Cancer stem cells (CSC) represent malignant cell subsets in hierarchically organized tumors, which are selectively capable of tumor initiation and self‐renewal and give rise to bulk populations of non‐tumorigenic cancer cell progeny through differentiation. Robust evidence for the existence of prospectively identifiable CSC among cancer bulk populations has been generated using marker‐specific genetic lineage tracking of molecularly defined cancer subpopulations in competitive tumor development models. Moreover, novel mechanisms and relationships have been discovered that link CSC to cancer therapeutic resistance and (...) clinical tumor progression. Importantly, proof‐of‐principle for the potential therapeutic utility of the CSC concept has recently been provided by demonstrating that selective killing of CSC through a prospective molecular marker can inhibit tumor growth. Herein, we review these novel and translationally relevant research developments and discuss potential strategies for CSC‐targeted therapy in the context of resistance mechanisms and molecular pathways preferentially operative in CSC. (shrink)

Dieser Beitrag nimmt als Ausganspunkt die gegenwärtige kontroverse Debatte um den adäquaten Erklärungsansatz in der Kognitionswissenschaft, und zwar zwischen Enaktivisten einerseits und Repräsentationalisten andererseits. Beispielhaft wurde aufgezeigt, dass in Bezug auf die soziale Kognition der enaktivistische Ansatz eine Voraussetzung machen muss, die er mit seinen eigenen Mitteln nicht einzufangen in der Lage ist. Denn der Versuch, das Verstehen des Anderen durch gemeinsame Sinnstiftung der Akteure innerhalb ihrer sozialen Interaktion zu erklären, gerät in einen Zirkel, da nicht erklärt wird, wie die (...) Kopplung und damit der Prozess der sozialen Interaktion allererst zustande kommen kann. Als Lösung dieses Problems wird eine repräsentationalistische Analyse der vorausgesetzten Fähigkeit, andere als potentielle Kooperationspartner anzusehen, entwickelt, und zwar mit den Mitteln von Millikans Teleosemantik. Diese Theorie aus dem Kontext der Debatte um die Naturalisierung mentaler Repräsentationen liefert mit den PP Repräsentationen den adäquaten Begriff, um sowohl verkörperte, handlungsorientierte Repräsentationen zur Analyse von Affordanzen, als auch verkörperte interaktionsorientierte Repräsentationen zur Analyse sozialer Affordanzen zu entwickeln. Dies erlaubt die Annahme einer zentralen Funktion für die soziale Wahrnehmung, die den blinden Fleck des enaktivistischen Ansatzes ausfüllen kann. Zugleich demonstriert diese Analyse der sozialen Wahrnehmung die explanatorische Überlegenheit (minimal) repräsentationalistischer Erklärungen gegenüber rein enaktivistischen Alternativen. (shrink)

Bullying often results in negative coping in victims, including an increased consumption of alcohol. Recently, however, an increase in alcohol use has also been reported among perpetrators of bullying. The factors triggering this pattern are still unclear. We investigated the role of empathy in the interaction between bullying and alcohol use in an adolescent sample (IMAGEN) at age 13.97 (±0.53) years (baseline (BL), N = 2165, 50.9% female) and age 16.51 (±0.61) years (follow-up 1 (FU1), N = 1185, 54.9% female). (...) General empathic distress served as a significant moderator of alcohol use in perpetrators (F9, 493 = 17.978, p < 0.01), which was specific for males and FU1. Male perpetrators, who are generally less sensitive to distress, might thus be more vulnerable to alcohol abuse. (shrink)

Physical environmental factors – or ‘artifacts’ – are linked to healthcare outcomes in the field of social psychology. However, the role of artifacts remains rarely examined in the burgeoning discipline of placebo studies. In this paper, we argue that a careful consideration of artifacts – such as provider clothing and office décor – may carry significant potential in eliciting placebo effects in clinical settings. We discuss three potential mechanisms by which artifacts may enhance or diminish placebo (or nocebo) effects: classical (...) conditioning, response expectancy, and mindsets. We propose testable hypotheses and conclude by providing innovative research designs that might help to better advance this novel research agendum. (shrink)

