We present a molecular model of eukaryotic gene transcription. For the β‐globin locus, we hypothesise that a transcription machine composed of multiple RNA polymerase II (PolII) assembles using the locus control region as a foundation. Transcription and locus remodelling can be achieved by pulling DNA through this multi‐PolII ‘reading head’. Once a transcription complex is formed, it may engage an active gene in several rounds of transcription. Observed intergenic sense and antisense transcripts may be the result of PolII pulling the (...) DNA through the reading head whilst searching for the promoter of a gene. Support for this hypothesis is provided using various data from the literature. In the model, DNA is packed in a 30‐nm chromatin fibre, thus gene regulatory regions separated by kilobases are close in space. This, and the need to store transcription‐induced supercoiling, may explain why functionally interacting regions are often separated by many kilobases. (shrink)

Delineation of the subthalamic nuclei on MRI is critical for deep brain stimulation surgery in patients with Parkinson’s disease. We propose this retrospective cohort study for quantitative analysis of MR signal-to-noise ratio, contrast, and signal difference-to-noise ratio of the STN on pre-operative three-dimensional stereotactic MRI in patients with medication-refractory PD. Forty-five consecutive patients with medication-refractory PD who underwent STN-DBS surgery in our hospital from January 2018 to June 2021 were included in this study. All patients had whole-brain 3D MRI, including (...) T2-weighted imaging, T2-weighted fluid-attenuated inversion recovery, and susceptibility-weighted imaging, at 3.0 T scanner for stereotactic navigation. The signal intensities of the STN, corona radiata, and background noise were obtained after placing regions of interest on corresponding structures. Quantitative comparisons of SNR, contrast, and SDNR of the STN between MR pulse sequences, including the T2WI, FLAIR, and SWI. Subgroup analysis regarding patients’ sex, age, and duration of treatment. We used one-way repeated measures analysis of variance for quantitative comparisons of SNR, contrast, and SDNR of the STN between different MR pulse sequences, and we also used the dependent t-test for the post hoc tests. In addition, we used Mann–Whitney U test for subgroup analyses. Both the contrast and SDNR were highest on FLAIR. The SNR was highest on SWI, and both the SNR and SDNR were lowest on T2WI. Subgroup analyses demonstrated significantly lower SDNR on SWI for patients receiving medication treatment for ≥13 years. In conclusion, on 3D stereotactic MRI of medication-refractory PD patients, the contrast and SDNR for the STN are highest on FLAIR, suggesting the optimal delineation of STN on FLAIR. (shrink)

Electroacupuncture (EA) and electroconvulsive therapy (ECT) are often used in the management of schizophrenia. This study sought to determine whether additional EA and ECT could augment antipsychotic response and reduce related side effects. In this retrospective controlled study, 287 hospitalized schizophrenic patients who received antipsychotics (controls, n = 50) alone or combined with EA (n = 101), ECT (n = 55) or both (EA+ECT, n = 81) were identified. EA and ECT were conducted for 5 and 3 sessions per week, (...) respectively, with a maximum of 12 sessions for ECT during hospitalization. The Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were used to assess the severity of psychotic symptoms. Clinical response on SAPS and SANS, weight gain, and adverse events were compared. Survival analysis revealed that the ECT and EA+ECT groups had markedly greater clinical response rate than controls on SAPS [72.7% and 90.1% vs. 64.0%; relative risk (RR), 1.974 and 2.628, respectively, P ≤ 0.004] and on SANS (67.3% and 70.4% vs. 42.0%; RR, 1.951 and 2.009, respectively, P ≤ 0.015). A significantly greater response rate on SANS than controls was also observed in the EA group (64.4% versus 42.0%; RR = 1.938, P = 0.008). EA-containing regimens remarkably reduced weight gain and incidences of headache, insomnia, dry mouth, and electrocardiographic abnormalities. These results suggest that EA and ECT can serve as additional treatment for enhancing antipsychotic response and reduce the side effects in hospitalized patients with schizophrenia. (shrink)

