5‐methylcytosine (5mC) was long thought to be the only enzymatically created modified DNA base in mammalian cells. The discovery of 5‐hydroxymethylcytosine, 5‐formylcytosine, and 5‐carboxylcytosine as reaction products of the TET family 5mC oxidases has prompted extensive searches for proteins that specifically bind to these oxidized bases. However, only a few of such “reader” proteins have been identified and verified so far. In this review, we discuss potential biological functions of oxidized 5mC as well as the role the presumed reader (...) proteins may play in interpreting the genomic signals of 5mC oxidation products. (shrink)

To decode the function and molecular recognition of several recently discovered cytosine derivatives in the human genome – 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine – a detailed understanding of their effects on the structural, chemical, and biophysical properties of DNA is essential. Here, we review recent literature in this area, with particular emphasis on features that have been proposed to enable the specific recognition of modified cytosine bases by DNA-binding proteins. These include electronic factors, modulation of base-pair stability, flexibility, and radical (...) changes in duplex conformation. We explore these proposals and assess whether or not they are supported by current biophysical data. This analysis is focused primarily on the properties of epigenetically modified DNA itself, which provides a basis for discussion of the mechanisms of recognition by different proteins. 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine have recently been discovered in mammalian DNA and appear to have essential regulatory roles. Here, we summarize recent investigations into their effects on the structural, chemical, and biophysical properties of DNA, an understanding of which is essential to decoding their behavior in the genome. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:BOOK REVIEWS 91 The passage which permitted such an interpretation is the following: This self-command is very different at different times.... Can we give any reason for these variations, except experience? Where then is the power of which we pretend to be conscious? Is there not here, either in a spiritual or a material substance, or both, some secret mechanism or structure of parts, upon which the effect depends...?" (...) (Enquiry, p. 68). This rhetorical question is, on the contrary, intended as the part of the third argument for the thesis "that even this command of the will gives us no real idea of force or energy" (Enquiry, p. 67). There is no evidence in the Enquiries that Hume concluded that self is a substance. On p. 45, Anderson "suggests that Hume employs 'impression'...in a less frequent usage, however.., to be a pressure, or pattern of light, or other means whereby objects are applied to the external organs of sense"t On p. 65 and also on p. 173, it is argued fallaciously that, "Hume considers mathematical ideas, like all other ideas, to be existences. If this be true, then the necessary relations ~mpposed to obtain among mathematical ideas cannot be discerned even though these ideas themselves be fully known." Now it is a matter of debate whether Hume believed that all mathematical ideas are derived from impressions (see my controversy with Flew on this issue, in Ratio, Vol. VI, No. 2, "Hume on Pure and Applied Geometry," and Flew's article, "Did Hume Distinguish Pure and Applied Geometry?," Ratio, Vol. VIII, No. 1). But even if we assume that this is his belief, it does not follow at all that the logical relations among these ideas are contingent. As Pap argued a long time ago, "A sensationalist might maintain that all the concepts that constitute a given proposition are derived from experience and might nevertheless admit that proposition itself is a priori in the sense of requiring no empirical verification in order to be assertable as true." Thus, Hume the sensationalist admitted that a priori knowledge is possible in mathematics, which is conversant exclusively about "relations of ideas" and not about "matters of fact." Finally, in the last chapter, it is argued that, "Hume's own suggestion concerning these three natural relations (resemblance, contiguity, and cause and effect) is that they are fundamentally material--that they consist in a certain characteristic movement of the animal spirit in the brain" (p. 163)I1 That, "The necessity is the relationship between cause and effect, Hume's remarks suggest, is ultimately their identity in essence. One passage which we have noted indicates that cause and effect are inseparable, and by use of Hume's own maxims we may strictly infer from their inseparability their identity" (p. 165)II And that, "Although Hume's doctrine of matter is ultimately of central importance in his system, his beginnings in moral philosophy doubtless led him to turn his attention away from the topic of matter" (p. 175). This book, though replete with quotations from Hume's works and exhibiting a great amount of microscopic observations, represents a mistaken view of Hume's epistemology. ~ARHANG ZABEEIq Roosevelt University, Chicago Hegel's Phenomenology. Dialogues on the Life of Mind. By Jacob Loewenberg. (La Salle, Ill. : The Open Court Publ. Co., 1965.Pp. xv + 377.) Hegel's Phenomenology o] Spirit, intriguing in its richness, has long remained one of the most forbidding of philosophical classics. Unfortunately, commentaries, though altogether indispensable, are sparse. Heretofore, the reader found himself referred mainly to two foreign language studies, G. A. Gabler's Kritik des Be~usst~ein~ of 1835, and J. Hyppolite's Gen~se et structure de la Phdnomdnologie de l'esprit; no full-scale work in English was available. And 92 HISTORY OF PHILOSOPHY even the reader prepared to turn to these works might register disenchantment: Gabler deals with two fifths of the book only, and Hyppolite is at times too close to the text to be much help. What remains is comment in the framework of more general studies of Hegel's philosophy (Royce, Haering, Kroner, Stace, Findlay and others). In this situation Loewenberg's contribution marks a... (shrink)

