Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, has been productive. However, (...) it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. (shrink)

In this paper, we study the path based continuous spatial keyword queries, which find the answer set continuously when the query point moves on a given path. Under this setting, we explore two primitive spatial keyword queries, namely k nearest neighbor query and range query. The technical challenges lie in that: retrieving qualified vertices in large road networks efficiently, and issuing the query continuously for points on the path, which turns out to be inapplicable. To overcome the above challenges, we (...) first propose a backbone road network index structure, which supports the distance computation efficiently and offers a global insights of the whole road network. Motivated by the safe zone technique, we then transform our queries to the issue of finding event points, which capture the changes of answer set. By this transformation, our queries are to be simple and feasible. To answer the queries, we propose a Two-Phase Progressive computing framework, which first computes the answer sets for some crucial vertices on the path, and then identifies the event points by the retrieved answer sets. Extensive experiments on both real and synthetic data sets are conducted to evaluate the performance of our proposed algorithms, and the results show that our algorithms outperform competitors by several orders of magnitude. (shrink)

Recent research has uncovered the dark side of creativity by finding that creative individuals are more likely to engage in unethical behavior. However, we argue that not all creative individuals make trouble. Using moral self-regulation theory as our overarching theoretical framework, we examine individuals’ moral identity as a boundary condition and moral disengagement as a mediating mechanism to explain when and how individual creativity is associated with workplace deviant behavior. We conducted two field studies using multi-source data to test our (...) hypotheses. In Study 1, the results indicated that creativity positively predicted moral disengagement for those low in moral identity. In Study 2 with multi-wave data, we replicated the finding that moral identity moderated the effect of creativity on moral disengagement in Study 1 and further revealed that moral disengagement mediated the interactive effects of creativity and moral identity on workplace deviant behavior. The theoretical and practical implications of these findings and directions for future research are discussed. (shrink)

本书包括罪刑法定主义、犯罪与犯罪构成论、行为论等十五个专题,论述的内容主要是大陆法系国家刑法的原理、原则和学说学派。.

Editors’ AbstractThis article conducts a detailed review of Sinologism and focuses on the conceptual core of “cultural unconscious.” It suggests that the concept is not merely intended to alert people to the phenomena of Sinologism, nor is it limited to the purpose of exposing the inherent, hidden logic of Sinologism. It goes a step further by cautioning people to be on guard against various snares of Sinologism, to treat de-Sinologization as a major focal point in China studies, and to make (...) the necessary changes to existing paradigms in Sinological studies. The article suggests that the strength of Sinologism lies in constructing a critical theory of self-conscious reflection. (shrink)

Ist das Politische Macht? Ist es öffentliches Handeln oder die beste Gesellschaftsordnung? Daniela Hüttinger sucht dort nach einer Antwort, wo die historische Wurzel des Politischen vermutet wird: im Griechenland des 5. und 4.

本文是关于逻辑哲学相关专题的研究成果,包括逻辑本身的整体性的哲学思考、现代逻辑发展中的一些具体问题的哲学研究等。.

本书对弘扬中华民族美德的经典篇章进行挖掘整理、条分缕析,涵盖古今代表篇什,导读、原文、赏析三位一体,帮助读者在阅读中得到思想的启迪、道德的升华。.

Um das Recht auf sich selbst zu erringen, mussten die Menschen den GÖTTERN das Recht auf den Menschen nehmen. Seither verstanden sie sich immer weniger von den Pflichten einem HETERONOMEN Willen gegenüber als von ihren autonomen Rechten her, ihre Bedürfnisse zu befriedigen. Diesem Selbstverständnis des westlichen Menschen sind jedoch, will es nicht zur gefährlichen Selbstgerechtigkeit erstarren, Grenzen gesetzt. Denn das ästhetisch-materielle Glück, welches diesem zu Grunde liegt, ist weltweit weder sozialisierbar noch im Hinblick auf die Zukunft der Menschheit ökologisch vertretbar. (...) So müssen erneut die GÖTTER, ein HETERONOMER Wille, herhalten, um ein Selbstverständnis zu legitimieren, das sich der Negation eben dieses Willens verdankt und dessen Handlungsfolgen die Menschen nur allein zu verantworten haben. Benno Hübner, ehemals Professor an der Universität Zaragoza, schreibt, reist und diskutiert weiterhin mit Studenten aus dem lateinamerikanischen und russischen Sprachraum. (shrink)

Veritists hold that the goal of inquiry is true belief, while justificationists contend that the goal of inquiry is justified belief. Recently, Christoph Kelp makes two new objections to both veritism and justificationism. Further, he claims that the two objections suggest that the goal of inquiry is knowledge. This paper defends a sophisticated version of veritism against Kelp's two objections.

