Microtubules are protein cylinders with functions in cell motility, signal sensing, cell organization, intracellular transport, and chromosome segregation. One of the key properties of microtubules is their dynamic architecture, allowing them to grow and shrink in length by adding or removing copies of their basic subunit, the heterodimer αβ‐tubulin. In higher eukaryotes, de novo assembly of microtubules from αβ‐tubulin is initiated by a 2 MDa multi‐subunit complex, the gamma‐tubulin ring complex (γ‐TuRC). For many years, the structure of the γ‐TuRC and (...) the function of its subunits remained enigmatic, although structural data from the much simpler yeast counterpart, the γ‐tubulin small complex (γ‐TuSC), were available. Two recent breakthroughs in the field, high‐resolution structural analysis and recombinant reconstitution of the complex, have revolutionized our knowledge about the architecture and function of the γ‐TuRC and will form the basis for addressing outstanding questions about biogenesis and regulation of this essential microtubule organizer. (shrink)

Examining a variety of bio-objects in contexts beyond the laboratory, Bio-Objects: Life in the 21st Century explores new ways of thinking about how novel bio-objects enter contemporary life, analysing the manner in which the boundaries between human and animal, organic and non-organic, and being 'alive' and the suspension of living, are questioned, destabilised and in some cases re-established.

Many philosophical disputes, most prominently disputes in ontology, have been suspected of being merely verbal and hence pointless. My goal in this paper is to offer an account of merely verbal disputes and to address the question of what is problematic with such disputes. I begin by arguing that extant accounts that focus on the semantics of the disputed statement S do not capture the full range of cases as they might arise in philosophy. Moreover, these accounts bring in heavy (...) theoretical machinery. I attempt to show that we can capture the full range of cases with an approach that is theoretically lightweight. This approach explains verbal disputes as a pragmatic phenomenon where parties use the same utterance type S with different speaker’s meaning. Moreover, it provides an answer to the crucial question Jackson’s pragmatic account leaves, at best, highly implicit. Based on my account, we can distinguish between different ways in which disputes can be verbal and different extents to which they are defective. Distinguishing between these varieties of verbalness furthermore allows us to specify what kind of substantive issues remain to be discussed once the linguistic confusion is resolved. (shrink)

When seriously ill patients reach the end of the standard treatment trajectory for their condition, they may qualify for the use of unapproved, investigational drugs regulated via expanded access programs. In medical-ethical discourse, it is often argued that expanded access to investigational drugs raises ‘false hope’ among patients and is therefore undesirable. We set out to investigate what is meant by the false hope argument in this discourse. In this paper, we identify and analyze five versions of the false hope (...) argument which we call: (1) the limited chance at benefit argument, (2) the side effects outweighing benefits argument, (3) the opportunity costs argument, (4) the impossibility of making informed decisions argument, and (5) the difficulty of gaining access argument. We argue that the majority of these five versions do not provide normative ground for disqualifying patients’ hopes as false. Only when hope is rooted in a mistaken belief, for example, about the likelihood of benefits or chances on medical risks, or when hope is directed at something that cannot possibly be obtained, should it be considered false. If patients are adequately informed about their odds of obtaining medical benefit, however small, and about the risks associated with an investigational treatment, it is unjustified to consider patients’ hopes to be false, and hence, to deny them access to investigational drug based on that argument. (shrink)

