Beyond protein synthesis and autophagy, emerging evidence has implicated mTORC1 in regulating protein folding and proteasomal degradation as well, highlighting its prominent role in cellular proteome homeostasis or proteostasis. In addition to growth signals, mTORC1 senses and responds to a wide array of stresses, including energetic/metabolic stress, genotoxic stress, oxidative stress, osmotic stress, ER stress, proteotoxic stress, and psychological stress. Whereas growth signals unanimously stimulate mTORC1, stresses exert complex impacts on mTORC1, most of which are repressive. mTORC1 suppression, as a (...) generic adaptive strategy, empowers cell survival under various stressful conditions. In this essay, we provide an overview of the emerging role of mTORC1 in proteostasis, the distinct molecular mechanisms through which mTORC1 reacts to diverse stresses, and the schemes exploited by cancer cells to circumvent stress‐induced mTORC1 suppression. Hence, acting as a stress sensor, mTORC1 intimately couples stresses to cellular proteostasis. (shrink)

The social, ethical and legal implications of discoveries in the neurosciences.

The Iowa Gambling Task (IGT) and the Soochow Gambling Task (SGT) are two experience-based risky decision-making tasks for examining decision-making deficits in clinical populations. Several cognitive models, including the expectancy-valence learning model (EVL) and the prospect valence learning model (PVL), have been developed to disentangle the motivational, cognitive, and response processes underlying the explicit choices in these tasks. The purpose of the current study was to develop an improved model that can fit empirical data better than the EVL and PVL (...) models and, in addition, produce more consistent parameter estimates across the IGT and SGT. Twenty-six opiate users (mean age 34.23; SD 8.79) and 27 control participants (mean age 35; SD 10.44) completed both tasks. Eighteen cognitive models varying in evaluation, updating, and choice rules were fit to individual data and their performances were compared to that of a statistical baseline model to find a best fitting model. The results showed that the model combining the prospect utility function treating gains and losses separately, the decay-reinforcement updating rule, and the trial-independent choice rule performed the best in both tasks. Furthermore, the winning model produced more consistent individual parameter estimates across the two tasks than any of the other models. (shrink)

What role does our knowledge about the ideal society play in guiding policymaking in the real world? One intuitive answer is to approximate. Namely, we have a duty to approximate the ideal within the relevant constraints of feasibility. However, political philosophers seem to have what might be called ‘approximatophobia'. Many philosophers, including idealists such as David Estlund, warn against approximation. Their criticism is chiefly motivated by ‘the problem of second best’, which points out that your second-best option may not be (...) closest to your best option. This paper aims to dispel ‘approximatophobia'. The difficulty posed by the problem of second best is often overstated. More positively, I present a novel defence of approximation, arguing that approximation of an ideal can be a reasonably reliable default strategy of action guidance in the real world. Difficulties that may afflict the project of approximation can be mitigated by sophistication of the project of approximation. After showing that critics of approximation overstep their mark in issuing the strong or moderate warning against approximation, I propose an account of sophisticated approximation. It seeks a series of reforms that make existing social institutions closer to the ideal based on careful selection of frame of analysis. Three virtuous correlations are identified as indicators for successful project of approximation, linking descriptive similarity to desirability, feasibility and knowledge of the ideal. I also explain a two-staged strategy of sophisticating the way you approximate the ideal, with an expected positive feedback effect. (shrink)

Content: Sprache, Recht und Rechtsverbindlichkeit: R. Fukawa: An Analysis of the aeRules of Recognition Statement' u W. Krawietz: What does it mean to follow an aeInstitutionalised Legal Rule'? u N. MacCormick: Citizens' Legal Reasoning and its Importance for Jurisprudence u Y. Morigiwa: Hart's Theories of Language and Law u R.Tuomela: Supervenience, Collective Action, and Kelsen's Organ Theory uRecht und politische Kultur: G. Haney: Recht als Form von Kultur u A. Kojder: Dysfunctionalities of Legal Cultur u A. Lopatka: Law and Religion (...) in Poland u M. Samu: Culture and Law: Legal Culture uWerteordnung als ideologische Basis des Rechtsstaats: R. Dreier: Konstitutionalismus und Legalismus u O. Maenpaa: Unilaterality and Consensualism in the Application of Law u K.-F. Lenz: Zivilprozea und Spiel u M. Pavcnik: Ideologie der Rechtsanwendung versus argumentierte Rechtsentscheidung u J. Uusitalo: Legal Dogmatics, Epistemology, Radical Hermeneutics u Entwicklung der Rechtsordnung und soziale Gerechtigkeit: V. Luizzi: Legal Validity and Justice u H. Rottleuthner: Recht und Technik in entwicklungstheor. Perspektive u S. Panou: Uber die aeGerechtigkeit' des Rechts u A. Squella: Legal Positivism and Democracy in the 20. Century u D. Wyduckel: Konsens und gesellschaftlich-technischer Fortschritt u Soziale Mechanismen der Rechtsanwendung und Rechtsfindung: H. Aoi: Richterliche Rechtsfindung als Pattern-Matching-Prozea uu.a. (Franz Steiner 1991). (shrink)

