Dynamic Probabilistic Entailment. Improving on Adams' Dynamic Entailment Relation

The inferences of contraposition (A ⇒ C ∴ ¬C ⇒ ¬A), the hypothetical syllogism (A ⇒ B, B ⇒ C ∴ A ⇒ C), and others are widely seen as unacceptable for counterfactual conditionals. Adams convincingly argued, however, that these inferences are unacceptable for indicative conditionals as well. He argued that an indicative conditional of form A ⇒ C has assertability conditions instead of truth conditions, and that their assertability ‘goes with’ the conditional probability p(C|A). To account for inferences, Adams developed the notion of probabilistic entailment as an extension of classical entailment. This combined approach (correctly) predicts that contraposition and the hypothetical syllogism are invalid inferences. Perhaps less well-known, however, is that the approach also predicts that the unconditional counterparts of these inferences, e.g., modus tollens (A ⇒ C, ¬C ∴ ¬A), and iterated modus ponens (A ⇒ B, B ⇒ C, A ∴ C) are predicted to be valid. We will argue both by example and by calling to the results from a behavioral experiment (N = 159) that these latter predictions are incorrect if the unconditional premises in these inferences are seen as new information. Then we will discuss Adams’ (1998) dynamic probabilistic entailment relation, and argue that it is problematic. Finally, it will be shown how his dynamic entailment relation can be improved such that the incongruence predicted by Adams’ original system concerning conditionals and their unconditional counterparts are overcome. Finally, it will be argued that the idea behind this new notion of entailment is of more general relevance.

Perturbation of Cellular Redox Homeostasis Dictates Divergent Effects of Polybutyl Cyanoacrylate (PBCA) Nanoparticles on Autophagy

Nanoparticles (NPs) are used in our everyday life, including as drug delivery vehicles. However, the effects of NPs at the cellular level and their impacts on autophagy are poorly understood. Here, we demonstrate that the NP drug delivery vehicle poly(butyl cyanoacrylate) (PBCA) perturbs redox homeostasis in human epithelial cells, and that the degree of redox perturbation dictates divergent effects of PBCA on autophagy. Specifically, PBCA promoted functional autophagy at low concentrations, whereas it inhibited autophagy at high concentrations. Both effects were completely abolished by the antioxidant N-acetyl cysteine (NAC). High concentrations of PBCA inhibited MAP1LC3B/GABARAP lipidation and LC3 flux, and blocked bulk autophagic cargo flux induced by mTOR inhibition. These effects were mimicked by the redox regulator H2O2. In contrast, low concentrations of PBCA enhanced bulk autophagic cargo flux in a Vps34-, ULK1/2- and ATG13-dependent manner, yet interestingly, without an accompanying increase in LC3 lipidation or flux. PBCA activated MAP kinase signaling cascades in a redox-dependent manner, and interference with individual signaling components revealed that the autophagy-stimulating effect of PBCA required the action of the JNK and p38–MK2 pathways, whose activities converged on the pro-autophagic protein Beclin-1. Collectively, our results reveal that PBCA exerts a dual effect on autophagy depending on the severity of the NP insult and the resulting perturbation of redox homeostasis. Such a dual autophagy-modifying effect may be of general relevance for redox-perturbing NPs and have important implications in nanomedicine.

Monitoring the binding and insertion of a single transmembrane protein by an insertase

Cells employ highly conserved families of insertases and translocases to insert and fold proteins into membranes. How insertases insert and fold membrane proteins is not fully known. To investigate how the bacterial insertase YidC facilitates this process, we here combine single-molecule force spectroscopy and fluorescence spectroscopy approaches, and molecular dynamics simulations. We observe that within 2 ms, the cytoplasmic α-helical hairpin of YidC binds the polypeptide of the membrane protein Pf3 at high conformational variability and kinetic stability. Within 52 ms, YidC strengthens its binding to the substrate and uses the cytoplasmic α-helical hairpin domain and hydrophilic groove to transfer Pf3 to the membrane-inserted, folded state. In this inserted state, Pf3 exposes low conformational variability such as typical for transmembrane α-helical proteins. The presence of YidC homologues in all domains of life gives our mechanistic insight into insertase-mediated membrane protein binding and insertion general relevance for membrane protein biogenesis.

