin proteasome system with proteolysis targeting chimeras (PROTACs) or dephosphorylation targeting chimeras (DEPTACs). Similar (...) effects can also be achieved through the lysosomal system with autophagy‐targeting chimeras (AUTACs), autophagosome tethering compounds (ATTECs), and lysosome targeting chimeras (LYTACs). Other methods act upstream to degrade RNAs (ribonuclease targeting chimeras; RIBOTACs) or transcription factors (transcription factor targeting chimeras; TRAFTACs), offering control throughout the gene expression process. We highlight the evolution and function of these methods and discuss their clinical implications in diverse disease contexts. (shrink)

Artificial intelligence (AI) systems are quickly gaining ground in healthcare and clinical decision-making. However, it is still unclear in what way AI can or should support decision-making that is based on incapacitated patients’ values and goals of care, which often requires input from clinicians and loved ones. Although the use of algorithms to predict patients’ most likely preferred treatment has been discussed in the medical ethics literature, no example has been realised in clinical practice. This is due, arguably, to the (...) lack of a structured approach to the epistemological, ethical and pragmatic challenges arising from the design and use of such algorithms. The present paper offers a new perspective on the problem by suggesting that preference predicting AIs be viewed as sociotechnical systems with distinctive life-cycles. We explore how both known and novel challenges map onto the different stages of development, highlighting interdisciplinary strategies for their resolution. (shrink)

Standard accuracy-based approaches to imprecise credences have the consequence that it is rational to move between precise and imprecise credences arbitrarily, without gaining any new evidence. Building on the Educated Guessing Framework of Horowitz (2019), we develop an alternative accuracy-based approach to imprecise credences that does not have this shortcoming. We argue that it is always irrational to move from a precise state to an imprecise state arbitrarily, however it can be rational to move from an imprecise state to a (...) precise state arbitrarily. (shrink)

This paper proposed a novel tactile-stimuli P300 paradigm for Brain-Computer Interface, which potentially targeted at people with less learning ability or difficulty in maintaining attention. The new paradigm using only two types of stimuli was designed, and different targets were distinguished by frequency and spatial information. The classification algorithm was developed by introducing filters for frequency bands selection and conducting optimization with common spatial pattern on the tactile evoked EEG signals. It features a combination of spatial and frequency information, with (...) the spatial information distinguishing the sites of stimuli and frequency information identifying target stimuli and disturbances. We investigated both electrical stimuli and vibration stimuli, in which only one target site was stimulated in each block. The results demonstrated an average accuracy of 94.88% for electrical stimuli and 95.21% for vibration stimuli, respectively. (shrink)

Recently, the pandemic caused by COVID-19 is severe in the entire world. The prevention and control of crimes associated with COVID-19 are critical for controlling the pandemic. Therefore, to provide efficient and convenient intelligent legal knowledge services during the pandemic, we develop an intelligent system for legal information retrieval on the WeChat platform in this paper. The data source we used for training our system is “The typical cases of national procuratorial authorities handling crimes against the prevention and control of (...) the new coronary pneumonia pandemic following the law”, which is published online by the Supreme People’s Procuratorate of the People’s Republic of China. We base our system on convolutional neural network and use the semantic matching mechanism to capture inter-sentence relationship information and make a prediction. Moreover, we introduce an auxiliary learning process to help the network better distinguish the relation between two sentences. Finally, the system uses the trained model to identify the information entered by a user and responds to the user with a reference case similar to the query case and gives the reference legal gist applicable to the query case. (shrink)

The present study investigated the lasting effects of sickness presenteeism on well-being and innovative job performance in the demanding Chinese work context compounded with the precarities of the post-pandemic business environment. Adopting the conservation of resources theory perspective, especially its proposition of compensation of resources, we incorporated social resources at work as joint moderators in the presenteeism–outcomes relationship. We employed a panel design in which all variables were measured twice with 6 months in between. Data were obtained from 323 Chinese (...) employees working in diverse industries in Taiwan. We found that after controlling for the baseline level of well-being, presenteeism did not have a lasting effect on employees' exhaustion. However, presenteeism did have a negative lasting effect on employees' innovative behavior 6 months later. Moreover, we found a significant three-way interaction of presenteeism, supervisory support, and collegial support on employees' innovative job performance, after controlling for the baseline level of performance. Specifically, when working under illness, employees displayed the best innovative performance with high levels of both supervisory and collegial support, the worst performance with both support being low, and the intermediate when any one of the support being high. This can be taken as the preliminary evidence to support the COR proposition of resource caravans, showing that supervisory support and collegial support compensated for each other as critical resources in alleviating the impact of working under sickness on employees' innovative performance. Theoretical implications of the findings are discussed, taking into account the macro-cultural context of the East Asian Confucian societies. We also reflected on the managerial implications of the lasting damages of sickness presenteeism and benefits of mobilizing social resources on employees' well-being and performance. (shrink)

