The greater implications of Bartelson’s Becoming International

Of all major International Relations (IR) scholars active today, it is Jens Bartelson who has done the most in terms of getting us to rethink our assumptions about the basic building blocks of our field. In a series of very significant books — A Genealogy of Sovereignty (1993), The Critique of the State (2001) and Sovereignty as Symbolic Form (2014)— as well as numerous articles, he has changed our understanding of both the concept of sovereignty and its conceptual history, with serious implications also for the history of ‘the state.’ His 2017 book War in International Thought has led the reader through the evolution of the thinking about war. And his most recent book Becoming International (2024), which is the subject of this review essay, joins Visions of World Community (2009) in getting us to rethink the very basic notion of ‘the international’ and how it came about

Connexin 43 is downregulated in advanced Parkinson’s disease in multiple brain regions which correlates with symptoms

Parkinson's disease (PD) is a neurodegenerative condition with the greatest increase in disability globally. Dysfunction of dopaminergic neurons is a well-known PD hallmark; however, changes in astrocytes also accompany PD progression. One aspect of astrocyte biology not yet investigated in PD is their network coupling. To assess this, we focussed on the major astrocytic gap junctional protein connexin 43 (Cx43, GJA1). A dataset of 20 post-mortem late-stage PD brain tissue samples from the cortex and basal ganglia alongside 20 age-matched control sets was collected, accompanied by clinical histories and data on -synuclein, tau, and amyloid-beta pathology. Protein levels and intracellular distribution of Cx43 and other key markers were measured. Computational re-analysis of open-source mRNA sequencing datasets from the striatum and midbrain complemented the original findings. Two novel observations were made: first, profound Cx43 loss in late-stage PD, and second, differential manifestation of this pathology in different brain areas, including those outside of the midbrain substantia nigra – the region that is most commonly used in PD research. Cx43 downregulation in specific regions correlated with non-motor symptoms of PD such as depression and sleep disturbance. Astrocytic tree simplification in the frontal cortex was further observed. In conclusion, astrocytic network decoupling through Cx43 downregulation in PD may contribute to astrocytic dysfunction and PD symptom development

Towards critical, anti-colonial and anti-racist education in national and global contexts

The fourth Sustainable Development Goal (SDG 4) of the United Nations (UN) 2030 Agenda aims to “ensure inclusive and equitable quality education and promote lifelong learning opportunities for all”. With over 122.6 million people worldwide forcibly displaced, and the number of refugees globally reaching 43.7 million by mid-2024, focusing on the importance of refugees accessing lifelong learning has become more urgent than ever. Despite this, refugees have been excluded from SDG-related national development plans, monitoring and reporting, raising questions about how the targets agreed in the Global Compact on Refugees and the SDGs are being implemented and met. Education, migration regulation and border regimes that reproduce injustices are fundamental elements of colonial education and have implications for lifelong learning. Education is often presented as crucial to the “integration” of migrants, including refugee people who have come to England. Nevertheless, the British government’s austerity policies, regarded by some as a form of racism, have underfunded the education system. This has made it more challenging for all learners from low-income families, and specifically refugee people, to access adequate education, amongst other rights. This article begins with a look at the assimilationist and apparent neutrality of approaches to education as sponsored by global and national commitments. The author then briefly discusses education as a practice of oppression, with colonial implications, including presenting perspectives from England and Brasil drawn from qualitative and mixed-methods doctoral and postdoctoral research. The article concludes by proposing approaches to enact education and lifelong learning as a practice of liberation rooted in critical, anti-racist and anti-colonial thinking and praxis

Chronic Auditory-Nerve Implant Enhances Brainstem Phase Locking to Electric Pulse Trains.