The concentration of high-frequency controls in a limited period of time constitutes an important feature of many law-enforcement policies around the world. In this paper, we offer a comprehensive investigation on the relative efficiency and effectiveness of various crackdown policies using a lab-in-the-field experiment with real passengers of a public transport service. We introduce a novel game, the daily public transportation game, where subjects have to decide, over many periods, whether to buy or not a ticket knowing that there might (...) be a control. Our results show that concentrated crackdowns are less effective and efficient than random controls; prolonged crackdowns reduce fare-dodging during the period of intense monitoring but induce a burst of fraud as soon as they are withdrawn; pre-announced controls induce more fraud in the periods without control. Overall, we also observe that real fare-dodgers fraud more in the experiment than non-fare-dodgers. (shrink)

According to the rumor mill in China: "The Central Discipline Inspection Commission is considering internal party disciplinary action against Song Renqiong and others ." I am truly happy for the CCP—by taking this stand there is still hope it can continue with its mission and transform China into a modern society.

We present a novel method, called graph sparse nonnegative matrix factorization, for dimensionality reduction. The affinity graph and sparse constraint are further taken into consideration in nonnegative matrix factorization and it is shown that the proposed matrix factorization method can respect the intrinsic graph structure and provide the sparse representation. Different from some existing traditional methods, the inertial neural network was developed, which can be used to optimize our proposed matrix factorization problem. By adopting one parameter in the neural network, (...) the global optimal solution can be searched. Finally, simulations on numerical examples and clustering in real-world data illustrate the effectiveness and performance of the proposed method. (shrink)

Kant’s published arguments for the non-spatiotemporality of things in themselves have not been well received. I argue that Kant has available to himself an argument for the non-spatiotemporality of things in themselves that is premised upon a disparity between the compositional structure of the intelligible world and the structure of space and time. I argue that Kant was unwaveringly committed to the premises of this argument throughout his career and that he was aware of their idealistic implications. I also argue (...) that this argument is consistent with Kant’s restrictive mature epistemology. If my argument is successful, then even if Kant’s published arguments for transcendental idealism fail, we need not regard his ambitious metaphysical project as a failure. (shrink)

Kant rejects the ontological argument on the grounds that the ontological argument inescapably must assume that existence is a “determination” or “real predicate,” which it is not. Most understand Kant’s argument for this claim to be premised upon his distinctive proto-Fregean theory of existence. But this leaves Kant dialectically vulnerable: the defender of the ontological argument can easily reject this as question-begging. I show that Kant relies upon two distinct arguments, both of which contend that the claim that existence is (...) a determination is inconsistent with bedrock ontological set pieces assumed by rationalist defenders of the ontological argument. (shrink)

Yuanfang Dai argues that, despite the many forms of gender oppression in different societies and cultures, it is still possible to speak generally of women’s oppression. This notion of shared oppression can inform a transcultural feminist solidarity that challenges structural gender oppression across social and cultural differences.

(2001). Preconception Sex Selection: The Perspective of a Person of the Undesired Gender. The American Journal of Bioethics: Vol. 1, No. 1, pp. 37-38.

Transnational articulation programmes are one way China is attempting to advance its higher education system. We report a study of twelve Chinese students’ experiences in two China-Australia 2...

