Actin plays several essential roles in cellular processes and is a vital component in the contractile apparatus. To accomplish its many cellular tasks, actin must interact with a wide range of other proteins in addition to self‐assembling into filaments. Characterization of these functional domains and localized binding regions on the actin monomer is therefore an important undertaking. Strategies for elucidating the many interaction sites include X‐ray diffraction, NMR and fluorescence spectroscopy, chemical modification, chemical cross‐linking, protein cleavage, and the study of (...) sequence homologies between the many isotypes of actin. Based on these varied data, we discuss the possible spatial relationships between the interaction sites. (shrink)

This book is an accessible text that explores what it means to be human. It is designed for an introductory course in Philosophy of the Human Being. This book contains an abundance of current examples, with embedded quotations from philosophers and selections from contemporary writers following the chapters.

The death of Socrates is often taken as the starting point for reflection on the relationship between the philosopher and established power. In the Apology, Plato gives an account of Socrates’s own...

Las distinciones conceptuales propuestas por Thomas Hobbes reflejan el problema político de considerar lo múltiple en la unidad o la convergencia de innumerables cuerpos, deseos y pasiones en la consolidación de una voluntad soberana unitaria. Ejemplo de ello son las nociones de potentiae (potencias) y potestas (poder), junto a otras como multitud y pueblo o súbditos y soberano. Todas ellas reflejan el problema de la estabilidad del Estado y su legitimidad institucional: la necesidad de generar, de manera continua, un poder (...) común. Con la intención de formular una lectura democrática, el propósito de este artículo es relacionar una lectura iconográfica del frontispicio del Leviatán con la presencia/ausencia de un cuerpo indómito. El trabajo concluye que un rasgo esencial de la teoría política hobbesiana es el sentido de lo democrático fundamentado en la presencia ineludible de cuerpos colectivos que deben ser representados. (shrink)

The present study sought to examine the extent to which the cultural portrayal of online gamers, often in comical, caricatured, or sensational forms, has become transformed into sets of cognitive associations between the category and traits. A total of 342 participants completed an online survey in which they rated how applicable each of a list of traits was to the group of online gamers. Ratings were made for both personal beliefs (how participants themselves see gamers) and stereotypical beliefs (how most (...) others see gamers). While these beliefs were highly consensual as stereotypes, personal beliefs varied, suggesting that the cultural portrayal of online gamers is beginning to shift into cognitive associations. The role of stereotypes in negotiating a group’s social position are discussed arguing that these stereotypes currently position online gamers as low in social status and socially peripheral. The function of the media in generating stereotypical representations of social groups and convincing the public of their validity is also discussed. (shrink)

Child sexual exploitation and abuse has grave implications for the mental health and wellbeing of children and young people. It has been linked to a wide range of difficulties which may extend into adulthood. School-based prevention programs that aim to raise awareness are popular, however, have historically lacked robust and consistent evaluation. The purpose of the present study was therefore to explore young people’s experiences of attending a school-based theater-in-education program, and the impact this had on their awareness and understanding (...) of CSEA. Four focus groups of between four to six participants each were conducted with young people from two co-educational State schools in the United Kingdom. The approach of Template Analysis was used to analyze the data, and revealed a number of themes related to the superordinate themes of “Information and Detail Delivered” and “Format and Timing.” The results suggest that participants gained new awareness and understanding of aspects related to CSEA, including other forms of exploitation, as well as how to avoid harm and what to do “if bad things happen.” Participants further reported that the theater performance/live element of the program was particularly impactful, feeling that this was delivered to them at the right time, but suggesting that younger people would also benefit from the important messages. In addition, areas for improvement were identified in terms of the delivery of the program, and the issue of victim blaming. Findings are discussed with a view to practical implications and directions for future research. (shrink)

The crystal δ‐endotoxins of Bacillus thuringiensis (Bt) are a family of insecticidal proteins which have been known for some time to kill insects by lysing their gut epithelial cells, but the precise molecular mechanism of toxicity has remained elusive. The recent publication of the crystal structure of a Bt δ‐endotoxin has made it possible for us to model the molecular events that occur as the toxin binds to its receptor and inserts into the membrane to form a pore. Using our (...) knowledge of insect gut physiology, we can also predict the effect on the insect of the formation of a toxic pore. We present a new model to explain the events that occur in the insect gut during toxin action. (shrink)