Cigarette smoking and other addictive behaviors are among the main preventable risk factors for several severe and potentially fatal diseases. It has been argued that addictive behavior is controlled by an automatic-implicit cognitive system and by a reflective-explicit cognitive system, that operate in parallel to jointly drive human behavior. The present study addresses the formation of implicit attitudes towards smoking in both smokers and non-smokers, using a Go/NoGo association task, and behavioral and electroencephalographic measures. The GNAT assesses, via quantifying participants’ (...) reaction times, the strength of association between a target category and either pole of an evaluative dimension. EEG analysis is performed to determine the temporal course of the event-related potential components underlying Go/NoGo decisions and implicit attitude formation. Both smokers and non-smokers showed prolonged reaction times to smoking-related pictures when the pictures were coupled with positive evaluative words. This indicates negative implicit attitudes towards smoking in both groups alike at the time point of the behavioral response. However, only the non-smokers, not the smokers, were found to show a delay of the N200 component in the incongruent condition. This is interpreted as reflecting ambivalent or even positive implicit attitudes towards smoking in the smoker group at the time point of the N200. Our study thus provides evidence for the hypothesis that implicit attitudes are subject to changes within several hundred milliseconds after stimulus presentation, and can be altered in the course of their formation. (shrink)

The Twin Earth thought experiment invites us to consider a liquid that has all of the superficial properties associated with water (clear, potable, etc.) but has entirely different deeper causal properties (composed of “XYZ” rather than of H2O). Although this thought experiment was originally introduced to illuminate questions in the theory of reference, it has also played a crucial role in empirically informed debates within the philosophy of psychology about people’s ordinary natural kind concepts. Those debates have sought to accommodate (...) an apparent fact about ordinary people’s judgments: Intuitively, the Twin Earth liquid is not water. We present results from four experiments showing that people do not, in fact, have this intuition. Instead, people tend to have the intuition that there is a sense in which the liquid is not water but also a sense in which it is water. We explore the implications of this finding for debates about theories of natural kind concepts, arguing that it supports views positing two distinct criteria for membership in natural kind categories – one based on deeper causal properties, the other based on superficial, observable properties. (shrink)

The Twin Earth thought experiment invites us to consider a liquid that has all of the superficial properties associated with water (clear, potable, etc.) but has entirely different deeper causal properties (composed of “XYZ” rather than of H2O). Debates about natural kind concepts have sought to accommodate an apparent fact about ordinary people's judgments: Intuitively, the Twin Earth liquid is not water. We present results showing that people do not have this intuition. Instead, people tend to judge that there is (...) a sense in which the liquid is not water but also a sense in which it is water. (shrink)

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the amygdala (...) and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p <.025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology. (shrink)

J. N. Adams, Michael Lapidge, and Tobias Reinhardt: IntroductionJ. H. W. Penney: Connections in Archaic Latin ProseJ. Briscoe: Language and Style of the Fragmentary Republican HistoriansJ. N. Adams: The Bellum AfricumChristina Shuttleworth Kraus: Hair, Hegemony, and Historiography: Caesar's Style and its Earliest CriticsJ. G. F. Powell: Cicero's Adaptation of Legal Latin in the De legibusTobias Reinhardt: Language of Epicureanism in Cicero: The Case of AtomismG. O. Hutchinson: Pope's Spider and Cicero's WritingR. G. Mayer: The Impracticability of 'Kunstprosa'H. M. Hine: (...) Poetic Influence on Prose: The Case of the Younger SenecaHarm Pinkster: The Language of Pliny the ElderD. R. Russell: Omisso speciosiore stili genereS. J. Harrison: The Poetics of Fiction: Poetic Influence on the Languages of Apuleius' MetamorphosesD. R. Langslow: 'Langues réduites au lexique'? The Languages of Latin Technical ProseDanuta Shanzer: of Tours and Poetry: Prose into Verse and Verse into ProseMichael Lapidge: Poeticism in Pre-Conquest Anglo-Latin ProseRichard Sharpe: The Varieties of Bede's ProseCarlotta Dionisotti: Translator's LatinWalter Berschin: Realistic Writing in the Tenth Century: : Gerhard of Ausburg's Vita S. UodalriciR. M. Thomson: William of Malmesbury and the Latin Classics RevisitedGiovanni Orlandi: Metrical and Rhythmical Clausulae in Medieval Latin Prose: Some Aspects and Problems. (shrink)