Curiosity as a Function of Confidence and Importance in Knowing Information

Curiosity appears to be the driving force for humans to find new information, but despite its general relevance, only few studies investigated the underlying mechanisms of curiosity. Kang et al. (2009) reported that curiosity follows an inverted U-shaped function of confidence, with highest curiosity on moderate confidence levels of knowing information. In addition, they found that the willingness to spend resources to reveal information increased with increasing curiosity. Given that replications of findings on curiosity are rare, this study sought to replicate these previous findings in two experiments, with the same stimulus material (Experiment 1) and new stimulus material using COVID-19-related information (Experiment 2). In addition, we extended previous findings by assessing the effect of the importance of information for the participant on the relationship between curiosity and confidence. Our findings replicated previous results in both experiments with (a) highest curiosity regarding information about which participants were moderately confident in knowing and (b) the level of curiosity affecting the decision to spend more time to reveal the answer. We also found that importance ratings positively scaled the level of curiosity. However, importance also interacted with confidence, showing that low-to-moderate confidence ratings, combined with high importance ratings, led to highest curiosity in both experiments – associated with an increased willingness to close this information-gap. Together, these results emphasize the modulatory effect of perceived importance on the interplay between curiosity and confidence in knowing information.

The number of Follicle Stem Cells in a Drosophila ovariole.

A paper by Reilein et al (2017) presented several fundamental new insights into the behavior of adult Follicle Stem Cells (FSCs) in the Drosophila ovary, including evidence that each ovariole hosts a large number of FSCs (14-16) maintained by population asymmetry (Reilein et al., 2017), rather than just two FSCs, dividing with largely individually asymmetric outcomes, as originally proposed (Margolis and Spradling, 1995; Nystul and Spradling, 2007). Fadiga and Nystul (2019) contest some of these conclusions on the basis of their repetition of a multicolor lineage strategy used by Reilein et al (2017) and repetition of earlier single-color lineage analysis. Here we outline a number of shortcomings in the execution and interpretation of those experiments that, in our opinion, undermine their conclusions. The central issue of general relevance concerns the importance of comprehensively analyzing all stem cell lineages, independent of any pre-conceptions, in order to identify all constituents and capture heterogeneous behaviors.

Disasters: An Additional (Legal) Dimension for the International Protection of Cultural Heritage

Even if disasters are a significant challenge for the protection of cultural and natural heritage, the interest of the international community towards this issue has been quite limited for a long period. Still, some changes more recently could be recorded. In particular, a more contextualized and evolutionary interpretation of existing treaty provisions provided by international cultural heritage law, and the development of innovative practices tailored to face this scenario, could provide states with pertinent guidance on measures to be adopted. At the same time cultural concerns have been able to progressively fertilize international disaster law instruments in light of their inherent general relevance. The chapter examines the ways in which these areas of the law interplay and how features commonly associated with community interest norms have characterized this scenario.

Looking into the Recent Past: Extending and Exploring the Field of Archaeology

The archaeology of the recent past is a growing field of research. Is this merely a chronological extension of the field of archaeology, or is it something more? What motivates an archaeological interest in a period of time for which there are so many other sources of information? Here it is argued that the archaeology of the recent past is important not only to bring to light other stories than those generally told, but also to bring to the forc theoretical issues of general relevance for archaeology. The latter concern what material remains can be more than just potential sources of information about the past.

Impact of ambient sound on risk perception in humans: neuroeconomic investigations

Research in the field of multisensory perception shows that what we hear can influence what we see in a wide range of perceptual tasks. It is however unknown whether this extends to the visual perception of risk, despite the importance of the question in many applied domains where properly assessing risk is crucial, starting with financial trading. To fill this knowledge gap, we ran interviews with professional traders and conducted three laboratory studies using judgments of financial asset risk as a testbed. We provide evidence that the presence of ambient sound impacts risk perception, possibly due to the combination of facilitatory and synesthetic effects of general relevance to the perception of risk in many species as well as humans. We discuss the implications of our findings for various applied domains (e.g., financial, medical, and military decision-making), and raise new questions for future research.

Precursor state of chemi-ionization reactions and confinement of valence electrons by anisotropic intermolecular forces

Modifications in atomic alignment and in molecular alignment/orientation determine a different structure of the adduct, formed by collisions of reagents, which represents the precursor state of many elementary chemical–physical processes. The following evolution of the system is directly controlled by the confinement of interacting partners in such a precursor state. However, a deep characterization of these phenomena is still today not fully available, especially when weak intermolecular forces are operative, although the inquiry is of general relevance for the control of the stereodynamics of processes, occurring under a variety of conditions both in gas phase and at surface. In this paper recent advances in the knowledge of the selective role of atomic alignment and molecular orientation effects on the stereodynamics of chemi-ionization reactions will be presented and discussed. These advances represent a basic step along a path whose final target is the complete and internally consistent rationalization and revaluation of the experimental findings already obtained, and published, in our and in other laboratories on chemi-ionization reactions involving as reagent molecules which are of great relevance in several fields. The basic idea is to export important guidelines provided by a recent detailed study of chemi-ionization of noble gas atoms to more complex reactions involving molecules. The main focus of the present paper is on the quantum confinement effects of valence electrons within the reaction transition state. Graphic abstract