Telomeres, the ends of chromosomes, shorten with each cell division. To expand their replicative potential, various cell types use the ribonucleoprotein telomerase, which lengthens telomeres by its reverse transcriptase activity. Because of its ability to immortalize cancer cells, telomerase also plays a significant role in tumor growth. However, in recent years, a wide variety of non‐canonical effects of telomerase that are independent of telomere lengthening have been discovered, and even the notion that telomerase is restricted to very few cell types (...) has been questioned. These effects also seem to be important in carcinogenesis and might explain the tumor‐promoting effects of telomerase independently of telomere elongation. Here, the current understanding of the extratelomeric roles of telomerase and their physiological and pathological significance is reviewed. BioEssays 30:728–732, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Christians, and those of the Roman Catholic Church, have made significant adjustments to their participation in Sunday liturgy in the wake of the coronavirus disease 2019 (COVID-19) pandemic. This is especially the case for Catholic Christians at the ‘Our Lady of Loreto’ (OLL) Church in Kempton Park in South Africa. Sunday Church services that used to be compulsory for most Catholic families and community members, are now attended by few and in some cases none from staunch Catholic families and communities. (...) However, this is not a new phenomenon in the Catholic Church. It signals the extent to which the COVID-19 pandemic has altered and continues to affect Christian families and their commitment to the Sunday liturgy. Drawing from qualitative interviews conducted with eight staunch Catholic community leaders of OLL Church in Kempton Park, Johannesburg, this paper explores the motivations for their continuous participation and/or non-participation in the Sunday liturgy in the wake of the pandemic. The findings reveal that certain behavioural patterns or activities associated with the COVID-19 pandemic motivate Catholic Christians and families to continue to participate and/or not participate in the Sunday liturgy. Contribution: The article explored and examined the way in which COVID-19 has affected Catholic Christians’ ability to attend Sunday liturgy. It discovered that while some Christians returned to church after the pandemic, others have continued to worship from home because of the influence of changes adopted during the pandemic. (shrink)

This book assesses the impact of the work of Chris Brown in the field of International Political Theory. The volume engages with general issues of IPT as well as basic issues such as the use and role of practical reasoning and presents a nuanced understanding about issues regarding the legitimacy of war and violence. It explores questions that pertain to human rights, morality, and ethics, and generally an outlook for devising a ‘better’ world. The project is ideal for audiences with (...) interest in International Relations, Ethics and Morality Studies and International Political Theory. (shrink)

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to (...) existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

We have benefited from conversations with Archon Fung, Brian Jacob, Todd Pittinsky, Peter Schuck, Ani Satz, Andrew Williams, and students in a joint class on statistics and ethics at the John F. Kennedy School of Government in October 2002. We are also grateful to our audience at the conference “The Priority of Practice,” organized by Jonathan Wolff at University College London in September 2003, and to Arthur Applbaum, Miriam Avins, Frances Kamm, Simon Keller, Frederick Schauer, Alan Wertheimer, and the Editors (...) of Phi- losophy & Public Affairs for insightful comments. We have benefited from prepublication reading of Schauer’s work on profiling, Profiles, Probabilities, and Stereotypes (Cambridge, Mass: Harvard University Press, 2003). We thank Avedis Koutoujian for research assistance. (shrink)

The so-called.Karlsschulrede. (1793) of the German naturalist Carl Friedrich Kielmeyer can be considered as a keystone to the understanding of"Naturphilosophie" both in German idealism (Schelling) and the romantic period.Kielmeyer's work considers life as the result of specific forces in the organic realm and thereby searches to explain the harmony of organic existence anddevelopment. Taking into account Kant.s outlines for a lifescience in the "Kritik der Urteilskraft" (1790), Kielmeyer's notion of teleological processes in nature is sketched. The historical and epistemological relevance (...) of this "vital-materialistic" (Lenoir) theory of life can be characterized by three major transformations in the understanding of nature in the "Karlsschulrede": First, the development of a holistic, organological view on the world, second, the emphasis on phenomena of life as historical processes and third the analogy between organism and mind. These issues found the strong influence of Kielmeyer's text on philosophy and science in the early 19th-century. (shrink)

La thèse du présent article est que l’opposition factice entre James, repré- sentant supposé des « relations externes », d’une part, et Bradley, représen- tant supposé des « relations internes », d’autre part, est due à une mauvaise appréhension des thèses de ce dernier. Ce premier contresens conduit alors à manquer le propos même de James.