Within translation studies, functionalist translations and even more specifically, translations guided by Skopos theory are very much purposeful activities. Skopos theory applied to Bible translation, however, is sometimes met with resistance by practitioners who believe that Skopos theory betrays too much of the source text. This article began by outlining Skopos theory and the additional notion of loyalty as introduced by Christiane Nord. Even with loyalty applied to the theory, many Bible translation practitioners continue to fear it. After the initial (...) presentation of Skopos theory plus loyalty, the Hebrew lexeme חֶסֶד ( ḥesed ) was introduced in this article and discussed in relation to its biblical use. The discussion of ḥesed was then widened to functionalist Bible translation to redeem the loyalty notion as applied to Bible translation. This article claimed that ḥesed as loyalty further helps to protect both the source text and target audiences from radical or unacceptable translations. Contribution: Bible translation is a purposeful activity. This article attempted to allay the fears that some Bible translation practitioners have about the possibility of radical translations undertaken using Skopos theory. Loyalty as understood through the lens of the Hebrew חֶסֶד ( ḥesed ) was utilised afresh to allay these fears. (shrink)

Upshot: Is education about memorising or about making meaning? Critics of constructivist instruction argue that it is more efficient to teach directly. However, there is an empowering engagement to making meaning and teachers need to know how to guide students in this process.

The potential for biases being built into algorithms has been known for some time, yet literature has only recently demonstrated the ways algorithmic profiling can result in social sorting and harm marginalised groups. We contend that with increased algorithmic complexity, biases will become more sophisticated and difficult to identify, control for, or contest. Our argument has four steps: first, we show how harnessing algorithms means that data gathered at a particular place and time relating to specific persons, can be used (...) to build group models applied in different contexts to different persons. Thus, privacy and data protection rights, with their focus on individuals, do not protect from the discriminatory potential of algorithmic profiling. Second, we explore the idea that anti-discrimination regulation may be more promising, but acknowledge limitations. Third, we argue that in order to harness anti-discrimination regulation, it needs to confront emergent forms of discrimination or risk creating new invisibilities, including invisibility from existing safeguards. Finally, we outline suggestions to address emergent forms of discrimination and exclusionary invisibilities via intersectional and post-colonial analysis. (shrink)

The article introduces and defends the Nomological Account of ground, a reductive account of the notion of metaphysical explanation in terms of the laws of metaphysics. The paper presents three desiderata that a theory of ground should meet: it should explain the modal force of ground, the generality of ground, and the interplay between ground and certain mereological notions. The bulk of the paper develops the Nomological Account and argues that it meets the three desiderata. The Nomological Account relies on (...) two central notions: the notion of a ‘law of metaphysics’ and the notion of ‘determination via the laws’. The paper offers the constructional conception of the laws of metaphysics, on which the metaphysical laws are general principles that characterize construction–operations such as composition, constitution, or set-formation. The role of determination in the account is explained and some reductive approaches to the notion are sketched. The case for the Nomological Account presented in this article is also a case for the laws of metaphysics. Since the Nomological Account offers a promising approach to metaphysical explanation we should take the laws of metaphysics seriously. (shrink)

Obtaining informed consent from patients is a moral and legal duty and, thus, a key legitimation for medical treatment. The pivotal prerequisite for valid informed consent is decision-making capacity of the patient. Related to the question of whether and when consent should be morally and legally valid, there has been a long-lasting philosophical debate about freedom of will and the connection of freedom and responsibility. The scholarly discussion on decision-making capacity and its clinical evaluation does not sufficiently take into account (...) this fundamental debate. It is contended that the notion of free will must be reflected when evaluating decision-making capacity. Namely, it should be included as a part of the appreciation-criterion for decision-making capacity. The argumentation is mainly drawn on the compatibilism of Harry Frankfurt. A solution is proposed which at the same time takes the notion of free will seriously and enriches the traditional understanding of decision-making capacity, strengthening its justificatory force while remaining clinically applicable. (shrink)

The paper explores a deductive-nomological account of metaphysical explanation: some truths metaphysically explain, or ground, another truth just in case the laws of metaphysics determine the latter truth on the basis of the former. I develop and motivate a specific conception of metaphysical laws, on which they are general rules that regulate the existence and features of derivative entities. I propose an analysis of the notion of ‘determination via the laws’, based on a restricted form of logical entailment. I argue (...) that the DN-account of ground can be defended against the well-known objections to the DN-approach to scientific explanation. The goal of the paper is to show that the DN-account of metaphysical explanation is a well-motivated and defensible theory. (shrink)

A new edition of the classic introduction to mathematics, first published in 1930 and revised in the 1950s, explains the history and tenets of mathematics, ...

