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Orbital Classification in Rotating Bar Potentials Using an Empirical Proxy of the Second Integral of Motion
Get PDFWe present a novel method for classifying two-dimensional orbits in rotating bar potentials based on an empirical proxy for the second integral of motion, calibrated angular momentum (CAM), which is defined as the ratio of the time-averaged angular momentum ( Lz¯ ) to its temporal dispersion ( σLz ) in the corotating frame. We show that CAM is determined by the ratio of the azimuthal to radial actions ( Jϕ′/Jr′ ) in the analytical Freeman bar model. We then construct a new parameter space defined by CAM versus the rms radius (Rrms) and apply this framework to orbits in several representative rotating bar potentials. In the CAM–Rrms plane, periodic orbits generate well-defined branches separating distinct regions corresponding to different orbital families. Several of these branches enclose isolated areas that can be associated with specific orbital families, such as the x2 orbital family. We further validate the method using orbits from test-particle simulations, which show a well-ordered and nonoverlapping distribution of orbital families in the CAM–Rrms plane. Since CAM is fundamentally linked to intrinsic orbital properties and readily applied to three-dimensional orbits in N-body simulations, our results establish the CAM–Rrms plane as a robust and efficient framework for orbit classification in rotating bars that complements conventional methods
Pangenome-guided sequence assembly via binary optimization
Get PDFDe novo genome assembly is challenging in highly repetitive regions; however, reference-guided assemblers often suffer from bias. We propose a framework for pangenome-guided sequence assembly that can resolve short-read data in complex regions without bias towards a single reference genome. Our primary contribution is to frame the assembly as a graph traversal optimization problem, which can be implemented classically or on a quantum computer. The workflow involves first annotating pangenome graphs with estimated copy numbers for each node, then finding a path on the graph that best explains those copy numbers. On simulated data, our approach significantly reduces the number of contigs compared with de novo assemblers. While they introduce a small increase in inaccuracies, such as false joins, our optimization-based methods are competitive with current exhaustive search techniques. They are also designed to scale more efficiently as the problem size grows and will run effectively on future quantum computers; a small experiment on a real quantum device showcases this behaviour. Moreover, they are more resilient to noise in copy number estimation inherent in short-read-based assembly. We also develop novel tools for creating realistic synthetic pangenomes, aligning reads to pangenomes and for evaluating assembly quality
Assessing and reducing stigma in infectious disease outbreaks
Get PDFStigma is a pervasive challenge in infectious disease outbreaks. It repeatedly hinders outbreak response efforts, deepens socioeconomic divides, and causes lasting harm to affected individuals and communities. Despite this, efforts to monitor and address stigma during outbreaks have often been ad hoc, delayed, or poorly integrated into response planning. This thesis sets out to advance the assessment and reduction of stigma in outbreak contexts by developing tools and recommendations for response teams, including those conducting operational research.The thesis contains four chapters of original research. Chapter 2 presents a systematic review of the content and psychometric properties of stigma scales used in outbreaks. Chapter 3 reports findings from qualitative interviews with international stakeholders examining how stigma is understood, experienced, and addressed in diverse settings. Chapter 4 includes a cross-sectional community survey conducted in three outbreak contexts (mpox in the UK, Ebola disease in Uganda, and Nipah virus disease in Bangladesh), with these data used to validate new stigma assessment tools. Chapter 5 brings together an evidence review and a structured expert consensus process to develop practical stigma mitigation guidelines for public health actors and response organisations.The findings demonstrate the value of more structured, evidence-informed responses to stigma. Existing stigma assessment tools were found to lack validity, largely due to scale development and validation processes that are poorly suited