We give topological characterizations of filters${\cal F}$onωsuch that the Mathias forcing${M_{\cal F}}$adds no dominating reals or preserves ground model unbounded families. This allows us to answer some questions of Brendle, Guzmán, Hrušák, Martínez, Minami, and Tsaban.

We present and analyze \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${F_\sigma}$$\end{document}-Mathias forcing, which is similar but tamer than Mathias forcing. In particular, we show that this forcing preserves certain weak subsystems of second-order arithmetic such as \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathsf{ACA}_0}$$\end{document} and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\mathsf{WKL}_0 + \mathsf{I}\Sigma^0_2}$$\end{document}, whereas Mathias forcing does not. We also show that the needed reals for \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} (...) \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${F_\sigma}$$\end{document}-Mathias forcing (in the sense of Blass in Ann Pure Appl Logic 109(1–2):77–88, 2001) are just the computable reals, as opposed to the hyperarithmetic reals for Mathias forcing. (shrink)

This landmark work provides a systematic introduction to systems of modal logic and stands as the first presentation of what have become central ideas in philosophy of language and metaphysics, from the "new theory of reference" and non-linguistic necessity and essentialism to "Kripke semantics.".

The grounds of justice -- "Un pouvoir ordinaire": shared membership in a state as a ground of -- Justice -- Internationalism versus statism and globalism: contemporary debates -- What follows from our common humanity? : the institutional stance, human rights, and nonrelationism -- Hugo Grotius revisited : collective ownership of the Earth and global public reason -- "Our sole habitation" : a contemporary approach to collective ownership of the earth -- Toward a contingent derivation of human rights -- Proportionate use (...) : immigration and original ownership of the Earth -- "But the earth abideth for ever" : obligations to future generations -- Climate change and ownership of the atmosphere -- Human rights as membership rights in the global order -- Arguing for human rights : essential pharmaceuticals -- Arguing for human rights : labor rights as human rights -- Justice and trade -- The way we live now -- "Imagine there's no countries" : a reply to John Lennon -- Justice and accountability : the state -- Justice and accountability : the World Trade Organization. (shrink)

This article illustrates instrumental variable (IV) estimation by examining an unexpected finding of the research on career adaptability and job satisfaction. Theoretical and empirical arguments suggest that in the general population, people’s abilities to adapt their careers are beneficial to their job satisfaction. However, a recent meta-analysis unexpectedly found no effect when personality traits are controlled for. We argue that a reverse effect of job satisfaction on career adaptability, originating from affective tendencies tied to personality, might explain this null effect. (...) Our argument implies that the estimates obtained with traditional ordinary least squares (OLS) regressions are biased by endogeneity, a correlation between an explanatory variable and the error term in a regression model. When experimental manipulations are impossible, IV estimations, such as two-stage least squares (2SLS) regressions, are one possible solution to the endogeneity problem. Analyzing three waves of data from a sample of 836 adults, the concurrent and time-lagged effect of job satisfaction on career adaptability was revealed to be more consistent than the reverse. Our results provide an explanation, rooted in affective dispositions, as to why recent meta-analytical estimates unexpectedly found that career adaptability does not predict job satisfaction at the interindividual level. We also discuss IV estimation in terms of its limits, weight the interpretation of its estimates against the temporality criterion for causal inference, and consider its possible extension to analyses of change. (shrink)

