In eukaryotic cells, heterochromatin is typically composed of tandem DNA repeats and plays crucial roles in gene expression and genome stability. It has been reported that silencing at individual units within tandem heterochromatin repeats exhibits a position‐dependent variation. However, how the heterochromatin is organized at an individual repeat level remains poorly understood. Using a novel genetic approach, our recent study identified a conserved protein Rex1BD required for position‐dependent silencing within heterochromatin repeats. We further revealed that Rex1BD (...) interacts with the 14‐3‐3 protein to regulate heterochromatin silencing by linking RNAi and HDAC pathways. In this review, we discuss how Rex1BD and the 14‐3‐3 protein coordinate to modulate heterochromatin organization at the individual repeat level, and comment on the biological significance of the position‐dependent effect in heterochromatin repeats. We also identify the knowledge gaps that still need to be unveiled in the field. (shrink)

X chromosome inactivation (XCI) is an essential epigenetic process that ensures X‐linked gene dosage equilibrium between sexes in mammals. XCI is dynamically regulated during development in a manner that is intimately linked to differentiation. Numerous studies, which we review here, have explored the dynamics of X inactivation and reactivation in the context of development, differentiation and diseases, and the phenotypic and molecular link between the inactive status, and the cellular context. Here, we also assess whether XCI is a uniform mechanism (...) in mammals by analyzing epigenetic signatures of the inactive X (Xi) in different species and cellular contexts. It appears that the timing of XCI and the epigenetic signature of the inactive X greatly vary between species. Surprisingly, even within a given species, various Xi configurations are found across cellular states. We discuss possible mechanisms underlying these variations, and how they might influence the fate of the Xi. (shrink)

We discuss here a series of testable hypotheses concerning the role of chromosome folding into topologically associating domains (TADs). Several lines of evidence suggest that segmental packaging of chromosomal neighborhoods may underlie features of chromatin that span large domains, such as heterochromatin blocks, association with the nuclear lamina and replication timing. By defining which DNA elements preferentially contact each other, the segmentation of chromosomes into TADs may also underlie many properties of long‐range transcriptional regulation. Several observations suggest that TADs (...) can indeed provide a structural basis to regulatory landscapes, by controlling enhancer sharing and allocation. We also discuss how TADs may shape the evolution of chromosomes, by causing maintenance of synteny over large chromosomal segments. Finally we suggest a series of experiments to challenge these ideas and provide concrete examples illustrating how they could be practically applied. (shrink)

This article focuses on the role of the interchromatin compartment (IC) in shaping nuclear landscapes. The IC is connected with nuclear pore complexes (NPCs) and harbors splicing speckles and nuclear bodies. It is postulated that the IC provides routes for imported transcription factors to target sites, for export routes of mRNA as ribonucleoproteins toward NPCs, as well as for the intranuclear passage of regulatory RNAs from sites of transcription to remote functional sites (IC hypothesis). IC channels are lined by less‐compacted (...) euchromatin, called the perichromatin region (PR). The PR and IC together form the active nuclear compartment (ANC). The ANC is co‐aligned with the inactive nuclear compartment (INC), comprising more compacted heterochromatin. It is postulated that the INC is accessible for individual transcription factors, but inaccessible for larger macromolecular aggregates (limited accessibility hypothesis). This functional nuclear organization depends on still unexplored movements of genes and regulatory sequences between the two compartments. (shrink)

This ambitious, interdisciplinary book seeks to explain the origins of religion using our knowledge of the evolution of cognition. A cognitive anthropologist and psychologist, Scott Atran argues that religion is a by-product of human evolution just as the cognitive intervention, cultural selection, and historical survival of religion is an accommodation of certain existential and moral elements that have evolved in the human condition.

Attention has a long history in philosophy, despite its near absence in the twentieth century. This chapter provides an overview of philosophical research on attention. It begins by explaining the concept of "selection from limitation," contrasting it with the more recent "selection for action." It reviews historical texts that discuss attention, focusing on those in the Western canon whose understanding of "attention" aligns with contemporary usage. It then describes the differential treatment of attention in phenomenology and behaviorism in the last (...) century. Finally, it discusses contemporary research by topic: attention, perception, and knowledge; attention and consciousness; attention and action; and attention and the self. It includes work by Allport,Aristotle, Astell, Augustine, Bergson, Berkeley, Block, Bradley, Buddhaghosa, Campbell, Cherry, De Brigard, Dehaene and Naccache, Descartes, Dickie, Du Bois, Ganeri, Hegel, Heidegger, James, Kant, Koch and Tsuchiya, LaBerge, Locke, Mack and Rock, Malebranche, Merleau-Ponty, Mole, Montemayor and Haladjian, Neumann, Pashler, Posner, Prinz, Reid, Rensink, Reynolds and Heeger, Treisman, Watzl, Wittgenstein, Wollstonecraft, and Wu. (shrink)

