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An open system approach to gravity
No full textSeveral major open problems in cosmology — including the nature of inflation, dark matter, and dark energy — share a common structure: they involve spacetime-filling media with unknown microphysics, and can be probed so far only through their gravitational effects. This observation motivates a systematic open-system approach to cosmology, in which gravity evolves in the presence of a generic, unobservable environment. In this work, we develop a general framework for open gravitational dynamics based on general relativity and the Schwinger-Keldysh formalism, carefully addressing the nontrivial constraints imposed by diffeomorphism invariance. At the quantum level, our path integral formulation computes the gravitational density matrix in perturbation theory around a semi-classical spacetime.As illustrative applications, we study inflation and the propagation of gravitational waves in classical regimes where environmental interactions are non-negligible. In the inflationary context, our framework reproduces the known Open Effective Field Theory of Inflation in the decoupling limit and extends it to include gravitational interactions. For gravitational waves, we derive the most general conservative and dissipative corrections to propagation. Remarkably, we find that the leading-order gravitational birefringence is dissipative in nature, whereas conservative birefringence appears only at higher derivative order — opposite to the electromagnetic case. Our results pave the way to modeling dissipative effects in the late universe
Hypoactive medial prefrontal cortex functioning in adults reporting childhood emotional maltreatment.
No full textChildhood emotional maltreatment (CEM) has adverse effects on medial prefrontal cortex (mPFC) morphology, a structure that is crucial for cognitive functioning and (emotional) memory and which modulates the limbic system. In addition, CEM has been linked to amygdala hyperactivity during emotional face processing. However, no study has yet investigated the functional neural correlates of neutral and emotional memory in adults reporting CEM. Using functional magnetic resonance imaging, we investigated CEM-related differential activations in mPFC during the encoding and recognition of positive, negative and neutral words. The sample (N = 194) consisted of patients with depression and/or anxiety disorders and healthy controls (HC) reporting CEM (n = 96) and patients and HC reporting no abuse (n = 98). We found a consistent pattern of mPFC hypoactivation during encoding and recognition of positive, negative and neutral words in individuals reporting CEM. These results were not explained by psychopathology or severity of depression or anxiety symptoms, or by gender, level of neuroticism, parental psychopathology, negative life events, antidepressant use or decreased mPFC volume in the CEM group. These findings indicate mPFC hypoactivity in individuals reporting CEM during emotional and neutral memory encoding and recognition. Our findings suggest that CEM may increase individuals' risk to the development of psychopathology on differential levels of processing in the brain; blunted mPFC activation during higher order processing and enhanced amygdala activation during automatic/lower order emotion processing. These findings are vital in understanding the long-term consequences of CEM
The role of KRAB zinc-finger proteins in expanding the domestication potential of transposable elements.
No full textKRAB zinc-finger proteins (KZFPs) are the most abundant family of DNA-binding proteins in humans and primarily induce the epigenetic silencing of transposable elements. While KZFPs use this ability to control the transposition potential of transposable elements, they can also act as epigenetic switches that gate transposable element-derived cis-regulatory modules in a cell context-specific manner. In this way, they participate in the domestication of mobile elements, expanding their ability to establish complex gene regulatory networks. In this Perspective, we discuss emerging evidence that mutations in KZFP genes can explain human disorders and that there is a need to understand the effect of mutations in their transposable element targets. We argue that increased focus on this large yet historically understudied family will greatly contribute to addressing gaps in our understanding of cell lineage specification during development, human phenotypes and related pathologies
Diabolical Affects: The Anxieties and Pleasures of Playing Demons in the Fifteenth Century
No full textAbstract
