150259 research outputs found
Sort by
Using 3D Printing to Improve the Impact Resistance of Sandwich Panels
Full text linkSandwich panels are a stiff, yet lightweight structure commonly found in aerospace applications. However, their low density cores can limit their performance in strength and impact resistance. Advances in 3D printing have created the potential to use new materials and create new geometries for sandwich panel cores to improve their impact resistance. A uniform-density honeycomb core made from ULTEM-1010 was designed. It was then tested in quasi-static compression, bending and indentation, low-velocity impact and high-velocity impact regimes and then compared against two typical reference designs.
The 3D printed ULTEM-1010 panel design showed a significant improvement in core compressive strength and indentation energy absorption in all testing regimes. However, it suffered from less bending stiffness compared to the reference panel designs. The ULTEM-1010 panel showed an increase in perforation energy during high-velocity impact when compared to quasi-static indentation. Through-thickness variation was introduced into the ULTEM-1010 core designs to improve the weaker bending performance of the 3D printed core. One graded design provided a small improvement in bending stiffness and perforation energy during quasi-static indentation. However, the introduction of additional failure modes meant that these improvements did not translate up to higher strain rates.
A high-resolution FE model was developed to predict the evolution of damage within each panel, to help support interpretation of the experiments and to aid the design process for 3D printed cores. A particular challenge of modelling the behaviour of the 3D printed polymer is its quasi-brittle nature. A novel approach for modelling this quasi-brittle behaviour was tested. This was found to provide a good match with experiments.
Overall, the new 3D printed core designs, designed using a combination of experiment, analytical and numerical modelling, met their objective in improving indentation resistance and impact damage tolerance. Furthermore, they showed potential for further development and several areas were identified with scope for further performance improvements
Strategies for CRISPR-based knock-ins in primary human B cells and lymphoma cell lines.
Full text linkSince its advent about ten years ago, the CRISPR-Cas9 system has been frequently used in biomedical applications. It has advanced various fields, and CRISPR-Cas9-based therapeutics have shown promising results in the treatment of specific hematological diseases. Furthermore, CRISPR gene editing technologies have revolutionized cancer research by enabling a broad range of genetic perturbations, including genetic knockouts and precise single nucleotide changes. This perspective focuses on the state-of-the-art methodology of CRISPR knock-ins to engineer immune cells. Since this technique relies on homology-directed repair (HDR) of double-strand breaks (DSBs) induced by the Cas9 enzyme, it can be used to introduce specific mutations into the target genome. Therefore, this methodology offers a valuable opportunity to functionally study specific mutations and to uncover their impacts not only on overall cell functions but also on the mechanisms behind cancer-related alterations in common signaling pathways. This article highlights CRISPR knock-in strategies, protocols, and applications in cancer and immune research, with a focus on diffuse large B cell lymphoma
Active Shell Engineering for Efficient Cascade Triplet Energy Transfer in Lanthanide Heterostructures.
Full text linkLanthanide-doped nanoparticles (LnNPs) exhibit unique optical properties but suffer from severe surface quenching and weak absorption that fundamentally limit their performance. Here, we demonstrate a breakthrough cascade triplet energy transfer (TET) mechanism in precisely engineered [email protected]:Nd0.2@9-anthracenecarboxylic acid (ACA) heterostructures. This core/active shell/organic molecule configuration combines both molecular sensitization with surface passivation, transforming conventional inert barriers into functional energy conduits. We explore in detail the synthetic conditions required to grow not just optimally active shells but also how best to assemble the organic ligands on the surface of core-shell LnNPs. Systematic shell thickness optimization (0.8-4.6 nm) reveals an optimal shell thickness of ∼2.0 nm. When coupled with an appropriate ligand exchange strategy, we achieve a remarkable 1200-fold emission enhancement compared to bare cores. Comprehensive spectroscopic investigations confirm near-unity TET efficiency and reveal the cascade TET mechanism utilizing Nd3+ ions as energy intermediates to maximize the Yb3+ emission. Thus, our mechanism and heterostructure design present one of the most promising synthetic strategies to overcome the existing limitations of traditional LnNPs, establishing new paradigms for high-performance heterostructures with broad applications in bioimaging, photon conversion, and optoelectronic devices
A cycling, progenitor-like cell population at the base of atypical teratoid rhabdoid tumor subtype differentiation trajectories.
Full text linkBACKGROUND: Atypical teratoid rhabdoid tumors (ATRTs) are highly aggressive pediatric central nervous system tumors defined by the inactivation of the SMARCB1 gene. Despite the identification of three distinct molecular subtypes, each defined by unique clinical and molecular characteristics, no subtype-specific therapeutic strategies are currently available. This highlights an urgent need to deepen our understanding of the cellular heterogeneity and developmental origins of ATRTs. METHODS: We generated a comprehensive single-nucleus transcriptomic atlas of ATRT samples, integrated it with single-nucleus ATAC-seq and spatial transcriptomics data, and validated our findings experimentally using patient-derived ATRT tumoroid models. RESULTS: Our analyses revealed distinct subtype-specific differentiation trajectories, each resembling different brain progenitor lineages. We identified key transcription factors that appear to drive these developmental pathways. Furthermore, a shared cycling, intermediate precursor cell (IPC)-like cell population, interspersed throughout tumors, was consistently present within all ATRT samples. We demonstrate that these subtype-specific differentiation pathways can be pharmacologically manipulated in patient-derived ATRT tumoroids. By directing tumor cells along their respective subtype-specific trajectories, we were able to induce a shift toward more differentiated, non-proliferative states. CONCLUSIONS: Collectively, our findings show that ATRTs recapitulate fetal brain signaling programs in a subtype-specific manner. This work provides a framework for understanding ATRT heterogeneity and supports the feasibility of maturation-based therapeutic strategies tailored to the molecular subtype of the tumor
Wafer-scale high-κ HfO2 dielectric films with sub-5-Å equivalent oxide thickness for 2D MoS2 transistors.
