The second messenger function of inositol 1,4,5‐ trisphosphate (InsP3) is now well‐defined – it mobilizes Ca2+ from intracellular stores so that cytosolic Ca2+ increases. However, the function of inositol 1,3,4,5‐ tetrakisphosphate (InsP4) has proved much more difficult to fathom, as it has been reported to exert a wide variety of effects in a collection of experimental systems. In this review, a proposed molecular mechanism for InsP4 actions is discussed; it is suggested that InsP4 is the second messenger that controls Ca2+ (...) entry into cells, and that it does so by binding to a receptor which itself interacts, directly or Indirectly, with the receptor for InsP3 It is proposed that this is InsP4's true physiological function, but the mechanism by which it exerts this function has led to confusing data concerning its action, and also to some misconceptions about how inositol phosphates control Ca2+ entry. (shrink)

By their own account, physicalists are committed to the claim that physics is causally complete, or closed. The claim is presented as an empirical one. However, detailed and explicit empirical arguments for the claim are rare. I argue that molecular models are a key source of evidence but that, on closer inspection, they do not support the completeness claim.

The earliest English culinary recipes occur in two Anglo-Norman manuscripts, both in the British Library: Additional 32085 and Royal 12.C.xii. A transcription of the latter, with a few footnotes citing recipes in the former, was published by Paul Meyer in 1893 . Meyer proposed to publish a full version of the earlier manuscript at a later date, but he never did. No new Anglo-Norman collections have turned up since that time, although we have searched in a great number of libraries (...) and their catalogues. In view of recent interest in medieval recipes and advances in our understanding of their terms, it seems time to publish the Additional manuscript, and with it a corrected and fully annotated transcript of the Royal manuscript, although our reading differs from Meyer's only occasionally. (shrink)

Emotional memories are vivid and lasting but not necessarily accurate. Under some conditions, emotion even increases people’s susceptibility to false memories. This review addresses when and why emotion leaves people vulnerable to misremembering events. Recent research suggests that pregoal emotions—those experienced before goal attainment or failure —narrow the scope of people’s attention to information that is central to their goals. This narrow focus can impair memory for peripheral details, leaving people vulnerable to misinformation concerning those details. In contrast, postgoal emotions—those (...) experienced after goal attainment or failure —broaden the scope of attention leaving people more resistant to misinformation. Implications for legal contexts, such as emotion-related errors in eyewitness testimony, are discussed. (shrink)

In Minds, Brains, and Norms , Pardo and Patterson deny that the activities of persons (knowledge, rule-following, interpretation) can be understood exclusively in terms of the brain, and thus conclude that neuroscience is irrelevant to the law, and to the conceptual and philosophical questions that arise in legal contexts. On their view, such appeals to neuroscience are an exercise in nonsense. We agree that understanding persons requires more than understanding brains, but we deny their pessimistic conclusion. Whether neuroscience can be (...) used to address legal issues is an empirical question. Recent work on locked-in syndrome, memory, and lying suggests that neuroscience has potential relevance to the law, and is far from nonsensical. Through discussion of neuroscientific methods and these recent results we show how an understanding of the subpersonal mechanisms that underlie person-level abilities could serve as a valuable and illuminating source of evidence in legal and social contexts. In so doing, we sketch the way forward for a no-nonsense approach to the intersection of law and neuroscience. (shrink)

