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.

This is the first complete, one-volume English translation of the ancient Chinese text Xunzi, one of the most extensive, sophisticated, and elegant works in the tradition of Confucian thought. Through essays, poetry, dialogues, and anecdotes, the Xunzi articulates a Confucian perspective on ethics, politics, warfare, language, psychology, human nature, ritual, and music, among other topics. Aimed at general readers and students of Chinese thought, Eric Hutton’s translation makes the full text of this important work more accessible in English than ever (...) before. Named for its purported author, the Xunzi has long been neglected compared to works such as the Analects of Confucius and the Mencius. Yet interest in the Xunzi has grown in recent decades, and the text presents a much more systematic vision of the Confucian ideal than the fragmented sayings of Confucius and Mencius. In one famous, explicit contrast to them, the Xunzi argues that human nature is bad. However, it also allows that people can become good through rituals and institutions established by earlier sages. Indeed, the main purpose of the Xunzi is to urge people to become as good as possible, both for their own sakes and for the sake of peace and order in the world. In this edition, key terms are consistently translated to aid understanding and line numbers are provided for easy reference. Other features include a concise introduction, a timeline of early Chinese history, a list of important names and terms, cross-references, brief explanatory notes, a bibliography, and an index. (shrink)

Introduction: Platonic dramatology -- The political and philosophical problems. Using pre-Socratic philosophy to support political reform: the Athenian stranger ; Plato's Parmenides: Parmenides' critique of Socrates and Plato's critique of Parmenides ; Becoming Socrates ; Socrates interrogates his contemporaries about the noble and good -- Paradigms of philosophy. Socrates' positive teaching ; Timaeus-Critias: completing or challenging Socratic political philosophy? ; Socratic practice -- The trial and death of Socrates. The limits of human intelligence ; The Eleatic challenge ; The trial (...) and death of Socrates -- Conclusion: Why Plato made Socrates his hero. (shrink)

In recent times there has been a growing focus on the process of building up the local church in the Reformed Churches of South Africa. Congregation building should not only take place through growing numbers, but also through spiritual growth. In this article a few basis-theoretical perspectives will be explored through a study of applicable literature, regarding the definition of 'disciple' and 'discipleship'. It is also the purpose of this article to establish whether or not there is any relation between (...) discipleship and congregation building. It is the premise of this article that discipleship, with the basis-theoretical perspectives in mind, can suffice as a ministry model towards congregation building for the church in the ever so changing times in which she finds herself when the kingdom of God is taken as the goal of discipleship, and love for God and your neighbour is taken as the underlying principle of discipleship. (shrink)

In 'Een handvol filosofen' staan de filosofen centraal die sinds de oprichting van de Vrije Universiteit in 1880 aan deze instelling verbonden zijn geweest. Het gaat hierbij niet alleen om de inhoud van hun werk, maar ook om de personen zelf. Er waren filosofiedocenten die zich met de universiteit identificeerden en zich volledig konden ontplooien. Er waren er echter ook voor wie dit niet gold, die geïsoleerd of in gewetensnood raakten. Veel filosofiestudenten waren actief betrokken bij wat er in hun (...) faculteit gebeurde. Zij namen initiatieven, protesteerden soms tegen de gang van zaken en kozen partij in conflictsituaties. Sinds het eind van de jaren zestig van de twintigste eeuw verloor de Vrije Universiteit geleidelijk haar christelijk karakter. Tegenwoordig werken alle stafleden vanuit hun eigen motivatie mee aan een hoofdzakelijk seculier geworden universiteit, die ruimte biedt voor religieuze en levensbeschouwelijke diversiteit. (shrink)

What role does the wild duck play in Ibsen's famous drama? I argue that, besides mirroring the fate of the human cast members, the duck is acting as animal subject in a quasi-experiment, conducted in a private setting. Analysed from this perspective, the play allows us to discern the epistemological and ethical dimensions of the new scientific animal practice (systematic observation of animal behaviour under artificial conditions) emerging precesely at that time. Ibsen's play stages the clash between a scientific and (...) a romantic understanding of animals that still constitutes the backdrop of most contemporary debates over animals in research. Whereas the scientific understanding reduces the animal's behaviour, as well as its environment, to discrete and modifiable elements, the romantic view regards animals as being at one with (or violently disconnected from) their natural surroundings. (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, ...

Standpoint epistemologies are based on two central theses: the situated knowledge thesis and the thesis of epistemic privilege. The bias paradox suggests that there is a tension between these two notions, in the sense that they are self-contradictory. In this paper, I aim to defend standpoint epistemologies from this challenge. This defense is based on a distinction between subjective and objective justifications. According to the former, a subject S is subjectively justified in believing a proposition P iff S's belief in (...) P coheres with S's pre-existing beliefs. According to the latter, a subject S is objectively justified in believing a proposition P iff S's subjective justification is truth-conducive. I argue that, if the situated knowledge thesis is spelled out in terms of subjective justification, and if the thesis of epistemic privilege is spelled out in terms of objective justification, then there is no contradiction. If this line of thought is correct, then the bias paradox does not show that standpoint epistemologies are self-contradictory. (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)

Some argue that robots could never be sentient, and thus could never have intrinsic moral status. Others disagree, believing that robots indeed will be sentient and thus will have moral status. But a third group thinks that, even if robots could never have moral status, we still have a strong moral reason to treat some robots as if they do. Drawing on a Kantian argument for indirect animal rights, a number of technology ethicists contend that our treatment of anthropomorphic or (...) even animal-like robots could condition our treatment of humans: treat these robots well, as we would treat humans, or else risk eroding good moral behavior toward humans. But then, this argument also seems to justify giving rights to robots, even if robots lack intrinsic moral status. In recent years, however, this indirect argument in support of robot rights has drawn a number of objections. In this paper I have three goals. First, I will formulate and explicate the Kant-inspired indirect argument meant to support robot rights, making clearer than before its empirical commitments and philosophical presuppositions. Second, I will defend the argument against a number of objections. The result is the fullest explication and defense to date of this well-known and influential but often criticized argument. Third, however, I myself will raise a new concern about the argument’s use as a justification for robot rights. This concern is answerable to some extent, but it cannot be dismissed fully. It shows that, surprisingly, the argument’s advocates have reason to resist, at least somewhat, producing the sorts of robots that, on their view, ought to receive rights. (shrink)