PURPOSE: Present-day cochlear implants (CIs) can deliver usable speech reception in quiet surroundings. Most CI users, however, show impaired sensitivity to temporal fine structure, which hampers their use of pitch contours and spatial cues to segregate competing talkers. In previous short-term animal studies, we used intraneural (IN) electrodes to stimulate pathways originating from various cochlear turns. Neurons in the inferior colliculus synchronized to apical stimulation at higher rates than to stimulation of the middle-to-basal pathways that are stimulated primarily by today's CIs. Here, we use non-invasive recordings to test the safety and efficacy of up to 6 months of IN implantation and stimulation in cats. METHODS: Deafened cats (ten female, two male) were implanted with IN and/or conventional CI electrodes. The IN electrodes were single activated-iridium shanks that targeted apical-turn fibers. Scalp recordings were made from sedated animals at 2-3-week intervals. Auditory brainstem responses to single electrical pulses (eABR) tracked sensitivity and growth of responses. Frequency following responses to electrical pulse trains (eFFR) assessed brainstem temporal transmission at varying pulse rates. RESULTS: Thresholds for eABR were lower for IN than for CI stimulation, dynamic ranges were wider, and (by inference) spread of activation was more restricted. The eFFR evaluated at latencies comparable to those of inferior-colliculus spikes synchronized at maximum pulse rates averaging > 360 pulses/s for IN compared to ~ 240 pulses/s for CI stimulation. The eABR thresholds and eFFR cutoff rates were stable out to 6 months after implantation. CONCLUSIONS: The results demonstrate the safety and efficacy of chronic IN stimulation in an animal model. In a future clinical device, an IN electrode could augment cochlear-implant performance by enhancing temporal acuity, thereby improving speech reception amid competing sounds

Multilevel frameworks for studying protein energy landscapes

Proteins, which constitute over 50% of dry cell mass, are essential to nearly all biochemical processes, with their functionality depending on correct folding into native structures. Accurately simulating their structural dynamics over biologically relevant timescales remains beyond the reach of quantum mechanical methods. To address this problem, mechanical force fields and coarse-grained models have been developed to reduce the number of interaction sites. While advances like AlphaFold have improved native structure prediction, understanding thermodynamic stability and folding pathways remains a major challenge. This thesis introduces multilevel computational frameworks that integrate diverse theoretical approaches (Chapter 2) to analyse protein energy landscapes. A key development is the lwONIOM library (Chapter 3), a freely accessible, multilevel, multicentre tool enabling accurate and efficient analysis of complex proteins over extended timescales. Applied to the bovine pancreatic trypsin inhibitor (BPTI), lwONIOM achieves a balance between computational cost and precision, providing deep insights into structural stability and dynamic behaviour. Energy landscapes described by the AMBER and UNRES potentials are also analysed. In parallel, the UNRES coarse-grained potential was integrated into the Cambridge energy landscape software, enabling efficient modelling of large biomolecular structures (Chapter 4). This method preserves accuracy while substantially reducing computational cost, yielding results consistent with experiment and all-atom models. UNRES includes a dynamic disulphide bond potential, allowing bond formation and breakage to be explored within a single landscape, and has recently been extended to model explicit lipids within the UNICORN framework. Additionally, we applied machine learning potential, coarse-grained energy landscape searches, and structural analysis to study amyloid monomers associated with Alzheimer’s disease (Chapter 5). These multilevel frameworks thus provide robust tools for the study of complex biomolecular systems, with potential applications in drug discovery and health-related research

Structural phase transitions and magnetic characterization of Ba₂GdNbO₆ for low-temperature magnetocaloric refrigeration

Ba2GdNbO6 has previously been reported to adopt either monoclinic, tetragonal, or cubic symmetry at room temperature. Using high-resolution synchrotron X-ray diffraction, neutron diffraction and neutron pair distribution function analysis we find that the compound adopts a tetragonal I4/m double-perovskite structure at room temperature (with a weak, temperature-independent second-order Jahn-Teller distortion in the NbO6 octahedra) and undergoes a phase transition to a monoclinic (P21)⁄n symmetry upon cooling to 2.4 K. Only upon heating above room temperature to T≈ 450 K does Ba2GdNbO6 reversibly transition to a cubic Fm3 ̅m symmetry. Magnetic susceptibility measurements indicate predominant paramagnetic behavior down to 1.8 K, with minimal ferromagnetic short-range correlations (θ = 0.20(5) K) and a small exchange interaction (J1 = -0.0032(8) K). At 2 K and 9 T, the compound exhibits a maximum magnetic entropy change of -∆Sm =15.75 J K-1 mol-1 and an adiabatic temperature change of ∆Tad =21 K, making it a promising candidate for low-temperature magnetocaloric applications. Heat capacity measurements confirm a rigid crystal lattice (TD= 267(3) K) and a corresponding small lattice entropy contribution in the low-temperature regime, highlighting the potential of Ba2GdNbO6 for effective cooling capability in magnetocaloric devices at cryogenic temperatures. This study elucidates the structural and magnetic characteristics of Ba2GdNbO6 and attests to its promise for low-temperature magnetocaloric refrigeration

