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Axion quality problem: keep calm and baryon
Get PDFAxion models generically suffer from a severe quality problem when coupled to gravity. In this article we provide a very simple model with a high quality axion. The axion is a pseudo-Nambu-Goldstone boson of the baryon number symmetry, U(1)B, of a new composite sector that breaks U(1)B spontaneously when it confines. A controlled example is a supersymmetric QCD (SQCD) with Nc = Nf. The axion shift symmetry is automatically protected due to the high dimension of the gauge-invariant baryon operator, with the Peccei-Quinn breaking operators arising at dimension Nc + 2. The standard model gauge group is embedded as a subgroup of the flavor symmetry group of SQCD that has an anomaly with U(1)B, generating the standard coupling with gluons
Separate transcription and splicing gene networks are linked and coordinated by the pRb-E2F pathway
Get PDFThe pRb-E2F pathway is involved in mediating diverse cell fates, and oncogenic disruption of the pathway is regarded as a hallmark of cancer. Recent studies highlighted the pRb-E2F axis as a regulator of a large gene network which includes RNA splicing and transcription targets. Here, we have performed a deep genome-wide analysis of differentially expressed genes (DEGs) and alternatively spliced (AS) RNA targets which highlighted broadly non-overlapping networks of genes that are independently regulated by the pRb-E2F pathway. Individual pathway components, including E2F1, pRb, and PRMT5, either as single or combined knockouts, were found to influence DEG and AS networks but to different extents. An analysis of the E2F1 interactome revealed SRSF2 and HNRNPC as candidate proteins that were able to functionally assist E2F1 in mediating AS events. Moreover, E2F1 AS activity was evident as cells progress through the cell cycle and during the DNA damage response, and apparent in tumour models. Our results highlight gene networks where transcription and splicing are linked and coordinated by the pRb-E2F pathway, and further establish the widespread influence that pRb, E2F1, and PRMT5 have on regulating biological diversity through RNA splicing control
Everyman out: personification drama and the English Reformation
No full textThis thesis is a study of the small-troupe Protestant personification interlude, between the split with the Roman church in the 1530s and the rise of the public playhouses in the 1580s. It is premised on the fact that the everyman, the representative of mankind who had been the defining protagonist of the morality play, suddenly falls away after the Reformation. Scholars have long recognized that the loss of such a mankind-figure happens at some point during the sixteenth century. I argue that it was a direct result of the changed conception of human nature in the Reformation, of which personification plays are an unusually direct bellwether. I study how Protestant playwrights consequently used personified virtue and vice to express their ideas and persuade their audiences, with a focus on John Bale in the 1530s, R. Wever around 1550, William Wager in the 1560s, George Wapull in the 1570s, and Robert Wilson in the 1580s.I frame my discussion in terms of ‘interest’, which I argue is a fruitful way of understanding how dramaturgy and theology were intertwined in the original morality play. To be interested in something, in its Tudor sense, referred to being a stakeholder, an interested party in it; it also meant a ‘right’ or ‘entitlement’ to it; and an ‘influence’ or control over it. The everyman had made us ‘interested parties’ in the action of the play, in the sense of making us unexempt – and he had thereby expressed every man’s own equal potential for virtue and vice. The idea that man has an equal ‘interest’ in his own salvation as in his damnation – an empowerment to be virtuous, or to earn Heaven – was what the Protestants fundamentally denied, and what put everyman out of English drama.Each chapter attempts to consider the theological, pastoral, or polemical use of disinterest in Protestant drama. I also consider aspects of Protestant personification drama which seem to reverse the original ‘interest’ of morality drama by creating a self-enclosed play-world, to which we are primarily curious bystanders. In chapter 1, I look at the earliest play in which the everyman’s absence seems a purposive feature: John Bale’s Three Laws. I argue that its extreme binary of supernatural vice against divine virtue allowed him to express the new disinterest of sinful man in the providential process of reformation, whether personal and national. Chapter 2 turns to the personification of virtue by Protestant playwrights, and argues for a previously untheorized problem: how should virtue be embodied when the idea of ‘human virtue’ has been exposed as a heretical lie? Chapter 3 argues for the figure of the reprobate in Protestant drama as a precursor to later humoral character, especially those of Ben Jonson’s comical satires. Chapter 4 considers the emergence of the city as an evoked locus in personification plays, and argues for George Wapull’s The Tide Tarrieth No Man as the first city comedy. The final chapter turns to the city comedies of Robert Wilson in the 1580s, the only personification playwright to write for the public playhouses. The effect of the public playhouses on personification drama is also the subject of the conclusion.What emerges is that the ideas which separated Protestant theology from medieval can also account for broader changes to theatrical fiction from medieval to early modern
The association between depot medroxyprogesterone acetate and meningiomas: Emerging data and their relevance to the South African context
Get PDFIn the past 2 years, evidence suggesting an association between depot medroxyprogesterone acetate (dMPA) use and meningioma has emerged. As dMPA remains one of the most widely used contraceptive methods worldwide, this finding has led to increasing media attention, and regulatory and legal proceedings. The South African Health Products Regulatory Authority (SAHPRA) has issued a statement acknowledging the association between dMPA exposure and the development for meningiomas. However, the paucity of local data on dMPA use and the incidence of and risk factors for meningioma in both the public and private health sector make it difficult to fully assess the implications in SA. This report discusses the relevance of the association between dMPA and meningiomas in the SA context. We provide a summary of the current data on the risk of meningioma with dMPA exposure, and suggest how this should impact on recommendations for the prescribing and use of dMPA from a public health perspective. We further identify gaps in local data, and propose where efforts should be directed to collect relevant data to inform a rational national contraceptive strategy
Metabolism in Tumour-Induced Bone Disease