International law enforcement have noted a rise in the use of the Dark Web to facilitate and commit sexual offenses against children, both prior to and since the start of the COVID-19 pandemic. The study presented here therefore aimed to investigate the characteristics and behaviors of anonymous users of Dark Web platforms who were suspected of engaging in the sexual abuse of children. Naturally-occurring data on 53 anonymous suspects, who were active on the Dark Web and had come to police (...) attention in the United Kingdom (UK), were sampled. Analysis of the data yielded 462 features that could be coded reliably. Analysis of these features provided novel insights into suspects’ characteristics, their motivations for using the Dark Web, the nature of the offending behavior they reported engaging in, their technical and security precautions, sexual interests, and the content of their interactions with one another. Findings are discussed in relation to theoretical and practical implications, as well as directions for future research. (shrink)

Background: Altering components of ecological momentary assessment measures to better suit the purposes of individual studies is a common and oftentimes necessary step. Though the inherent flexibility in EMA has its benefits, no resource exists to provide an overview of the variability in how convergent constructs and symptoms have been assessed in the past. The present study fills that gap by examining EMA measurement design for mood and anxiety symptomatology.Methods: Various search engines were used to identify 234 relevant studies. Items (...) administered, data collection schedules, response scales, data collection platforms, and psychometric properties were extracted.Results: Study designs varied greatly in all aspects across the identified papers. Over 4,600 extracted items were qualitatively analyzed, resulting in the identification of 12 themes. The most EMA items focused on affect, with categories such as “happiness” and “tension” appearing most frequently. We provide all of our data extraction in the format of an open-source database.Limitations: Despite our best attempts to include as much of the relevant literature as possible, this review and the accompanying database are not exhaustive, but can easily be built upon to include other, newer studies.Conclusions: The fact that the affect theme featured both positive and negative emotional constructs highlights the dichotomous focus on valence and affect within the literature surrounding anxious and depressive symptomatology. We hope that our database will act as a helpful design decision-making resource for researchers studying this kind of symptomatology in the future.Systematic Review Registration: PROSPERO. (shrink)

Adrian Viens, Guest Editor of this Olivieri symposium, and Julian Savulescu, the Editor of JME, set the scene for the symposium."In failing...[her] when she needed them most, it is now clear that some members of the University’s Faculty of Medicine heard her muffled cries of academic freedom from the back room, yet their response was to serve another round of drinks and turn the music up louder. With the bombshell revelations in the...affair, the plug may have been pulled on (...) this business sponsored party, and hopefully a sober re-examination of the university’s neglected role and responsibility toward independent inquiry and academic freedom can begin.1" "These guys don’t get one thing—we’re not going away. This isn’t a personal vendetta. This is something I want patients to be protected from when I’m dead, fifty years from now.2" "[The Olivieri affair is] not a mystery novel, but instead the latest skulduggery at Toronto’s Hospital for Sick Children.1" "The legal assaults which you have endured in your battle against the drug company, and in your battle against the medical establishment appear to have been fought with the type of uncommon bravery that is rarely seen. It is for this reason that our trustees have unanimously chosen to recognise you for this most prestigious award.3" "[The Olivieri affair resulted from] a fundamental misreading of the issue as a mere contractual and scientific dispute...[it is] Canada’s worst academic and research scandal in decades...[Since 1998, Olivieri has been] demoted, then restored, then harassed. She has been smeared with allegations attacking her competence, integrity, sanity and personality....4"The Olivieri affair is one of the most important events to occur in research ethics. From its dominance in the Canadian and international news media, to changes in the governance of public health, academic medicine, …. (shrink)

Synaesthesia is a neurodevelopmental condition characterised by anomalous sensory perceptions and associated alterations in cognitive function. This chapter summarises what is known about the familial transmission of synaesthesia and its genetic underpinnings. Early familiality studies showed evidence for a strong genetic predisposition, a highly skewed female: male ratio, and an absence of male-to-male transmission. These patterns supported an early hypothesis of a single-gene X-linked dominant mode of inheritance with male lethality. Subsequent analyses in larger samples indicated that the mode of (...) inheritance was likely to be more complex, with both the strong female skew and absence of male-to-male transmission brought into question. We review in detail the first whole genome linkage scan for auditory-visual synaesthesia and a subsequent family linkage study on coloured sequence synaesthesia. Together these results suggest linkage to five chromosomes but give no support for linkage to the X-chromosome. We discuss candidate genes within these regions and potential implications for the aetiology of synaesthesia. We also discuss the implications of these pioneering genome scans for our understanding of synaesthesia and of how different synaesthetic phenotypes may arise from different genetic predispositions interacting with other genes and with the environment. (shrink)

