Argument and explanation.

In this paper, we bring together two closely related, but distinct, notions: argument and explanation. We clarify their relationship. We then provide an integrative review of relevant research on these notions, drawn both from the cognitive science and the artificial intelligence (AI) literatures. We then use this material to identify key directions for future research, indicating areas where bringing together cognitive science and AI perspectives would be mutually beneficial. This article is part of a discussion meeting issue 'Cognitive artificial intelligence'.

Science Communication as a Collective Intelligence Endeavor: A Manifesto and Examples for Implementation.

Effective science communication is challenging when scientific messages are informed by a continually updating evidence base and must often compete against misinformation. We argue that we need a new program of science communication as collective intelligence-a collaborative approach, supported by technology. This would have four key advantages over the typical model where scientists communicate as individuals: scientific messages would be informed by (a) a wider base of aggregated knowledge, (b) contributions from a diverse scientific community, (c) participatory input from stakeholders, and (d) better responsiveness to ongoing changes in the state of knowledge.

BARD: A Structured Technique for Group Elicitation of Bayesian Networks to Support Analytic Reasoning.

In many complex, real-world situations, problem solving and decision making require effective reasoning about causation and uncertainty. However, human reasoning in these cases is prone to confusion and error. Bayesian networks (BNs) are an artificial intelligence technology that models uncertain situations, supporting better probabilistic and causal reasoning and decision making. However, to date, BN methodologies and software require (but do not include) substantial upfront training, do not provide much guidance on either the model building process or on using the model for reasoning and reporting, and provide no support for building BNs collaboratively. Here, we contribute a detailed description and motivation for our new methodology and application, Bayesian ARgumentation via Delphi (BARD). BARD utilizes BNs and addresses these shortcomings by integrating (1) short, high-quality e-courses, tips, and help on demand; (2) a stepwise, iterative, and incremental BN construction process; (3) report templates and an automated explanation tool; and (4) a multiuser web-based software platform and Delphi-style social processes. The result is an end-to-end online platform, with associated online training, for groups without prior BN expertise to understand and analyze a problem, build a model of its underlying probabilistic causal structure, validate and reason with the causal model, and (optionally) use it to produce a written analytic report. Initial experiments demonstrate that, for suitable problems, BARD aids in reasoning and reporting. Comparing their effect sizes also suggests BARD's BN-building and collaboration combine beneficially and cumulatively.

When Science Becomes Embroiled in Conflict: Recognizing the Public's Need for Debate while Combating Conspiracies and Misinformation.

Most democracies seek input from scientists to inform policies. This can put scientists in a position of intense scrutiny. Here we focus on situations in which scientific evidence conflicts with people's worldviews, preferences, or vested interests. These conflicts frequently play out through systematic dissemination of disinformation or the spreading of conspiracy theories, which may undermine the public's trust in the work of scientists, muddy the waters of what constitutes truth, and may prevent policy from being informed by the best available evidence. However, there are also instances in which public opposition arises from legitimate value judgments and lived experiences. In this article, we analyze the differences between politically-motivated science denial on the one hand, and justifiable public opposition on the other. We conclude with a set of recommendations on tackling misinformation and understanding the public's lived experiences to preserve legitimate democratic debate of policy.

Conditionals and testimony.

Conditionals and conditional reasoning have been a long-standing focus of research across a number of disciplines, ranging from psychology through linguistics to philosophy. But almost no work has concerned itself with the question of how hearing or reading a conditional changes our beliefs. Given that we acquire much-perhaps most-of what we believe through the testimony of others, the simple matter of acquiring conditionals via others' assertion of a conditional seems integral to any full understanding of the conditional and conditional reasoning. In this paper we detail a number of basic intuitions about how beliefs might change in response to a conditional being uttered, and show how these are backed by behavioral data. In the remainder of the paper, we then show how these deceptively simple phenomena pose a fundamental challenge to present theoretical accounts of the conditional and conditional reasoning - a challenge which no account presently fully meets.

Cancellation, negation, and rejection.

In this paper, new evidence is presented for the assumption that the reason-relation reading of indicative conditionals ('if A, then C') reflects a conventional implicature. In four experiments, it is investigated whether relevance effects found for the probability assessment of indicative conditionals (Skovgaard-Olsen, Singmann, & Klauer, 2016a) can be classified as being produced by (a) a conversational implicature, (b) a (probabilistic) presupposition failure, or (c) a conventional implicature. After considering several alternative hypotheses, and the accumulating evidence from other studies as well, we conclude that the evidence is most consistent with the Relevance Effect being the outcome of a conventional implicature. This finding indicates that the reason-relation reading is part of the semantic content of indicative conditionals, albeit not part of their primary truth-conditional content.