In spite of advances in medicine and public health, malaria and other mosquito‐borne diseases are on the rise worldwide. Although vaccines, genetically modified mosquitoes and safer insecticides are under development, herein we examine a promising new approach to malaria control through better repellents. Current repellents, usually based on DEET, inhibit host finding by impeding insect olfaction, but have significant drawbacks. We discuss how comparative genomics, using data from the Anopheles genome project, allows the rapid identification of members of three protein (...) classes critical to insect olfaction: odorant‐binding proteins, G‐protein‐coupled receptors, and odorant‐degrading enzymes. A rational design approach similar to that used by the pharmaceutical industry for drug development can then be applied to the development of products that interfere with mosquito olfaction. Such products have the potential to provide more complete, safer and longer lasting protection than conventional repellents, preventing disease transmission by interrupting the parasite life cycle. BioEssays 25:1011–1020, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The comorbidity of chronic pain and opioid addiction is a serious problem that has been growing with the practice of prescribing opioids for chronic pain. Neuroimaging research has shown that chronic pain and opioid dependence both affect brain structure and function, but this is the first study to evaluate the neurophysiological alterations in patients with comorbid chronic pain and addiction. Eighteen participants with chronic low back pain and opioid addiction were compared with eighteen age- and sex-matched healthy individuals in a (...) pain-induction fMRI task. Unified structural equation modeling (SEM) with Lagrange multiplier (LM) testing yielded a network model of pain processing for patient and control groups based on 19 a priori defined regions. Tests of differences between groups on specific regression parameters were determined on a path-by-path basis using z-tests corrected for the number of comparisons. Patients with the chronic pain and addiction comorbidity had increased connection strengths; many of these connections were interhemispheric and spanned regions involved in sensory, affective, and cognitive processes. The affected regions included those that are commonly altered in chronic pain or addiction alone, indicating that this comorbidity manifests with neurological symptoms of both disorders. Understanding the neural mechanisms involved in the comorbidity is crucial to finding a comprehensive treatment, rather than treating the symptoms individually. (shrink)

Douglass North once emphasized that development takes centuries, but he did not have a theory of how and why change occurs. This groundbreaking book advances such a theory by examining in detail why England and Spain developed so slowly from 1000 to 1800. A colonial legacy must go back centuries before settlement, and this book points to key events in England and Spain in the 1260s to explain why Mexico lagged behind the United States economically in the twentieth century. Based (...) on the integration of North's institutional approach with Mancur Olson's collective action theory, Max Weber's theory of value change, and North's focus on dominant coalitions based on rent and military in In the Shadow of Violence, this theory of change leads to exciting new historical interpretations, including the crucial role of the merchant-navy alliance in England and the key role of George Washington's control of the military in 1787. (shrink)

This volume explores how Catholicism began and continues to open its doors to the wider world and to other confessions in embracing ecumenism, thanks to the vision and legacy of the Second Vatican Council. It explores such themes as the twentieth century context preceding the council; parallels between Vatican II and previous councils; its distinctively pastoral character; the legacy of the council in relation to issues such as church-world dynamics, as well as to ethics, social justice, economic activity. Several chapters (...) discuss the role of women in the church before, during, and since the council. Others discern inculturation in relation to Vatican II. The book also contains a wide and original range of ecumenical considerations of the council, including by and in relation to Free Church, Reformed, Orthodox, and Anglican perspectives. Finally, it considers the Council’s ongoing promise and remaining challenges with regard to ecumenical issues, including a groundbreaking essay on the future of ecumenical dialogue by Cardinal Walter Kasper. (shrink)

As I shall be taking issue with Michael Durrant for the bulk of this paper, it is appropriate, as well as a good way to start, to register my endorsement of his arguments in chapter 4 of The Logical Status of God l for the conclusion that sentences about God are typically used to express propositions, and that acts of thanksgiving and petition to God presuppose that some such propositions are true. The present paper is therefore a continuation of Mr (...) Durrant's attempt to locate the status of the term ‘God’ in propositions expressed by sentences of the form ‘God is F’. (shrink)

Interviewet er lavet i juli 2021. Dets formål er at belyse emner, der er centrale i Celikates’ tænkning, f.eks. den voksende højrefløjspopulisme, migration, voldelige versus ikke-voldelige protester, civil ulydighed og den kritiske filosofis rolle i dag. -/- When Celikates and I sat down digitally in July 2021, the interview’s primary purpose was to examine topics central to Celikates’ thinking, such as the rise of right-wing populism, migration, violent versus non-violent protest, civil disobedience, and the role of critical philosophy today.