An international team of ethicists refresh the debate about human enhancement by examining whether resistance to the use of technology to enhance our mental and physical capabilities can be supported by articulated philosophical reasoning, or explained away, e.g. in terms of psychological influences on moral reasoning.

Recent research has relied on trolley-type sacrificial moral dilemmas to study utilitarian versus nonutili- tarian modes of moral decision-making. This research has generated important insights into people’s attitudes toward instrumental harm—that is, the sacrifice of an individual to save a greater number. But this approach also has serious limitations. Most notably, it ignores the positive, altruistic core of utilitarianism, which is characterized by impartial concern for the well-being of everyone, whether near or far. Here, we develop, refine, and validate a (...) new scale—the Oxford Utilitarianism Scale—to dissociate individual differences in the ‘negative’ (permissive attitude toward instrumental harm) and ‘positive’ (impartial concern for the greater good) dimensions of utilitarian thinking as manifested in the general population. We show that these are two independent dimensions of proto-utilitarian tendencies in the lay population, each exhibiting a distinct psychological profile. Empathic concern, identification with the whole of humanity, and concern for future generations were positively associated with impartial beneficence but negatively associated with instrumental harm; and although instrumental harm was associated with subclinical psychopathy, impartial beneficence was associated with higher religiosity. Importantly, although these two dimensions were independent in the lay population, they were closely associated in a sample of moral philosophers. Acknowledging this dissociation between the instrumental harm and impartial beneficence components of utilitarian thinking in ordinary people can clarify existing debates about the nature of moral psychology and its relation to moral philosophy as well as generate fruitful avenues for further research. (shrink)

Recent research has begun treating the perennial philosophical question, “what makes a person the same over time?” as an empirical question. A long tradition in philosophy holds that psychological continuity and connectedness of memories are at the heart of personal identity. More recent experimental work, following Strohminger & Nichols (2014), has suggested that persistence of moral character, more than memories, is perceived as essential for personal identity. While there is a growing body of evidence supporting these findings, a critique by (...) Starmans & Bloom (2018) suggests that this research program conflates personal identity with mere similarity. To address this criticism, we explore how loss of someone’s morality or memories influence perceptions of identity change, and perceptions of moral duties towards the target of the change. We present participants with a classic ‘body switch’ thought experiment and after assessing perceptions of identity persistence, we present a moral dilemma, asking participants to imagine that one of the patients must die (Study 1) or be left alone in a care home for the rest of their life (Study 2). Our results highlight the importance of the continuity of moral character, suggesting lay intuitions are tracking (something like) personal identity, not just mere similarity. (shrink)

Self-awareness is thought to be tied to processes of higher-order perspective taking including empathy. These abilities appear to be reserved for humans, great apes, and possibly, dolphins. Recent examinations reveal that both self-awareness and empathy may have origins in the right hemisphere. It is possible that, as in language, lateralization plays a key role in the development of higher-order perspective taking and self-awareness.

Recent sequencing of the metazoan Oikopleura dioica genome has provided important insights, which challenges the current understanding of eukaryotic genome evolution. Many genomic features of O. dioica show deviation from the commonly observed trends in other eukaryotic genomes. For instance, O. dioica has a rapidly evolving, highly compact genome with a divergent intron‐exon organization. Additionally, O. dioica lacks the minor spliceosome and key DNA repair pathway genes. Even with a compact genome, O. dioica contains tandem repeats, comparable to other eukaryotes, (...) and shows lineage‐specific expansion of certain protein domains. Here, we review its genomic features in the context of current knowledge, discuss implications for contemporary biology and identify areas for further research. Analysis of the O. dioica genome suggests that non‐adaptive forces such as elevated mutation rates might influence the evolution of genome architecture. The knowledge of unique genomic features and splicing mechanisms in O. dioica may be exploited for synthetic biology applications, such as generation of orthogonal splicing systems. (shrink)