to acute outbreaks. A new conceptual model of outbreak-related stigma was developed based on stakeholder interviews spanning 25 outbreak-prone infectious diseases, offering practical insights for considering stigma in response planning. Survey data from over 1000 respondents supported the development of a set of stigma scales that performed well across the three diverse outbreak contexts. Building on these empirical foundations, an international expert panel reached consensus on nine guiding principles and 18 actionable recommendations to support more effective, stigma-sensitive public health responses.Together, the outputs of this research offer a basis for integrating stigma considerations into outbreak preparedness and response. In doing so, they support efforts to improve the recovery, reintegration, and wellbeing of affected individuals and communities. Future research is needed to explore longitudinal monitoring and evaluate promising stigma reduction strategies now that these are more clearly defined
Design and development of influenza neuraminidase nanoparticle vaccine
Get PDFLay abstract Influenza continues to cause significant illness and death worldwide, with existing vaccines offering only limited protection. While these vaccines focus on a surface protein called haemagglutinin (HA), another key protein, neuraminidase (NA), has been less extensively studied as a vaccine target. NA facilitates viral spread by releasing the virus from infected cells, and NA monoclonal antibodies have been found to be protective and broadly reactive. In this thesis, we explore NA as a vaccine target. Our research developed a NA-based vaccine platform using nanoparticles to enhance the immune response. This NA vaccine, combined with an adjuvant, protected mice against deadly doses of three different influenza strains, even at very low vaccine doses. We also explored a multivalent version of this vaccine to prepare for potential future pandemics. Additionally, we addressed challenges in producing a soluble NA vaccine at high yield by engineering the NA sequence based on its structure. The engineered vaccine NA generated a strong antibody response in mice and showed protection against severe influenza infections. Our findings highlight that NA-based vaccines hold great promise for improving flu prevention and preparing for future outbreaks. Scientific abstract Influenza remains a major cause of morbidity and mortality worldwide. Current vaccines are based on haemagglutinin (HA), and the vaccine effectiveness remains sub-optimal. Neuraminidase (NA), another surface glycoprotein, has been underexplored as a vaccine target. The NA tetramer catalyses the sialic acid, facilitating the release of virions from infected cells. NA protein vaccines have been reported to generate protective antibodies in several animal models, as well as in humans. We previously established a nanoparticle-based NA vaccine platform, achieved through covalent linkage between SpyTag and SpyCatcher tags on the NA and mi3 virus-like particle (VLP) respectively. NA-VLP, adjuvanted with AddaVax, generated a better antibody response in mice compared to NA protein alone, demonstrating a dose sparing effect when challenged with three different influenza strains from H1N1 and H3N2 subtypes (X-179A, X31, and PR8). Animals were protected against a lethal virus challenge with as low as 0.1 µg NA-VLP protein conjugate. Additionally, we tested a multivalent NA-VLP mix vaccine in mice to evaluate its potential for future pandemic preparedness. Production of soluble NA as stable tetramers and at high yield has been a significant hurdle in NA vaccine development. We overcame this challenge by creating a hybrid NA, in which the surface antigenic loops from the vaccine NA were transplanted onto the scaffold of a stable, high-yielding NA. The hybrid NA was produced as stable tetramers at yields up to ~5 - 50-fold higher than the original NA. Immunization of mice with the hybrid NA induced protective antibodies. These findings highlight NA as a promising target for influenza vaccines and provide valuable insights into future vaccine design and manufacturing
Chronotopic mechanisms of sedentary subjectification: Territorializing Venezuela’s communes