This essay argues that the performance of demonic, idolatrous, and other illicit acts and identities in fifteenth-century religious drama provoked risky and conflicting feelings in its participants in order to engage them in a competition between licit and illicit spiritual affiliations. By examining a protestatio made by an anxious player in fifteenth-century Avignon, various written saints’ lives, and the two saints’ plays found in MS Digby 133, The Conversion of St Paul and Mary Magdalene, I emphasize the dynamic between ‘sincerity’ and ‘play’ through which participants in these texts—writers, readers, dramatists, performers, audience members—engage in fraught negotiations of how the emotional responses stirred by performance define their ethical and spiritual identities. I argue therefore that the tensions in these texts between pious, spiritual edification and idolatrous, demonic subversion are affective tensions between the competing identities that are formed from the licit or illicit feelings provoked by the performance. By regarding this ‘risky play’ as affective, therefore, I challenge readings of medieval ‘play’ as a straightforward defence against the risk of sacrilege in sacred drama, drawing out the ways in which such a sophisticated dramatic theory still struggles to definitively manage or expel the illicit affects of diabolical play.</jats:p
Theory and realism in economics: Richard R. Nelson, equilibrium and economic change
No full textThis paper revisits the work of Richard R. Nelson (1930–2025), focusing on his critique of equilibrium theory, to explore persistent methodological debates within the field of economics. It examines the tension between theoretical abstraction and empirical realism, arguing that Nelson’s evolutionary approach offers a compelling alternative to the dominant general equilibrium framework. By foregrounding processes of change, uncertainty, and adaptive behaviour, Nelson (alongside Sidney G. Winter) challenges the discipline’s tendency to model economies as static, fully understood systems. While this paper does not aim to provide a comprehensive review of their contributions, it highlights how their critique remains strikingly relevant today. Despite methodological refinements, shifts in research topics and policy engagement, mainstream economics continues to struggle with dynamic, out-of-equilibrium analysis. Revisiting Nelson’s legacy is not only timely, but also essential for those seeking a more realistic and responsive economics
Combining synthetic biology platforms for broad-spectrum influenza vaccine development
No full textInfluenza A viruses (IAVs), the cause of flu, are respiratory pathogens circulating between humans and zoonotic reservoirs. Annual seasonal outbreaks, occasional global pandemics and sporadic zoonotic IAV infections contribute to substantial mortality and morbidity worldwide. Due to rapid antigenic evolution of the viral glycoproteins, licensed, strain-specific seasonal influenza vaccines exhibit suboptimal effectiveness despite annual reformulations. In this thesis, I explore synthetic biology platforms for vaccine antigen design and delivery to develop and assess broad-spectrum influenza immunogens in mice. I produce and validate computationally designed group 1 H5DIOS and H1DIOS haemagglutinins (HAs), generated by the Digitally Immune Optimised Synthetic Vaccine (DIOSynVax) pipeline, as soluble, recombinant proteins. I also engineer and evaluate wild-type (WT) H5 and H1 HAs, which are candidate vaccine viruses recommended by the World Health Organization, as homotypic nanocages, where ordered arrays of the same HA protein are presented on the surface of a self-assembling SpyCatcher003-mi3 protein shell. I show that immunisations with H5DIOS Soluble, H1DIOS Soluble, WT H5 Homotypic Nanocage or WT H1 Homotypic Nanocage immunogens induce cross-reactive neutralising antibody responses within the given IAV subtype. To combine the two platforms, I modify H5DIOS and H1DIOS for homotypic nanocage display. I demonstrate that immunisations with H5DIOS and H1DIOS Homotypic Nanocages expand neutralisation breadth and elicit pan-H5 or -H1 responses, respectively. To assess group 1 synergy, I mix equimolar amounts of H5 and H1 homotypic nanocages to produce admix-2 immunogens and show additive increases in neutralisation breadth against the two matched subtypes. To extend vaccine-induced immunity beyond group 1, I include two additional group 2 HA subtypes, WT H3 and WT H7, to produce admix-4 and mosaic-4 immunogens. I mix equimolar amounts of H5, H1, H3 and H7 homotypic nanocages to produce admix-4 immunogens. I co-display H5, H1, H3 and H7 on nanocages to produce mosaic-4 immunogens. I show that immunisations with admix-4 and mosaic-4 immunogens potently neutralise the four matched strains but generate limited additional neutralisation against other HA subtypes that are not included in the immunogens. These results showcase the potential for computationally designed HA nanocages to enhance seasonal vaccine effectiveness, support pandemic preparedness initiatives and protect high-risk individuals from zoonotic IAV exposure
Electrolyte Effects on Disorder-Enhanced Capacitance in Nanoporous Carbons.