In this paper we present a study of adjectival/adverbial modification using modern type theories, i.e. type theories within the tradition of Martin-Löf. We present an account of various issues concerning adjectival/adverbial modification and argue that MTTs can be used as an adequate language for interpreting NL semantics. MTTs are not only expressive enough to deal with a range of modification phenomena, but are furthermore well-suited to perform reasoning tasks that can be easily implemented given their proof-theoretic nature. In MTT-semantics, common (...) nouns are interpreted as types rather than predicates. Therefore, in order to capture the semantics of adjectives adequately, one needs to meet the challenge of modeling CNs modified by adjectives as types. To explicate that this can be done successfully, we first look at the mainstream classification of adjectives, i.e. intersective, subsective and non-subsective adjectives. There, we show that the rich type structure available in MTTs, along with a suitable subtyping framework, offers an adequate mechanism to model these cases. In particular, this modelling naturally takes care of the characterising inferences associated with each class of adjectives. Then, more advanced issues on adjectival modification are discussed: degree adjectives, comparatives and multidimensional adjectives. There, it is shown that the use of indexed types can be usefully applied in order to deal with these cases. In the same vein, the issue of adverbial modification is discussed. We study two general typings for sentence and VP adverbs respectively. It is shown that the rich type structure in MTTs further provides useful organisational mechanisms in giving formal semantics for adverbs. In particular, we discuss the use of \-types to capture the veridicality/non-veridicality distinction and further discuss cases of intensional adverbs using the type theoretic notion of context. We also look at manner, subject and speech act adverbials and propose solutions using MTTs. Finally, we show that the current proof technology can help mechanically check the associated inferences. A number of our proposals concerning adjectival and adverbial modification have been formalised in the proof assistant Coq and many of the associated inference patterns are checked to be correctly captured. (shrink)

Many thanks to Professor Stuart White, Professor Matthew Adams, and Professor Melanie Nolan for their sensitive readings and insightful comments. All raise different but important points which I sh...

Lors d’une table ronde organisée à KADIST le 10 décembre 2021 intitulée After Àsìkò. Artistic and Curatorial Practices in Africa, les commissaires Iheanyi Onwuegbucha et Aude Christel Mgba ont pu mettre en parallèle différentes initiatives pédagogiques du continent africain, comme Àsìkò ou encore Artbakery créé par l’artiste camerounais Goddy Leye. Dominique Malaquais a fréquenté ses différents lieux, en son hommage voici l’histoire d’ Àsìkò, une initiative curatoriale et pédagogique fondée au CCA, Lagos par Bisi Silva en 2010.

This commentary focuses on evidence from autism concerning the relation between metacognition and mindreading. We support Carruthers' rejection of models 1 (independent systems) and 3 (metacognition before mindreading), and provide evidence to strengthen his critique. However, we also present evidence from autism that we believe supports model 2 (one mechanism, two modes of access) over model 4 (mindreading is prior).

The study examines the creation of gene-edited infants from the perspective of biopolitics. Through an analysis at the level of “body-power”, we show that the infants are a product of an advanced stage of biopolitics. On the other hand, considering the level of “space-power”, we indicate that the mechanism of space deepens the governance of population through biopower, leading to real conflicts between past and future in the present. The infants can be seen as “heterotopias of mirrors”, where super-reality replaces (...) the reality, culminating in a rational dilemma. We must also consider how to maintain our self-contemplation and naturalness when faced with the physical nature of humans and how to ensure that the state is fulfilling its role in regulating the use of gene-editing technology. Ultimately, we need to engage in a deeper rethinking and criticism of modernity to safeguard our values from being lost in the tide of modernization. (shrink)

Several researchers point to disorganized attachment as a core feature of borderline personality disorder (BPD). However, recent studies suggest that specific internal working models (IWMs) of each parent combine to account for child outcomes and that a secure relationship with one parent can protect against the deleterious effects of an insecure relationship with the other parent. It was thus hypothesized that adolescents with BPD are more likely to be disorganized with both their parents, whereas non-clinical controls are more secure with (...) at least one of their caregivers. Thirty-six adolescents with BPD and 30 control participants (aged 13-19) were included. Psychiatrist diagnosis was verified with the SIDP-IV and comorbidity was assessed using the Kiddie-SADS. Reported trauma was assessed with the Childhood Trauma Questionnaire. Attachment IWMs of each parent were assessed with the Attachment Multiple Model Interview (AMMI), which enables separate coding for each attachment figure and in which disorganization is conceptualized as conflicting attachment strategies within a specific relationship. Results of a logistic regression analysis suggested that beyond insecure attachment, being disorganized not just with one but with both parents is particularly characteristic of adolescents with BPD. Conversely, belonging to the non-clinical group was predicted by higher security scores with the father and lower deactivation with the mother. Although higher levels of childhood abuse or neglect were reported by adolescents with BPD, the retained attachment dimensions predicted group membership over and above reported trauma. These findings have important implications for clinical intervention and highlight the protective role fathers may have. (shrink)