本卷收入胡适哲学与文化方面的论文、函牍、讲演、札记80余篇。其中包括实验主义、我们对于西洋近代文明的态度等重要文章。所收文章全面反映了胡适哲学思想、学术主张和对于中西文化的态度,对于了解和研究胡适本人 以及现代中国学术史、现代中国启蒙运动等内容。.

本书作者以一名学者所特有的理想主义与批判主义精神,对法学研究和法制建设中的基本问题进行了探讨,并就法学基本内涵及其精神理念等提出了自己的见解。.

As a promising Social Science Methodology, Structural/Mechanism Explanation (SME) retains the advantages of mechanism-based explanation (ME), particularly its focus on “identifying causal patterns from micro-level social phenomena.” It also acknowledging the role of “structure”—seen as “macro-level conditions”—in incentivizing or disincentivizing key mechanisms, thus proving valuable for forecasting their emergence and decline. This article explores the theory of SME and applies it to examine how a revitalized “Legalist political structure coupled with a Confucianist ideological structure” can forecast the mechanisms by which (...) China’s National Social Credit System disciplines and punishes the citizens. This is observed across domains of legislation, administration, judiciary, and propaganda. (shrink)

In this paper, I challenge the standard reading of complete virtue (ἀρετή τελεία) in those disputed passages of Nicomachean Ethics and Eudemian Ethics. I argue that, for Aristotle, complete virtue is neither (i) wisdom nor (ii) a whole set of all virtues. Rather, it is a term used by Aristotle to denote any virtue that is in its complete or perfect form. In light of this reading, I offer a pluralist interpretation of Aristotelian happiness. I argue that for Aristotle, the (...) life-long exercise of a predominant virtue—as long as it is exercised in its complete or perfect form—will suffice for human happiness. The so-called inclusivist and intellectualist notions of Aristotelian happiness, thus understood, are merely two forms (viz. the composite and the non-composite form) of the pluralist notion of Aristotelian happiness. And if I am right, my pluralist interpretation provides an alternative, if not better, solution to the long-standing problem of “dual happiness” in Aristotle. (shrink)

In this paper, I wish to defend Aristotle’s naturalness thesis. First, I argue against the claim that the city fails to meet the criteria (e.g. separability, continuity, etc.) Aristotle sets for substantiality in the Metaphysics. Second, I examine the problem of the Principle of Transitivity of End in Aristotle’s telic argument for the naturalness of the city. I argue that the city exists for its own end. Finally, I discuss the problem of the legislator in the genesis of the city. (...) I argue that the legislator is only responsible for the actualization of the potential form that Nature has set forward. (shrink)