Enhancing antibody-antigen interaction prediction with atomic flexibility

Antibodies are indispensable components of the immune system, known for their specific binding to antigens. Beyond their natural immunological functions, they are fundamental in developing vaccines and therapeutic interventions for infectious diseases. The complex architecture of antibodies, particularly their variable regions responsible for antigen recognition, presents significant challenges for computational modeling. Recent advancements in deep learning have markedly improved protein structure prediction; however, accurately modeling antibody-antigen (Ab-Ag) interactions remains challenging due to the inherent flexibility of antibodies and the dynamic nature of binding processes. In this study, we examine the use of predicted Local Distance Difference Test (pLDDT) scores as indicators of residue and side-chain flexibility to model Ab-Ag interactions through a fingerprint-based approach. We demonstrate the significance of flexibility in different antibody-specific tasks, enhancing the predictive accuracy of Ab-Ag interaction models by 4%, resulting in an AUC-ROC of 92%. In addition, we showcase state-of-the-art performance in paratope prediction. These results emphasize the importance of accounting for conformational flexibility in modeling antibody-antigen interactions and show that pLDDT can serve as a coarse proxy for these dynamic features. By optimizing antibody flexibility using pLDDT, they can be engineered to improve affinity or breadth for a specific target. This approach is particularly beneficial for addressing highly variable pathogens like HIV and SARS-CoV-2, as greater flexibility enhances tolerance to sequence variations in target antigens.</jats:p

Assumptions about behaviour influence the policy preferences of public officials

Public officials often aim to change people’s behaviour to achieve policy goals. Policy design and behavioural perspectives suggest that individual factors such as officials’ assumptions about behaviour — or implicit theories — can influence officials’ policy choices. This pre-registered survey study examines how assumptions about cooperation, behavioural malleability, and self-control influence policy preferences among 1,015 public officials in the Netherlands. Results show that officials who believe in high levels of cooperative behaviour and behavioural malleability support more government intervention, while assumptions about self-control have no significant effect. Additionally, a quasi-experiment with an information-based intervention led officials to update their assumptions towards greater accuracy

The Perverse Incentives of Climate Integration: Why Researchers Can't Deliver What Funding Institutions Demand

ABSTRACTResearch funders increasingly require integration of future climate projections across health, agriculture, fisheries, and development economics, creating perverse incentives: institutions demand what current climate science cannot reliably deliver. I use “perverse incentive” here in its standard economic sense: an incentive that unintentionally produces counterproductive behavior, rather than implying ill will on the part of funders. Climate models designed for global, long‐term analysis are being misapplied for short‐term, regional uses beyond their validated scope. This paper identifies three problems arising from this mismatch: maladaptation in scientific labor allocation, erosion of trustworthiness through representational overextension, and representational risk from harmful signaling and normalization of inappropriate methodological norms. Researchers include climate projections not because they are justified, but because they are required, transforming models from tools of inquiry into performances of compliance. This threatens both scientific integrity and the legitimacy of science underwritten by democratic norms. Three institutional reforms are proposed to realign incentives with epistemic responsibility and ensure climate science serves as a reliable policy foundation rather than mere signaling.</jats:p

Adaptive Biomarker-Based Design for Early Phase Clinical Trials.

Identifying and quantifying predictive biomarkers is a critical issue of Precision Medicine approaches and patient-centric clinical development strategies. Early phase adaptive designs can improve trial efficiency by allowing for adaptations during the course of the trial. In this work, we are interested in adaptations based on interim analysis permitting a refinement of the existing study population according to their predictive biomarkers. At an early stage, the goal is not to precisely define the target population, but to not miss an efficacy signal that might be limited to a biomarker subgroup. In this work, we propose a one-arm two-stage early phase biomarker-guided design in the setting of an oncology trial where at the time of the interim analysis, several decisions can be made regarding stopping the entire trial early or continuing to recruit patients from the full or a selected patient population. Via simulations, we show that, although the sample size is limited, the proposed design leads to better decision-making compared to a classical design that does not consider an enrichment expansion