The multifunctional zinc‐finger protein CCCTC‐binding factor (CTCF) is a very strong candidate for the role of coordinating the expression level of coding sequences with their three‐dimensional position in the nucleus, apparently responding to a “code” in the DNA itself. Dynamic interactions between chromatin fibers in the context of nuclear architecture have been implicated in various aspects of genome functions. However, the molecular basis of these interactions still remains elusive and is a subject of intense debate. Here we discuss the nature (...) of CTCF‐DNA interactions, the CTCF‐binding specificity to its binding sites and the relationship between CTCF and chromatin, and we examine data linking CTCF with gene regulation in the three‐dimensional nuclear space. We discuss why these features render CTCF a very strong candidate for the role and propose a unifying model, the “CTCF code,” explaining the mechanistic basis of how the information encrypted in DNA may be interpreted by CTCF into diverse nuclear functions. (shrink)

Ethical decision-making frameworks assist in identifying the issues at stake in a particular setting and thinking through, in a methodical manner, the ethical issues that require consideration as well as the values that need to be considered and promoted. Decisions made about the use, sharing, and re-use of big data are complex and laden with values. This paper sets out an Ethics Framework for Big Data in Health and Research developed by a working group convened by the Science, Health and (...) Policy-relevant Ethics in Singapore Initiative. It presents the aim and rationale for this framework supported by the underlying ethical concerns that relate to all health and research contexts. It also describes a set of substantive and procedural values that can be weighed up in addressing these concerns, and a step-by-step process for identifying, considering, and resolving the ethical issues arising from big data uses in health and research. This Framework is subsequently applied in the papers published in this Special Issue. These papers each address one of six domains where big data is currently employed: openness in big data and data repositories, precision medicine and big data, real-world data to generate evidence about healthcare interventions, AI-assisted decision-making in healthcare, public-private partnerships in healthcare and research, and cross-sectoral big data. (shrink)

High degrees of uncertainty and a lack of effective therapeutic treatments have characterized the COVID-19 pandemic and the provision of drug products outside research settings has been controversial. International guidelines for providing patients with experimental interventions to treat infectious diseases outside of clinical trials exist but it is unclear if or how they should apply in settings where clinical trials and research are strongly regulated. We propose the Professional Oversight of Emergency-Use Interventions and Monitoring System as an alternative pathway based (...) on guidance developed for the ethical provision of experimental interventions to treat COVID-19 in Singapore. We support our proposal with justifications that establish moral duties for physicians to record outcomes data and for institutions to establish monitoring systems for reporting information on safety and effectiveness to the relevant authorities. Institutions also have a duty to support generation of evidence for what constitutes good clinical practice and so should ensure the unproven intervention is made the subject of research studies that can contribute to generalizable knowledge as soon as practical and that physicians remain committed to supporting learning health systems. We outline key differences between POEIMS and other pathways for the provision of experimental interventions in public health emergencies. (shrink)

In a world that has become increasingly dependent upon employee ownership, commitment, and initiative, organizations need leaders who can inspire their␣employees and motivate them individually. Love, forgiveness, and trust are critical values of today’s organization leaders who are committed to maximizing value for organizations while helping organization members to become their best. We explain the importance of love, forgiveness, and trust in the modern organization and identify 10 commonalities of these virtues.

Beethoven is a classic study of the composer's music, written by one of the most important thinkers of our time. Throughout his life, Adorno wrote extensive notes, essay fragments and aides-memoires on the subject of Beethoven's music. This book brings together all of Beethoven's music in relation to the society in which he lived. Adorno identifies three periods in Beethoven's work, arguing that the thematic unity of the first and second periods begins to break down in the third. Adorno follows (...) this progressive disintegration of organic unity in the classical music of Beethoven and his contemporaries, linking it with the rationality and monopolistic nature of modern society. Beethoven will be welcomed by students and researchers in a wide range of disciplines - philosophy, sociology, music and history - and by anyone interested in the life of the composer. (shrink)

Critics of the target article objected to our account of art appreciators' sensitivity to art-historical contexts and functions, the relations among the modes of artistic appreciation, and the weaknesses of aesthetic science. To rebut these objections and justify our program, we argue that the current neglect of sensitivity to art-historical contexts persists as a result of a pervasive aesthetic–artistic confound; we further specify our claim that basic exposure and the design stance are necessary conditions of artistic understanding; and we explain (...) why many experimental studies do not belong to a psycho-historical science of art. (shrink)

