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Radial canonical AdS 3 gravity and T T ¯
No full textWe employ an ADM deparametrization strategy to discuss the radial canonical formalism of asymptotically AdS3 gravity. It leads to the identification of a radial ‘time’ before quantization, which is the volume time, canonically conjugate to York time. Holographically, this allows to interpret the semi-classical path integral of TT¯ theory as a Schrödinger wavefunctional satisfying a Schrödinger evolution equation in volume time, and the TT¯ operator expectation value in terms of the Hamiltonian that generates volume time translations — both consistent with cut-off holography. We make use of the canonical perspective to construct the rotating BTZ solution from the Hamilton-Jacobi equation, with a finite cut-off energy spectrum that has a known holographic TT¯ interpretation, as well as semi-classical Wheeler-DeWitt states for that solution
Repetition positivity following auditory intensity or frequency changes in young normal-hearing adults.
No full textINTRODUCTION: Generative mechanisms of perception such as predictive coding are used to explain how the brain perceives the world; such mechanisms are often experimentally probed using "deviant" stimuli that violate established patterns (including mismatch negativity), which also elicit responses related to lower-level processes such as stimulus-specific adaptation. However, little is still known about brain responses that indicate the strength of sensory predictions or reinforcement of sensory representations. Repetition positivity (RP) is a positive polarity evoked potential that gradually increases with each repetition of a stimulus, and is thought to reflect progressive strengthening of auditory sensory memory and/or habituation to repetitive stimuli. The aim of this study was to compare RP that follows a change in stimulus frequency with that following a change in stimulus intensity, the latter having not previously been studied. METHODS: We used roving sequences of isochronous 5 kHz pure tones (300 ms duration, 300ms inter-stimulus interval), which changed in frequency by 1 kHz (Experiment 1) or in intensity by 12 dB (Experiment 2) after every 30 stimuli. All changes were roving, such that an increase would be followed by a decrease, and vice versa. RESULTS: Event-related potentials recorded with EEG indicated that frequency changes in either direction were followed by RP, whilst only intensity increases were followed by RP, and only a weak visual trend toward RP was apparent for intensity decreases. Observed RP was best explained by a logarithmic function over successive stimuli. CONCLUSIONS: RP robustly follows increases, but not necessarily decreases, in stimulus intensity, which appears smaller in amplitude than that elicited by similarly salient frequency changes, and reaches a plateau sooner. These observations offer insight into how intensity is processed similarly yet differently to other sensory attributes in an adaptive or predictive coding framework, and might have future utility in the study of clinical conditions related to aberrant predictive mechanisms
A progressive framework for green industrial policy
No full textIn the age of ecological breakdown, there is a growing need for ‘green’ industrial policy. However, existing frameworks for green industrial policy fail to address unsustainable growth in energy and resource use in high-income economies. In this sense, they are not adequate to achieve core ecological objectives. This paper fills a gap in the literature by offering a progressive framework for green industrial policy that combines traditional green industrial policy perspectives with insights from ecological economics and literature on post-growth and degrowth. The framework has three key pillars: (1) scale down ecologically harmful industries and sectors to directly reduce energy and resource use; (2) organise production more around public benefit, with greater democratic control and guidance over investment and production; and (3) work towards global ecological justice and enable greater ‘ecological policy space’ for the global South to pursue industrial development. The paper argues that this progressive approach to green industrial policy is necessary due to the scale and urgency of the ecological crisis. The framework shows how productive capacity can be liberated and redirected towards more socially and environmentally beneficial ends, while also democratising control over the economy
A Twist of Fate: The Helix-Turn-Helix Motif in Pseudomonas aeruginosa ExsA Can Allosterically Stabilize the Ligand-Binding Domain.