Priority setting in health care is ubiquitous and health authorities are increasingly recognising the need for priority setting guidelines to ensure efficient, fair, and equitable resource allocation. While cost-effectiveness concerns seem to dominate many policies, the tension between utilitarian and deontological concerns is salient to many, and various severity criteria appear to fill this gap. Severity, then, must be subjected to rigorous ethical and philosophical analysis. Here we first give a brief history of the path to today’s severity criteria in (...) Norway and Sweden. The Scandinavian perspective on severity might be conducive to the international discussion, given its long-standing use as a priority setting criterion, despite having reached rather different conclusions so far. We then argue that severity can be viewed as a multidimensional concept, drawing on accounts of need, urgency, fairness, duty to save lives, and human dignity. Such concerns will often be relative to local mores, and the weighting placed on the various dimensions cannot be expected to be fixed. Thirdly, we present what we think are the most pertinent questions to answer about severity in order to facilitate decision making in the coming years of increased scarcity, and to further the understanding of underlying assumptions and values that go into these decisions. We conclude that severity is poorly understood, and that the topic needs substantial further inquiry; thus we hope this article may set a challenging and important research agenda. (shrink)

The associative theory of creativity states that creativity is associated with differences in the structure of semantic memory, whereas the executive theory of creativity emphasises the role of top-down control for creative thought. For a powerful test of these accounts, individual semantic memory structure was modelled with a novel method based on semantic relatedness judgements and different criteria for network filtering were compared. The executive account was supported by a correlation between creative ability and broad retrieval ability. The associative account (...) was independently supported, when network filtering was based on a relatedness threshold, but not when it was based on a fixed edge number or on the analysis of weighted networks. In the former case, creative ability was associated with shorter average path lengths and higher clustering of the network, suggesting that the semantic networks of creative people show higher small-worldness. (shrink)

This article highlights the continuing relevance of a classic bioethical text, “Bioethics as a Discipline,” published by the Hastings Center’s cofounder Daniel Callahan in 1973. Connecting the text’s programmatic recommendations with later reflections and interventions Callahan wrote about the development of bioethics illuminates how the vision Callahan established and the reality this vision helped create were interrelated—just not in the way Callahan had hoped for. Although this portrait relies on an individual perception of the development of bioethics, it might nevertheless, (...) through its unique linkage of different bioethical temporalities, contribute to a broader reassessment of what bioethics became and why. (shrink)

In a recent extended essay, philosopher Daniel Hausman goes a long way towards dismissing severity as a morally relevant attribute in the context of priority setting in healthcare. In this response, we argue that although Hausman certainly points to real problems with how severity is often interpreted and operationalised within the priority setting context, the conclusion that severity does not contain plausible ethical content is too hasty. Rather than abandonment, our proposal is to take severity seriously by carefully mapping the (...) possibly multiple underlying accounts to well-established ethical theories, in a way that is both morally defensible and aligned with the term’s colloquial uses. (shrink)

Poly(ADP‐ribosyl)ation is a post‐translational modification occurring in the nucleus. The most abundant and best‐characterized enzyme catalyzing this reaction, poly(ADP‐ribose) polymerase 1 (PARP1), participates in fundamental nuclear events. The enzyme functions as molecular “nick sensor”. It binds with high affinity to DNA single‐strand breaks resulting in the initiation of its catalytic activity. Activated PARP1 promotes base excision repair. In addition, PARP1 modifies several transcription factors and thereby precludes their binding to DNA. We propose that a major function of PARP1 includes the (...) silencing of transcription preventing expression of damaged genes. Concomitant stimulation of DNA repair suggests that PARP1 acts as a switch between transcription and DNA repair. Another PARP‐type enzyme, tankyrase, is involved in the regulation of telomere elongation. Tankyrase modifies a telomere‐associated protein and thereby prevents it masking telomeric repeats providing access of telomerase for telomere elongation. Therefore, poly(ADP‐ribosyl)ation reactions may act as molecular switches in DNA metabolism. BioEssays 23:543–548, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

This essay reconstructs the place of utopia in realist political theory, by examining the ways in which the literary genre of critical utopias can productively unsettle ongoing discussions about “how to do political theory.” I start by analyzing two prominent accounts of the relationship between realism and utopia: “real utopia” and “dystopic liberalism”. Elaborating on Raymond Geuss’s recent reflections, the essay then claims that an engagement with literature can shift the focus of these accounts. Utopian fiction, I maintain, is useful (...) for comprehending what is and for contemplating what might be. Ursula K. Le Guin’s novel The Dispossessed deploys this double function in an exemplary fashion: through her dynamic and open-ended portrayal of an Anarchist community, Le Guin succeeds in imagining a utopia that negates the status quo, without striving to construct a perfect society. The book’s radical, yet ambiguous, narrative hence reveals a strategy for locating utopia within realist political theory that moves beyond the positions dominating the current debate. Reading The Dispossessed ultimately demonstrates that realism without utopia is status quo–affirming, while utopia without realism is wishful thinking. (shrink)