English summary: Philosophy of history is a comparatively young discipline. Beginning with the Enlightenment the historical is viewed as a philosophic topic. Through German Idealism it is emphatically placed at the centre of attention. The idealistic perspective on history was important for further development. The author presents the integral components of Kant's, Fichte's, Schelling's and Hegel's philosophy of history. He explains Kant's regulative idea on advancement, Fichte's model of the development of reason in five main eras, Schelling's three steps in (...) the absolute, speculative and revelation and Hegel's historical conception of a comprehensive Weltgeist. The most important opposing positions to an idealistic philosophy of history are described in the final chapter - reaching from new Kantianism, hermeneutics and science theory to the recent narratological approaches. German description: Geschichtsphilosophie, d. h. die bewusste Reflexion des Historischen als eines besonderen Gegenstands fur das menschliche Erkennen und Handeln, ist eine vergleichsweise junge Disziplin. Erst mit der Aufklarung wird Geschichte ernsthaft als eigenstandiges Thema wahrgenommen, und erst im deutschen Idealismus ruckt sie nachdrucklich ins Zentrum des philosophischen Interesses. Dabei ist die idealistische Sicht auf das Historische fur die weitere Entwicklung der Geschichtsphilosophie uberaus pragend gewesen - sei es indem ihre spekulativen Fortschrittsszenarien ubernommen und fur ahnlich umfassende Geschichtsbilder zugrunde gelegt wurden, sei es indem abweichende Geschichtsauffassungen in ihr das wesentliche Gegenkonzept fanden. Das Buch stellt die Hauptaspekte der Geschichtsphilosophie bei Kant, Fichte, Schelling und Hegel dar. Dabei wird besonderes Augenmerk darauf gelegt, wie diese Geschichtsentwurfe in die jeweilige philosophische Gesamtarchitektur der vier Autoren eingebettet sind. Zudem werden die wichtigsten Gegenpositionen zur idealistischen Geschichtssicht skizziert - von der Historikerschule und dem Neukantianismus uber die Hermeneutik und die Wissenschaftstheorie bis hin zu den narratologischen Ansatzen der jungeren Zeit. (shrink)

你自己去寻出一个本不成问题的问题，“人生有何意义？”其实这个问题是容易解答的。人生的意义全是各人自己寻出来、造出来的：高尚、卑劣、清贵、污浊、有用、无用，……全靠自己的作为。生命本身不过是一件生物学的 事实，有什么意义可说？一个人与一只猫，一只狗，有什么分别？人生的意义不在于何以有生，而在于自己怎样生活。你若情愿把这六尺之躯葬送在白昼作梦之上，那就是你这一生的意义。你若发愤振作起来，决心去寻求生命的 意义，去创造自己的生命的意义，那么，你活一日便有一日的意义，作一事便添一事的意义，生命无穷，生命的意义也无穷了。.

Academic journal publications may be retracted following institutional investigations that confirm allegations of research misconduct. Retraction notices can provide insight into the role institutional investigations play in the decision to retract a publication. Through a content analysis of 7,318 retraction notices published between 1927 and 2019 and indexed by the Web of Science, we found that most retraction notices (73.7%) provided no information about institutional investigations that may have led to retractions. A minority of the retraction notices (26.3%) mentioned an (...) institutional investigation either by journal authorities (12.1%), research performing organizations (10.3%), joint institutions (1.9%), research integrity and ethics governing bodies (1.0%), third-party institutions (0.5%), unspecified institutions (0.4%), or research funding organizations (0.1%). Comparing retraction notices issued before and after the introduction of retraction guidelines by the Committee on Publication Ethics (COPE) in 2009 revealed that those published after the guidelines’ publication were more likely to report investigations by journal authorities. Comparing retraction notices from different disciplines revealed that those from social sciences and the humanities were more likely to disclose investigations by research performing organizations than those from biomedical and natural sciences. Based on these findings, we suggest that the COPE retraction guidelines in the future make it mandatory to disclose in retraction notices institutional investigations leading to retractions. (shrink)

The radical forms of naturalistic epistemology look more like revolutionary manifestos than a reasonable alternatives. A modest form of naturalism is worth promoting. This modest form can cooperate with hermeneutics to solve epistemic problems, and therefore wins the title of cooperative naturalism, and benefits from the hermeneutic account of experience. Cooperative naturalism somewhat bridges the gap between analytic and continental philosophy.

Normal interpersonal treatment is often based on the existence of the rational nature of both the agent and the target of the treatment, and their relationship is reciprocal and mutual. However, when the rational person confronts the irrational person, such as the mentally retarded or vegetative person, the reciprocal relationship cannot be maintained because the targeted person loses his or her rational capacity. But this inequality does not deprive the object of action of the right to be treated rationally, because (...) people treat the irrationally disabled not according to the principle of reason but according to the principle of emotion - specifically, the principle of love. The principle of love often disregards the specific conditions of the object of treatment and still treats them reasonably. Thus, the emotional principle has a broader application in interpersonal treatment. (shrink)