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Pore network tortuosity controls fast charging in supercapacitors.
No full textIonic transport within porous carbon electrodes is crucial for optimizing charge and discharge rates in supercapacitors, yet the material properties governing ion dynamics remain poorly understood. Unlike the traditional viewpoint, here we find that mesoporosity does not necessarily correlate with a high supercapacitor rate capability. We employed pulsed-field-gradient nuclear magnetic resonance to directly measure the anionic effective diffusivities in the carbon pores. This technique probes ionic transport in supercapacitors. Our findings reveal a major discrepancy between short-range and long-range diffusivities, which captures the tortuosity of the pore network. Short-range diffusivities lack correlation with supercapacitor rate capability, whereas long-range diffusivities correlate strongly. Low-tortuosity nanoporous carbon exhibited superior rate capability, which highlights the importance of well-interconnected pore networks for efficient ion transport. Our study reveals that the pore network tortuosity is a key factor governing charging rates in amorphous nanoporous carbon and that it can be used to guide the design of electrodes with optimized transport channels to enhance supercapacitor performance
Search for the decay B 0 → ϕϕ
No full textA search for the decay B0→ ϕϕ is made using pp collision data collected with the LHCb detector at centre-of-mass energies of 7, 8 and 13 TeV, corresponding to an integrated luminosity of 9 fb−1. No significant signal is observed, and an upper limit on the branching fraction of 1.3 (1.4) × 10−8 at 90 (95)% confidence level is set. This result supersedes the previous LHCb study and improves the upper limit by a factor of two
<scp>GCN2</scp> in proteostasis: structural logic, signalling networks and disease
No full textProteostasis is the finely tuned balance of protein synthesis, folding and degradation essential for cellular health. When this equilibrium is disrupted, misfolded proteins accumulate, triggering adaptive stress responses such as the unfolded protein response and the integrated stress response (ISR). Central to the ISR is the kinase GCN2, a sensor of amino acid deprivation and ribosomal stress. Upon activation, GCN2 phosphorylates eIF2α, dampening global translation while selectively enhancing the synthesis of the stress‐responsive transcription factors ATF4 and CHOP. ATF4 orchestrates a broad transcriptional programme that supports amino acid metabolism, redox homeostasis, autophagy and proteasomal degradation, which are key processes for restoring proteostasis. Beyond its canonical role, GCN2 interfaces with other regulatory networks modulating mTORC1 to promote autophagic clearance of damaged proteins and organelles, facilitating stress granule formation, and integrating signals from oxidative and endoplasmic reticulum stress to rebalance the proteome. Dysregulated GCN2 activity has been implicated in diverse pathologies including neurodegeneration, cancer and pulmonary vascular disease, positioning it as a promising therapeutic target. In this review, we explore how GCN2 links nutrient sensing to translational control and metabolic adaptation, and how its central role in proteostasis may inform new strategies for treating diseases driven by protein misfolding and stress pathway imbalance.</jats:p
The influence of the trait-like tendency to rely on declarative- or procedural- like memory systems on the development of habits and compulsive behaviours in the rat
No full textConvergent evidence supports a multi-systems organisation of long-term memory in mammals, where different types of memory are underpinned by dissociable neural systems which can operate independently of one another. A key distinction in this regard is that between declarative memory and procedural memory, which differ with respect to whether the information that is stored, encoded and retrieved can be represented in a manner that is independent of the animal’s performance.
Individual differences in the reliance on the dissociable neural systems that subserve declarative- like versus procedural-like memory have been characterised in the rat in a spatial discrimination task. In a version of the task that is solvable using either a declarative-like, allocentric place or a procedural-like, egocentric response spatial learning strategy, a “direct opposition” probe can reveal which strategy any individual relies on to solve the task.
The distinction among declarative and procedural memory parallels, but is not identical to, the distinction among two behaviourally and neurally dissociable instrumental learning processes that are recruited to acquire and perform behaviours under the control of their consequences: goal-directed (action-outcome) actions and stimulus-response habits. The latter, and in particular its excessive rigidity, has been implicated in the development of compulsive behaviours that are a transdiagnostic feature of various neuropsychiatric disorders such as obsessive-compulsive disorder and substance/alcohol use disorders.
Theoretical frameworks and some empirical findings suggest a correspondence between declarative memory and goal-directed actions, on the one hand, and procedural memory and stimulus- response habits, on the other. This might, in turn, suggest that an individual's tendency to rely on response versus place memory systems is associated with a greater tendency to develop stimulus-response habits and the ensuing increased vulnerability to develop compulsive behaviours. The purpose of this thesis is to test this hypothesis.