We describe and analyse how large herbivores strongly diminished a woody vegetation, dominated by the unpalatable shrub Sambucus nigra L. and changed it into grassland. Density of woody species and cover of vegetation were measured in 1996, 2002 and 2012 in the grazed Oostvaardersplassen. In 2002 and 2012 we also measured density and cover in an ungrazed control site. In 2002 we measured intensity of browsing and bark loss of Sambucus shrubs in the grazed and control sites. In the grazed (...) site the density of Sambucus and Salix spp. declined significantly between 1996 and 2012, and large areas changed into grassland. In the control site the density of Sambucus increased significantly during this period, the density of Salix spp. did not change, and the vegetation consisted of a mixture of woody species and a field layer dominated by tall herbs. In 2002 and 2012 the percentages of dead Sambucus shrubs were significantly higher in the grazed site than in the control site. In 2002 the percentages of twigs browsed and ring barked stems of Sambucus shrubs were significantly higher in the grazed site than in the control site. Our results show that debarking caused mature Sambucus shrubs to die, but that heavy browsing may have helped this process. Our results also point to a significant neighbour effect on the break down of Sambucus, suggesting that Aggregational Resistance and Associational Palatability were both active. Essential conditions for the break down of this woody vegetation were the presence of large herbivores, the low ratio between the areas of summer and winter feeding habitats and the competition amongst herbivores. Browsing may have been responsible for seedling death, as seedlings were found only in the control site and not on the old and newly established grasslands in the grazed site. (shrink)

In this paper we describe a framework for the construction of entities that can serve as interpretations of arbitrary contiguous chunks of text. An important part of the paper is devoted to describing stacking cells, or the proposed meanings for bracket-structures.

In this paper a semantics for dynamic predicate logic is developed that uses sequence valued assignments. This semantics is compared with the usual relational semantics for dynamic predicate logic: it is shown that the most important intuitions of the usual semantics are preserved. Then it is shown that the refined semantics reflects out intuitions about information growth. Some other issues in dynamic semantics are formulated and discussed in terms of the new sequence semantics.

High and low alexithymia scorers were confronted with a modified visual oddball task that allowed the study of categorical perception of emotional expressions on faces. Participants had to quickly detect a deviant (rare) morphed face that shared or did not share the same emotional expression as the frequent one. Expected categorical perception effects, which were also neurophysiologically indexed, showed that rare stimuli were detected faster if they depicted a different emotional expression compared to rare stimuli depicting the same emotional expression (...) than the frequent one. Even if no differences were observed at a behavioural level, high alexithymia scorers evidenced overall delayed neurophysiological responses in components related to the attentional processing of rare emotional faces. Moreover, the categorical perception effects for event-related components associated with the attentional processing were smaller in high alexithymia scorers and were even absent for anger. These results show that high alexithymia scorers present discrimination delays that are already observed at the attentional level. (shrink)

Recent models of the conceptual system hold that concepts are grounded in simulations of actual experiences with instances of those concepts in sensory-motor systems (e.g., Barsalou, 1999, 2003; Solomon & Barsalou, 2001). Studies supportive of such a viewhave shown that verifying a property of a concept in one modality, and then switching to verify a property of a different concept in a different modality generates temporal processing costs similar to the cost of switching modalities in perception. In addition to non-emotional (...) concepts, the present experiment investigated switching costs in verifying properties of positive and negative (emotional) concepts. Properties of emotional concepts were taken from vision, audition, and the affective system. Parallel to switching costs in neutral concepts, the study showed that for positive and negative concepts, verifying properties from different modalities produced processing costs such that reaction times were longer and error rates were higher. Importantly, this effect was observed when switching from the affective system to sensory modalities, and vice-versa. These results support the embodied cognition view of emotion in humans. (shrink)

Recent models of the conceptual system hold that concepts are grounded in simulations of actual experiences with instances of those concepts in sensory-motor systems (e.g., Barsalou, 1999, 2003; Solomon & Barsalou, 2001). Studies supportive of such a viewhave shown that verifying a property of a concept in one modality, and then switching to verify a property of a different concept in a different modality generates temporal processing costs similar to the cost of switching modalities in perception. In addition to non-emotional (...) concepts, the present experiment investigated switching costs in verifying properties of positive and negative (emotional) concepts. Properties of emotional concepts were taken from vision, audition, and the affective system. Parallel to switching costs in neutral concepts, the study showed that for positive and negative concepts, verifying properties from different modalities produced processing costs such that reaction times were longer and error rates were higher. Importantly, this effect was observed when switching from the affective system to sensory modalities, and vice-versa. These results support the embodied cognition view of emotion in humans. (shrink)