Although fairness is a key moral trait, limited research focuses on participants' observed fairness behavior because moral traits are generally measured through self-report. This experiment focused on day-to-day interpersonal fairness rather than impersonal justice, and fairness was assessed as observed behavior. The experiment investigated whether a self-reported fairness trait would moderate a situational influence on observed fairness behavior, such that individuals with a stronger fairness trait would be less affected by a situational influence than those with a weaker fairness trait. (...) We used an iterated resource game in which participants could withdraw resources as they chose, and we manipulated the number of resources bogus players withdrew. The number of resources participants withdrew was the behavioral measure of fairness. Results confirmed the expected moderation of the unfairness manipulation by a fairness trait on observed behavior. Those reporting a stronger fairness trait were unaffected by the manipulation, whereas those reporting a weaker fairness trait were more strongly influenced. (shrink)

This chapter puts to rest for all of eternity the self-undermining charge against conciliationism.

For millennia, diagnosticians distinguished natural sadness that arose from social circumstances from depressive disorders that were disproportionate to their contexts. In 1980, the DSM-III transformed this tradition through equating depressive disorders with symptoms without regard to context. Nevertheless, it excluded grieving people without especially severe or enduring symptoms from diagnosis. Subsequently, considerable empirical research indicated that bereavement was not unique but a model for all stressor-maintained conditions. Yet, despite the evidence showing that the causes, prognoses, and optimal treatments for context-specific (...) depressions differ from those that aren’t, the DSM-5 removed the bereavement exclusion from the diagnostic criteria for major depression. This article considers the reasons behind this elimination and its implications for the research, labeling, and treatment of depression. (shrink)

A large part of the controversy surrounding the publication of DSM-5 stems from the possibility of replacing the purely descriptive approach to classification favored by the DSM since 1980. This paper examines the question of how mental disorders should be classified, focusing on the issue of whether the DSM should adopt a purely descriptive or theoretical approach. I argue that the DSM should replace its purely descriptive approach with a theoretical approach that integrates causal information into the DSM’s descriptive diagnostic (...) categories. The paper proceeds in three sections. In the first section, I examine the goals (viz., guiding treatment, facilitating research, and improving communication) associated with the DSM’s purely descriptive approach. In the second section, I suggest that the DSM’s purely descriptive approach is best suited for improving communication among mental health professionals; however, theoretical approaches would be superior for purposes of treatment and research. In the third section, I outline steps required to move the DSM towards a hybrid system of classification that can accommodate the benefits of descriptive and theoretical approaches, and I discuss how the DSM’s descriptive categories could be revised to incorporate theoretical information regarding the causes of disorders. I argue that the DSM should reconceive of its goals more narrowly such that it functions primarily as an epistemic hub that mediates among various contexts of use in which definitions of mental disorders appear. My analysis emphasizes the importance of pluralism as a methodological means for avoiding theoretical dogmatism and ensuring that the DSM is a reflexive and self-correcting manual. (shrink)

This chapter gives a truthmaker-based account of the semantics of 'reifying' quantifiers like 'something' when they act as complements of intensional transitive verbs ('need', 'look for'). It argues that such quantifiers range over 'variable satisfiers' of the attitudinal object described by the verb (e.g. the need or the search).