Are acts of violence performed in virtual environments ever morally wrong, even when no other persons are affected? While some such acts surely reflect deficient moral character, I focus on the moral rightness or wrongness of acts. Typically it’s thought that, on Kant’s moral theory, an act of virtual violence is morally wrong (i.e., violate the Categorical Imperative) only if the act mistreats another person. But I argue that, on Kant’s moral theory, some acts of virtual violence can be morally (...) wrong, even when no other persons or their avatars are affected. First, I explain why many have thought that, in general on Kant’s moral theory, virtual acts affecting no other persons or their avatars can’t violate the Categorical Imperative. For there are real world acts that clearly do, but it seems that when we consider the same sorts of acts done alone in a virtual environment, they don’t violate the Categorical Imperative, because no others persons were involved. But then, how could any virtual acts like these, that affect no other persons or their avatars, violate the Categorical Imperative? I then argue that there indeed can be such cases of morally wrong virtual acts—some due to an actor’s having erroneous beliefs about morally relevant facts, and others due not to error, but to the actor’s intention leaving out morally relevant facts while immersed in a virtual environment. I conclude by considering some implications of my arguments for both our present technological context as well as the future. (shrink)

In the Transcendental Aesthetic of the Critique of Pure Reason, Immanuel Kant famously claims that we have an a priori intuition of space as an ‘infinite given magnitude’. Later on, in the Transcendental Analytic, he seems to add that the intuition of space presupposes a synthetic activity of the transcendental imagination. Several authors have recently pointed out that these two claims taken together give rise to two problems. First, it is unclear how the transcendental imagination of a finite mind could (...) ever result in the intuition of an entity that is infinitely large. Second, Kant claims that our intuition of space has a ‘whole-prior-to-its-parts’ structure, such that its parts are given only as limitations of the whole, while synthesis is compositional and has a ‘parts-prior-to-their-whole’ structure, because it consists in first running through and then taking together the parts of a sensible manifold. I will solve these two problems by showing that Kant thought that synthesis does not always have a compositional structure but that there is also a form of ‘decomposing’ synthesis, which has a whole-prior-to-its-parts structure. Building on similarities between Kant, Edmund Husserl and G. W. F. Hegel, I will argue that infinite space is given to us in intuition by precisely such an activity of decomposition, one that allows us to differentiate between finite spatial objects and the unlimited phenomenal horizon in which they appear. (shrink)

Realists about laws of nature and their Humean opponents disagree on whether laws ‘govern’. An independent commitment to the ‘governing conception’ of laws pushes many towards the realist camp. Despite its significance, however, no satisfactory account of governance has been offered. The goal of this article is to develop such an account. I base my account on two claims. First, we should distinguish two notions of governance, ‘guidance’ and ‘production’, and secondly, explanatory phenomena other than laws are also candidates for (...) governance. My goal is to develop a unified account which captures both guidance and production as well as the governance of phenomena, such as essence and logical consequence. The account of governance I develop belongs to the family of modal accounts, which was popularized by David Armstrong, but it also employs essentialist resources. If successful, this modal-essentialist account not only reveals the costs that proponents of governance incur, but it also puts that important notion on a solid theoretical foundation. (shrink)

The enforcement of racial segregation during apartheid was aimed not only at regulating public spaces, residential areas and the workforce, but also at shaping the subjectivities of individuals who were socialised to see themselves through the lens of a white racial hierarchy. The ideology of white supremacy and superiority that informed apartheid policy was largely justified using Christonormative epistemologies that sought to legitimate the racial hierarchy as having basis in Holy Scripture and as an extension of God’s will. At the (...) same time, apartheid policy fragmented religious communities, entrenching race as a central component of spiritual subjectivities. Twenty years after the end of apartheid, the legacy of apartheid continues to shape the lives and opportunities of all people living in South Africa, despite many gains made in working towards a non-racial, non-sexist democracy. While much scholarly attention has been paid to postapartheid contexts of work, residency and recreation, relatively little attention has been paid to spaces of worship. This is surprising, given that religious belief and practice are widespread in South Africa in the first instance, and that Christian belief, in particular, was so central to the social imaginary of apartheid, in the second. Thus, in efforts to transform society and advance social justice, it is imperative to consider diversity, difference and otherness from the perspective of, and in relation to, contemporary religious communities and contexts. This article will consider some of the factors shaping dynamics of diversity and difference within the context of religious communities in South Africa, over 20 years into democracy. (shrink)