In Study 1, we examined the moderating impact of alexithymia (i.e., a difficulty identifying and describing feelings to other people and an externally oriented cognitive style) on the automatic processing of affective information. The affective priming paradigm was used, and lower priming effects for high alexithymia scorers were observed when congruent (incongruent) pairs involving nonverbal primes (angry face) and verbal target were presented. The results held after controlling for participants' negative affectivity. The same effects were replicated in Studies 2 and (...) 3, with trait anxiety and depression entered as additional covariates. In Study 3, no moderating impact of alexithymia was found for verbal-facial pairs suggesting that the results cannot be merely explained in terms of transcoding limitations for high alexithymia scorers. Overall, the present results suggest that alexithymia could be related to a difficulty in processing and automatically using high arousal emotional information to respond to concomittant behavioural demands. (shrink)

This essay complements Roberto Esposito’s analysis of the political category of the person by outlining the role of literature, and especially the genre of the novel, in consolidating this category and allowing it to do its political and affective work. The essay shows how Ben Lerner’s 2014 novel 10:04 dismantles three central features of the traditional novel’s poetics of the person: its investment in the notion of literary character, its use of fictionality, and its structural reliance on the narrative future. (...) Lerner’s novel, like Esposito’s biopolitical work, aims to overcome the hierarchical divisions within human life that are endemic to the category of the person and that have historically fostered biopolitical violence. Both projects intimate a less destructive politics—what Lerner calls “the transpersonal” and Esposito “the impersonal.”. (shrink)

The notion of exemplification is essential for Goodman’s theory of symbols. But Goodman’s account of exemplification has been criticized as unclear and inadequate. He points out two conditions for an object x exemplifying a label y: (C1) y denotes x and (C2) x refers to y. While (C1) is uncontroversial, (C2) raises the question of how “refers to” should be interpreted. This problem is intertwined with three further questions that consequently should be discussed together with it. Are the two necessary (...) conditions (C1) and (C2) conjointly sufficient? Do they amount to a definition of “exemplification”? Which notions of Goodman’s theory are basic, and hence undefined? In this paper, we address these questions and defend a reconstruction of the notion of exemplification that interprets “refers to” in (C2) as exemplificational reference and hence treats “exemplification” as a basic notion of Goodman’s theory. Firstly, we argue that even though the notion of exemplification is not defined, it is still sufficiently clear. This ensures its contribution to Goodman’s theory of symbols. Secondly, we show that our account is plausible as an interpretation of Goodman’s and Elgin’s writings, although it implies that some of Goodman’s theorems about selfreference have to be weakened. Thirdly, we argue that it is the only materially adequate reconstruction of Goodman’s notion of exemplification, whereas the alternative definitional accounts fail. (shrink)

To stimulate research and innovation (R&I), to contribute to the solution of societal challenges and to align R&I with societal values, the European Commission has launched the governance framework of Responsible Research and Innovation (RRI). RRI figures in many high-level EU policies as a means to promote smart growth, and a growing community of R&I practitioners from both the public and private sectors appears committed to it. Although debates on what RRI precisely entails have not reached closure yet, RRI provides (...) an interesting avenue to explore ways of making R&I more societally germane. While recognizing the usefulness of keeping critical reflection on RRI’s meaning alive, we suggest that to make the step from theorizing to implementation, RRI could benefit from a clearer conceptualization. This chapter presents the iterative trajectory in conceptualizing RRI followed as part of RRI Tools, one of a number of EC-funded research projects and support acts aimed at fleshing out what RRI can and should be, and the conceptualization of RRI that this led to. It suggests that RRI is best captured if in R&I governance attention is paid to the five p’s of Purpose, Products, Processes, Preconditions and People, and that further elaborations on the meaning of RRI should happen in dialogue with attempts at practicing RRI. (shrink)

Introduction Jan Abbink and Hans Vermeulen This volume consists of essays and studies by authors inspired by the work of Eric Wolf, a central figure in ...