This article outlines and compares current and proposed global institutional mechanisms to increase equitable access to COVID-19 vaccines, focusing on their institutional and operational complementarities and overlaps. It specifically considers the World Health Organization's (WHO’s) COVAX (COVID-19 Vaccines Global Access) model as part of the Access to COVID-19 Tools Accelerator (ACT-A) initiative, the WHO’s COVID-19 Technology Access Pool (C-TAP) initiative, the proposed TRIPS (Trade-Related Aspects of Intellectual Property Agreement) intellectual property waiver and other proposed WHO and World Trade Organization technology (...) transfer proposals. We argue that while various individual mechanisms each have their specific individual merits—and in some cases weaknesses—overall, many of these current and proposed mechanisms could be highly complementary if used together to deliver equitable global access to vaccines. Nonetheless, we also argue that there are risks posed by the proliferation of proposals in this context, including the potential to disperse stakeholder attention or to delay decisive action. Therefore, we argue that there is now a clear need for concerted global multilateral action to recognise the complementarities of specific models and to provide a pathway for collaboration in attaining global equitable access to vaccines. The institutional infrastructure or proposals to achieve this amply exist at this point in time—but much greater cooperation from industry and clear, decisive and coordinated action from states and international organisations are urgently needed. (shrink)

Heterochromatin remains condensed throughout the cell cycle, is generally transcriptionally inert and is built and maintainedbygroupsoffactors witheachgroupmember sharing a similar function. In mammals, these groups include sequence-specific transcriptional repressors, functionalRNAandproteinsinvolvedinDNAandhistone methylation. Heterochromatin is cemented together via interactions within and between each protein group and ismaintainedbythecell’sreplicationmachinery.Itcanbe constitutive (permanent) or facultative (developmentally regulated) and be any size, from a gene promotor to a whole genome. By studying the formation of facultative heterochromatin, we have gained information about how heterochromatin (...) is assembled. We have discovered that there are many different architectural plans for the building of heterochromatin, leading to a seemingly never-ending variety of heterochromatic loci, with each built according to a general rule. (shrink)

In this article, we identify three key design dimensions along which cryptocurrencies differ -- privacy, censorship-resistance, and consensus procedure. Each raises important normative issues. Our discussion uncovers new ways to approach the question of whether Bitcoin or other cryptocurrencies should be used as money, and new avenues for developing a positive answer to that question. A guiding theme is that progress here requires a mixed approach that integrates philosophical tools with the purely technical results of disciplines like computer science and (...) economics. Note: this article is the second entry within a two-part sequence on the Philosophy, Politics, and Economics of Cryptocurrency. (shrink)

The abbey of Conques and its dominant church dedicated to St Foy are today one of the most prominent examples of the harmonic relationship between medieval sacred architecture and nature. This article considers the medieval landscape of Conques from an environmental-historical perspective by analyzing early medieval writings about the abbey. It focuses on early descriptions, which often contain literary, hagiographical topoi depicting ideal, symbolic, or imagined landscapes - sometimes, however, also partially reflecting reality. These descriptions serve, with caution, to (...) investigate the local environment, its transformation, and its effect on the early history of the monastery. In addition, the article delves into the eleventh-century Liber miraculorum sanctae Fidis to investigate strategies that the monastic community used to control St Foy’s estates not only close to the abbey but also in the wider region. Analysis reveals the environment conditions, their impact on the history, and ways in which the monastic community sacralized the landscape through real processions and miracle stories to control it. (shrink)

From analysis of the cartari of the monasteries of Casotto and Montebenedetto - the first Carthusian monasteries of twelfth-century Piedmont - this article examines the close link between the Monastery of the Grande-Chartreuse and the two Italian Carthusian monasteries. These ties become especially apparent in the ways in which territorial matters are dealt with in the Consuetudines Cartusiae. Reading monastic sources against historical cartography yields the analytic means to reconstruct, graphically, the shifting possession of land areas between the two Italian (...) monasteries. This, in turn, leads to improved understanding of the Carthusian landscape heritage from the twelfth century to the fourteenth, as well as the pre-existing structures still present in the territory. (shrink)