Preparing the lethal hit: interplay between exo- and endocytic pathways in cytotoxic T lymphocytes.

Cytotoxic T lymphocytes patrol our body in search for infected cells which they kill through the release of cytotoxic substances contained in cytotoxic granules. The fusion of cytotoxic granules occurs at a specially formed contact site, the immunological synapse, and is tightly controlled to ensure specificity. In this review, we discuss the contribution of two intracellular compartments, endosomes and cytotoxic granules, to the formation, function and disassembly of the immunological synapse. We highlight a recently proposed sequential process of fusion events at the IS upon target cell recognition. First, recycling endosomes fuse with the plasma membrane to deliver cargo required for the docking of cytotoxic granules. Second, cytotoxic granules arrive and fuse upon docking in a SNARE-dependent manner. Following fusion, membrane components of the cytotoxic granule are retrieved through endocytosis to ensure the fast, efficient serial killing of target cells that is characteristic of cytotoxic T lymphocytes.

How We Can Rebuild Trust in Science-And Why We Must.

"… Achieving our core mission, namely progress through knowledge, now requires two kinds of communication: one to our scientific peers, but another, more fraught yet critical, to the broader public. As scientists, we need to forge a better relationship between the world of research and the general public …" Read more in the Guest Editorial by K. Boele-Woelki, J. S. Francisco, U. Hahn, and J. Herz.

Scholarly Integrity.

"… Scholarly integrity is not only the foundational bedrock of scientific inquiry, it is also the prerequisite for a positive image of scholarship … For individuals, integrity is an aspect of moral character and experience. For institutions, it is about creating an environment that promotes responsible conduct … In the first instance, research institutions must provide guidelines and codes of practice on scholarly integrity …" Read more in the Editorial by J. S. Francisco, U. Hahn, and H. Schwarz.

A pessimistic view of optimistic belief updating.

Received academic wisdom holds that human judgment is characterized by unrealistic optimism, the tendency to underestimate the likelihood of negative events and overestimate the likelihood of positive events. With recent questions being raised over the degree to which the majority of this research genuinely demonstrates optimism, attention to possible mechanisms generating such a bias becomes ever more important. New studies have now claimed that unrealistic optimism emerges as a result of biased belief updating with distinctive neural correlates in the brain. On a behavioral level, these studies suggest that, for negative events, desirable information is incorporated into personal risk estimates to a greater degree than undesirable information (resulting in a more optimistic outlook). However, using task analyses, simulations, and experiments we demonstrate that this pattern of results is a statistical artifact. In contrast with previous work, we examined participants' use of new information with reference to the normative, Bayesian standard. Simulations reveal the fundamental difficulties that would need to be overcome by any robust test of optimistic updating. No such test presently exists, so that the best one can presently do is perform analyses with a number of techniques, all of which have important weaknesses. Applying these analyses to five experiments shows no evidence of optimistic updating. These results clarify the difficulties involved in studying human 'bias' and cast additional doubt over the status of optimism as a fundamental characteristic of healthy cognition.

Novel substituted isoxazole FXR agonists with cyclopropyl, hydroxycyclobutyl and hydroxyazetidinyl linkers: Understanding and improving key determinants of pharmacological properties.

Several isoxazole-containing series of FXR agonists have been published over the last 15years, subsequent to the prototypical amphiphilic 'hammerhead'-type structure that was originally laid out by GW4064, the first potent synthetic FXR agonist. A set of novel compounds where the hammerhead is connected to the terminal carboxylic acid-bearing aryl or heteroaryl moiety by either a cyclopropyl, a hydroxycyclobutyl or a hydroxyazetidinyl linker was synthesized in order to improve upon the ADME properties of such isoxazoles. The resulting compounds all demonstrated high potencies at the target receptor FXR but with considerable differences in their physicochemical and in vivo profiles. The structure-activity relationships for key chemical features that have a major impact on the in vivo pharmacology of this series are discussed.

Perceptuo-motor, cognitive, and description-based decision-making seem equally good.

Classical studies suggest that high-level cognitive decisions (e.g., choosing between financial options) are suboptimal. In contrast, low-level decisions (e.g., choosing where to put your feet on a rocky ridge) appear near-optimal: the perception-cognition gap. Moreover, in classical tasks, people appear to put too much weight on unlikely events. In contrast, when people can learn through experience, they appear to put too little weight on unlikely events: the description-experience gap. We eliminated confounding factors and, contrary to what is commonly believed, found results suggesting that (i) the perception-cognition gap is illusory and due to differences in the way performance is assessed; (ii) the description-experience gap arises from the assumption that objective probabilities match subjective ones; (iii) people's ability to make decisions is better than the classical literature suggests; and (iv) differences between decision-makers are more important for predicting peoples' choices than differences between choice tasks.