In Study 1, we examined the moderating impact of alexithymia (i.e., a difficulty identifying and describing feelings to other people and an externally oriented cognitive style) on the automatic processing of affective information. The affective priming paradigm was used, and lower priming effects for high alexithymia scorers were observed when congruent (incongruent) pairs involving nonverbal primes (angry face) and verbal target were presented. The results held after controlling for participants' negative affectivity. The same effects were replicated in Studies 2 and (...) 3, with trait anxiety and depression entered as additional covariates. In Study 3, no moderating impact of alexithymia was found for verbal-facial pairs suggesting that the results cannot be merely explained in terms of transcoding limitations for high alexithymia scorers. Overall, the present results suggest that alexithymia could be related to a difficulty in processing and automatically using high arousal emotional information to respond to concomittant behavioural demands. (shrink)

Drawing on ethical and legal frameworks in the Netherlands, the United States and France, we examine whether physicians are expected to inform patients about potentially relevant opportunities for expanded access to investigational drugs. While we found no definitive legal obligation, we argue that physicians have a moral obligation to discuss opportunities for expanded access with patients who have run out of treatment options to prevent inequality, to promote autonomy, and to achieve beneficence.

We consider substitutions in order sensitive situations, having in the back of our minds the case of dynamic predicate logic (DPL) with a stack semantics. We start from the semantic intuition that substitutions are move instructions on stacks: the syntactic operation [y/x] is matched by the instruction to move the value of the y-stack to the x-stack. We can describe these actions in the positive fragment of DPLE. Hence this fragment counts as a logic for DPL-substitutions. We give a calculus (...) for the fragment and prove soundness and completeness. (shrink)

An axiomatization is presented of the denotational semantics for first order language of Apt [1]. The goal is to obtain a rational reconstruction of the intuitions underlying this semantics. The axiomatization combines ideas about four valued logic with facts about substitutions. Soundness and completeness of the axiomatization are established. From the completeness proof a decision procedure is obtained that shows how four valued logic and order sensitivity of substitution together add up in a natural way to the denotational semantics for (...) the language of first order logic as proposed by Apt. (shrink)

This article discusses the lack of inclusive language in the Liedboek van die kerk, which still remains the official hymnal of the Afrikaans Reformed churches in South Africa. Because there seems to be a general misconception about inclusive language, especially in this particular religious context, I will argue that the use of inclusive language will not only help to counteract the current identity crisis the church is experiencing, but will also reflect Christ's theology of inclusivity during his time on earth. (...) A broader understanding of the God image, rooted in biblical hermeneutics, is imperative and should be incorporated in the text of the Afrikaans hymn. I will argue that this inclusive spirituality may also lead to greater spiritual well-being of all Christians in the Afrikaans Reformed churches. This paper is critical qualitative research and arguments from the feminist theology will be interpreted and applied to the Afrikaans context. (shrink)

Recent research suggests that human memories are stored not between neurons as synaptic weights, but within individual neurons themselves. This opens the possibility to replace the dominant paradigm of brain function – neural networks – with a new one. In this article, I explore how “identified neurons” could explain how memories are stored, and how human traits are implemented in the brain.

The rise and fall of spectators performing “the wave” in a football stadium offers an analogy for how brain waves ripple across the cortex and lower brain. In both, the underlying actors (humans, neurons) serve multiple roles.

What if subconscious brain processes are actually independent consciousnesses, each resembling an independent advisor whispering advice to the main consciousness, or “I”? This multi-consciousness model would support free will, as our choices are informed by other consciousnesses, not the subconscious. Each independent consciousness allows a movable perspective through its rich representation of the world and constantly seeks harmony and resonance between its internal concepts, other consciousnesses, external reality, and the genetic worm hole to the evolutionary past.

