R‐spondins (RSPOs) are a family of secreted proteins and stem cell growth factors that are potent co‐activators of Wnt signaling. Recently, RSPO2 and RSPO3 were shown to be multifunctional, not only amplifying Wnt‐ but also binding BMP‐ and FGF receptors to downregulate signaling. The common mechanism underlying these diverse functions is that RSPO2 and RSPO3 act as “endocytosers” that link transmembrane proteins to ZNRF3/RNF43 E3 ligases and trigger target internalization. Thus, RSPOs are natural protein targeting chimeras for cell surface proteins. (...) Conducting data mining and cell surface binding assays we report additional candidate RSPO targets, including SMO, PTC1,2, LGI1, ROBO4, and PTPR(F/S). We propose that there is an “R‐spondin code” that imparts combinatorial signaling ON‐OFF states of multiple growth factors. This code involves the modular RSPO domains, notably distinct motifs in the divergent RSPO‐TSP1 domains to mediate target interaction and internalization. The RSPO code offers a novel framework for the understanding how diverse signaling pathways may be coordinately regulated in development and disease. (shrink)

This volume brings together a collection of ten original essays which present new analyses of social and relational equality in philosophy and political theory. The essays analyze the nature of social equality and its relationship with justice and with politics.

This book investigates the nature of the relationship between phonology and syntax and proposes a theory of Minimal Indirect Reference that solves many classic problems relating to the topic. Seidl shows that all variation across languages in phonological domain size is due to syntactic differences and a single domain parameter specific to phonology.

Much research is currently being conducted on health care practitioners' experiences of moral distress, especially the experience of nurses. What moral distress is, however, is not always clearly delineated and there is some debate as to how it should be defined. This article aims to help to clarify moral distress. My methodology consists primarily of a conceptual analysis, with especial focus on Andrew Jameton's influential description of moral distress. I will identify and aim to resolve two sources of confusion about (...) moral distress: the compound nature of a narrow definition of distress which stipulates a particular cause, i.e. moral constraint, and the distinction drawn between moral dilemma and moral distress, which implies that the two are mutually exclusive. In light of these concerns, I argue that the definition of moral distress should be revised so that moral constraint should not be a necessary condition of moral distress, and that moral conflict should be included as a potential cause of distress. Ultimately, I claim that moral distress should be understood as a specific psychological response to morally challenging situations such as those of moral constraint or moral conflict, or both. (shrink)

Word co‐occurrence patterns in language corpora contain a surprising amount of conceptual knowledge. Large language models (LLMs), trained to predict words in context, leverage these patterns to achieve impressive performance on diverse semantic tasks requiring world knowledge. An important but understudied question about LLMs’ semantic abilities is whether they acquire generalized knowledge of common events. Here, we test whether five pretrained LLMs (from 2018's BERT to 2023's MPT) assign a higher likelihood to plausible descriptions of agent−patient interactions than to minimally (...) different implausible versions of the same event. Using three curated sets of minimal sentence pairs (total n = 1215), we found that pretrained LLMs possess substantial event knowledge, outperforming other distributional language models. In particular, they almost always assign a higher likelihood to possible versus impossible events (The teacher bought the laptop vs. The laptop bought the teacher). However, LLMs show less consistent preferences for likely versus unlikely events (The nanny tutored the boy vs. The boy tutored the nanny). In follow‐up analyses, we show that (i) LLM scores are driven by both plausibility and surface‐level sentence features, (ii) LLM scores generalize well across syntactic variants (active vs. passive constructions) but less well across semantic variants (synonymous sentences), (iii) some LLM errors mirror human judgment ambiguity, and (iv) sentence plausibility serves as an organizing dimension in internal LLM representations. Overall, our results show that important aspects of event knowledge naturally emerge from distributional linguistic patterns, but also highlight a gap between representations of possible/impossible and likely/unlikely events. (shrink)

Previous research has shown that stimulus–response (SR) binding and retrieval processes also occur when responses are only observed in another person ( Giesen et al., 2014 ). Importantly, this effect depends on the two individuals interacting interdependently during the task (e.g., competition or cooperation). Interdependence, however, must not necessarily result from task-related demands, but can also reflect an intrinsic feature of a given relationship. The present study examines whether observing responses of one’s romantic partner also produces stimulus-based retrieval of observed (...) responses even if the task itself does not involve interdependence. Participants performed a task pairwise, either with their romantic partner or with a stranger. In a sequential prime-probe design, both participants of a pair gave color responses themselves (actors) or merely observed these (observers) in alternating fashion. As expected, stimulus-based retrieval of observationally acquired SR-bindings occurred only in romantically involved pairs; participants interacting with a stranger showed no retrieval effects. We conclude that mental representations of self and other are more closely intertwined in romantic couples, which produces automatic retrieval of observationally acquired SR binding effects even independently of the task itself. (shrink)