Speech planning is a sophisticated process. In dialog, it regularly starts in overlap with an incoming turn by a conversation partner. We show that planning spoken responses in overlap with incoming turns is associated with higher processing load than planning in silence. In a dialogic experiment, participants took turns with a confederate describing lists of objects. The confederate’s utterances (to which participants responded) were pre‐recorded and varied in whether they ended in a verb or an object noun and whether this (...) ending was predictable or not. We found that response planning in overlap with sentence‐final verbs evokes larger task‐evoked pupillary responses, while end predictability had no effect. This finding indicates that planning in overlap leads to higher processing load for next speakers in dialog and that next speakers do not proactively modulate the time course of their response planning based on their predictions of turn endings. The turn‐taking system exerts pressure on the language processing system by pushing speakers to plan in overlap despite the ensuing increase in processing load. (shrink)

After critical appraisal of mathematical and biological characteristics of the model, we discuss how a classical hippocampal neural network expresses functions similar to those of the chaotic model, and then present an alternative stimulus-driven chaotic random recurrent neural network (RRNN) that learns patterns as well as sequences, and controls the navigation of a mobile robot.

In this paper we present applications of the ACGT Master Ontology (MO) which is a new terminology resource for a transnational network providing data exchange in oncology, emphasizing the integration of both clinical and molecular data. The development of a new ontology was necessary due to problems with existing biomedical ontologies in oncology. The ACGT MO is a test case for the application of best practices in ontology development. This paper provides an overview of the application of the ontology within (...) the ACGT project thus far. (shrink)

Much has been written on the role of causal notions and causal reasoning in the so-called 'special sciences' and in common sense. But does causal reasoning also play a role in physics? Mathias Frisch argues that, contrary to what influential philosophical arguments purport to show, the answer is yes. Time-asymmetric causal structures are as integral a part of the representational toolkit of physics as a theory's dynamical equations. Frisch develops his argument partly through a critique of anti-causal arguments and (...) partly through a detailed examination of actual examples of causal notions in physics, including causal principles invoked in linear response theory and in representations of radiation phenomena. Offering a new perspective on the nature of scientific theories and causal reasoning, this book will be of interest to professional philosophers, graduate students, and anyone interested in the role of causal thinking in science. (shrink)

Mathias Frisch provides the first sustained philosophical discussion of conceptual problems in classical particle-field theories. Part of the book focuses on the problem of a satisfactory equation of motion for charged particles interacting with electromagnetic fields. As Frisch shows, the standard equation of motion results in a mathematically inconsistent theory, yet there is no fully consistent and conceptually unproblematic alternative theory. Frisch describes in detail how the search for a fundamental equation of motion is partly driven by pragmatic considerations (...) (like simplicity and mathematical tractability) that can override the aim for full consistency. The book also offers a comprehensive review and criticism of both the physical and philosophical literature on the temporal asymmetry exhibited by electromagnetic radiation fields, including Einstein's discussion of the asymmetry and Wheeler and Feynman's influential absorber theory of radiation. Frisch argues that attempts to derive the asymmetry from thermodynamic or cosmological considerations fail and proposes that we should understand the asymmetry as due to a fundamental causal constraint. The book's overarching philosophical thesis is that standard philosophical accounts that strictly identify scientific theories with a mathematical formalism and a mapping function specifying the theory's ontology are inadequate, since they permit neither inconsistent yet genuinely successful theories nor thick causal notions to be part of fundamental physics. (shrink)

Volume 52, Issue 6, June - July 2020, Page 602-612.

In diesem Buch werden die zwei Grundsäulen der "Kritischen Patriarchatstheorie" - die Matriarchale Naturphilosophie und die Patriarchatskritische Geschichtsphilosophie - vorgestellt und im Rahmen einer kritischen Auseinandersetzung mit der Naturphilosophie Giordano Brunos sowie der Geschichtsphilosophie Martin Heideggers erläutert.