This paper endeavors to understand the research landscape of finance research in Vietnam during the period 2008 to 2020 and predict the key defining future research directions. Using the comprehensive database of Vietnam’s international publications in social sciences and humanities, we extract a dataset of 314 papers on finance topics in Vietnam from 2008 to 2020. Then, we apply a systematic approach to analyze four important themes: Structural issues, Banking system, Firm issues, and Financial psychology and behavior. Overall, there (...) have been three noticeable trends within finance research in Vietnam: (1) assessment of financial policies or financial regulation, (2) deciphering the correlates of firms’ financial performances, and (3) opportunities and challenges in adopting innovations and ideas from foreign financial market systems. Our analysis identifies several fertile areas for future research, including financial market analysis in the post-COVID-19 eras, fintech, and green finance. (shrink)

We focus here on the intercalary heterochromatin (IH) of Drosophila melanogaster and, in particular, its molecular properties. In the polytene chromosomes of Drosophila, IH is represented by a reproducible set of dense bands scattered along the euchromatic arms. IH contains mainly unique DNA sequences, and shares certain features with other heterochromatin types such as pericentric, telomeric, and PEV‐induced heterochromatin, the inactive mammalian X‐chromosome and the heterochromatized male chromosome set in coccids. These features are transcriptional silencing, chromatin compactness, (...) late DNA replication, underrreplication or elimination in somatic cells, and formation of the heterochromatin state in early embryogenesis. Post‐translational modification of histones and the specific nonhistone protein complexes are shown to participate in the establishment and maintenance of silencing for all heterochromatin types. Many IH regions contain binding sites for HP1 and/or Pc‐G proteins and all the regions are sites of heterochromatin‐associated SuUR protein. Some IH regions are known to contain homeotic genes. Summarizing these data, we suggest that IH regions comprise stable inactivated genes, whose silencing is developmentally programmed. BioEssays 25:1040–1051, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

From Joan Lindsay and cinematic master Peter Weir to Ted Kotcheff and Warwick Thornton, over past decades authors, screenwriters and filmmakers have produced films that depict the vast Australian landscape—simply referred to as terra nullius during colonial times by settlers literally confronting a continent vastly different from anything they were culturally and geographically accustomed to—as mysterious, impenetrable and ominous. Just like the dark cold of Scandinavia lends itself perfectly to contemporary Nordic Noir, the Australian New Wave or Australian Film (...) Revival of the 1970s and 1980s saw the release of films that encapsulated the eeriness of this largely rugged, arid and windswept continent, which opens up possibilities for anything to happen within those very, limitless, territories. This article analyses Weir’s Picnic at Hanging Rock (1975), Kotcheff’s horror flick par excellence Wake in Fright (1971); "the best and most terrifying film about Australia in existence" and with a TV-series remake in 2017, and Thornton’s more recent portrayal of Aboriginal misery and poverty Samson and Delilah (2009) set against a hostile urban backdrop, from a Foucauldian perspective. In its theoretical framework it also draws primarily on Freud. Heterotopia is used as a term to refer to strange, bewildering spaces that are disturbing and undecipherable—also described as “an unimaginable space, representable only in language, and as a kind of semimythical real site” (as articulated in Knight, 2017, 141). Foucault’s concept is applied in a cinematic context and used in conjunction with Freud’s notion of the uncanny as a feeling of uneasiness; or, as has been explained in his seminal text “The Uncanny” (1919), “that class of the terrifying that leads back to something long known to us, once very familiar.” We argue that these eerie, fear-induced screened narratives represent a nation whose weather-beaten, freedom-loving yet at heart anxiety-ridden people are most definitely a product of their environment. (shrink)

There are two main ways in which the notion of mereological fusion is usually defined in the current literature in mereology which have been labelled ‘Leśniewski fusion’ and ‘Goodman fusion’. It is well-known that, with Minimal Mereology as the background theory, every Leśniewski fusion also qualifies as a Goodman fusion. However, the converse does not hold unless stronger mereological principles are assumed. In this paper I will discuss how the gap between the two notions can be filled, focussing in particular (...) on two specific sets of principles that appear to be of particular philosophical interest. The first way to make the two notions equivalent can be used to shed some interesting light on the kind of intuition both notions seem to articulate. The second shows the importance of a little-known mereological principle which I will call ‘Mild Supplementation’. As I will show, the mereology obtained by adding Mild Supplementation to Minimal Mereology occupies an interesting position in the landscape of theories that are stronger than Minimal Mereology but weaker than what Achille Varzi and Roberto Casati have labelled ‘Extensional Mereology’. (shrink)

