DNA replication is both highly conserved and controlled. Problematic DNA replication can lead to genomic instability and therefore carcinogenesis. Numerous mechanisms work together to achieve this tight control and increasing evidence suggests that post‐translational modifications (phosphorylation, ubiquitination, SUMOylation) of DNA replication proteins play a pivotal role in this process. Here we discuss such modifications in the light of a recent article that describes a novel role for the deubiquitinase (DUB) USP7/HAUSP in the control of DNA replication. USP7 achieves this function (...) by an unusual and novel mechanism, namely deubiquitination of SUMOylated proteins at the replication fork, making USP7 also a SUMO DUB (SDUB). This work extends previous observations of increased levels of SUMO and low levels of ubiquitin at the on‐going replication fork. Here, we discuss this novel study, its contribution to the DNA replication and genomic stability field and what questions arise from this work. (shrink)

This contribution honours the memory of Hans- Georg Gadamer from a theological perspective. A first section reflects on the complex and often ambiguous nature of his relationship with theology and theologians, and with issues of faith and religion. Anecdotes and biographical information point to the seeming lack of interest, at least in contemporary theology, reflected in his work, but also to the warm reception that he continued to receive in theological circles, both with regard to his person and his work. (...) A second section briefly illus trates how his description of the hermeneutical conversation is practically demonstrated in what is called ecumenical hermeneutics, and how many of the notions and convictions of contemporary hermeneutical theory have indeed become common in these circles. The official study document A Treasure in Earthen Vessels. An Instru ment for an Ecumeni cal Re flection on Hermeneutics (1998, Faith and Order Paper No. 182) of the World Council of Churches is used to illustrate this. A third and final section underlines some of the formal similarities between this form of ecumenical hermeneutics and Gadamer's self- understanding of his own life project. It is argued that, whether his impact on the ecumenical church was direct or indirect, the matter-of-factness with which present-day ecumenism uses hermeneutical categories and convictions underscores Gadamer's own insight that “theologians see in my work a confirmation of their own needs.” S. Afr. J. Philos. Vol.22(1) 2003: 19-39. (shrink)

In this paper we describe a test for Nijhout's hypothesis that the eyespot patterns on butterfly wings are the result of a threshold reaction of the epidermal cells to a concentration gradient of a diffusing degradable morphogen produced by focal cells at the centre of the future eyespot. The wings of the nymphalid butterfly, Bicyclus anynana, have a series of eyespots, each composed of a white pupil, a black disc and a gold outer ring. In earlier extirpation and transplantation experiments (...) it has been established that these eyespots are indeed organised around groups of signalling cells active during the first hours of pupal development. If these cells were to supply the positional information for eyespot formation in accordance with Nijhout's diffusion-degradation gradient model, then, when two foci are close together, the signals should sum, and this effect should be apparent in the detailed shape of the resulting pigment pattern. We give an equation for the form of the contours that would be obtained in this manner. We use this to test the morphogen gradient hypothesis on measurements of the outlines of fused eyespots obtained either by grafting focal cells close together, or by using a mutation that produces adjacent fused eyespots. The contours of the fused patterns were found to satisfy our equation, thus corroborating Nijhout's hypothesis to the extent possible with this particular type of experiment. (shrink)

ABSTRACTMemory bias is a risk factor for depression. In two independent studies, the efficacy of one CBM-Memory session on negative memory bias and depressive symptoms was tested in vulnerable samples. We compared positive to neutral CBM-Memory trainings in highly-ruminating individuals and individuals with elevated depressive symptoms. In both studies, participants studied positive, neutral, and negative Swahili words paired with their translations. In five study–test blocks, they were then prompted to retrieve either only the positive or neutral translations. Immediately following the (...) training and one week later, we tested cued recall of all translations and autobiographical memory bias; and also measured mood, depressive symptoms, and rumination. Retrieval practice resulted in training-congruent recall both immediately after and one week after the training. Overall, there was no differential decrease in symptoms or difference in autobiographical memory bias between the tra... (shrink)