The increasing number of quick response code mobile payment users heralds the coming of a cashless society. However, the extent to which the coronavirus disease 2019 pandemic accelerated the adoption of QR code mobile payment has not been sufficiently researched. Based on social learning theory, this study models how external interaction with the environment has affected the internal appraisal and behavioral intention to adopt QR code mobile payment during COVID-19. Empirical results from 248 respondents revealed that perceived severity and social (...) influence positively affected the perception of utilitarian and health benefits of respondents, which in turn influenced the behavioral intention to use the QR code mobile payment. The theoretical contribution and managerial implications of this study are also discussed. (shrink)

本书简要介绍了从明中叶至辛亥革命这一历史时期中国文化史上的主流思潮。全书按历史顺序分别评介了晚明人文主义思潮、明清之际启蒙主义思潮、嘉道之际实学思潮和19世纪末—20世纪初的新民思潮。.

David B. Wong proposes that there can be a plurality of true moralities, moralities that exist across different traditions and cultures, all of which address facets of the same problem: how we are to live well together. Wong examines a wide array of positions and texts within the Western canon as well as in Chinese philosophy, and draws on philosophy, psychology, evolutionary theory, history, and literature, to make a case for the importance of pluralism in moral life, and (...) to establish the virtues of acceptance and accommodation. Wong's point is that there is no single value or principle or ordering of values and principles that offers a uniquely true path for human living, but variations according to different contexts that carry within them a common core of human values. We should thus be modest about our own morality, learn from other approaches, and accommodate different practices in our pluralistic society. (shrink)

This essay explains the inescapability of moral demands. I deny that the individual has genuine reason to comply with these demands only if she has desires that would be served by doing so. Rather, the learning of moral reasons helps to shape and channel self- and other-interested motivations so as to facilitate and promote social cooperation. This shaping happens through the “embedding” of reasons in the intentional objects of motivational propensities. The dominance of the instrumental conception of reason, according to (...) which reasons must be based in desires of the individual, has made it harder to recognize that reasons shape desires. I attempt to undermine this dominance by arguing that the concept of a self that extends over time is constructed to meet the demands of social cooperation. Prudential reasons to act on behalf of the persisting self's desires are often taken to constitute the paradigm of reasons based on desires of the individual. But such reasons, along with the very concept of the persisting self, are constructed to promote human cooperation and to shape the individual's desires. (shrink)

I thought the paper by Kai-yee Wong and Chris Fraser was fascinating and insightful. Two things I especially appreciated are the clarity with which they summarize my views. I think they are quite fair and accurate. Second, I appreciate their suggestion that the way to deal with the practical problem of weakness of will has much to do with the role of the Background in shaping our actions. I think they are especially on the right track when they say (...) that the improvement of Background skills may actually narrow the range of real options for action, (p. 21) nonetheless, they do not decrease freedom. As they say, “It is a process of strengthening the self, and the agent is likely to experience the concomitant restriction of ‘live’ options not as a limitation but as strength of character.” (p. 21). That seems to me very much on the right track. What they are suggesting, and it is a powerful addition to my own writings, is that we should not just think of the Background as facilitating languages, games and social practices generally, but for morality as well (p. 23). (shrink)

Ben shu chan shu de nei rong shi zhi shi zhong ya fang wen hua de shen tou yu jiao liu.