No full textThe impact of pore structure and surface functionality on the capacitance of nanoporous carbons has been widely studied across different electrolytes, yet the role of electrolyte chemistry in structural disorder-driven and ion adsorption capacity-related capacitance remains largely unexplored. In this study, we investigate the relationship between capacitance and the degree of structural order in 20 nanoporous carbons using ionic liquid electrolytes, aiming to establish the generality of disorder-driven capacitance and explore its underlying mechanisms. Our results demonstrate that carbons with smaller graphene-like domains and larger ion adsorption capacities exhibit higher capacitance in 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIBF4) ionic liquid, consistent with our previous findings in 1 M tetraethylammonium tetrafluoroborate (TEABF4) in acetonitrile (ACN). More generally, we find that the capacitance of a given carbon remains similar across different ionic liquid and organic electrolytes, provided that the pores are accessible to the electrolyte ions. This study shows the generality of disorder-driven and adsorption-dependent capacitance in nanoporous carbons in organic and ionic liquid systems and suggests that factors such as the nature of the defects and how they affect quantum capacitance may play an important role in disorder-driven capacitance, ultimately providing insights for designing high-performance supercapacitor electrodes
Decoding Bisexuality: Media Power, Audience Agency, and the Deconstructive Threat of a Bisexual Perspective
No full textWhile there is a growing body of research on the representation of bisexuality in popular culture and the media, very few researchers have consulted bisexual audiences regarding their thoughts, feelings, and practices related to these representations (Hayfield, 2021). Literature on bisexual representations often addresses bisexual erasure and stereotypes and their presumed effects without empirical audience data, which are unable to account for a diverse range of reception practices (Corey, 2017; Nelson, 2023). This thesis addresses this absence, using qualitative interviews with 35 bisexual people living in the UK to begin developing our understanding of the complex relationship between bisexual people and their cultural representation in Western media. I draw on queer and bisexual theories to explore how hetero- and mononormative power constrain the domains of the visual, temporal, epistemic, and ontologic, and to trouble the fixed identity categories that are both the effects and conditions of the oppressive gender binary (Angelides, 2001; Butler, 1990; Doty, 1993; Halberstam, 2005; Hemmings, 2002; Muñoz, 1999). Synthesising theories of power, knowledge, and representation, I explore how media power facilitates the erasure and marginalisation of bisexual people through its central role in maintaining the hegemonic order, reproducing a biphobic regime of representation (Couldry, 2001; Foucault, 1976; Freedman, 2014; Hall, 1997). While media power is difficult to challenge, I utilise audience theories to explore the ways its limitations and contradictions allow for resistant and subversive audience practices, complicating the current presumed effects of bisexual representation (Ang, 1987; Banaji, 2013; Hall, 1973).
As a result of bisexual erasure, my participants described being unable to see and learn about bisexuality in the media, which rendered their fluid subjectivities unintelligible. In reinforcing bisexuality’s deviance, stereotypical bisexual representations impeded my participant’s ability to construct a comfortable identity for themselves, perpetuating feelings of shame and isolation. The erasure and stereotyping that my participants experienced compounded with their additional marginalised identities, perpetuating intersectional harms and exclusions. While some bisexual researchers advocate for increased media representations that directly oppose stereotypes (Chickerella et al., 2021; Corey, 2017), I argue that this approach does not necessarily challenge the hegemonic order which renders bisexuality impossible and deviant, as seeking validation within a system simultaneously validates the system itself.