In twelfth-century Europe schools flourished in many centres. There were schools in monasteries and cathedrals, primarily for the education of monks and priests but often open also to laymen. In Italian towns, especially, there were lay schools teaching law and commercial skills to fee-paying students. In France, especially, also in England and other countries, there were schools for feepaying students of the liberal arts. The traditional list of the liberal arts included seven: grammar, logic and rhetoric (the "trivium"), and arithmetic, (...) geometry, astronomy and music (the "quadrivium"): most of the schools we're talking about taught the trivium, grammar, logic and rhetoric. These three disciplines in one way or other taught language skills; they were sometimes called the artes sermocinales. Students who had completed these "trivial" studies sometimes moved on to theology, or sometimes set up as teachers themselves of grammar, logic and rhetoric. Some students travelled from country to country looking for a good school, and sometimes made their living for a while by teaching before becoming students again. (shrink)

Ex 5,22-6.1 presents Moses appealing to the Lord and God's answer to the prophet. Moses' prayer is configured as a cry of despair stemming from a bewilderment of his vocation as a promoter of liberty, subdued by human conditions. The prophet of failure is paradoxical, since it reveals both as a personal and divine failure. For these reasons, Moses has faith put to the test. His reaction shown by a fiery prayer and full of fervor. God responds with the renewal (...) of the promise of liberation. (shrink)

Phosphatidylinositol 5‐phosphate (PtdIns5P), the least characterized among the three phosphatidylinositol monophosphates, is emerging as a bioactive lipid involved in the control of several cellular functions. Similar to PtdIns3P, it is present in low amounts in mammalian cells, and can be detected at the plasma membrane and endomembranes as well as in the nucleus. Changes in PtdIns5P levels are observed in mammalian cells following specific stimuli or stresses, and in human diseases. Recently, the contribution of several enzymes such as PIKfyve, myotubularins, (...) and type II PtdInsP‐kinases to PtdIns5P metabolism has gained a strong experimental support. Here, we provide a picture emerging from recent studies showing how this lipid can be generated and act as a regulator of membrane and cytoskeleton dynamics, and as a modulator of gene expression. We briefly summarize the current methods and tools for studying PtdIns5P, and discuss how PtdIns5P can integrate and coordinate different functions in a spatiotemporal manner. (shrink)

One of the most important paraconsistent logics is the logic mCi, which is one of the two basic logics of formal inconsistency. In this paper we present a 5-valued characteristic nondeterministic matrix for mCi. This provides a quite non-trivial example for the utility and effectiveness of the use of non-deterministic many-valued semantics.

_English_ ASD VII, 5 contains the second part of Erasmus’ _Paraphrasis_ on the apostolic letters. It is the first scientific edition of these Paraphrases. _German_ ASD VII, 5 enthält der zweite Teil von Erasmus' Paraphrasis zur apostolische Briefe des Neuen Testaments. Diese ist die erste wissenschaftliche Edition dieser Parafrasen.

On the basis of PM2.5 data of the national air quality monitoring sites, local population data, and baseline all-cause mortality rate, PM2.5-related health economic benefits of the Air Improvement Action Plan implemented in Wuhan in 2013–2017 were investigated using health-impact and valuation functions. Annual avoided premature deaths driven by the average concentration of PM2.5 decrease were evaluated, and the economic benefits were computed by using the value of statistical life (VSL) method. Results showed that the number of avoided premature deaths (...) in Wuhan are 21,384 (95% confidence interval (CI): 15,004 to 27,255) during 2013–2017, due to the implementation of the Air Improvement Action Plan. According to the VSL method, the obtained economic benefits of Huangpi, Wuchang, Hongshan, Xinzhou, Jiang’an, Hanyang, Jiangxia, Qiaokou, Jianghan, Qingshan, Caidian, Dongxihu, and Hannan District were 8.55, 8.19, 8.04, 7.39, 5.78, 4.84, 4.37, 4.04, 3.90, 3.30, 2.87, 2.42, and 0.66 billion RMB (1 RMB = 0.1417 USD On 14 October 2019), respectively. These economic benefits added up to 64.35 billion RMB (95% CI: 45.15 to 82.02 billion RMB), accounting for 4.80% (95% CI: 3.37% to 6.12%) of the total GDP of Wuhan in 2017. Therefore, in the process of formulating a regional air quality improvement scheme, apart from establishing hierarchical emission-reduction standards and policies, policy makers should give integrated consideration to the relationship between regional economic development, environmental protection and residents’ health benefits. Furthermore, for improving air quality, air quality compensation mechanisms can be established on the basis of the status quo and trends of air quality, population distribution, and economic development factors. (shrink)