In this article we consider the forms of democratic participation that revolve around issues of religious faith and Islam. The context of such work is one in which a concern with the levels of participation in the political institutions of Western Europe and North America feature prominently in both journalistic and academic debate. The article speaks to debates that are concerned with the efficacy of specific forms of participation. In doing so we argue that we need to think carefully about (...) the forms of social action that constitute participation in the democratic process. We also need to think precisely about definitions of the political with which people engage. If we take the political as a domain in which the ethical settlement of society is contestable, the sorts of mobilization around faith communities that this article describes are clearly a form of political participation. Yet the article argues that the reasons many become involved in these forms of social organization in contemporary East London is precisely because they are seen as less complicit with mainstream political institutions of the British state. (shrink)

Some individuals facing dementia contemplate hastening their own death: weighing the possibility of living longer with dementia against the alternative of dying sooner but avoiding the later stages of cognitive and functional impairment. This weighing resonates with an ethical and legal consensus in the United States that individuals can voluntarily choose to forgo life‐sustaining interventions and also that medical professionals can support these choices even when they will result in an earlier death. For these reasons, whether and how a terminally (...) ill individual can choose to control the timing of their death is a topic that cannot be avoided when considering the dementia trajectory. With a focus on the U.S. context, this landscape review considers the status of provisions that would legally permit people facing dementia to hasten death with appropriate support from medical professionals. This review can be used to plan and guide clinical and legal practitioner discussion and policy development concerning evolving questions not fully covered by existing medical decision‐making provisions. (shrink)

Stem cell research. Drug company influence. Abortion. Contraception. Long-term and end-of-life care. Human participants research. Informed consent. The list of ethical issues in science, medicine, and public health is long and continually growing. These complex issues pose a daunting task for professionals in the expanding field of bioethics. But what of the practice of bioethics itself? What issues do ethicists and bioethicists confront in their efforts to facilitate sound moral reasoning and judgment in a variety of venues? Are those immersed (...) in the field capable of making the right decisions? How and why do they face moral challenge -- and even compromise -- as ethicists? What values should guide them? In The Ethics of Bioethics, Lisa A. Eckenwiler and Felicia G. Cohn tackle these questions head on, bringing together notable medical ethicists and people outside the discipline to discuss common criticisms, the field's inherent tensions, and efforts to assign values and assess success. Through twenty-five lively essays examining the field's history and trends, shortcomings and strengths, and the political and policy interplay within the bioethical realm, this comprehensive book begins a much-needed critical and constructive discussion of the moral landscape of bioethics. (shrink)

I forgive the slight spin of sloganeering conveyed by the motto so frequently cited by proponents of a cosmos chock full of organisms: "Life will fed a way." Life is resilient and quite capable (especially in bacterial form) of living in the most damnably improbable places-from nearly boiling ponds in Yellowstone National Park to tiny pores in rocks as deep as two miles below the earth's surface. But even this degree of resilience must work within limits; if life ever evolved (...) on the Martian surface during its initial billion years with running water, the planet's later desiccation probably extinguished our solar system's second experiment in advanced carbon chemistry. (shrink)

Due to an unfortunate miscommunication with the copy editor an important reference was omitted from this recently published article. The reference that should be included is.

The European Union is working towards harmonizing legislation across Europe, in order to improve cross-border interchange of legal information. This goal is supported for instance via standards such as the European Law Identifier and the European Case Law Identifier, which provide technical specifications for Web identifiers and suggestions for vocabularies to be used to describe metadata pertaining to legal documents in a machine readable format. Notably, these ECLI and ELI metadata standards adhere to the RDF data format which forms the (...) basis of Linked Data, and therefore have the potential to form a basis for a pan-European legal Knowledge Graph. Unfortunately, to date said specifications have only been partially adopted by EU member states. In this paper we describe a methodology to transform the existing legal information system used in Austria to such a legal knowledge graph covering different steps from modeling national specific aspects, to population, and finally the integration of legal data from other countries through linked data. We demonstrate the usefulness of this approach by exemplifying practical use cases from legal information search, which are not possible in an automated fashion so far. (shrink)