While the biphobic regime of representation denied my participants the opportunity to see themselves as legitimate members of the social world, they were still able to resist media power in their decoding practices. The threat of bisexual fluidity is dealt with through differentiated and often contradictory mechanisms of domination, allowing for a variety of avenues of resistance to open up. When faced with representations that erase and marginalise bisexuality, my participants resisted harm through practices of turning away from media, looking back critically, disidentifying with stereotypical representations (Muñoz, 1999), and employing a bifocal perspective to see bisexuality where it has seemingly been erased. These findings challenge the often-presumed linear effects of bisexual erasure and stereotypes which deny possibilities of audience agency.
Although media power constrains the domain of the thinkable and imaginable, it simultaneously produces it. I argue that bisexual audiences do more than resist media power, as they engage in cultural production through media consumption. My participants described utilising media representations in their imaginative work, where seeing bisexuality opened up possibilities for their identities and futures. Through media consumption, my participants learned a language to contest their unintelligibility by constructing fluid identities, challenged their feelings of isolation through imagining communities, and fostered hope by imagining alternative futures. While media power works to reinforce the hegemonic order, its limits are exposed in the process. Through locating these limits and exposing their constructed nature, bisexual people can use media to imagine the possibilities and potentialities that exist just beyond our sightlines. I explore the generative tensions that emerge within bisexual decoding practices, where contradictions are not treated as problems to be solved but as productive sites of necessary trouble where alternative ways of knowing, seeing, and being are produced (Butler, 1999). A bifocal perspective recognises both the necessity and the impossibility of seeing bisexuality, exposing the very limits of representation and fixed identity categories. The perpetual failure of bisexual representation does not signal the final victory of the hegemonic order but is instead the site of its undoing, where the threatening spectre of bisexuality persists in its deconstructive promise
Predation via motion parallax in one of two gleaning insects.
No full textA predator's survival is highly dependent on correctly deciding whether to attack potential prey. Pursuit predators, for example, can estimate the size of a moving target from the ratio between its angular speed and size. Such heuristic rules are not available, however, when ambushing stationary prey. Here, we investigated how pixie robber flies (Psilonyx annulatus) and damselflies (Ischnura posita) hunt stationary prey using different sensory strategies, relating to their marked differences in eye morphology. We show that pixie robber flies assess prey using whole-body translational movements. During this assessment, the prey is outside the pixie robber fly's stereopsis range, yet attacks are launched from a distance dictated by absolute, not angular, prey size. These findings suggest that pixie robber flies use motion parallax to infer three-dimensional cues, such as prey distance and/or size, before attacking. Motion parallax may be particularly suitable for pixie robber flies as they hunt in cluttered, low-lighting conditions and have a small size, making it difficult for potential prey to detect their movement, even in close proximity. Damselflies probably rely on alternative processes to assess prey, as translational movements are absent in the assessment phase
Retinal analysis of a mouse model of Alzheimer's disease with multicontrast optical coherence tomography.
Get PDFSignificance. Recent Alzheimer's disease (AD) patient studies have focused on retinal analysis, as the retina is the only part of the central nervous system that can be imaged noninvasively by optical methods. However, as this is a relatively new approach, the occurrence and role of retinal pathological features are still debated. Aim. The retina of an APP/PS1 mouse model was investigated using multicontrast optical coherence tomography (OCT) in order to provide a documentation of what was observed in both transgenic and wild-type mice. Approach. Both eyes of 24 APP/PS1 transgenic mice (age: 45 to 104 weeks) and 15 age-matched wild-type littermates were imaged by the custom-built OCT system. At the end of the experiment, retinas and brains were harvested from a subset of the mice (14 transgenic, 7 age-matched control) in order to compare the in vivo results to histological analysis and to quantify the cortical amyloid beta plaque load. Results. The system provided a combination of standard reflectivity data, polarization-sensitive data, and OCT angiograms. Qualitative and quantitative information from the resultant OCT images was extracted on retinal layer thickness and structure, presence of hyper-reflective foci, phase retardation abnormalities, and retinal vasculature. Conclusions. Although multicontrast OCT revealed abnormal structural properties and phase retardation signals in the retina of this APP/PS1 mouse model, the observations were very similar in transgenic and control mice