The nuclear bile acid receptor FXR controls the liver derived tumor suppressor histidine-rich glycoprotein.

The nuclear bile acid receptor Farnesoid X receptor (FXR) is strongly expressed in liver and intestine, controls bile acid and lipid homeostasis and exerts tumor-protective functions in liver and intestine. Histidine-rich glycoprotein (HRG) is an abundant plasma protein produced by the liver with the proposed function as a pattern recognition molecule involved in the clearance of immune complexes, necrotic cells and pathogens, the modulation of angiogenesis, the normalization of deranged endothelial vessel structure in tumors and tumor suppression. FXR recognition sequences were identified within a human HRG promoter fragment that mediated FXR/FXR-agonist dependent reporter gene activity in vitro. We show that HRG is a novel transcriptional target gene of FXR in human hepatoma cells, human upcyte® primary hepatocytes and 3D human liver microtissues in vitro and in mouse liver in vivo. Prolonged administration of the potent nonsteroidal FXR agonist PX20606 increases HRG levels in mouse plasma. Finally, daily oral administration of this FXR agonist for seven days resulted in a significant increase of HRG levels in the plasma of healthy human male volunteers during a clinical Phase I safety study. HRG might serve as a surrogate marker indicative of liver-specific FXR activation in future human clinical studies. Furthermore, potent FXR agonists might be beneficial in serious health conditions where HRG is reduced, for example, in hepatocellular carcinoma but also other solid cancers, liver failure, sepsis and pre-eclampsia.

Individuals, Collectives, and Individuals in Collectives: The Ineliminable Role of Dependence.

Our beliefs are inextricably shaped through communication with others. Furthermore, even conversation we conduct in pairs may itself be taking place across a wider, connected social network. Our communications, and with that our thoughts, are consequently typically those of individuals in collectives. This has fundamental consequences with respect to how our beliefs are shaped. This article examines the role of dependence on our beliefs and seeks to demonstrate its importance with respect to key phenomena involving collectives that have been taken to indicate irrationality. It is argued that (with the benefit of hindsight) these phenomena no longer seem surprising when one considers the multiple dependencies that govern information acquisition and the evaluation of cognitive agents in their normal (i.e., social) context.

Knowledge through social networks: Accuracy, error, and polarisation.

This paper examines the fundamental problem of testimony. Much of what we believe to know we know in good part, or even entirely, through the testimony of others. The problem with testimony is that we often have very little on which to base estimates of the accuracy of our sources. Simulations with otherwise optimal agents examine the impact of this for the accuracy of our beliefs about the world. It is demonstrated both where social networks of information dissemination help and where they hinder. Most importantly, it is shown that both social networks and a common strategy for gauging the accuracy of our sources give rise to polarisation even for entirely accuracy motivated agents. Crucially these two factors interact, amplifying one another's negative consequences, and this side effect of communication in a social network increases with network size. This suggests a new causal mechanism by which social media may have fostered the increase in polarisation currently observed in many parts of the world.

The impact of explanations as communicative acts on belief in a claim: The role of source reliability.

Providing an explanation is a communicative act. It involves an explainee, a person who receives an explanation, and an explainer, a person (or sometimes a machine) who provides an explanation. The majority of research on explanation has focused on how explanations alter explainees' beliefs. However, one general feature of communicative acts is that they also provide information about the speaker (explainer). Work on argumentation suggests that the speaker's reliability interacts with the content of the speaker's message and has a significant impact on argument strength. In five experiments we explore the interplay between explanation, the explainee's confidence in what is being explained, and the explainer's reliability. Experiment 1 replicates results from previous literature on the impact of explanations on an explainee's confidence in what is being explained using real-world explanations. Experiments 2 and 3 show that providing an explanation not only impacts the explainee's confidence about what is being explained but also influences beliefs about the reliability of the explainer. Additionally, the two experiments demonstrate that the impact of explanation on the explainee's confidence is mediated by the reliability of the explainer. In Experiment 4, we experimentally manipulated the explainer's reliability and found that both the explainer's reliability and whether or not an explanation was provided have a significant effect on the explainee's confidence in what is being explained. In Experiment 5, we observed an interaction between providing an explanation and the explainer's reliability. Specifically, we found that providing an explanation has a significantly greater impact on the explainee's confidence in what is being explained when the explainer's reliability is low compared to when that reliability is high. Throughout the study we point to the important impact of background knowledge, warranting further studies on this matter.