The aim of this study was to investigate the consequences of the use of text-matching software on teachers’ and students’ conceptions of plagiarism and problems in academic writing. An electronic questionnaire included scale items, structured questions, and open-ended questions. The respondents were 85 teachers and 506 students in a large Finnish university. Methods of analysis included exploratory factor analysis, t-test, and inductive content analysis. Both teachers and students reported increased awareness of plagiarism and improvements in writing habits, as well as (...) concerns and limitations related to the system. The results suggest that teachers are inclined to think of plagiarism as part of a learning process rather an issue of morality, which may have consequences for how they understand the role of text matching. The introduction of text-matching software has supported teachers’ work, but at the same time teachers emphasized their own responsibility in detecting problems in student writing. The survey provides a limited sample of “Case Finland,” where implementation of text-matching software nationwide has been remarkably rapid; it offers a glimpse into one institution’s implementation of a newly introduced policy for mandatory plagiarism detection. (shrink)

With its potential to contribute to the ethical governance of AI, eXplainable AI (XAI) research frequently asserts its relevance to ethical considerations. Yet, the substantiation of these claims with rigorous ethical analysis and reflection remains largely unexamined. This contribution endeavors to scrutinize the relationship between XAI and ethical considerations. By systematically reviewing research papers mentioning ethical terms in XAI frameworks and tools, we investigate the extent and depth of ethical discussions in scholarly research. We observe a limited and often superficial (...) engagement with ethical theories, with a tendency to acknowledge the importance of ethics, yet treating it as a monolithic and not contextualized concept. Our findings suggest a pressing need for a more nuanced and comprehensive integration of ethics in XAI research and practice. To support this, we propose to critically reconsider transparency and explainability in regards to ethical considerations during XAI systems design while accounting for ethical complexity in practice. As future research directions, we point to the promotion of interdisciplinary collaborations and education, also for underrepresented ethical perspectives. Such ethical grounding can guide the design of ethically robust XAI systems, aligning technical advancements with ethical considerations. (shrink)

Metaphysics is, historically as well as systematically, mostly taken to be the inquiry into reality, insofar it is considered to be: (1) the totality of everything there is; (2) of everything that exists; or (3) what is fundamental. This paper sets out to analyze the relation between all three metaphysical core notions and sketch the landscape of metaphysical theories that emerges from it. Taking The Fundamental, The Existent, and Totality to be the domains corresponding to each metaphysical object of (...) inquiry, it is argued that they stand in the settheoretical relations of: The Fundamental ⊆ The Existent ⊆ Totality. This general structure allows for a plurality of more detailed structures when we differentiate between the ones that treat at least two notions as extensionally equal and those that take them to be proper subsets. Furthermore, reductive and inflationary strategies between equating two of the notions will be differentiated, allowing for a detailed sketch of the landscape of metaphysical theories and their views on the nature of reality. In closing, it is argued that the metaphysical structure allowing for most differentiation in metaphysical status is to be preferred as it allows to adequately capture metaphysical disputes, constituting evidence for the importance of each metaphysical notion and a short plea against their conflation. (shrink)

This article examines and analyses Biko’s contribution to the liberation struggle in South Africa from the perspective of politics and religion. Through his leading participation in Black Consciousness Movement and Black Theology Project, Biko has not only influenced the direction of the liberation agenda, but he has also left a legacy that if the liberated and democratic South Africa were to follow, this country would be a much better place for all to live in. In fact, the continent as a (...) whole through its endeavours in the African Union underpinned by the African Renaissance philosophy would go a long way in forging unity among the continent’s nation states. Biko’s legacy covers among other things identity, human dignity, education, research, health and job creation. This article will have far reaching implications for the relations between the democratic state and the church in South Africa, more so that there has been such a lack of the church’s prophecy for the past 25 years. (shrink)

Come along with David Hinton on a series of walks through the wild beauty of Hunger Mountain, near his home in Vermont—excursions informed by the worldview he's imbibed from his many years translating the classics of Chinese poetry and ...

The article examines the role played by policy advice institutions in the governance of ethically controversial new and emerging science and technology in Europe. The empirical analysis, which aims to help close a gap in the literature, focuses on the evolution, role and functioning of national ethics advisory bodies (EABs) in Europe. EABs are expert bodies whose remit is to issue recommendations regarding ethical aspects of new and emerging science and technology. Negative experiences with the impacts of science and technology (...) in the past have resulted in calls for increased transparency and broader participation and pluralism in expert advice and policy decision-making. Do national EABs function as inclusive, anticipatory “hybrid forums”? Or do they resemble more “classical” expert-oriented bodies, inspired by technocratic or decisionist approaches? As part of the empirical analysis of the role and functioning of institutional ethical advisory structures in 32 European countries, an extensive analysis of EAB websites and the content of publicly available documents on such institutions has been carried out, supplemented by an online survey of representatives of the EABs. One major finding of the empirical analysis is the very uneven distribution of “hybrid forum” features of EABs across Europe. (shrink)