Perception of music and speech is based on similar auditory skills, and it is often suggested that those with enhanced music perception skills may perceive and learn novel words more easily. The current study tested whether music perception abilities are associated with novel word learning in an ambiguous learning scenario. Using a cross-situational word learning (CSWL) task, nonmusician adults were exposed to word-object pairings between eight novel words and visual referents. Novel words were either non-minimal pairs differing in all sounds (...) or minimal pairs differing in their initial consonant or vowel. In order to be successful in this task, learners need to be able to correctly encode the phonological details of the novel words and have sufficient auditory working memory to remember the correct word-object pairings. Using the Mistuning Perception Test (MPT) and the Melodic Discrimination Test (MDT), we measured learners’ pitch perception and auditory working memory. We predicted that those with higher MPT and MDT values would perform better in the CSWL task and in particular for novel words with high phonological overlap (i.e., minimal pairs). We found that higher musical perception skills led to higher accuracy for non-minimal pairs and minimal pairs differing in their initial consonant. Interestingly, this was not the case for vowel minimal pairs. We discuss the results in relation to theories of second language word learning such as the Second Language Perception model (L2LP). (shrink)

We performed an EEG graph analysis on data from 31 typical readers and 24 dyslexics, recorded while they were engaged in an audiovisual task and during resting-state. The task simulates reading acquisition as participants learned new letter-sound mappings via feedback. EEG data was filtered for the delta, theta, alpha, and beta bands. We computed the Phase Lag Index to provide an estimate of the functional connectivity between all pairs of electrodes per band. Then, networks were constructed using a Minimum Spanning (...) Tree, a unique sub-graph connecting all nodes without loops, aimed at minimizing bias in between groups and conditions comparisons. Both groups showed a comparable accuracy increase during task blocks, indicating that they correctly learned the new associations. The EEG results revealed lower task-specific theta connectivity, and lower theta degree correlation over both rest and task recordings, indicating less network integration in dyslexics compared to typical readers. This pattern suggests a role of theta oscillations in dyslexia and may reflect differences in task engagement between the groups, although robust correlations between MST metrics and performance indices were lacking. (shrink)

In The Construction of Social Reality, John Searle develops a theory of institutional facts and objects, of which money, borders and property are presented as prime examples. These objects are the result of us collectively intending certain natural objects to have a certain status, i.e. to ‘count as’ being certain social objects. This view renders such objects irreducible to natural objects. In this paper we propose a radically different approach that is more compatible with standard economic theory. We claim that (...) such institutional objects can be fully understood in terms of actions and incentives, and hence the Searlean apparatus solves a non-existent problem. (shrink)

Contemporary discussion concerning institutions focus on, and mostly accept, the Searlean view that institutional objects, i.e. money, borders and the like, exist in virtue of the fact that we collectively represent them as existing. A dissenting note has been sounded by Smit et al. (Econ Philos 27:1–22, 2011), who proposed the incentivized action view of institutional objects. On the incentivized action view, understanding a specific institution is a matter of understanding the specific actions that are associated with the institution (...) and how we are incentivized to perform these actions. In this paper we develop the incentivized action view by extending it to institutions like property, promises and complex financial organisations like companies. We also highlight exactly how the incentivized action view differs from the Searlean view, discuss the method appropriate to such study and discuss some of the virtues of the incentivized action view. (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)

What does being money consist in? We argue that something is money if, and only if, it is typically acquired in order to realise the reduction in transaction costs that accrues in virtue of agents coordinating on acquiring the same thing when deciding what thing to acquire in order to exchange. What kinds of things can be money? We argue against the common view that a variety of things (notes, coins, gold, cigarettes, etc.) can be money. All monetary systems are (...) best interpreted as implementing the same basic protocol. Money, i.e. the thing that we coordinate on acquiring in order to lower our transaction costs, is, in all cases, a set of positions on an abstract mathematical object, namely a relative ratio scale. The things that we ordinarily call ‘money’ are merely records of positions on such a scale. (shrink)

Contemporary theories of institutions as clusters of stable solutions to recurrent coordination problems can illuminate and explain some unresolved difficulties and problems adhering to institutional definitions of art initiated by George Dickie and Arthur Danto. Their account of what confers upon objects their institutional character does not fit well with current work on institutions and social ontology. The claim that “the artworld” confers the status of “art” onto objects remains utterly mysterious. The “artworld” is a generic notion that designates a (...) sphere of human activity that involves practices that create goals that have led to the emergence of formal and informal institutions. But those institutions, rather than magically “creating” objects subjected to esthetic appreciation, merely solve familiar and ubiquitous coordination problems created by artistic activity in ways other institutions in other areas solve similar and/or analogous coordination problems. (shrink)

In our earlier work, we argued, contra Searle, that institutional facts can be understood in terms of non-institutional facts about actions and incentives. Butchard and D’Amico claim that we have misinterpreted Searle, that our main argument against him has no merit and that our positive view cannot account for institutional facts created via joint action. We deny all three charges.