A recent and growing discussion in philosophy addresses the construction of models and their use in scientific reasoning by comparison with fiction. This comparison helps to explore the problem of mediated observation and, hence, the lack of an unambiguous reference of representations. Examining the usefulness of the concept of fiction for a comparison with non-denoting elements in science, the aim of this paper is to present reasonable grounds for drawing a distinction between these two kinds of representation. In particular, my (...) account will suggest a demarcation between fictional and non-fictional discourse as involving two different ways of interpreting representations. This demarcation, leading me to distinguish between fictional and non-fictional forms of enquiry, will provide a useful tool to explore to what extent the descriptions given by a model can be justified as making claims about the world and to what degree they are a consequence of the model’s particular construction. (shrink)

In both political science and political theory, democratization has largely been considered a problem for non-liberal democratic countries. Drawing on Chinese political thinker Jiwei Ci’s writings on freedom, democracy, agency, plausibility, and legitimacy, I critically reconstruct Ci’s theory of democratization and his method of theorizing. I argue that a normative account of democratization is embedded in Ci’s political thought, which is based upon a philosophical anthropology of the modern man and focuses on broadening political possibilities in a given society. Ci’s (...) theory allows us to think about democratization beyond the binary of democracy and authoritarianism, as his theory places democratization as an inherent and persistent challenge for all political communities. (shrink)

In order to explore the correlation between students’ seat choice and interaction preference in the open gamification scenario, an experiment has been carried out on the platform of provincial virtual simulation experiment teaching center of a university, and tested the relationship between absolute distance, seat type, workstation type, and students’ interaction preference. The results show that in the virtual-reality fusion gamification scenario where students can move freely: The inner circle students can stimulate the outer circle students’ willingness to invest in (...) learning. The task attribute and the seat distribution of the group may lead to the difference of students’ interaction preference. Students are more likely to learn knowledge and skills by interacting with “people” rather than “object.” Gender and major influence students’ experience of participating in gamified teaching. The results confirm that the interactive engagement effect of location does exist in immersive virtual-reality fusion gamification teaching scenario, and suggestions are put forward to adjust the effect of location through instructional design and teacher intervention. (shrink)

In a multilateral bargaining game where a proposer and responders can set up a “principal–agent” relationship by means of binding cash-offer contracts, we show that there is a Markov SPE with a delay in reaching an agreement. We also show that all the individually rational and efficient payoffs can be supported by SPE.

本书选收有梁漱溟、马浮、熊十力、冯友兰等8位学者的文章52篇,其中有《论西来学术亦统于六艺》、《佛法》、《考治与民文》等。.

Kindergarten teachers’ professional commitment affects their emotional input and turnover intention, and it is affected by the spiritual and material factors of teachers’ families, kindergartens, and society. Therefore, this study aimed to investigate the mediating effect of the dimensions of subjective well-being in the relationship between social support and professional commitment. The study is grounded in human ecology theory and social exchange theory. We surveyed 778 kindergarten teachers from different educational systems in Guangdong Province in China. We used the “Appreciative (...) Social Support” and “Subjective Well-being” Scales and the “Professional Commitment Questionnaire.” The results showed that the four variables of social support, positive affect, life satisfaction, and professional commitment of kindergarten teachers were significantly and positively correlated with each other: social support positively predicted positive affect and life satisfaction, positive affect and life satisfaction positively predicted professional commitment, and social support indirectly influenced professional commitment through the parallel and chain path of positive affect and life satisfaction. This represents a compound multiple mediating effects on professional commitment. (shrink)

The article deals with the virtues of the procedural conception of justice for justifying multiculturalism. While proceduralism is at first sight poorly equipped to make democratic equality more inclusive of ethnocultural minorities, it has been supported by liberal philosophers as an efficient method to provide a principled defense of minority rights. By analysing this theoretical path and its limits, and by suggesting more particularly how Alan Patten’s “full proceduralism” fails to solve the difficulties of Will Kymicka’s “multicultural citizenship”, the article (...) raises doubts about the promise to ground multiculturalism on proceduralism. (shrink)