One of the most controversial issues in many health care systems is health care rationing. In essence, rationing refers to the denial of - or delay in - access to scarce goods and services in health care, despite the existence of medical need. Scarcity of financial and medical resources confronts society with painful questions. Who should decide which medicine or new treatment will be covered by social security and on which criteria such decisions must be based? Can age, for example, (...) be justified as a selection criterion? Should decision-making be left to health care policymakers, hospital administrators, or rather, to treating physicians? And finally: is there a role for individual patients? These are difficult questions that suggest the need for transparent and democratic decision-making. In reality, however, the rationing debate occurs in a sub rosa world, based on imperfect information, distorted interpretations of effectiveness, and hidden cost concerns. This book explores these and other questions from various perspectives. Each of the book's contributors analyzes the debate from a different angle, in search of fair and just rationing decisions. (shrink)

A cultura digital vem provocando mudanças nas experiências leitoras, sobretudo quando se observa a condição ontológica da mídia digital, exigindo olhares atentos acerca da condição da imagem. O artigo – a partir da pesquisa bibliográfica e da observação de objetos empíricos –, considerando a materialidade livresca e os protocolos de leitura próprios dos livros-aplicativos, reflete acerca do lugar da imagem diante da leitura em contexto digital. Tomando como arcabouços teóricos as noções acerca dos protocolos de leitura e a pragmática computacional, (...) o trabalho defende, a partir de uma breve análise dos caminhos da imagem no livro, a reversão hierárquica conquistada por essa matriz de linguagem nos atuais contextos, apontando a imagem como elemento narrativo e janela de acesso à informação em ambientes informáticos. (shrink)

The origin and evolutionary dynamics of the spatial heterogeneity in genomic base composition have been debated since its discovery in the 1970s. With the recent availability of numerous genome sequences from a wide range of species it has been possible to address this question from a comparative perspective, and similarities and differences in base composition between groups of organisms are becoming evident. Ample evidence suggests that the contrasting dynamics of base composition are driven by GC‐biased gene conversion (gBGC), a process (...) that is associated with meiotic recombination. In line with this hypothesis, base composition is associated with the rate of recombination and the evolutionary dynamics of the recombination landscape, therefore, governs base composition. In addition, and at first sight perhaps surprisingly, the relationship between demography and genomic base composition is in agreement with the gBGC hypothesis: organisms with larger populations have higher GC content than those with smaller populations. (shrink)

BackgroundResearch has demonstrated that personality characteristics, such as optimism are associated with placebo/nocebo responding. The present study investigated whether written information about the optimism of a placebo/nocebo provider can influence the occurrence of reported placebo/nocebo side effects.MethodWe analyzed data from 201 females who participated in a “clinical study on a new massage oil with stone clover extract.” The oil was introduced as either eliciting a negative side effect or a positive side effect. The administration of the oil was combined with (...) written information about the maker of the product. The oil maker was either portrayed as a very optimistic person or no personal information was provided. The participants had no personal contact with the experimenter and received all materials and instructions per post.ResultsThe participants reported more frequent and intense itching when they received a nocebo suggestion compared to a placebo suggestion. Positive tingling sensations were reported more frequently than itching but did not differ between the placebo/nocebo conditions. Information about the optimism of the oil maker was associated with a lower frequency of reported side effects.ConclusionThis study demonstrated that it is sufficient to provide participants with written information about an inert substance to elicit the suggested side effect. Information about the provider’s optimistic personality did not specifically influence reported side effects. Future studies should focus on how to adapt written information about a drug/product to minimize adverse side effects and to maximize positive side effects. (shrink)

The controversies in our time between teleological and deontological ethics which come down to the problem "from being to ought," referring to human being or nature, can be resolved only by an adequate conception of human nature. Taking up the ancient tradition again, we can re-examine the teleological conception of human nature as primarily instinctive and selfish, and say that human nature is constituted also by reason and that the instinctive nature is predisposed to be guided by reason or intellect. (...) The constitutive order of the human soul, with the subordination of the instinct under the intellect, involves already some natural goodness, of which the intellect is aware and for which the will strives. This is the basis for the "moral law" and for normative ethics. Thus, human nature is not selfish in itself. Although moral goodness as humankind’s perfection is an ideal, it has in us already imperfect natural beginnings, a "natural morality." In a certain sense, the moral ought of actions comes from one’s being, from the natural moral goodness of which the intellect is aware in itself, and from its good intentions. (shrink)