Declarations like “this meeting is adjourned” make certain facts the case by representing them as being the case. Yet surprisingly little attention has been paid to the mechanism whereby the utterance of a declaration can bring about a new state of affairs. In this paper, we use the incentivization account of institutional facts to address this issue. We argue that declarations can serve to bring about new states of affairs as their utterance have game theoretical import, typically in virtue of (...) the utterer signaling a commitment to act in an incentive-changing way. (shrink)

I-theories of bare demonstratives take the semantic referent of a demonstrative to be determined by an inner state of the utterer. E-theories take the referent to be determined by factors external to the utterer. I argue that, on the Standard view of communication, neither of these theories can be right. Firstly, both are committed to the existence of conventions with superfluous content. Secondly, any claim to the effect that a speaker employs the conventions associated with these theories cannot have any (...) content, i.e. nothing can count as following these conventions. Bare demonstratives may well not be devices of semantic reference at all, i.e. may not actually contribute a referent to the proposition semantically expressed by an utterance. (shrink)

Russell claims that ordinary proper names are eccentric, i.e. that the semantic referent of a name is determined by the descriptive condition that the individual utterer of the name associates with the name. This is deeply puzzling, for the evidence that names are subject to interpersonal coordination seems irrefutable. One way of making sense of Russell’s view would be to claim that he has been systematically misinterpreted and did not, in fact, offer a semantic theory at all. Such a view (...) is put forward in Sainsbury Departing from Frege, Routledge, London, 2002). Sainsbury claims that Russellian descriptivism is not the theory that the thought in the mind of the speaker determines the semantic reference of a name, but simply a theory about the thought in the mind of the speaker using a name. I argue that the truth is subtly different, and points the way towards an intuitive explanation of Russell’s eccentricity. (shrink)

CITATION: Smith, J. P. 2014. A note on name individuation and identifying descriptions. Stellenbosch Papers in Linguistics, 43:165-170, doi:10.5774/43-0-165.

Joseph Almog pointed out that Kripkean causal chains not only exist for names, but for all linguistic items (Almog 1984: 482). Based on this, he argues that the role of such chains is the presemantic one of assigning a linguistic meaning to the use of a name (1984: 484). This view is consistent with any number of theories about what such a linguistic meaning could be, and hence with very different views about the semantic reference of names. He concludes that (...) the causal theory is ‘rather trivial’ (1984: 487). In this paper I argue that Almog is correct to hold that the causal theory is trivial, but, contra Almog, argue that the triviality of the existence of causal chains is not a matter of such chains having a presemantic role in assigning linguistic meanings to utterances. Instead, such triviality is due to the fact that the causal theory reflects no more than a truism about the epistemology of convention acquisition. (shrink)

Publics are key stakeholders in population genomic screening and their perspectives on ethical considerations are relevant to programme design and policy making. Using semi-structured interviews, we explored social views and attitudes towards possible future provision of personalised genomic risk information to populations to inform prevention and/or early detection of relevant conditions. Participants were members of the public who had received information on their personal genomic risk of melanoma as part of a research project. The focus of the analysis presented here (...) is participants’ views regarding ethical considerations relevant to population genomic screening more generally. Data were analysed thematically and four key themes related to ethical considerations were identified: personal responsibility for health: ‘forewarned is forearmed’; perceptions of, and responses to, genetic fatalism; implications for parenting and reproduction; divided views on choosing to receive genomic risk information. Ethical considerations underlying these themes include the valorisation of information and choice, paternalism, non-directiveness and increasing responsibilisation of individuals in health and healthcare. These findings arguably indicate a thin public conceptualisation of population genomic testing, which draws heavily on how these themes tend to be described in existing social discourses. Findings suggest that further public engagement is required to increase complexity of debate, to consider the appropriate place of individual and social interests in population genomic testing. Further discernment of relevant ethical approaches, drawing on ethical frameworks from both public health and clinical settings, will also assist in determining the appropriate implementation of population genomic screening for complex conditions. (shrink)