La présente contribution s’attache à l’étude, dans un corpus d’articles scientifiques en sciences humaines, de la zone préverbale, c’est-à-dire des éléments initiaux (EI) et du sujet préverbal. Il s’agit de déterminer les combinaisons attestées des différents EI (11 catégories définies par des critères sémantiques et morpho-syntaxiques) en relation avec la nature du sujet. L’étude permet tout d’abord de déterminer que les séquences sans EI (sujet initial) excèdent celles avec EI, et que, parmi ces dernières, celles avec un seul EI sont, (...) de loin, les plus fréquentes. L’analyse porte ensuite sur la fréquence des différents EI (viennent en tête les éléments logico-pragmatiques, spatio-temporels et les relations logiques), ainsi que sur les chaînes dans lesquelles ils entrent préférentiellement, tant du point de vue du nombre d’EI possible et de leur catégorie, que de leur position dans ces chaînes. La première position s’avère ainsi associée de manière nettement préférentielle aux EI logico-pragmatiques. La nature du sujet apparaît par ailleurs corrélée à certaines caractéristiques des EI. Il ressort de l’étude que les textes du corpus présentent une relative homogénéité, même si des divergences ponctuelles apparaissent entre certaines disciplines. (shrink)

The haploid male germ cell differentiation program controls essential steps of male gametogenesis and relies partly on a significant number of sex chromosome‐linked genes. These genes need to escape chromosome‐wide transcriptional repression of sex chromosomes, which occurs during meiosis and is largely maintained in post‐meiotic cells. A newly discovered histone lysine modification, crotonylation (Kcr), marks X/Y‐linked genes that are active in post‐meiotic male germ cells. Histone Kcr, by conferring resistance to transcriptional repressors, could be a dominant element in maintaining these (...) genes active in the globally repressive environment of haploid cell sex chromosomes. Furthermore, the same mark was found associated with post‐meiotically activated genes on autosomes. Histone Kcr therefore appears to be an indicator of the male haploid cell gene expression program and a notable element of genome programming in the post‐meiotic phases of spermatogenesis. (shrink)

"Traditionnellement, la philosophie a pensé la connaissance de soi sur le mode problématique d'un sujet faisant de lui-même son propre objet de connaissance. Constatant l'impasse où mène cette approche contemplative de la connaissance de soi, Richard Moran propose de la repenser à partir de la responsabilité de la personne vis-à-vis de ses propres attitudes et de l'autorité de l'agent sur ses propres actions. En abordant la connaissance de soi sous l'angle d'une psychologie morale, Autorité et aliénation la renouvelle en profondeur (...) en mettant en évidence non seulement l'autorité de la première personne, mais aussi ses défaillances et ses limites. Faisant dialoguer la philosophie analytique et la philosophie continentale, de Wittgenstein à Sartre, Richard Moran montre que l'aliénation, comprise comme une forme d'étrangeté à soi (à ce qui, de nous, nous échappe), délimite, autant que l'autorité, les contours de la connaissance de soi."--Page 4 de la couverture. (shrink)

Based on the ethical thinking of the pre-Qin Dynasty, this book discusses the formation and development of traditional Chinese ethics, the refinement of the Confucian ethical normative system and the establishment of its orthodoxy, as well as the deepening and maturation of feudal ethics. The book is simple in style and clear in context. It contains not only the essence of traditional Chinese morality but also the achievements of modern civilization. It analyzes the implications of traditional Chinese ethics on the (...) governance and moral construction of modern society and can be used as a reference for governance and revitalization of the country and moral development. (shrink)

This study examines the relative contribution of vocabulary breadth and vocabulary depth to three different listening comprehension measures. One hundred and thirteen English majors were given VB and VD tests, and three listening comprehension tests. Based on three pairs of hierarchical multiple regression analyses, we found that the relative contribution of VB and VD varied across the three listening comprehension tests. Specifically, for the listening test with an expository text dictation to assess integrative skills, both VB and VD made a (...) unique positive contribution to comprehension, but this was greater in the case of depth. For the listening test involving narrative conversations to assess literal comprehension, neither VB nor VD could independently predict comprehension, whereas for the listening test that comprises expository passages to assess inferential comprehension, VD could separately predict comprehension but VB could not. These findings suggest that the relative contribution of VD and VB to listening comprehension may depend on how a listening test is constructed. Therefore, the findings will contribute to listening comprehension and vocabulary knowledge research, and vocabulary teaching and learning. (shrink)

本书包括:天人论;人性论;处世论;道德论;纲常论;忠教论;存理、养性、致良知等内容。.