This book is written for middle and high school students, for teachers and for those with a passion for math, containing 150+1 problems (which are followed by solutions) to make it more accessible to the reader. The last problem (150+1), a very interesting one, leaves some space for comments and generalizations. The book is a collaboration between a multi-awarded student at Romania’s National Mathematics Olympiad (Carina Maria Viespescu, student in year 10 at Liceul International of Informatics Bucuresti), a teacher (...) from Colegiul National “Fratii Buzesti” din Cravoia and prof. Dr. Emeritus Florentin Smarandache from the University of New Mexico. A couple of problems are proposed by colleagues, and their names indicated in footnotes. (shrink)

What kind of equality should we value and why? Current debate centres around whether distributive equality is valuable. However, it is not the only (potentially) morally significant form of equality. David Miller and T. M. Scanlon have emphasised the importance of social equality—a strongly egalitarian notion distinct from distributive equality, and which cannot be reduced to a concern for overall welfare or the welfare of the worst-off. However, as debate tends to focus on distribution, social equality has been neglected and (...) we do not have a clear understanding of what it is and why it might be valuable. This paper aims to address this gap. (shrink)

All species continuously evolve to adapt to changing environments. The genetic variation that fosters such adaptation is caused by a plethora of mechanisms, including meiotic recombination that generates novel allelic combinations in the progeny of two parental lineages. However, a considerable number of eukaryotic species, including many fungi, do not have an apparent sexual cycle and are consequently thought to be limited in their evolutionary potential. As such organisms are expected to have reduced capability to eliminate deleterious mutations, they are (...) often considered as evolutionary dead ends. However, inspired by recent reports we argue that such organisms can be as persistent as organisms with conventional sexual cycles through the use of other mechanisms, such as genomic rearrangements, to foster adaptation. (shrink)

This chapter serves as an introduction to the collected volume. In the first section, we aim to provide background on important themes in social egalitarianism and to set the context for understanding which significant questions the chapters in this book pose and attempt to answer. In this section we focus especially on what could be said to characterize socially egalitarian relationships, on which relationships are of concern, and on what might make social egalitarianism distinct. In the second section, we provide (...) a brief explanation of the structure of the book and each of its chapters. (shrink)

Benzodiazepines and antidepressants have been shown to change responses to unfairness; however, the effects of their combined use on unfairness evaluation are unknown. This study examines the effects of concomitant benzodiazepines and antidepressants long-term use on the evaluation of fair and unfair offers. To analyze behavioral changes on responses to unfairness, we compared the performance of medicated participants and healthy controls in the Ultimatum Game, both in the proposer and in the respondent role. The results showed that long-term psychotropic users (...) had the worse economic strategy by accepting less offers than control subjects. However, in the proposer role, the unfair offers made by participants were similar between groups. The present results suggest that long-term use of psychotropic medication, specifically the combination of benzodiazepines and antidepressants, may increase the sensitivity to unfairness, resulting in higher rejection rates in conditions where this strategy is the most disadvantageous. (shrink)

El presente art í culo analiza el sentimiento de verg ü enza en la experiencia escolar de j óvenes indígenas de una escuela secundaria rural-albergue del Norte de Argentina. Los testimonios recuperados expresan el dolor social y la búsqueda de reparaci ón simbó lica de la subjetividad herida.

Schillers Anthropologie und die Philosophische Anthropologie – dahinter stehen zwei Denksysteme mit zahlreichen Parallelen. Während den Theorien selbst in den letzten Jahrzehnten große Aufmerksamkeit geschenkt wurde, ist die Analogie zwischen ihnen bislang nur wenig erforscht. Die Studie nutzt Schlüsselbegriffe und konstante Denkfiguren, die aus den Werken Schelers, Plessners und Gehlens herausgearbeitet und vor ihrem wissenschaftlichen wie gesellschaftlichen Hintergrund erklärt werden, zu dem heuristischen Zweck einer Neuinterpretation der schillerschen Philosophie vom Menschen. So deckt der typologische Vergleich zwischen den Schriften des späten (...) 18. und des frühen 20. Jahrhunderts strukturelle Parallelen ihrer gedanklichen Konfliktsituationen auf und macht Schillers Theorie vom Menschen als spezifische Philosophie der Moderne begreiflich, die auf die Krisenerfahrungen ihrer Epoche mit einer ästhetischen Anthropologie der Freiheit unter der Bedingung menschlicher Lebendigkeit antwortet. Auf diesem Wege eröffnen sich neue Perspektiven, durch die der Anthropologe Schiller gegenüber dem 'Moraltrompeter von Säckingen' ins rechte Licht rückt und Spannungen seines Denkens, wenn auch nicht aufgelöst, so doch verständlich gemacht werden. (shrink)

On the collective work edited by P. Rossi, E. Berti has written the section dedicated to metaphysics. A review of this contribution is attempted. Some personal remarks about modem critics to metaphysics are introduced whenever they differ from Berti's.