Similarity and structured representation in human and nonhuman apes.

How we judge the similarity between objects in the world is connected ultimately to how we represent those objects. It has been argued extensively that object representations in humans are 'structured' in nature, meaning that both individual features and the relations between them can influence similarity. In contrast, popular models within comparative psychology assume that nonhuman species appreciate only surface-level, featural similarities. By applying psychological models of structural and featural similarity (from conjunctive feature models to Tversky's Contrast Model) to visual similarity judgements from adult humans, chimpanzees, and gorillas, we demonstrate a cross-species sensitivity to complex structural information, particularly for stimuli that combine colour and shape. These results shed new light on the representational complexity of nonhuman apes, and the fundamental limits of featural coding in explaining object representation and similarity, which emerge strikingly across both human and nonhuman species.

Synthetic farnesoid X receptor agonists induce high-density lipoprotein-mediated transhepatic cholesterol efflux in mice and monkeys and prevent atherosclerosis in cholesteryl ester transfer protein transgenic low-density lipoprotein receptor (-/-) mice.

Farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor, plays an important role in the regulation of cholesterol and more specifically high-density lipoprotein (HDL) homeostasis. Activation of FXR is reported to lead to both pro- and anti-atherosclerotic effects. In the present study we analyzed the impact of different FXR agonists on cholesterol homeostasis, plasma lipoprotein profiles, and transhepatic cholesterol efflux in C57BL/6J mice and cynomolgus monkeys and atherosclerosis development in cholesteryl ester transfer protein transgenic (CETPtg) low-density lipoprotein receptor (LDLR) (-/-) mice. In C57BL/6J mice on a high-fat diet the synthetic FXR agonists isopropyl 3-(3,4-difluorobenzoyl)-1,1-dimethyl-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylate (FXR-450) and 4-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methoxy]phenyl]cyclopropyl]benzoic acid (PX20606) demonstrated potent plasma cholesterol-lowering activity that affected all lipoprotein species, whereas 3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]benzoic acid (GW4064) and 6-ethyl chenodeoxycholic acid (6-ECDCA) showed only limited effects. In FXR wild-type mice, but not FXR(-/-) mice, the more efficacious FXR agonists increased fecal cholesterol excretion and reduced intestinal cholesterol (re)uptake. In CETPtg-LDLR(-/-) mice PX20606 potently lowered total cholesterol and, despite the observed HDL cholesterol (HDLc) reduction, caused a highly significant decrease in atherosclerotic plaque size. In normolipidemic cynomolgus monkeys PX20606 and 6-ECDCA both reduced total cholesterol, and PX20606 specifically lowered HDL(2c) but not HDL(3c) or apolipoprotein A1. That pharmacological FXR activation specifically affects this cholesterol-rich HDL(2) subclass is a new and highly interesting finding and sheds new light on FXR-dependent HDLc lowering, which has been perceived as a major limitation for the clinical development of FXR agonists.

Knowing when to move on: cognitive and perceptual decisions in time.

We investigated people's ability to decide how much time to spend on the task at hand. To make such decisions well, one must take into account, among other things, the cost of failing and how one's task performance changes as a function of time. We first investigated timing decisions when the underlying task was perceptual. Decisions were highly efficient and suggested that people can make good use of perceptual knowledge and abstract reward information. Previous studies have found that perceptual decisions are generally optimal, but that cognitive decisions are generally suboptimal--a perception-cognition gap. Does a similar gap exist for timing decisions? We compared timing decisions for a perceptual task with timing decisions for more cognitive tasks. Performance was highly similar across the tasks, which suggests that knowledge can be acquired, and used to make timing decisions, in an equally efficient way regardless of whether that knowledge is derived through perceptual or cognitive experience.

Collectives and Epistemic Rationality.

Consideration of collectives raises important questions about human rationality. This has long been known for questions about preferences, but it holds also with respect to beliefs. For one, there are contexts (such as voting) where we might care as much, or more, about the rationality of a collective than the rationality of the individuals it comprises. Here, a given standard may yield competing assessments at the individual and the collective level, thus giving rise to important normative questions. At the same time, seemingly rational strategies of individuals may have surprising consequences, or even fail, when exercised by individuals within collectives. This paper will illustrate these considerations with examples, provide an overview of different formal frameworks for understanding and assessing the beliefs of collectives, and it will illustrate how such frameworks can combine with simulations in order to elucidate epistemic norms.