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Characterising the force exerted on obstacles by non-Boussinesq gravity currents using implicit large-eddy simulations
No full textThree-dimensional non-Boussinesq gravity currents propagating past square and circular cylinders in a lock-exchange configuration have been simulated using implicit large-eddy simulations. The variation in the drag and lift forces in the spanwise direction increases substantially with widening density ratios, resulting in non-uniform loading and regions of high load concentration that are not predicted by the overall force calculation. The variation is greatest immediately before the maximum impact force when the obstacle interacts with the lobe-and-cleft structure of the non-Boussinesq currents, but continues throughout the interaction. Improved normalisation of the drag and lift coefficients is proposed based on the dynamic pressure with the average density of the two fluids, which was found to evolve consistently regardless of the density ratio
Patient perceptions on lipoprotein(a) testing and treatment for secondary prevention of cardiovascular disease: results from the INTERASPIRE study in seven countries across five World Health Organization regions
No full textAims
Lipoprotein(a) [Lp(a)], an inherited lipoprotein, was measured in patients with coronary disease participating in the INTERASPIRE study. The aim of this study was to survey patients’ knowledge and perceptions of cardiovascular risk and their views on Lp(a) testing, consequences, and treatment.
Methods and results
In seven participating countries, recruited patients were divided into those with elevated Lp(a) [≥ 50 mg/dL (≥115 mmol/L)] and those with normal levels. In the elevated group, patients were given an educational leaflet about Lp(a), advised to see their physician and subsequently attended a telephone interview that included study-specific questionnaires assessing knowledge, risk perception, and interest in and acceptability of Lp(a) testing. A random sample of patients with normal Lp(a) were interviewed in the same way. Eight hundred fifty-six patients were interviewed, 523 (22.6% female) with normal Lp(a) and 333 (29.1% female) with elevated Lp(a). Knowledge of cardiovascular disease (CVD) was similar in both groups with a score of 62.1% in normal Lp(a) and 59.6 in elevated Lp(a) P = 0.073. Knowledge of Lp(a) and its management in both groups was poor. Patients with elevated Lp(a) were worried by their result but found testing acceptable and appreciated the benefits. They were motivated to reduce their risk of CVD despite the absence of medical therapies and were eager to receive advice.
Conclusion
Health professionals working in CVD care should be aware of the need to investigate patients with coronary disease for Lp(a) and be equipped to give advice on how to reduce overall cardiovascular risk especially given the absence of licenced therapies to treat Lp(a)
Parental Relative Abundance Does Not Consistently Predict Microbial Community Coalescence in Soil Microcosms
No full textImperial Users onl
Impaired axon regeneration and heightened synaptic dynamics in the injured aged mammalian cortex
No full textAging is a key risk factor for impaired neural repair, yet its effects on axon regeneration and synaptic remodeling in the brain remain unclear. To investigate age-related repair mechanisms in neural circuits, we developed an axonal injury model in the aged (>2 years) mouse somatosensory cortex and tracked fluorescently labeled axons using in vivo multiphoton imaging. Axon degeneration rates were similar to young adults, but regeneration was markedly reduced. Six hours post-lesion, en passant boutons (EPBs)—the most common cortical synapse—showed transient increases in number and size. To assess functional consequences, we used a recurrent neural network model to simulate memory dynamics, revealing distinct changes compared to young adults. Our results suggest that increased synaptic turnover in the aged brain may facilitate partial recovery from injury through synaptic re-wiring, highlighting potential mechanisms supporting neural adaptation in aging
A static modelling and evaluation framework for soft continuum robots with reinforced chambers
No full textElastomer-based soft manipulators with fibre-reinforced chambers, represent a prevalent design paradigm in soft robotics. These robots incorporate multiple actuation chambers, enabling elongation and bending motions. However, the inherent compliance of materials and the pressurised chambers inevitably introduce significant nonlinearity to these robots. Moreover, design of such robots often relies on a trial-and-error approach. Consequently, a comprehensive robot prototyping framework is of paramount importance. To achieve this, we present a static modelling, design and evaluation framework for soft robots with densely reinforced chambers (i.e., the angle between the reinforcement fibre and the axial direction of soft robots is 90°). We first propose a static analytical modelling framework to achieve both the forward kinematics and the tip force generation modelling. This modelling framework accommodates the effects of pressurised chambers and (non)linear material behaviours. Furthermore, our design and evaluation framework incorporates an open-accessible simulation toolbox with a user-friendly graphical interface, along with a physical evaluation platform. The entire framework is validated by eight kinds of manipulators with varying diameters and lengths. Meanwhile, the nonlinearity introduced by geometrical deformation resulting from the elongation, the pressurised actuation chambers (i.e., the chamber stiffening effect), and material hyper-elasticity are investigated. Results also enable informed decision-making on design specifications prior to robot fabrication
Testing the directional recording ability of natural chemical remanent magnetisations using historical sediments
No full textRocks containing magnetic minerals capture the Earth’s magnetic field during their formation and growth, and
acquire a chemical remanent magnetisation (CRM). However, the ability of magnetic minerals in sediments to accurately record the direction of the Earth’s magnetic field during CRM acquisition has yet to be field tested. In this study, the directional recording ability of CRMs in nature was tested using historical salt marsh sediments from Norfolk, UK. Our results find greigite is the dominant remanence carrier in the salt marsh sediments. Evidence for this includes a gyroremanent magnetisation acquired during alternating field demagnetisation and abundant authigenic iron sulphides identified in SEM-EDX analysis. These iron sulphides appeared as clusters and framboids of equidimensional grains. This morphology is typical of natural iron sulphides. SEM analysis shows these grains on the surface of existing grains and within cracks, indicating that the iron sulphides grew authigenically. During the authigenic growth of greigite, it will acquire a grain-growth CRM of the geomagnetic field. A consistent direction (declination 356°, inclination 68°) with an 95 of 8° was found throughout the sediments. This direction is indistinguishable from the average geomagnetic field direction during greigite formation for the last 100 years. Therefore, the CRM carried by greigite has accurately recorded the Earth’s field direction. This is the first study to directly demonstrate that natural grain-growth CRMs reliably record magnetic field direction