This paper is concerned with the structure of texts in which aproof is presented. Some parts of such a text are assumptions, otherparts are conclusions. We show how the structural organisation of thetext into assumptions and conclusions helps to check the validity of theproof. Then we go on to use the structural information for theformulation of proof rules, i.e., rules for the (re-)construction ofproof texts. The running example is intuitionistic propositional logicwith connectives , and. We give new proofs of some (...) familiar results aboutthe proof theory of this logic to indicate how the new techniques workout. (shrink)

In this essay I consider the device of depthlessness in film. I am interested in particular in the ways in which this device can determine, or at least raise questions about, the nature of the fictional world. Taking my cue from two films from the turn of the century – Gary Ross' 1998 film Pleasantville and Matthieu Kassovitz' 1995 La Haine – as well as, more broadly, arts historical and cultural theoretical debates, where rather more attention has been devoted to (...) the issue of depthlessness, I focus on moments in which depth, that is, in Andre Bazin's oft-cited words, the “continuity” of the fictional realm, is flattened so as to trace the correlation between depthlessness and the ontology of the fictional world. The two strategies I look at are shallow focus and the dolly zoom. What I intend, here, is to offer some first, superficial, reflections that may allow us to begin thinking about this cinematic notion of the depthless as a device and concept in its own right, with its own ration... (shrink)

Recently, Cluckers et al. developed a new axiomatic framework for tame non-Archimedean geometry, called Hensel minimality. It was extended to mixed characteristic together with the author. Hensel minimality aims to mimic o-minimality in both strong consequences and wide applicability. In this paper, we continue the study of Hensel minimality, in particular focusing on [Formula: see text]-h-minimality and [Formula: see text]-h-minimality, for [Formula: see text] a positive integer. Our main results include an analytic criterion for [Formula: see text]-h-minimality, preservation of [Formula: (...) see text]-h-minimality under coarsening of the valuation and [Formula: see text]-dimensional geometry. (shrink)

In 2016, I published an article in which I explained the purpose and benefits of using inclusive and expansive language in the Afrikaans Dutch Reformed Church's hymns which, to this day, remain notably exclusive in gender references and when addressing God. I hoped that my article would inspire the workgroup responsible for the creation of new Afrikaans hymns to consider the possibilities and advantages of inclusive language. When I submitted a new melody and text to said workgroup earlier this year, (...) the melody was accepted, but the text rejected on grounds that it was seen as a 'forced adaptation of how the Father chooses to reveal himself to us'. This blatant and continuing aversion to incorporate some form of inclusive or expansive language in their hymns, despite my research article I sent them, lead me to investigate this apparent opposition in the DRC context even further. After exploring the comparative stance of the three biggest reformed churches in America with regard to inclusive and expansive language, I come to the conclusion that the DRC's reservation towards inclusive and expansive language cannot be explained on sober theological objections alone. In fact, I show that these reservations are the direct consequence of protecting the interests of the church's ingroup, the heterosexual white male. I identify this ingroup based on the discriminatory way the DRC treated women, non-whites and the LGBTIQ community in the recent past. I conclude that when a church continues to protect and promote the interests of an exclusive ingroup the use of inclusive language in their songs of faith would indeed seem to be 'forced'. The title refers to Mary Daly's statement in 1973: 'If God is male then the male is god.'. (shrink)

Vigil suggests that expressed emotions are inherently learned and triggered in social contexts. A strict reading of this account is not consistent with the findings that individuals, even those who are congenitally blind, do express emotions in the absence of an audience. Rather, grounded cognition suggests that facial expressions might also be an embodied support used to represent emotional information.

Dans le cadre de nos recherches sur la correspondance de Descartes, nous avons découvert une lettre inédite du philosophe. La lettre, qui se trouve à la Staatsbibliothek zu Berlin, Preußischer Kulturbesitz, est addressee à Joachim de Wicquefort, datée de Leyde, le 2 octobre 1640. Dans sa lettre Descartes réclame, par l' intermédiaire de Wicquefort, la traduction latine de ses Meteores, qui avait été remis au professeur de philosophie d'Amsterdam, Caspar Barlaeus. Elle précède de trois jours la lettre, déjà connue, à (...) Wicquefort sur le même sujet. L'importance de notre lettre est qu'elle confirme certaines hypothèses concernant l'édition latine du Discours, et le projet abandonné de la publication des objections faites au Discours et aux Essais et des réponses du philosophe. (shrink)