It is often claimed that the social sciences cannot be reduced to a lower-level individualistic science. The standard argument for this position is the Fodorian multiple realizability argument. Its defenders endorse token–token identities between “higher-level” social objects and pluralities/sums of “lower-level” individuals, but they maintain that the properties expressed by social science predicates are often multiply realizable, entailing that type–type identities between social and individualistic properties are ruled out. In this paper I argue that the multiple realizability argument for explanatory (...) holism is unsound. The social sciences are indeed irreducible, but the principled reason for this is that the required token–token identifications cannot in general be carried through. In consequence, paradigmatic social science predicates cannot be taken to apply to the objects quantified over in the lower-level sciences. The result is that typical social science predicates cannot even be held to be co-extensive with individualistic predicates, which means type–type identifications are ruled out too. Multiple realizability has nothing to do with this failure of co-extensiveness, because the relevant social science predicates are not multiply realized in the sense intended by the explanatory holists, a sense which presupposes reductive token–token identifications. (shrink)

In this review essay, I examine the central tenets of sociologist Dave Elder-Vass’s recent contribution to social ontology, as put forth in his book The Causal Power of Social Structures: Emergence, Structure and Agency. Elder-Vass takes issue with ontological individualists and maintains that social structures exist and have causal powers in their own right. I argue that he fails to establish his main theses: he shows neither that social structures have causal powers “in their own right” (in any sense of (...) this expression) nor that they exist. (shrink)

One version of moral error theory maintains that the central problem with morality is an ontological commitment to irreducible normativity. This paper argues that this version of error theory ultimately depends on an appeal to Ockham’s Razor, and that Ockham’s Razor should not be applied to irreducible normativity. This is because the appeal to Ockham’s Razor always contains an intractable element of epistemic circularity; and if this circularity is not vicious, we can construct a sound argument for the existence of (...) irreducibly normative truths that contains a similar kind of epistemic circularity. This argument is a version of Pascal’s Wager which I call “Parfit’s Wager,” because it is based on a passage from Derek Parfit’s On What Matters. It states that, if we believe that there are some irreducibly normative truths, we are more likely to be believing what we ought to believe compared to not believing that there are such truths, and that this indicates that we ought rationally to believe that there are such truths, justifying the ontological commitment to irreducible normativity in the process. (shrink)

Appraisal theories have described elaborate mechanisms underlying the elicitation of emotion at the psychological-cognitive level, but typically do not integrate neuroscientific concepts and findings. At the same time, theoretical developments in appraisal theory have been pretty much ignored by researchers studying the neuroscience of emotion. We feel that a stronger integration of these two literatures would be highly profitable for both sides. Here we outline a blueprint of the “appraising brain.” To this end, we review neuroimaging research investigating the processing (...) of major appraisal variables, and sketch a neuro-cognitive process model of appraisal with a special emphasis on the chronometry and the recursive aspect of emotional evaluation. We hope that this contribution will stimulate more hypothesis-driven research on the neuroscience of appraisal. (shrink)

This paper argues that ‘that’-clauses are not singular terms (without denying that their semantical values are propositions). In its first part, three arguments are presented to support the thesis, two of which are defended against recent criticism. The two good arguments are based on the observation that substitution of ‘the proposition that p’ for ‘that p’ may result in ungrammaticality. The second part of the paper is devoted to a refutation of the main argument for the claim that ‘that’-clauses are (...) singular terms, namely that this claim is needed in order to account for the possibility of quantification into ‘that’-clause position. It is shown that not all quantification in natural languages is quantification into the position of singular terms, but that there is also so-called ‘non-nominal quantification’. A formal analysis of non-nominal quantification is given, and it is argued that quantification into ‘that’-clause position can be treated as another kind non-nominal quantification. (shrink)