The theoretical background of and experimental techniques used in this thesis are detailed in the General Introduction (Chapter 1) and General Methods (Chapter 2) respectively.
Chapter 3 describes a preparation for measuring the individual tendency to rely on place versus response memory systems in a spatial discrimination task in male and female rats.
Chapter 4 uses this approach to characterise place/response learning tendency in terms of behavioural traits in rats that have been implicated in the development of habits and compulsive behaviours: trait-like anxiety, novelty preference and sign- versus goal-tracking tendency. I show that “place learner” and “response learner” identity can be predicted by the individuals’ novelty place preference, but not their trait-like anxiety nor their sign- versus goal-tracking tendency.
In Chapter 5, I investigate whether the individual tendency to rely on place versus response memory systems influences the development of stimulus-response versus action-outcome control over instrumental responding for food in a free-operant task. I demonstrate that, surprisingly, place learners are more likely to develop stimulus-response habits after extensive instrumental conditioning, a relationship that is confined to females.
In Chapter 6, I determine whether place/response learning tendency shapes the acquisition and performance of adjunctive drinking, an instrumental coping response to stress or physiological arousal that can become excessive and thereby compulsive in a subset of individuals. I subsequently determined the place/response learning-dependent associative nature of this instrumental coping response. I show that place and response learners are equally likely to develop coping responses and their compulsive manifestations. However, only in response learners does the locus of control over adjunctive drinking devolve to the habit system. Analysis of the transcriptional signatures of neuronal activation and plasticity in rats given the opportunity to adjunctively consume alcohol revealed a selective reduction in neural activity in the anterior insula and its afferent network in place learners.
These results, taken together, challenge conventional thought regarding the relationship between declarative and procedural memory systems and the development of habits and compulsive behaviours
Bound by History: How Antecedents Shaped the League of Nations Institutional Design
No full textAbstract
The founding of the League of Nations marked a turning point in international governance. It entrenched great-power privilege by creating a bifurcated structure that separated an exclusive Council from a representative Assembly. Despite its significance, the origins of this institutional choice remain poorly understood. This article argues that the dual Assembly-Council design emerged through a process whereby policymakers, bound by historical experience, vetted and adapted alternative proposals in light of what we call “negative antecedents.” In particular, the separation of universal membership from great-power control reflected efforts to manage the legacy of pre-1914 demands for sovereign equality. Drawing on secondary literature and original archival research, the article shows how U.S. and British policymakers invoked the Second Hague Conference to resist pressure from smaller and often racialized states, especially those in Latin America, to participate on equal terms in international organizations. The League’s designers responded more directly to inherited political conflicts than to abstract, forward-looking considerations of institutional functionality. Since the League’s creation, trade-offs among membership, efficacy, and control have continued to shape debates over intergovernmental organizations. By engaging historical institutionalist scholarship in IR, this article offers new insights into how past conflicts constrain and channel contingent institutional choices.</jats:p
Harnessing Sequence Structure Relationships in Peptide Self-Assembly
No full textBiomolecular self-assembly is a key mechanism by which essential materials evolve within
living systems. In proteins, structures are generated by combinatorial arrangement of amino
acids (AAs) that form specific molecular interactions to drive assembly. While nature uses
this to form large proteins, careful manipulation and design of peptides as short as a 2
AAs can be utilised to tune intermolecular interactions and form a wide range of functional
systems from structural materials to enzymes and therapeutics. In this thesis, I systematically
explore the relationship between peptide sequence, molecular and supra-molecular assembly.
Using microfluidics and imaging, I explore how Boc protected AAs can form biomolecular
condensates to give insights into the sequence-property relationships governing liquid liquid phase separation. I then explore the subsequent liquid to solid transition of these
condensates, exemplifying how small changes to chemical structure can have drastic effects
on microstructures. In addition, hybrid amino acid systems incorporating non-coded amino
acid DOPA are shown to form rigid hydrogels with antibacterial properties. This highlights
the versatility of amino acid assemblies with respect to accessible material architectures.