What role does our knowledge about the ideal society play in guiding policymaking in the real world? One intuitive answer is to approximate. Namely, we have a duty to approximate the ideal within the relevant constraints of feasibility. However, political philosophers seem to have what might be called ‘approximatophobia'. Many philosophers, including idealists such as David Estlund, warn against approximation. Their criticism is chiefly motivated by ‘the problem of second best’, which points out that your second-best option may not be (...) closest to your best option. This paper aims to dispel ‘approximatophobia'. The difficulty posed by the problem of second best is often overstated. More positively, I present a novel defence of approximation, arguing that approximation of an ideal can be a reasonably reliable default strategy of action guidance in the real world. Difficulties that may afflict the project of approximation can be mitigated by sophistication of the project of approximation. After showing that critics of approximation overstep their mark in issuing the strong or moderate warning against approximation, I propose an account of sophisticated approximation. It seeks a series of reforms that make existing social institutions closer to the ideal based on careful selection of frame of analysis. Three virtuous correlations are identified as indicators for successful project of approximation, linking descriptive similarity to desirability, feasibility and knowledge of the ideal. I also explain a two-staged strategy of sophisticating the way you approximate the ideal, with an expected positive feedback effect. (shrink)

Since the 1990s, contemporary Chinese aesthetics has radually fallen into depressions and became silence after the two heated domestic debates in the 1950s and 1980s. Nowadays it is high time for Chinese scholars to make reflections on these setbacks and frustrations. Firstly we need to clarify what are the real problems that contemporary Chinese aesthetics encounters. To be short, that is, the arrival of globalization has caused a series of profound turns from aesthetics to arts. With the further expansion and (...) penetration of globalization, theoretical aesthetic subjects and relevant problems are more salient, including the shift of contemporary aesthetic research paradigm, the basic method that we borrow western theories to interpret Chinese art works and aesthetic phenomena, the constant advancing interdisciplinary research, etc. The author’s main aim in this paper will be to explore some workable methods, which are significant to the development of the present Chinese aesthetics in this new century. (shrink)

Typically, fair machine learning research focuses on a single decision maker and assumes that the underlying population is stationary. However, many of the critical domains motivating this work are characterized by competitive marketplaces with many decision makers. Realistically, we might expect only a subset of them to adopt any non-compulsory fairness-conscious policy, a situation that political philosophers call partial compliance. This possibility raises important questions: how does partial compliance and the consequent strategic behavior of decision subjects affect the allocation outcomes? (...) If k% of employers were to voluntarily adopt a fairness-promoting intervention, should we expect k% progress (in aggregate) towards the benefits of universal adoption, or will the dynamics of partial compliance wash out the hoped-for benefits? How might adopting a global (versus local) perspective impact the conclusions of an auditor? In this paper, we propose a simple model of an employment market, leveraging simulation as a tool to explore the impact of both interaction effects and incentive effects on outcomes and auditing metrics. Our key findings are that at equilibrium: (1) partial compliance by k% of employers can result in far less than proportional (k%) progress towards the full compliance outcomes; (2) the gap is more severe when fair employers match global (vs local) statistics; (3) choices of local vs global statistics can paint dramatically different pictures of the performance vis-a-vis fairness desiderata of compliant versus non-compliant employers; (4) partial compliance based on local parity measures can induce extreme segregation. Finally, we discuss implications for auditors and insights concerning the design of regulatory frameworks. (shrink)

Interpretation from the perspective of the historical development of global imbalances can be defined as the persistent global imbalances, the current scale is not balanced and financial imbalances. Historically there have been two of the largest global imbalances, which lasted until World War I nearly half the world's imbalances and since the 1990s until 2007, before the outbreak of the financial crisis of the contemporary global imbalances. The external imbalance is sustained by the national economic systems, economic policy, the global (...) economic system system system and the global political system and other important systemic factors, it has brought the global economy a great threat to sustainable development, and eventually lead to crisis. The problem of global imbalances could be regarded as persistent, sweeping imbalances of current account and financial account from the historical perspective. There were two largest global imbalances, one lasted about a half century before the First World War, and the other lasted from 1990s to the financial crisis of 2007. There were several reasons for the long term external imbalance, such as the national economy policies, global economic system, global political system and other important systemic factors which led the sustained development of global economy to the economic crisis. (shrink)

The term "public lover" has been a staple term in the Chinese language. Yet another term—"public concern" —has only lately become part of our language. This is largely because China lacks any sense of pluralism and any sense of limitations imposed on rulers by the common people. At present, if we consider both magnitude and timeliness, the "public concern" of both the Chinese people and foreigners is as follows: Will Jiang Zemin, whom Deng Xiaoping appointed, come to the same end (...) as Hua Guofeng, whom Mao Zedong appointed? (shrink)