Reliability and external validity are two fundamental values that pose incompatible constraints on neurobiological experiments. The more reliability an experimental result achieves, the less external validity it earns, and vice versa. In this article, I propose an externalist interpretation of external validity: the external validity of an experimental result depends not only on how much complexity is built into an experimental design, but also on the relationship between the experimental result and other related experiments. This externalist interpretation, which explains how (...) a neurobiological experiment can be reliable and externally valid simultaneously, suggests a new way to understand the epistemology of neurobiological experimentation. (shrink)

Emergence is a notorious philosophical term of art. A variety of theorists have appropriated it for their purposes ever since George Henry Lewes gave it a philosophical sense in his 1875 Problems of Life and Mind. We might roughly characterize the shared meaning thus: emergent entities (properties or substances) ‘arise’ out of more fundamental entities and yet are ‘novel’ or ‘irreducible’ with respect to them. (For example, it is sometimes said that consciousness is an emergent property of the brain.) Each (...) of the quoted terms is slippery in its own right, and their specifications yield the varied notions of emergence that we discuss below. There has been renewed interest in emergence within discussions of the behavior of complex systems and debates over the reconcilability of mental causation, intentionality, or consciousness with physicalism. (shrink)

Algorithms can now identify patterns and correlations in the (big) datasets, and predict outcomes based on those identified patterns and correlations with the use of machine learning techniques and big data, decisions can then be made by algorithms themselves in accordance with the predicted outcomes. Yet, algorithms can inherit questionable values from the datasets and acquire biases in the course of (machine) learning, and automated algorithmic decision-making makes it more difficult for people to see algorithms as biased. While researchers have (...) taken the problem of algorithmic bias seriously, but the current discussion on algorithmic fairness tends to conceptualize ‘fairness’ in algorithmic fairness primarily as a technical issue and attempts to implement pre-existing ideas of ‘fairness’ into algorithms. In this paper, I show that such a view of algorithmic fairness as technical issue is unsatisfactory for the type of problem algorithmic fairness presents. Since decisions on fairness measure and the related techniques for algorithms essentially involve choices between competing values, ‘fairness’ in algorithmic fairness should be conceptualized first and foremost as a political issue, and it should be (re)solved by democratic communication. The aim of this paper, therefore, is to explicitly reconceptualize algorithmic fairness as a political question and suggest the current discussion of algorithmic fairness can be strengthened by adopting the accountability for reasonableness framework. (shrink)

Depression is vastly heterogeneous in its symptoms, neuroimaging data, and treatment responses. As such, describing how it develops at the network level has been notoriously difficult. In an attempt to overcome this issue, a theoretical “negative prediction mechanism” is proposed. Here, eight key brain regions are connected in a transient, state-dependent, core network of pathological communication that could facilitate the development of depressive cognition. In the context of predictive processing, it is suggested that this mechanism is activated as a response (...) to negative/adverse stimuli in the external and/or internal environment that exceed a vulnerable individual’s capacity for cognitive appraisal. Specifically, repeated activation across this network is proposed to update an individual’s brain so that it increasingly predicts and reinforces negative experiences over time—pushing an individual at-risk for or suffering from depression deeper into mental illness. Within this, the negative prediction mechanism is poised to explain various aspects of prognostic outcome, describing how depression might ebb and flow over multiple timescales in a dynamically changing, complex environment. (shrink)

The argument for metaethical relativism, the view that there is no single true or most justified morality, is that it is part of the best explanation of the most difficult moral disagreements. This Element discusses the latest arguments in ethical theory in an accessible manner, with many examples and cases.

The following framework of theses, roughly hewn, shapes contemporary discussion of the problem of mental causation: (1) Non-Identity of the Mental and the Physical Mental properties and states cannot be identified with specific physical properties and states. (2) Causal Closure (Completeness) of the Physical The objective probability of every physical event is fixed by prior physical events and laws alone. (This thesis is sometimes expressed in terms of explanation: In tracing the causal history of any physical event, one need not (...) advert to any non-physical events or laws. To the extent that there is any explanation available for a physical event, there is a complete explanation available couched entirely in physical vocabulary. We prefer the probability formulation, as it should be acceptable to any physicalist, though some reject the explanation formulation.) (3) Causal Exclusion There is at most one complete and wholly independent explanation for any given event or sequence of events. (shrink)

This title is part of UC Press's Voices Revived program, which commemorates University of California Press’s mission to seek out and cultivate the brightest minds and give them voice, reach, and impact. Drawing on a backlist dating to 1893, Voices Revived makes high-quality, peer-reviewed scholarship accessible once again using print-on-demand technology. This title was originally published in 1984.