This paper argues, based on Lewis’ claim that communication is a coordination game (Lewis in Minnesota studies in the philosophy of science, University of Minnesota Press, Minneapolis, pp 3–35, 1975), that we can account for the communicative function of demonstratives without assuming that they semantically refer. The appeal of such a game theoretical version of the case for non-referentialism is that the communicative role of demonstratives can be accounted for without entering thecul de sacof trying to construct conventions of ever-increasing (...) complexity. Instead communicationviademonstratives is explained with reference to the general, non-domain specific ability of human beings to solve games of coordination. Furthermore, there is empirical support for such a view. Judgments concerning demonstrative reference have been shown to be sensitive to judgments concerningcommon ground(Clark et al. in J Verb Learn Verb Behav 22:245–258, 1983), which is exactly what the non-referentialist account would predict. The game theoretical account also allows for an intuitively plausible, non-referentialist treatment of Speaks’ ‘trumping argument’ (Speaks in Philos Stud 174:709–734, 2017), as well as the Carnap/Agnew puzzle (Kaplan in Syntax Semant 9:221–43, 1970). (shrink)

Traditional descriptivism and Kripkean causalism are standardly interpreted as rival theories on a single topic. I argue that there is no such shared topic, i.e. that there is no question that they can be interpreted as giving rival answers to. The only way to make sense of the commitment to epistemic transparency that characterizes traditional descriptivism is to interpret Russell and Frege as proposing rival accounts of how to characterize a subject’s beliefs about what names refer to. My argument relies (...) on a development of the distinction between speaker’s reference and semantic reference. (shrink)

Semantic theories that violate semantic innocence, that is require reference shifts when terms are embedded in ‘that’ clauses and the like, are often challenged by producing sentences where an anaphoric expression, while not itself embedded in a context in which reference shifts, is anaphoric on an antecedent expression that is embedded in such a context. This, in conjunction with a widely accepted principle concerning unproblematic anaphora (the ‘Principle of Anaphoric Reference’), is used to show that such reference shifting has absurd (...) consequences. We show that it is the widely accepted principle concerning anaphora that is to be blamed for these consequences and not the supposed sin of reference shifting. (shrink)

A wide variety of philosophers seem to agree that there is something dubious about the distinction between fact and value. This paper evaluates some of the arguments made for such a contention. It is argued that only the crudest form of pragmatism leads to a conflation of fact and value. Other arguments against the fact/value distinction, mostly drawn from Putnam's Reason, Truth and History, are examined in order to show that they are either false or trivial. S. Afr. J. Philos. (...) Vol.22(1) 2003: 51-62. (shrink)

On creating a grammar for living together The article is about the question whether it is possible for South Africans to learn a new common moral language. Six well-known positions are considered: a common political language, a common economic language, a common Biblical language, a common Christian language, a common language of survival, and a common rational language.

AimThe neurocognitive basis of Developmental Coordination Disorder remains an issue of continued debate. This combined systematic review and meta-analysis provides a synthesis of recent experimental studies on the motor control, cognitive, and neural underpinnings of DCD.MethodsThe review included all published work conducted since September 2016 and up to April 2021. One-hundred papers with a DCD-Control comparison were included, with 1,374 effect sizes entered into a multi-level meta-analysis.ResultsThe most profound deficits were shown in: voluntary gaze control during movement; cognitive-motor integration; practice-/context-dependent (...) motor learning; internal modeling; more variable movement kinematics/kinetics; larger safety margins when locomoting, and atypical neural structure and function across sensori-motor and prefrontal regions.InterpretationTaken together, these results on DCD suggest fundamental deficits in visual-motor mapping and cognitive-motor integration, and abnormal maturation of motor networks, but also areas of pragmatic compensation for motor control deficits. Implications for current theory, future research, and evidence-based practice are discussed.Systematic Review RegistrationPROSPERO, identifier: CRD42020185444. (shrink)