Studies associating interactions of 5-HTTLPR and life adversities with depression have yielded equivocal results. Studying endophenotypes may constitute a more powerful approach. In the current study, it was assessed whether interactions of 5-HTTLPR with childhood emotional abuse (CEA) and recent negative life events (RNLE) affect possible cognitive endophenotypes of depression, namely, attention-allocation bias and the ability to recognise others' mind states in 215 young adults of North-West European descent. The ability to classify others' negative mind states was found to be (...) increased with increasing RNLE in carriers of low-expressing Serotonin Transporter Linked Polymorphic Region (5-HTTLPR) alleles. Carriers of two low-expressing alleles also preferentially oriented attention towards negative information. Gene-environment interactions were not observed for attention allocation bias. No effects involving CEA were observed. These results suggest that low-expressing 5-HTTLPR alleles may confer increased risk for depression through enhanced recognition of negative facial expressions following RNLE. (shrink)

QUESTIONS Objects seem to have some properties in themselves (like shape), and some other properties that depend on other things around them (like being alone or accompanied). The distinction between primary and secondary qualities is a special case of this more general contrast: what, according to Locke, is the basis for the distinction? Is there more than one way to understand Locke’s argument: what is the best reading of Locke? What wider significance does the distinction between primary and secondary qualities (...) have? (shrink)

This is Chapter 5 of my Commonsense Consequentialism: Wherein Morality Meets Rationality. In this chapter, I argue that those who wish to accommodate typical instances of supererogation and agent-centered options must deny that moral reasons are morally overriding and accept both that the reason that agents have to promote their own self-interest is a non-moral reason and that this reason can, and sometimes does, prevent the moral reason that they have to sacrifice their self-interest so as to do more to (...) promote the interests of others from generating a moral requirement. Furthermore, I argue that given that an act’s deontic status of both moral and non-moral reasons, the consequentialist must adopt dual-ranking act-consequentialism. I then defend dual-ranking act-consequentialism against a number of objections. (shrink)

Few people have thought so hard about the nature of the quantum theory as has Jeff Bub,· and so it seems appropriate to offer in his honor some reflections on that theory. My topic is an old one, the consistency of our microscopic theories with our macroscopic theories, my example, the Aspect experiments (Aspect et al., 1981, 1982, 1982a; Clauser and Shimony, l978;_Duncan and Kleinpoppen, 199,8) is familiar, and my sirnplrcation of it is borrowed. All that is new here is (...) a kind of diagonalization: an argument that the fundamental principles found to be violated by the quantum theory must be assumed to be true of the experimental apparatus used in the experiments.. (shrink)

Are science and religion compatible when it comes to understanding cosmology (the origin of the universe), biology (the origin of life and of the human species), ethics, and the human mind (minds, brains, souls, and free will)? Do science and religion occupy non-overlapping magisteria? Is Intelligent Design a scientific theory? How do the various faith traditions view the relationship between science and religion? What, if any, are the limits of scientific explanation? What are the most important open questions, problems, or (...) challenges confronting the relationship between science and religion, and what are the prospects for progress? These and other questions are explored in Science and Religion: 5 Questions--a collection of thirty-three interviews based on 5 questions presented to some of the world's most influential and prominent philosophers, scientists, theologians, apologists, and atheists. Contributions by Simon Blackburn, Susan Blackmore, Sean Carroll, William Lane Craig, William Dembski, Daniel C. Dennett, George F.R. Ellis, Owen Flanagan, Owen Gingerich, Rebecca Newberger Goldstein, John F. Haught, Muzaffar Iqbal, Lawrence Krauss, Colin McGinn, Alister McGrath, Mary Midgley, Seyyed Hossein Nasr, Timothy O'Connor, Massimo Pigliucci, John Polkinghorne, James Randi, Alex Rosenberg, Michael Ruse, Robert John Russell, John Searle, Michael Shermer, Victor J. Stenger, Robert Thurman, Michael Tooley, Charles Townes, Peter van Inwagen, Keith Ward, Rabbi David Wolpe. (shrink)

This paper examines the analysis of judgements of belief that Wittgenstein offers in 5.54-5.5423 of the Tractatus. We offer an interpretation of these paragraphs wich also pays attention to 5.5423, usually forgotten. In our opinion, this interpretation fits with Wittgenstein's doctrines, and makes clear that such non-genuine propositions are nonsense. These are not, as has sometimes been proposed, the propositions of psychology. In the second part of the article we give a detailed discussion of interpretations of these paragraphs which have (...) been offered previously. (shrink)