Metaphors of adorning, crafting, water flowing downward, and growing sprouts appear in the Analects , the Mencius , and the Xunzi 荀子. They express and guide thinking about what there is in human nature to cultivate and how it is to be cultivated. The craft metaphor seems to imply that our nature is of the sort that must be disciplined and reshaped to achieve goodness, while the adorning, water, and sprout metaphors imply that human nature has an inbuilt directionality toward (...) the ethical that should be protected or nurtured. I argue that all the metaphors capture different aspects of human nature and how one must work with these aspects. There is much in contemporary psychology and neuroscience to suggest that the early Confucians were on the right track. It is also argued that they point to a fruitful conception of ethical development that is relational and holistic. (shrink)

A closer look at the theories and questions in philosophy of technology and ethics of technology shows the absence and marginality of non-Western philosophical traditions in the discussions. Although, increasingly, some philosophers have sought to introduce non-Western philosophical traditions into the debates, there are few systematic attempts to construct and articulate general accounts of ethics and technology based on other philosophical traditions. This situation is understandable, for the questions of modern sciences and technologies appear to be originated from the West; (...) at the same time, the situation is undesirable. The overall aim of this paper, therefore, is to introduce an alternative account of ethics of technology based on the Confucian tradition. In doing so, it is hoped that the current paper can initiate a relatively uncharted field in philosophy of technology and ethics of technology. (shrink)

The burgeoning literature on the ethical issues raised by climate engineering has explored various normative questions associated with the research and deployment of climate engineering, and has examined a number of responses to them. While researchers have noted the ethical issues from climate engineering are global in nature, much of the discussion proceeds predominately with ethical framework in the Anglo-American and European traditions, which presume particular normative standpoints and understandings of human–nature relationship. The current discussion on the ethical issues, therefore, (...) is far from being a genuine global dialogue. The aim of this article is to address the lack of intercultural exchange by exploring the ethics of climate engineering from a perspective of Confucian environmental ethics. Drawing from the existing discussion on Confucian environmental ethics and Confucian ethics of technology, I discuss what Confucian ethics can contribute to the ethical debate on climate engineering. (shrink)

Naïve realism is the view that veridical experiences are fundamentally relations of acquaintance to external objects and their features, and multidisjunctivism is the conjunction of naïve realism and the view that hallucinatory experiences don’t share a common fundamental kind. Multidisjunctivism allegedly removes the screening-off worry over naïve realism, and the relevant literature suggests that multidisjunctivism is one of the naïve realist responses to the worry. The present paper argues that the multidisjunctive solution is implicitly changing the subject, so the impression (...) that the multidisjunctivist is addressing the screening-off problem is illusory. (shrink)

Political liberals assume an accessibility requirement, which means that, for ensuring civic respect and non-manipulation, public officials should offer accessible reasons during political advocacy. Recently, critics have offered two arguments to show that the accessibility requirement is unnecessary. The first is the pluralism argument: Given the pluralism in evaluative standards, when officials offer non-accessible reasons, they are not disrespectful because they may merely try to reveal their strongest reason. The second is the honesty argument: As long as officials honestly confess (...) their beliefs after offering non-accessible reasons, disrespect and non-manipulation do not occur. This paper defends the accessibility requirement and asserts that these two arguments overlook a unique feature of the political domain. While all citizens collectively own political power as a corporate body, an official does not privately own her political power. Instead, she is a trustee who has a duty to act on behalf of the corporate body, that is, she has to make decisions on grounds that are accessible to others. This duty explains why, despite pluralism, the accessibility requirement is necessary. Moreover, given that political decisions are profoundly influential to each person, requiring people to be honest is ineffective in discouraging disrespectful and manipulative acts. (shrink)