Get PDFTime is wielded as a socio-political tool to regulate people’s (im)mobility. This article examines how the moral framing of space–time functions as migration governance. In Venezuela, where outmigration is taking place on a large scale, the government has devised a moral discourse based on a specific construction of the past, present, and future. In so doing, it has formed a ‘chronotope of containment’ that attempts to minimize the emigration of government supporters to safeguard its stability and claim to power. Socially constructed boundaries and categories emerge from the chronotope, naturalizing sedentarism through the control of affects, habits, and the formation of subjectivity. Based on interviews with government supporters, government statements, and documents, I identify three ‘chronotopic mechanisms of sedentary subjectification’ within this chronotope that generate immobility among government supporters: 1. Spatio-temporal acceleration, 2. Commune (De)territorialization, and 3. Geographies of terror. By identifying how these discursive mechanisms operate, this article shows how chronotopes of containment produce immobility in a context of large-scale outmigration where staying put is not the default but a complex and politicized choice
Cooperation-Enhanced N–H···π Hydrogen Bonds: Liquid Pyrrole and Its Mixture with Benzene
Get PDFWeak intermolecular interactions are central to the chemical and biological sciences as they dictate the stability, growth, and geometry of larger assemblies. Among weak interactions, NH···π hydrogen bonds are abundant in structural biology, where amines interact with aromatic systems: liquid pyrrole is the ideal test solvent containing both motifs. We therefore combined total neutron scattering and simulation-based refinement to study pure pyrrole and its mixture with benzene. The NH···π interaction between pyrroles is remarkably directional, with NH approaching the center of the ring perpendicularly at 2.11 Å. While the NH···π bond lengths are similar in pyrrole–pyrrole and pyrrole–benzene, the occurrence of the latter is suppressed by a factor of 2. This difference originates from cooperative mechanisms arising from the ability of pyrrole to donate and simultaneously accept a hydrogen bond. Our results clearly show that this traditionally weak interaction can become as short and directional as classical hydrogen bonds
Structural and Functional Validation of Pseudomonas Savastanoi Ethylene Forming Enzymes Reveals Flexibility in 2‐Oxoglutarate Binding Mode and Conformation
Get PDFPseudomonas savastanoi pv. phaseolicola PK2 employs an Fe(II)‐dependent ethylene/succinate‐forming enzyme (PK2 PsEFE) to produce ethylene from 2‐oxoglutarate (2OG). Here we report NMR‐based assays showing that the putative P. savastanoi pv. glycinea PsEFE, which differs from PK2 PsEFE by a single residue, and the P. savastanoi pv.1449B PsEFE, which differs from PK2 PsEFE by 28 residues and a C‐terminal 13‐residue truncation, catalyze ethylene production from 2OG. Like the PK2 PsEFE, they catalyze oxidation of naturally occurring 2OG derivatives to give alcohol and diacid products. Crystallographic analysis demonstrates that the overall fold and active site of 1449B PsEFE is similar to that of PK2 PsEFE. Interestingly, 2OG was observed to adopt an atypical inverse metal ion binding mode in complex with 1449B PsEFE:Mn in which its 2‐oxoacid group is positioned to interact with the guanidinium group of R277, but not the Mn ion, which substitutes for catalytically active Fe(II). Together with reported crystallographic results, this observation indicates that 2OG metal ion binding modes and conformations at the active sites of 2OG oxygenases can vary, possibly in a functionally or disease relevant manner
Vacuum–Laser Fabrication of Programmable Soft Actuators
Get PDFSoft robotic actuators enable lightweight and compliant motion, but their fabrication typically relies on silicone molding, 3D printing, or textile lamination—processes that require expensive materials, long production times, or complex fabrication protocols. We introduce a rapid manufacturing strategy using low‐cost thermoplastic pouches that combines vacuum processing and laser cutting. By removing air gaps between layers, this method enables precise sealing and cutting, allowing complex inflatable geometries to be fabricated in under 10 min at a material cost below $0.10 per actuator. Compared to silicone elastomers, the reduced compliance of thermoplastics minimizes deformation losses and channels more energy into effective stiffening. The reliability of the method is verified through material testing and repeatable pressurization experiments, including response times of approximately 0.4s at operating pressure of 50–70kPa. We further use finite element modeling to predict bending behavior, derive geometric rules for programmable deformation, and construct a surrogate model for inverse design of homogeneous and heterogeneous bending actuators. Using this framework, target shapes such as alphabetic letters and spirals are achieved, and functional soft robotic prototypes, including crawlers, swimmers, and soft grippers, are demonstrated. These results position vacuum–laser processing as an accessible and scalable platform for rapid fabrication of adaptive soft robotic systems