The article explores the concept of infodemics during the COVID-19 pandemic, focusing on the propagation of false or inaccurate information proliferating worldwide throughout the SARS-CoV-2 health crisis. We provide an overview of disinformation, misinformation and malinformation and discuss the notion of “fake news”, and highlight the threats these phenomena bear for health policies and national and international security. We discuss the mis-/disinformation as a significant challenge to the public health, intelligence, and policymaking communities and highlight the necessity to design measures (...) enabling the prevention, interdiction, and mitigation of such threats. We then present an overview of selected opportunities for applying technology to study and combat disinformation, outlining several approaches currently being used to understand, describe, and model the phenomena of misinformation and disinformation. We focus specifically on complex networks, machine learning, data- and text-mining methods in misinformation detection, sentiment analysis, and agent-based models of misinformation spreading and the detection of misinformation sources in the network. We conclude with the set of recommendations supporting the World Health Organization’s initiative on infodemiology. We support the implementation of integrated preventive procedures and internationalization of infodemic management. We also endorse the application of the cross-disciplinary methodology of Crime Science discipline, supplemented by Big Data analysis and related information technologies to prevent, disrupt, and detect mis- and disinformation efficiently. (shrink)

Great Thinkers A-Z is the ideal book for anyone interested in the history of Western thought and a valuable reference resource for students of philosophy and related disciplines.

This book, the first comprehensive study in English of Heidegger's philosophy of art, starts in the mid-1930s with Heidegger's discussion of the Greek temple and his Hegelian declaration that a great artwork gathers together an entire culture in affirmative celebration of its foundational 'truth', and that, by this criterion, art in modernity is 'dead'. His subsequent work on Hölderlin, whom he later identified as the decisive influence on his mature philosophy, led him into a passionate engagement with the art of (...) Rilke, Ce;zanne, Klee and Zen Buddhism, liberating him not only from the overly restrictive conception of art of the mid-1930s but also from the disastrous politics of the period. Drawing on material hitherto unknown in the anglophone world, Young establishes a new account of Heidegger's philosophy of art and shows that his famous essay 'The Origin of the Work of Art' is its beginning, not its end. (shrink)

In a revolutionary new book, a theoretical physicist attacks the foundations of modern scientific theory, including the notion of time, as he shares evidence of ...

A long-debated question in the philosophy of health, and contingent disciplines, is the extent to which wise clinical practice (“clinical wisdom”) is, or could be, compatible with empirically validated medicine (“evidence-based medicine”—EBM). Here we respond to Baum-Baicker and Sisti, who not only suggest that these two types of knowledge are divided due to their differing sources, but also that EBM can sometimes even hurt wise clinical practice. We argue that the distinction between EBM and clinical wisdom is poorly defined, unsupported (...) by the methodology employed, and ultimately incorrect; crucial differences exist, we argue, not in the source of a particular piece of clinical knowledge, but in its dependability. In light of this subtle but fundamental revision, we explain how clinical wisdom and EBM are—by necessity—complementary, rather than in conflict. We elaborate on how recognizing this relationship can have far-reaching implications for the domains of clinical practice, medical education, and health policy. (shrink)

A Bioética, que podemos qualificar, sem a menor dúvida, como uma ciência jovem - embora cheia de vigor, dinamismo e em plena expansão - se ocupa, desde as multifacetadas óticas das grandes perguntas que se formula a cada dia, o homem moderno, em torno da vida. Neste livro, os autores tratam de alguns aspectos conceituais que, às vezes, são obliterados no discurso bioético. Por exemplo, quais as relações que se interpõem entre Bioética e Direito, começando por delimitar cada uma destas (...) disciplinas. (shrink)