No full textPseudomonas aeruginosa is an opportunistic human pathogen. One of the most potent virulence factors in its arsenal is the type III secretion system (T3SS). This secretion apparatus injects effector toxins directly into host cells, thereby causing cytotoxicity. The expression of all components of T3SS is regulated by a master transcriptional regulator, ExsA. The inhibition of the latter should therefore lead to the suppression of P. aeruginosa virulence. However, to date, no drugs targeting ExsA have reached the market, and only static structural models of the protein have been generated, focusing on the C-terminal domain (CTD). Here, we used μs atomistic molecular dynamics (MD) simulations to investigate the conformational dynamics of full-length ExsA bound to DNA or DNA free, investigated as monomers or dimers. Our data show how the CTD and NTD of ExsA likely interact with one another and how ExsA binds to DNA. We also analyzed the MD trajectories to predict potential druggable pocket(s) in the structure and relevant geometry. This revealed a lipid-binding pocket within the β-sheet bundle and identified two novel potentially druggable pockets at the NTD/CTD interface, which could be used in future structure-based drug discovery campaigns. Overall, a single helix-turn-helix motif seems to drive DNA recognition in each ExsA monomer and to stabilize the putative ligand-binding domain
Hydrogen Vacancy Induced Superconductivity Collapse in A15 Lanthanum Hydride
No full textHydrogen-rich lanthanum compounds show the highest known superconducting transition temperatures at high pressure. Despite the pivotal role of hydrogen within these systems, there has been no systematic exploration of how the composition and superconducting properties are intertwined. Our experimental and computational studies demonstrate that A15-type LaH 5.75 − x hosts high- T c superconductivity ( T c = 98 K at 94 GPa) when available interstitial sites are fully occupied with hydrogen. Upon decompression, a site-selective hydrogen depopulation drives a superconductor-to-insulator transition with a threshold composition of LaH 5 . Strikingly, the A15 framework is experimentally retained from 120 to 4 GPa, with reversible pressure-dependent hydrogen content changes from LaH 5.75 down to LaH 3.25 . Our results demonstrate the exceptional stability and tunability of the A15 framework, offering a unique platform to probe the interplay between composition, structure, and superconductivity in hydrogen-rich materials
The colloidal stability of albumin-based drug delivery systems has a profound effect on tumoricidal activity.
No full textHuman serum albumin (HSA) has attracted significant attention in drug delivery since the approval of Abraxane in 2005. Abraxane is a nanoparticle albumin-bound paclitaxel (nab-PTX) formulation. Although HSA offers advantages such as prolonged circulation time (half-life ~19 days) and intrinsic hydrophobic pockets, the translation of other HSA-based nanomedicines remains limited. In fact, the significant differences between native and pharmaceutical HSA in protein structure and biological interactions could hinder their translational use in drug delivery. In this study, we demonstrate that pharmaceutical HSA (α-helix = 17%) is structurally denatured compared with native HSA (α-helix = 68%), leading to rapid clearance (<1 h) from the circulation and that drug loading is driven by pharmaceutical HSA's amphiphilicity rather than by its hydrophobic pockets. Here, we revealed that Nab-PTX is composed of protein-coated PTX solid cores. These nanosystems have insufficient surface charge (ζ = -13.7 mV), leading to aggregation, and low colloidal stability, resulting in premature drug release upon dilution (<0.1 mg/mL). To address these shortcomings, we developed HSA-polylactic acid (HSA-PLA) nanoparticles with enhanced negative surface charge (ζ = -27.4 mV) and improved colloidal stability to reduce the premature release of encapsulated PTX upon dilution (<0.01 mg/mL). In tumor models, comparative pharmacokinetics, biodistribution, and efficacy studies demonstrated that HSA-PLA (PTX) nanoparticles reduce premature drug release, resulting in greater tumor exposure (129 ± 3 vs. 90 ± 12 µg·h/g, p < 0.01) and superior antitumor efficacy compared with Abraxane. These improvements further suggest that optimization may require only a simple modification when guided by proper theoretical principles
Spin Glass to Paramagnetic Transition and Triple Point in Spherical SK Model
No full textThis paper studies spin glass to paramagnetic transition in the Spherical Sherrington–Kirkpatrick model with ferromagnetic Curie-Weiss interaction with coupling constant J and inverse temperature β. The disorder of the system is represented by a general Wigner matrix. We confirm a conjecture of Baik and Lee (Stat Phys 165(2):185–224, 2016; Ann Henri Poincaré 18(6):1867–1917, 2017), that the critical window of temperatures for this transition is β=1+bN-1/3logN with b∈R. The limiting distribution of the scaled free energy is Gaussian for negative b and a weighted linear combination of independent Gaussian and Tracy–Widom components for positive b. In the special case where the Wigner matrix is from the Gaussian Orthogonal or Unitary Ensemble, we describe the triple point transition between spin glass, paramagnetic, and ferromagnetic regimes in a critical window for (β,J) around the triple point (1, 1): the Tracy–Widom component is replaced by the one parameter family of deformations described by Bloemendal and Virág [9]
Feeling Time Differently: Autistic Temporality, Self-Care Technologies & Social Imaginaries of the Good Life
No full textDominant cognitive theories of autism often emphasise a deficit-oriented perspective, framing challenges in social communication, perspective-taking, and emotional comprehension as impairments in Theory of Mind. This narrative reinforces autistic people’s mental health struggles, as prevailing accounts of social difficulties frequently overshadow the nuances of autistic lived experiences. This thesis moves beyond deficit-based characterisations by conceptualising autism as a form of life that Ian Hacking describes, wherein autistic temporality represents an alternative mode of being – one shaped by a misalignment between the autistic body’s rhythms, embodiment, and intersubjective connectedness within a predominantly neurotypical world.