Zwitterion-assisted growth and strain optimisation of perovskite single crystals for high-performance photon counting radiation detection
Get PDFSolution-grown perovskite single crystals (SCs) have attracted great interest in the radiation detection community due to their easier growth process and cost-effectiveness compared to conventional semiconductor materials such as cadmium telluride (CdTe) and cadmium zinc telluride (CdZnTe), as well as melt-grown perovskite materials such as CsPbBr3 (CPB). However, their performance as photon-counting radiation detectors is inferior to that of melt-grown semiconductor materials. This is due to the potential of the solution-growth method to cause unregulated crystal growth and poor scalability of high-quality SCs due to spontaneous nucleation. In this work, using the sulfonic zwitterionic ligand 3-(decyldimethylammonio)propanesulfonate inner salt (DPSI), we have grown high-quality FAPbBr3 (FPB) SCs with low defect densities. Also, by optimising the crystal growth temperature ramp, we have obtained ‘low-strained’ FPB SCs with reduced internal strain. These SC devices show excellent charge transport properties, showing a high hole mobility of 190 cm2 V−1 s−1 and a high hole mobility–lifetime (µτ) product of 2.7 × 10−3 cm2 V−1, with a low dark current of 2.9 nA cm−2 at a field strength of 1000 V cm−1. These devices have achieved an energy resolution of 10.5% FWHM for 241Am 5.49 MeV α-particles and 25.6% FWHM for 241Am 59.5 keV γ-rays, and a high X-ray photocurrent sensitivity of 5111 µC Gyair−1 cm−2 for 50 kV X-rays, showing great promise as room-temperature radiation detectors capable of operating efficiently in both photon-counting and current modes
Mapping dementia research in Indonesia: A scoping review of evidence, gaps, and future directions
Get PDFDementia, a syndrome that progressively impairs cognitive functions, is a growing global health challenge. Indonesia, the world’s fourth most populous country, faces a growing dementia burden compounded by stigma and inequities in prevention, diagnosis, and care. This scoping review aims to synthesise dementia research in Indonesia, identify gaps, and propose directions for future research. Following the Joanna Briggs Institute and PRISMA-ScR guidelines, a comprehensive search across eight databases (MEDLINE, Embase, CINAHL, Global Health, Web of Science, PubMed, PsycINFO, and GARUDA) were conducted to identify studies in English and Indonesian. 105 studies were included, with most (93.3%) studies published after 2016, aligning with Indonesia’s National Dementia Plan and the WHO Global Action Plan on Dementia. Studies were predominantly cross-sectional (73.3%) and concentrated in urban areas. When mapped against the WHO Global Action Plan on Dementia (2017–2025), studies clustered around seven key themes. Key risk factors examined included older age, low education, female sex, low socioeconomic status, smoking, hypertension, diabetes, and physical inactivity. Work on diagnosis, treatment, and care has expanded, particularly through validation of cognitive screening tools (e.g., MoCA-INA, BCSB-INA) and emerging use of neuroimaging and biomarkers, though implementation remains limited by cost and workforce capacity. Intervention studies are typically small-scale, short-term, and lack longitudinal evaluation. Findings consistently showed high psychosocial and financial burden, especially among female family carers, with unmet needs for training and emotional support. Finally, policy and systems-level research highlighted limited integration of dementia into primary healthcare, inadequate data infrastructure, and minimal progress in translating the 2016 National Dementia Plan into sustainable support systems. Dementia research in Indonesia has expanded, yet geographical and methodological gaps persist. Future priorities should include nationally representative studies, implementation research, and multisectoral collaborations to advance the WHO’s vision of dementia as a public health priority and strengthen preparedness for its ageing population