ABSTRACTAccumulating evidence suggests that emotional information is often recognised faster than neutral information. Several studies examined the effects of valence and arousal on word recognition, but yielded partially diverging results. Here, we used two alternative versions of a constructive recognition paradigm in which a target word is hidden by a visual mask that gradually disappears, to investigate whether the emotional properties of words influence their speed of recognition. Participants were instructed either to classify the incrementally appearing word as emotional or (...) non-emotional or to decide whether the appearing letter string is an existing word or not. Results from both tasks revealed faster recognition times for high- compared to low-arousing words, and for positive compared to negative or neutral words. These findings indicate a recognition advantage for emotionally positive and highly arousing stimuli that persists even when visua... (shrink)

In this paper we discuss the treatment of variables in dynamic semantics. Referent systems are introduced as a flexible mechanism for working with variables. In a referent system we carefully distinguish the variables themselves both from the machinery by which we manipulate them - their names - and from the information that we store in them - their values. It is shown that the referent systems provide a natural basis for dynamic semantics. The semantics with referent systems is compared with (...) the familiar formalisms in dynamic semantics, DRT and DPL. (shrink)

Cho and Martinez-Martin provide a wide-ranging analysis of what they label “digital simulacra”—which are in essence data-driven AI-based simulation models such as digital twins or models used for i...

Due to the rapid changes in the medical world and the aging population, the need for advanced care planning grows. Despite efforts to make this topic discussed, only a minority of patients discusses the advance directive with their general practitioner. This study aimed to map thresholds: What barriers are identified by GPs and patients in preparing and discussing an advance directive? A cross section survey in patients and GP’s was performed. Citizens were recruited by multimedia and by street interviews. GP’s (...) were recruited by mailing. Most of the 502 citizens already heard of an advance directive but only 17 had declared one while 21 never want one. Eighty percent wants to take the initiative themselves but half of the participants wants the GP to be actively involved. Thirty percent finds the document too difficult to understand. The need to draw an advance directive grew with increasing age. Of the 117 GP’s involved, 65% drafted five or less advance directives the past year. A lack of time, experience and a poor access to the correct administrative requirements were only a few of the barriers. Preparing and drafting an advance directive is a time-consuming and difficult procedure. Patients and GP’s have the right to be informed and instructed on how to prepare an advance directive. (shrink)

Exposome research is put forward as a major tool for solving the nature-versus-nurture debate because the exposome is said to represent “the nature of nurture.” Against this influential idea, we argue that the adoption of the nature-versus-nurture debate into the exposome research program is a mistake that needs to be undone to allow for a proper bioethical assessment of exposome research. We first argue that this adoption is originally based on an equivocation between the traditional nature-versus-nurture debate and a debate (...) about disease prediction/etiology. Second, due to this mistake, exposome research is pushed to adopt a limited conception of agential control that is harmful to one's thinking about the good that exposome research can do for human health and wellbeing. To fully excise the nature-versus-nurture debate from exposome research, we argue that exposome researchers and bioethicists need to think about the exposome afresh from the perspective of actionability. We define the concept of actionability and related concepts and show how these can be used to analyze the ethical aspects of the exposome. In particular, we focus on refuting the popular “gun analogy” in exposome research, returning results to study participants and risk-taking in the context of a well-lived life. (shrink)

The severe hereditary progeroid disorder Cockayne syndrome is a consequence of a defective transcription‐coupled repair (TCR) pathway. This special mode of DNA repair aids a RNA polymerase that is stalled by a DNA lesion in the template and ensures efficient DNA repair to permit resumption of transcription and prevent cell death. Although some key players in TCR, such as the Cockayne syndrome A (CSA) and B (CSB) proteins have been identified, the exact molecular mechanism still remains illusive. A recent report (...) provides new unexpected insights into TCR in yeast.1 The identification and characterisation of a novel protein co‐purifying with the yeast homologue of CSB (Rad26) imposes reassessment of our current understanding of TCR in yeast. What about humans? BioEssays 24:780–784, 2002. © 2002 Wiley Periodicals, Inc. (shrink)