Through an analysis of human-technology entanglements, particularly digital self-tracking tools, assistive technologies, and alternative communication strategies, I argue that autistic individuals engage in an ongoing (re)configuration of temporal experiences – both accommodating and resisting neurotypical pressures of immediacy, synchronisation, and productivity. Attending to the alternative temporalities and rhythmic particularities of autistic embodiment reveals broader contingencies within the spectrum of the human condition, fostering reflections on a renewed social imaginary of neurodivergence and harmonised coexistence.
Theoretically, this study integrates phenomenologically inspired approaches to time and temporality with insights from symbolic interactionism, critical disability studies, and the sociology of the good life. I draw on Thomas Fuchs’s conceptualisation of mental health conditions as disruptions of synchronization to situate autism within a temporal framework that unites the associated themes. This research offers an experimental intervention into the lived realities of autism, positioning time as a key dimension of autistic subjectivity.
Methodologically, I adopt an autoethnographic approach from the perspective of a wounded researcher, informed by my self-discovery and recovery trajectory following a formal autism diagnosis. My fieldwork is based on 32 in-depth semi-structured online interviews with highly abled autistic adults in the UK, a group whose struggles often remain obliterated by their perceived success. By triangulating these interviews with my own self-narratives, I highlight the paradox of perceived ability – revealing how highly abled autistic individuals continue to experience social exclusion, vulnerability, and barriers to accessibility, despite their achievements.
My procedural exploration of autistic temporality unfolds in three interconnected parts:
1. (Digital) self-tracking practices, DIY infographics, and mediated visibility – examining how autistic individuals externalise cognitive labour, emotionality, and communicative preferences through assistive technologies, prompting a critical reflection on the ethics of care.
2. Temporal (de)synchronisation and autistic camouflaging – proposing five typifications of autistic time expressions: speeding up, winding down, temporal (dis)continuities, and intersubjective (de)synchronisation. This section critiques the pressures of fitting in, exposing the interdependencies between autistic individuals, care provision, and assistive/self-tracking technologies.
3. Autistic people’s search for the good life – challenging ableist assumptions about social participation and productivity by exploring how self-determined temporalities shape autistic individuals’ everyday life, emotionality, and sense of belonging. This discussion advances practical adjustments for a neurodivergent-friendly sensory environment that prioritises inclusivity and specific sensory needs.
Ultimately, this thesis provides sociological insights into the disparity between autistic people’s potential, structural obstacles, and actual life outcomes in adulthood. By theorising autistic temporality as both an alternative mode of being and a site of resistance, this work reimagines the intersection of autism, time, and technology – not as compensatory mechanisms, but as tools for reclaiming agency, reconfiguring visibility, and constructing a more inclusive social world
Augmenting military decision making with artificial intelligence
No full textAbstract
As artificial intelligence (AI) plays an increasing role in operations on battlefields, we should consider how it might also be used in the strategic decisions that happen before a military operation even occurs. One such critical decision that nations must make is whether to use armed force. There is often only a small group of political and military leaders involved in this decision-making process. Top military commanders typically play an important role in these deliberations around whether to use force. These commanders are relied upon for their expertise. They provide information and guidance about the military options available and the potential outcomes of those actions. This article asks two questions: (1) how do military commanders make these judgements? and (2) how might AI be used to assist them in their critical decision-making processes? To address the first, I draw on existing literature from psychology, philosophy, and military organizations themselves. To address the second, I explore how AI might augment the judgment and reasoning of commanders deliberating over the use of force. While there is already a robust body of work exploring the risks of using AI-driven decision-support systems, this article focuses on the opportunities, while keeping those risks firmly in view.</jats:p