Get PDFPurpose of Review: This review highlights recent studies that investigate the metabolic reprogramming that occurs in specific types of bone metastatic cancers, including different types of breast cancer, prostate cancer and multiple myeloma. Recent Findings: Metastatic cancer cells use altered metabolic pathways to adapt in alternate environments. Cancer cells that home towards the bone are able to manipulate their metabolism to survive in the hypoxic microenvironment, shifting between oxidative phosphorylation and glycolysis, whilst also exploiting neighbouring cells within the bone to provide energy and protect against chemotherapies. Summary: Targeting the altered metabolic pathways in cancer cells could be used to improve treatments, reduce tumour burden and prevent the destruction of the bone that occurs in tumour-induced bone disease
Activity in human dorsal raphe nucleus signals changes in behavioural policy
Get PDFThe dorsal raphe nucleus (DRN) is an important source of serotonin to the human forebrain, however there is little consensus about its behavioural function. We build on recent results from animal models to demonstrate that activity in human DRN implements changes in behavioural policy that reflect the distribution of rewards in the environment. We use a foraging-inspired behavioural task to show that human participants change their policy to pursue or reject reward opportunities as a function of the average value of opportunities in the environment. Activity in DRN-but no other neuromodulatory nucleus-signals such policy changes. Patterns of multivariate activity in dorsal anterior cingulate cortex (dACC) and anterior insular cortex (AI), meanwhile, track the relative value of reward opportunities given the average value of the environment. We therefore suggest that DRN, dACC and AI form a circuit in which dACC/AI construct representations of reward opportunities given the current context, and DRN implements changes in behavioural policy based on these representations
Anticipation and prevention of real risks of virtual environments in psychiatry
Get PDFExtended reality (=XR) provides promising opportunities for psychiatry in the future. However, psychiatric patients appear to be particularly vulnerable to virtual exposure. With a focus on virtual embodiment and virtual social interaction, we therefore, 1. describe the specific risks of virtual exposures, 2. discuss them in relation to specific psychopathological symptoms and 3. outline initial strategies that enable safe exposure with a strong emphasis on participatory designs
Is joint attention an essentially communicative relation?
Get PDFIn this paper I provide an elaboration and defence of the claim that joint attention is an essentially communicative relation (‘The Communication Claim’). The Communication Claim is typically advanced with the aim of providing an informative characterisation of what makes joint attention ‘truly joint’ in a way that is not committed to an overly-intellectualistic characterisation of joint attention in early infancy. I argue that existing interpretations of the communication claim fail to live up to this ambition insofar as they succumb either to the charge of over-intellectualism or the charge of under-informativeness. I then argue that this dilemma can be avoided if the communicative relation at play in joint attention is understood minimally, as a form of perceptual interaction that is grounded in our power to capture and direct the attention of others
Perceptions of Biomechanical Devices in Collegiate Baseball Pitchers and Training Staff: A Qualitative Study
Get PDFBackgroundBaseball players, coaches, and clinicians have sought to leverage biomechanical devices to inform training load and injury prevention. A novel biomechanical pitching sleeve and portable force plate have been proposed to track training load, kinetic, and kinematic data. The objective of this study was to identify the barriers and facilitators for use of wearable and portable biomechanical devices among elite baseball pitchers and training staff.Study designQualitative descriptive study nested within a pilot feasibility study.MethodsThis study was conducted at participating team facilities. Collegiate baseball players, coaches, and support staff were recruited. Nine semi-structured focus groups/interviews were conducted using a qualitative guide book and transcribed verbatim. An abductive conventional content analysis was adopted to construct themes for barriers and facilitators for implementation of the novel biomechanical pitching sleeve and portable force plate.ResultsThree themes emerged related to facilitators for the use of the devices. First, knowledge users valued individualized data-informed training. Second, athletes felt empowered to make training decisions through self-awareness. Third, users had a new appreciation for injury prevention strategies. Two themes emerged related to barriers for the use of the devices. First, the data interpretation imposed implementation challenges. Second, the addressing challenges in systemization and integration.ConclusionsThis study provides insight into barriers and facilitators that may improve future implementation of wearable or portable biomechanical devices among players, coaches, and clinicians to aid in informing training regimens and injury prevention strategies
Who Benefits From Right‐to‐Disconnect Legislation in Europe? Cross‐National and Gendered Effects on Employee Wellbeing
Get PDFThe effectiveness of labour regulation depends not only on the formal articulation of rights, but on the institutional arrangements through which those rights are enforced and distributed across workers. This is particularly salient for regulations governing working time and employee availability, where outcomes are shaped by power relations in the workplace and persistent gendered divisions of paid and unpaid labour. The introduction of right‐to‐disconnect (R2D) legislation in several European countries provides a valuable opportunity to examine how procedural labour rights operate across different industrial relations systems and how they generate gender‐differentiated outcomes. Rather than constituting a single policy model, R2D provisions vary substantially in their reliance on collective bargaining, firm‐level discretion and individual characteristics. Using data from the European Social Survey between 2010 and 2022 and exploiting the staggered introduction of R2D policies in France, Belgium, Spain, Ireland and Portugal, this study estimates effects on subjective wellbeing among employees in teleworkable occupations. Applying a dynamic difference‐in‐differences approach, the analysis identifies modest average improvements in wellbeing in countries where R2D provisions are embedded within stronger industrial relations systems. Gendered analyses show that these benefits accrue more consistently to men than to women, highlighting how digital labour regulation may interact with unequal distributions of paid and unpaid work