Safety, the Preface Paradox and Possible Worlds Semantics

This paper contains an argument to the effect that possible worlds semantics renders semantic knowledge impossible, no matter what ontological interpretation is given to possible worlds. The essential contention made is that possible worlds semantic knowledge is unsafe and this is shown by a parallel with the preface paradox

Toward a Theory of the Pragmatic A Priori: From Carnap to Lewis and Beyond

The aim of this paper is make a contribution to the ongoing search for an adequate concept of the a priori element in scientific knowledge. The point of departure is C.I. Lewis’s account of a pragmatic a priori put forward in his "Mind and the World Order" (1929). Recently, Hasok Chang in "Contingent Transcendental Arguments for Metaphysical Principles" (2008) reconsidered Lewis’s pragmatic a priori and proposed to conceive it as the basic ingredient of the dynamics of an embodied scientific reason. The present paper intends to further elaborate Chang’s account by relating it with some conceptual tools from cognitive semantics and certain ideas that first emerged in the context of the category-theoretical foundations of mathematics

Euler diagrams through the looking glass: From extent to intent

Extension and intension are two ways of indicating the fundamental meaning of a concept. The extent of a concept, C, is the set of objects which correspond to C whereas the intent of C is the collection of attributes that characterise it. Thus, intension denotes the set of objects corresponding to C without naming them individually. Mathematicians switch comfortably between these perspectives but the majority of logical diagrams deal exclusively in extension. Euler diagrams indicate sets using curves to depict their extent in a way that intuitively matches the relations between the sets. What happens when we use spatial diagrams to depict intension? What can we infer about the intension of a concept given its extension, and vice versa? We present the first steps towards addressing these questions by defining extensional and intensional Euler diagrams and translations between the two perspectives. We show that translation in either direction leads to a loss of information, yet preserves important semantic properties. To conclude, we explain how we expect further exploration of the relationship between the two perspectives could shed light on connections between diagrams, extension, intension, and well-matchedness

Educ' Alcool's misinformation: more mixed messages about alcohol harms.

Commentary - No abstract available

Finite Minds and Open Minds

One of the most persistent complaints about Peter Klein’s infinitism involves the finite mind objection: given that we are finite, how can we ever handle an infinite series of reasons? Klein’s answer has been that we need not actually produce an infinite series; it is enough that such a series be available to us. In this paper a different reply is presented through the reconstruction of epistemic justification as a trade-off. In acting as responsible agents, we are striking a balance between the number of reasons that we can handle and the level of precision that we want our beliefs to have. If we are unable or unwilling to manage a large number of reasons, then we have to pay the price in terms of justificatory inexactitude and thereby of accepting relatively untrustworthy beliefs. As well as being intuitively attractive, this idea of a trade-off is warranted by the mathematics of epistemic justification, understood as involving probabilistic relations

Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations

Photoswitchable diacylglycerols enable optical control of protein kinase C.

Increased levels of the second messenger lipid diacylglycerol (DAG) induce downstream signaling events including the translocation of C1-domain-containing proteins toward the plasma membrane. Here, we introduce three light-sensitive DAGs, termed PhoDAGs, which feature a photoswitchable acyl chain. The PhoDAGs are inactive in the dark and promote the translocation of proteins that feature C1 domains toward the plasma membrane upon a flash of UV-A light. This effect is quickly reversed after the termination of photostimulation or by irradiation with blue light, permitting the generation of oscillation patterns. Both protein kinase C and Munc13 can thus be put under optical control. PhoDAGs control vesicle release in excitable cells, such as mouse pancreatic islets and hippocampal neurons, and modulate synaptic transmission in Caenorhabditis elegans. As such, the PhoDAGs afford an unprecedented degree of spatiotemporal control and are broadly applicable tools to study DAG signaling

Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity.

This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape

The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae)

The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce.In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships.This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds

Dispelling urban myths about default uncertainty factors in chemical risk assessment - Sufficient protection against mixture effects?

© 2013 Martin et al.; licensee BioMed Central LtdThis article has been made available through the Brunel Open Access Publishing Fund.Assessing the detrimental health effects of chemicals requires the extrapolation of experimental data in animals to human populations. This is achieved by applying a default uncertainty factor of 100 to doses not found to be associated with observable effects in laboratory animals. It is commonly assumed that the toxicokinetic and toxicodynamic sub-components of this default uncertainty factor represent worst-case scenarios and that the multiplication of those components yields conservative estimates of safe levels for humans. It is sometimes claimed that this conservatism also offers adequate protection from mixture effects. By analysing the evolution of uncertainty factors from a historical perspective, we expose that the default factor and its sub-components are intended to represent adequate rather than worst-case scenarios. The intention of using assessment factors for mixture effects was abandoned thirty years ago. It is also often ignored that the conservatism (or otherwise) of uncertainty factors can only be considered in relation to a defined level of protection. A protection equivalent to an effect magnitude of 0.001-0.0001% over background incidence is generally considered acceptable. However, it is impossible to say whether this level of protection is in fact realised with the tolerable doses that are derived by employing uncertainty factors. Accordingly, it is difficult to assess whether uncertainty factors overestimate or underestimate the sensitivity differences in human populations. It is also often not appreciated that the outcome of probabilistic approaches to the multiplication of sub-factors is dependent on the choice of probability distributions. Therefore, the idea that default uncertainty factors are overly conservative worst-case scenarios which can account both for the lack of statistical power in animal experiments and protect against potential mixture effects is ill-founded. We contend that precautionary regulation should provide an incentive to generate better data and recommend adopting a pragmatic, but scientifically better founded approach to mixture risk assessment. © 2013 Martin et al.; licensee BioMed Central Ltd.Oak Foundatio