Donnellan famously argued that while one can fix the reference of a name with a definite description, one cannot thereby have a de re belief about the named object. All that is generated is meta-linguistic knowledge that the sentence “If there is a unique F, then N is F” is true. Donnellan’s argument and the sceptical position are extremely influential. This article aims to show that Donnellan’s argument is unsound, and that the Millian who embraces Donnellan’s scepticism that the reference-fixer (...) cannot secure the relevant de re belief faces a serious problem: Millianism about names plus scepticism about the reference-fixer’s de re belief conflicts with what seems to be an analytical thesis about the relationship between semantic content and understanding. The upshot is that the Millian has good reason to seek an alternative to scepticism. (shrink)

Neural substrates of fatigue in traumatic brain injury are not well understood despite the considerable burden of fatigue on return to productivity. Fatigue is associated with diminishing performance under conditions of high cognitive demand, sense of effort, or need for motivation, all of which are associated with cognitive control brain network integrity. We hypothesize that the pathophysiology of TBI results in damage to diffuse cognitive control networks, disrupting coordination of moment-to-moment monitoring, prediction, and regulation of behavior. We investigate the cingulo-opercular (...) and frontoparietal networks, which are engaged to sustain attention for task and maintain performance. A total of 61 individuals with mild TBI and 42 orthopedic control subjects participated in functional MRI during performance of a constant effort task requiring altering the amount of effort utilized to manually squeeze a pneumostatic bulb across six 30-s trials. Network-based statistics assessed within-network organization and fluctuation with task manipulations by group. Results demonstrate small group differences in network organization, but considerable group differences in the evolution of task-related modulation of connectivity. The mild TBI group demonstrated elevated CO connectivity throughout the task with little variation in effort level or time on task, while CO connectivity diminished over time in controls. Several interregional CO connections were predictive of fatigue in the TBI group. In contrast, FP connectivity fluctuated with task manipulations and predicted fatigue in the controls, but connectivity fluctuations were delayed in the mild traumatic brain injury group and did not relate to fatigue. Thus, the mTBI group’s hyper-connectivity of the CO irrespective of task demands, along with hypo-connectivity and delayed peak connectivity of the FP, may allow for attainment of task goals, but also contributes to fatigue. Findings are discussed in relation to performance monitoring of prediction error that relies on internal cues from sensorimotor feedback during task performance. Delay or inability to detect and respond to prediction errors in TBI, particularly evident in bilateral insula-temporal CO connectivity, corresponds to day-to-day fatigue and fatigue during task performance. (shrink)

In this article I sketch G. N. Lewis’s views on chemical bonding and Linus Pauling’s attempt to preserve Lewis’s insights within a quantum‐mechanical theory of the bond. I then set out two broad conceptions of the chemical bond, the structural and the energetic views, which differ on the extent in which they preserve anything like the classical chemical bond in the modern quantum‐mechanical understanding of molecular structure. †To contact the author, please write to: Department of Philosophy, Durham University, 50 Old (...) Elvet, Durham DH1 3HN, UK; e‐mail: [email protected]. (shrink)

The temperature is 90◦F The temperature is rising..

The epistemological argument against descriptivism about proper names is extremely simple. Fora proper name ‘N’ and definite description ‘F’, the proposition expressed by “If N exists, then N is F is not normally known a priori. But descriptivism about proper names entails otherwise. So descriptivism is false. The argument is widely regarded as sound. This paper aims to establish that the epistemological argument is highly unstable. The problem with the argument is that there seems to be no convincing rationale for (...) the first premise that is independent of a view about the nature of the proposition expressed by the sentence “If N exists, then N is F”. (shrink)

Let S be a signature of operations and relations definable in relation algebra, let R be the class of all S-structures isomorphic to concrete algebras of binary relations with concrete interpretations for symbols in S, and let F be the class of S-structures isomorphic to concrete algebras of binary relations over a finite base. To prove that membership of R or F for finite S-structures is undecidable, we reduce from a known undecidable problem—here we use the tiling problem, the partial (...) group embedding problem and the partial group finite embedding problem to prove undecidability of finite membership of R or F for various signatures S. It follows that the equational theory of R is undecidable whenever S includes the boolean operators and composition. We give an exposition of the reduction from the tiling problem and the reduction from the group embedding problem, and summarize what we know about the undecidability of finite membership of R and of F for different signatures S. (shrink)