During the set-up phase of an international study of genetic influences on outcomes from sepsis, we aimed to characterise potential differences in ethics approval processes and outcomes in participating European countries. Between 2005 and 2007 of the FP6-funded international Genetics Of Sepsis and Septic Shock project, we asked national coordinators to complete a structured survey of research ethic committee approval structures and processes in their countries, and linked these data to outcomes. Survey findings were reconfirmed or modified in 2017. Eighteen (...) countries participated in the study, recruiting 2257 patients from 160 ICUs. National practices differed widely in terms of composition of RECs, procedures and duration of the ethics approval process. Eight countries used a single centralised process for approval, seven required approval by an ethics committee in each participating hospital, and three required both. Outcomes of the application process differed widely between countries because of differences in national legislation, and differed within countries because of interpretation of the ethics of conducting research in patients lacking capacity. The RECs in four countries had no lay representation. The median time from submission to final decision was 1.5 months; in nine approval was received within 1 month; six took over 6 months, and in one 24 months; had all countries been able to match the most efficient approvals processes, an additional 74 months of country or institution-level recruitment would have been available. In three countries, rejection of the application by some local RECs resulted in loss of centres; and one country rejected the application outright. The potential benefits of the single application portal offered by the European Clinical Trials Regulation will not be realised without harmonisation of research ethics committee practices as well as national legislation. (shrink)

Introduction -- The type/token theory introduced -- Motivating the type/token theory : repeatability -- Nominalist approaches to the ontology of music -- Musical anti-realism -- The type/token theory elaborated -- Types I : abstract, unstructured, unchanging -- Types introduced and nominalism repelled -- Types as abstracta -- Types as unstructured entities -- Types as fixed and unchanging -- Types II : platonism -- Introduction : eternal existence and timelessness -- Types and properties -- The eternal existence of properties reconsidered -- (...) Types and patterns -- Defending the type/token theory I -- Unstructuredness and analogical predication -- Musical works as fixed and unchanging -- Abstractness and audibility (again) -- Works and interpretations -- Conclusion and resumé -- Defending the type/token theory II : musical platonism -- Platonism it is : replies to Anderson and Levinson -- The existence conditions of works of music -- Composition as creative discovery -- The nature of the compositional process : replies to objections -- Composition and aesthetic appraisal : a reply to Levinson -- Composition and aesthetic appraisal : understanding, interpretation, and correctness -- Musical works as continuants : a theory rejected -- A theory introduced -- Explicating and motivating the continuant view -- The continuant view and repeatability -- Further objections to the continuant view -- Musical works as compositional actions : a critique -- Currie's action-type hypothesis -- Davies's performance theory -- Sonicism I : against instrumentalism -- Sonicism introduced -- Sonicism motivated : moderate empiricism -- Instrumentation : timbral sonicism introduced -- Scores -- Instrumentation, artistic properties, and aesthetic content -- Levinson's rejoinder -- Sonicism II : against contextualism -- Introduction : formulating contextualism -- Contextualist ontological proposals -- Levinson's doppelgänger thought-experiments -- Artistic, representational, and object-directed expressive properties -- Aesthetic and non-object-directed expressive properties -- Conclusion : the place of context. (shrink)

This groundbreaking work considers one of the central themes of archaeology, time, which until recently has been taken for granted. It considers how time is used and perceived by archaeology and also how time influences the construction of identities. The book presents case studies, eg, transition from hunter gather to farming in early Neolithic, to examine temporality and identity. Drawing upon the work of Martin Heidegger, Thomas develops a way of writing about the past in which time is seenm as (...) central to the emergence of the identities of peoples and things. He questions the modern western distinction between nature and culture, mind and body, object and subject, and argues that in some senses the temporal structure of human beings, artefacts and places are similar. (shrink)

Development-oriented funding schemes such as the UK Global Challenges Research Fund (GCRF) have opened up opportunities for collaborations between low-middle income countries (LMICs) and high-income country (HIC) researchers. In particular, funding for medical technology research has seen a rise in previously under-represented disciplines such as physics and engineering. These collaborations have considerable potential to advance healthcare in LMICs, yet can pose challenges experienced to researchers undertaking these collaborations. Key challenges include a lack of tradition of HIC/LMIC collaborations within participating departments, (...) lack of experience with development agendas, designing contextually-appropriate technologies and ensuring long-term viability of research outputs. This paper reflects on these key challenges, using the experiences of the authors on the Open Laboratory Instrumentation (OLI) project as a focalizing lens. This project was a GCRF-funded collaboration between physicists in the UK and engineers in Tanzania to develop an open-source, 3D-printed, fully-automated laboratory microscope. The paper highlights key ethics lessons learnt. (shrink)