Experimental study on the effect of impactor hardness and shape on the impact response of composite panels
No full textIn recent decades, the application of composite materials in aerostructures has significantly increased, with modern commercial aircraft progressively replacing aluminum alloys with composite components. This shift is exemplified by comparing the material compositions of the Boeing 777 and the Boeing 787 (Dreamliner). The Boeing 777 incorporates approximately 50% aluminum alloy and 12% composite materials, whereas the Dreamliner reverses this ratio, utilizing around 50% composites and 12% aluminum alloy. While metals remain advantageous due to their availability and ease of machining, composites offer greater potential for property tailoring to meet specific performance requirements. They also provide superior strength-to-weight ratios and enhanced resistance to corrosion and fatigue. To ensure the reliability of composites in aerospace applications, comprehensive testing under various loading conditions, particularly impact, is essential. Impacts were performed on quasi-isotropic (QIT) carbon-fiber reinforced epoxy panels with stainless steel, round-nosed and flat-ended impactors with rubber discs of 1-, 1.5- and 2 mm thickness, adhered to the flat-ended impactor to simulate the transition between hard and soft impact loading conditions. QIT composite panels were tested in this research employing similar lay-ups often being implemented in aircraft wings and other structures. The rubber discs were applied in the flat-ended impactor case but not for the round-nosed impactor due to the limited adhesion between the rubber and the rounded stainless-steel surface. Impact energies of 7.5, 15 and 30 J were investigated, and the performance of the panels was evaluated using force-time and force-displacement data alongside post-impact ultrasonic C-scan imaging to assess the damaged area. Damage was observed at all three energy values for the round-nosed impacts but only at the highest impact energy when using the flat-ended impactor, leading to the hardness study with adhered rubber discs being performed at 30 J. The most noticeable difference with the addition of rubber discs was the reduction in the damage in the plies nearest the top (impacted) surface. This suggests that the rubber reduces the severity of the impact, but increasing the thickness of the rubber from 1 to 2 mm does not notably increase this effect. Indentation clearly plays a significant role in promoting delamination at low-impact energies for the round-nosed impactors
Investigation on the Microplastic pollution in benthic fish species (Escenius pulcher) from the warmest reef in the world (Arabian Gulf)
No full textImperial Users onl
TRIM24 as a therapeutic target in endocrine treatment-resistant breast cancer
No full textWhile Estrogen receptor alpha (ERα)+ breast cancer treatment is considered effective, resistance to endocrine therapy is common. Since ERα is still the main driver in most therapy-resistant tumors, alternative therapeutic strategies are needed to disrupt ERα transcriptional activity. In this work, we position TRIM24 as a therapeutic target in endocrine resistance, given its role as a key component of the ERα transcriptional complex. TRIM24 interacts with ERα and other well-known ERα cofactors to facilitate ERα chromatin interactions and allows for maintenance of active histone marks including H3K23ac and H3K27ac. Consequently, genetic perturbation of TRIM24 abrogates ERα-driven transcriptional programs and reduces tumor cell proliferation capacity. Using a recently developed degrader targeting TRIM24, ERα-driven transcriptional output and growth were blocked, effectively treating not only endocrine-responsive cell lines but also drug-resistant derivatives thereof as well as cell line models bearing activating ESR1 point mutations. Finally, using human tumor-derived organoid models, we could show the efficacy of TRIM24 degrader in the endocrine-responsive and -resistant setting. Overall, our study positions TRIM24 as a central component for the integrity and activity of the ERα transcriptional complex, with degradation-mediated perturbation of TRIM24 as a promising therapeutic avenue in the treatment of primary and endocrine resistance breast cancer
Analytical benchmark problems and methodological framework for the assessment and comparison of multifidelity optimization methods
No full textAs engineering systems increase in complexity and performance demands intensify, Multidisciplinary Design Optimization (MDO) methodologies are becoming essential for integrating models from multiple disciplines to optimize complex multi-physics systems. Within this context, major challenges remain in selecting appropriate disciplinary fidelity levels, and how to couple them effectively. Multifidelity methods offer a promising path forward by strategically combining information sources of varying fidelity - whether computational or experimental - to enable efficient and scalable design exploration and optimization. Despite the development of numerous multifidelity methods, their comparative performance remains difficult to assess due to the absence of standardized benchmark frameworks capable of evaluating performance across diverse optimization tasks. To address this gap, this paper introduces a comprehensive benchmarking framework that includes: (i) a suite of analytical benchmark optimization problems designed to stress-test and validate multifidelity methods; (ii) a set of assessment metrics for quantifying and comparing performance over measurable objectives; and (iii) the classification, evaluation, and comparison of several families of multifidelity optimization methods and frameworks using the proposed benchmarks to identify their respective strengths and weaknesses in real-world scenarios. The proposed benchmark problems are analytically defined functions carefully selected to capture mathematical challenges commonly encountered in real-world applications, including high dimensionality, multimodality, discontinuities, and noise. Their closed-form nature ensures computational efficiency, high reproducibility, and a clear separation of algorithmic behavior from numerical artifacts. The accompanying performance metrics support the systematic evaluation of multifidelity methods, measuring both optimization effectiveness and global approximation accuracy. By providing a rigorous, reproducible, and accessible benchmarking framework, this work aims to enable the broader community to understand, compare, and advance multifidelity optimization methods for complex problems in science and engineering