Theories in the usual sense, as characterized by a language and a set of theorems in that language ("statement view"), are related to theories in the structuralist sense, in turn characterized by a set of potential models and a subset thereof as models ("non-statement view", J. Sneed, W. Stegmüller). It is shown that reductions of theories in the structuralist sense (that is, functions on structures) give rise to so-called "representations" of theories in the statement sense and vice versa, where representations (...) are understood as functions that map sentences of one theory into another theory. It is argued that commensurability between theories should be based on functions on open formulas and open terms so that reducibility does not necessarily imply commensurability. This is in accordance with a central claim by Stegmüller on the compatibility of reducibility and incommensurability that has recently been challenged by D. Pearce. (shrink)

ZusammenfassungDer Text versucht in Auseinandersetzung mit den Ansätzen von Jürgen Moltmann, Johann Baptist Metz und Odo Marquard und im Anschluss an lutherische Theologie zu einer Verhältnisbestimmung von Theodizeefrage und Kreuzestheologie zu gelangen. Dabei wird Luthers Einsicht fruchtbar gemacht, dass Gott verborgen im Leiden wirkt, das Leiden aber nicht zu seiner Wesenseigenschaft wird. Vielmehr eröffnet sich in der Klage des leidenden Menschen die Möglichkeit, das Leiden an Gott zu beenden und gegen Gott zu Gott zu fliehen. Von Luthers Kreuzestheologie her ist (...) eine gegenseitige Durchdringung von Theodizeefrage, Hamartiologie, Kreuzestheologie und Eschatologie anzumahnen. Gleichzeitig verhelfen Klage und Anklage dazu, sich aufgrund von erfahrenen Leiden nicht in sich selbst zu verschließen, sondern kontrafaktisch an Gott festzuhalten.SummaryDiscussing the thoughts of J. Moltmann, J. B. Metz and O. Marquard the essay attempts – whilst following Martin Luther's theologia crucis – to find a relation between the theodicy-question and the theology of the cross. For this concern it refers to the aspect that God acts in suffering in a hidden way but does not posses suffering as an intrinsic characteristic. Rather, the lament of suffering people address to God, as we find it in the Psalms, gives the opportunity of bringing suffering from God's hiddenness to an end and to “flee from God to God”. Returning to Luther's theologia crucis should lead to further reflections on theodicy, sin, theology of the cross and eschatology. At the same time, lamentation as bringing human suffering before God provides an aid for suffering people not to lock their suffering in themselves, but to maintain the relationship to God – even against the supposedly factual evidence of the experience of suffering. (shrink)

Expectations are growing that literature may contribute to clinical skills. Narrative medicine is a quickly expanding area of research. However, many people remain sceptical to the idea of literature having a capacity to save the life of medicine . It is therefore urgent to scrutinize both the arguments in favour of and those against the potential of literature for increasing medical understanding. This article attempts to do this. It does in fact support the assertion that literature is important, but it (...) stresses precisely its character of potential. There is no simple connection between acquaintance with literary texts and understanding of the different aspects of medical work. Much more need to be known about the conditions which allow the experiences residing in texts to be transformed into lived personal knowledge. (shrink)

The following article is a response to K. Mainzer's ‘Knowledge-Based Systems; Remarks on the Philosophy of Technology and Artificial Intelligence’. We show, that Mainzer does not reach any of his aimsto analyse the possibilities and limits of AI-technology.to reduce anxiousness and hostility against AI, which is motivated by phantastic speculations.to evaluate the factual impact of AI on our lives and on society.His article contributes on the contrary to phantastic speculations, which are not technologically justified in any way. There are two (...) main reasons for his misleading view: (a) the state of the art of knowledge-based systems is incorrectly described; (b) the roots, paradigms and alternatives to AI are not in the least sufficiently analysed. We examine issues (a) and (b) in Chapter 1 and Chapter 2. In Chapter 3 we discuss, how the conclusions, which Mainzer draws, have to be modified. In analysing the lines of argumentation of Mainzer we try to clarify the methodological errors and the philosophical attitude of Mainzer, which is in many respects not adequate to the subject of the article. (shrink)