Further work explores the relationship between peptide sequences and the Young’s modulus
of their assemblies, an essential materials property that determines the viability of a peptide to
be used in materials applications. Combining computational approaches and nano-mechanical
atomic force microscopy to calculate, predict and validate the modulus for peptides allows us
to scan large amounts of sequence space and develop a deeper understanding of the ways in
which specific residues promote structural rigidity. Ultimately, my work provides a unique
approach to exploring how specific AAs directly promote the formation of intermolecular
interactions leading to structures and phases with fine-tuned functionalities. This will enable
us to more effectively tune AA sequence for a desired property when generating sustainable
materials and therapeutics in the future
Mariwan Archaeological Survey: a systematic field project in north-west Iran
No full textSpanning 760km 2 and identifying 603 sites covering thousands of years of (pre)history, the Mariwan Archaeological Survey provides a comprehensive examination of settlement history in north-western Iran. By employing advanced survey methods and targeting previously unexplored regions, evidence and understanding of Mariwan’s cultural dynamics and historical interactions is substantially enhanced
Graph in Graph Neural Network
No full textExisting Graph Neural Networks (GNNs) are limited to process graphs each of whose vertices is represented by a vector or a single value, limited their representing capability to describe complex objects. In this paper, we propose a novel GNN (called Graph in Graph Neural (GIG) Network) which can process graph-style data (called GIG sample) whose vertices are further represented by graphs. Given a set of graphs or a data sample whose components can be represented by a set of graphs (called multi-graph data sample), our GIG network starts with a GIG sample generation (GSG) module which encodes the input as a GIG sample, where each GIG vertex includes a graph. Then, a set of GIG hidden layers are stacked, with each consisting of: (1) a GIG vertex-level updating (GVU) module that individually updates the graph in every GIG vertex based on its internal information; and (2) a global-level GIG sample updating (GGU) module that updates graphs in all GIG vertices based on their relationships, making the updated GIG vertices become global context-aware. This way, both internal cues within the graph contained in each GIG vertex and the relationships among GIG vertices could be utilized for down-stream tasks. Experimental results demonstrate that our GIG network generalizes well for not only various generic graph analysis tasks but also real-world multi-graph data analysis (e.g., human skeleton video-based action recognition), which achieved the new state-of-the-art results on 15 out of 16 evaluated datasets. Our code is publicly available at https://github.com/wangjs96/Graph-in-Graph-Neural-Network
RAS-driven chromatin rewiring in slow-cycling cells
No full textCell identity loss or lineage infidelity is a common feature of cancer, ageing, and major disorders. We have previously demonstrated that oncogene-induced senescence (OIS) is a differentiation-like process characterised by both loss of the original identity and functional augmentation. Our recent study revealed a RAS spectrum, with models demonstrating variable cell cycle arrest, and consequences in vivo for immune clearance and tumour initiation. Slow-cycling cells (SCCs), such as drug-tolerant persisters, are rare, difficult to detect, and share features with tumour-initiating cells, including enhanced survival under stress and the capacity to adopt alternative lineage programs. In this work, I outline the links between the phenotypic features of the RAS spectrum, such as the slow-cycling behaviour, and the underlying epigenetic and metabolic changes in a RAS-titratable model in RPE1 cells.
I integrated multiomic approaches: transcriptomic profiling (RNA-seq), histone modification and accessibility mapping (ChIP-seq, ATAC-seq), as well as 3D chromatin capture analysis (Hi-C), and targeted cell biology assays. Chromatin network construction revealed distinct regulatory patterns, and integration with epigenetic maps clarified how the chromatin context modulates transcriptional outputs.
SCCs in our model were distinguished not only by the attenuated cell cycle progression - more reminiscent of quiescence than canonical OIS, but also by a stronger senescence-associated secretory program (SASP), including secreted neuronal proteins, downregulation of MYC signalling and mitochondrial metabolism, and a cell identity shift, including loss of RPE identity and upregulation of progenitor genes.
Transcriptomic changes were paralleled by epigenetic shifts, with differential enhancer activity supporting both OIS-like and unique SCC features. Neuronal gene derepression coincided with increased chromatin accessibility in formerly heterochromatic regions, enriched for neuronal TF motifs, including OTX2 - an RPE developmental regulator upregulated in SCCs. At the 3D genome level, SCCs gained loops in heterochromatic domains, whereas they lost loops in euchromatic regions, contrary to OIS. These spatial changes were accompanied by alterations in histone modifications and a recurring adenine-thymine (AT) bias.
In conclusion, not only can different RAS signalling levels trigger distinct responses, but also diverging shifts in cell identity and cell cycle features, which are likely intertwined, depending on the pre-existing cellular context. Given the recent studies on the vulnerabilities of different tissues to oncogenic stimuli, this highlights the importance of studying cell identity to predict cellular responses