Does South Africa need a common moral language? Many people are of the opinion that South Africa finds itself 'after Babel’ and needs a common moral language (1). The author considers some of the arguments of people who disagree with this analysis, because they do not define the problem in this way (2); because they find the language- or Babel-methaphor confusing (3); because they agree with the description of the problem, but not with the suggested solution, namely a common moral (...) language (4); or because they accept the solution, but do not regard it as the proper task of the Christian church to be involved in this search for a common moral language (5). (shrink)

In the study of expertise, few debates come as big as that between constructivists and realists. This chapter discusses the signal debate between realists and constructivists about expertise. It sets out a view that includes aspects of both the constructivist and realist position to show that insights from what is often considered to be rival camps can be incorporated in a position that does justice to both. The chapter argues that, while expertise is real, there are two distinct social dimensions (...) to the concept of expertise. It attempts to demonstrate two distinct ways in which expertise has a social dimension. First, the chapter develops an account according to which 'is an expert' is a triadic predicate. Second, it considers the fact that attributions of expertise are often done by institutions, i.e. by medical boards certifying doctors, etc. Both dimensions can be acknowledged without undermining the basic case for realism about expertise. (shrink)

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of (...) parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

It is widely recognized that police performance may be hindered by psychophysiological state changes during acute stress. To address the need for awareness and control of these physiological changes, police academies in many countries have implemented Heart-Rate Variability biofeedback training. Despite these trainings now being widely delivered in classroom setups, they typically lack the arousing action context needed for successful transfer to the operational field, where officers must apply learned skills, particularly when stress levels rise. The study presented here aimed (...) to address this gap by training physiological control skills in an arousing decision-making context. We developed a Virtual-Reality breathing-based biofeedback training in which police officers perform deep and slow diaphragmatic breathing in an engaging game-like action context. This VR game consisted of a selective shoot/don’t shoot game designed to assess response inhibition, an impaired capacity in high arousal situations. Biofeedback was provided based on adherence to a slow breathing pace: the slower and deeper the breathing, the less constrained peripheral vision became, facilitating accurate responses to the in-game demands. A total of nine male police trainers completed 10 sessions over a 4-week period as part of a single-case experimental ABAB study-design. Results showed that eight out of nine participants showed improved breathing control in action, with a positive effect on breathing-induced low frequency HRV, while also improving their in-game behavioral performance. Critically, the breathing-based skill learning transferred to subsequent sessions in which biofeedback was not presented. Importantly, all participants remained highly engaged throughout the training. Altogether, our study showed that our VR environment can be used to train breathing regulation in an arousing and active decision-making context. (shrink)

IntroductionBrain tumours frequently cause language impairments and are also likely to co-occur with localised abnormal slow-wave brain activity. However, it is unclear whether this applies specifically to low-grade brain tumours. We investigate slow-wave activity in resting-state electroencephalography in low-grade glioma and meningioma patients, and its relation to pre- and postoperative language functioning.MethodPatients with a glioma infiltrating the language-dominant hemisphere and patients with a meningioma with mass effect on this hemisphere underwent extensive language testing before and 1 year after surgery. EEG (...) was registered preoperatively, postoperatively, and once in healthy individuals. Slow-wave activity in delta- and theta- frequency bands was evaluated visually and quantitatively by spectral power at three levels over the scalp: the whole brain, the affected hemisphere, and the affected region.ResultsGlioma patients had increased delta activity and increased theta activity before and after surgery. In these patients, increased preoperative theta activity was related to the presence of language impairment, especially to poor word retrieval and grammatical performance. Preoperative slow-wave activity was also related to postoperative language outcomes. Meningioma patients showed no significant increase in EEG slow-wave activity compared to healthy individuals, but they presented with word retrieval, grammatical, and writing problems preoperatively, as well as with writing impairments postoperatively.DiscussionAlthough the brain-tumour pathology in low-grade gliomas and meningiomas has a different effect on resting-state brain activity, patients with low-grade gliomas and meningiomas both suffer from language impairments. Increased theta activity in glioma patients can be considered as a language-impairment marker, with prognostic value for language outcome after surgery. (shrink)