Full text linkHigh-κ gate dielectrics are indispensable in modern transistor technology and play a pivotal role in efficient capacitive gating and suppression of leakage currents. However, the realization of industry-compatible high-κ gate dielectrics at a sub-5-Å equivalent oxide thickness (EOT) remains challenging. Here we report the realization of 1.3-nm thick hafnium oxide (HfO2) dielectrics via an industry-compatible multiple oxidation atomic layer deposition process at 200 °C. A low EOT down to 2.5 Å is demonstrated for 1.3-nm thick HfO2 dielectrics on metal gates with a low leakage current of 10-6 A/cm2 and a robust breakdown electric field of ~22.3 MV/cm. Remarkably, such low EOT high-κ/metal gates can be directly implanted into emerging two-dimensional (2D) transistors and low-power logic circuits on 8-inch wafer scale to showcase their potentials. The as-fabricated molybdenum disulfide (MoS2) transistors exhibit a large on-state current density of 260 µA/µm at source-drain bias of 0.5 V, a high on/off ratio of 108, an average subthreshold slope (SS) of 75 mV/dec, and small capacitance equivalent thickness (CET) values of 0.34 nm for gate-first transistors and 0.50 nm for gate-last transistors. Our ultra-scaled dielectrics hold significant promise for advanced semiconductor fabrication processes towards the angstrom era
Rapid diagnosis and treatment of inflammatory bowel diseases.
No full textBoth Crohn's disease and ulcerative colitis are associated with heterogeneity of presentation, disease course, and outcomes between individuals. The frequency of flares and progression to complications can have a profound impact on quality of life for people living with IBD. Indeed, many patients report suboptimal disease control and major disruption to their lives from active, uncontrolled inflammation. Two major factors potentially contributing to adverse outcomes are delays to establish a diagnosis of IBD and delays in the introduction of effective treatment. Several recent studies have addressed the role of early diagnosis and early treatment, including differences to consider between Crohn's disease and ulcerative colitis. In this review we summarize the important insights obtained and highlight how outcomes for patients can be improved with a focus on timely diagnosis and timely, effective treatment interventions
Vaccines and antimicrobial resistance: from science to policy-summary and outcomes.
No full textIn April 2024, the Royal Society convened a Science+ meeting in London on 'Vaccines and antimicrobial resistance: from science to policy'. The purpose was to review the science of how vaccines reduce antimicrobial resistance (AMR) and discuss policy in advancing development and equitable deployment of such vaccines. The meeting adopted a One Health approach with international speakers presenting from both human and veterinary perspectives. Presentations on Day 1 focused on scientific aspects of the AMR threat and the role of vaccines as counter measures. On Day 2, presentations covered associated policy implications based on this scientific understanding. A closing panel discussion looked towards the United Nations High-Level Meeting on AMR in New York in September 2024. This article is the closing contribution to an issue of Philosophical Transactions of the Royal Society B based on the meeting. It serves as a summary of the two days of proceedings, including key outcomes and recommendations, and provides an overall conclusion to the meeting. This article is part of the Royal Society Science+ meeting issue 'Vaccines and antimicrobial resistance: from science to policy'
Roundtable Review
No full textIn 2023, Princeton University Press published Richard Langlois’s The Corporation and the Twentieth Century: The History of American Business Enterprise. It is a book of comparable mass to Alfred Chandler’s 1977 The Visible Hand and equally ambitious. 1 The erudition is vast. (The bibliography alone runs 78 closely-printed pages. There are 122 pages of equally closely-printed footnotes to the 522-page main text whose own font is not large.) A production such as this seemed worth more than the usual traditional-form reviews, and in the September following its publication, the Penn Economic History Forum put on a symposium to discuss it. Interest was widespread: attendance in the room was agreeably substantial and came from far beyond the seminar’s usual catchment area, and there were requests for the Zoom link to the proceedings from around the world. (The expense was not vast and the ratio of impact to expense was almost certainly favorable relative to ordinary seminars. The economic history community might not suffer from putting on more such events when suitable occasions arise.
Metastability and high- superconductivity in A15-type ternary hydride YSbH at moderate pressure
No full textThe discovery of high-temperature superconductors remains a central challenge in materials science. Hydrogen-rich compounds are among the most promising candidates, as they can exhibit phonon-mediated superconductivity at elevated critical temperatures, though their stabilization typically requires extreme pressures.
%
Here, we report the identification of YSbH as a promising superconductor by a multi-stage high-throughput screening on ternary A15-type hydrides, followed by a high-throughput computational search of the Y--Sb--H system, accelerated by ephemeral data derived potentials.
%
The cubic Pm\Bar{3} YSbH phase exhibits a predicted critical temperature of 118\,K at 50\,GPa, among the highest reported to date for an A15-hydride at this pressure. Thermodynamic analysis shows that YSbH lies 100\,meV/atom above the convex hull at 50\,GPa, but only 26\,meV/atom above the hull at 120\,GPa, suggesting possible metastability and synthesis at similar high pressure conditions. The phase is dynamically stable over a wide pressure range (20--120\,GPa), displays kinetic stability at 50\,GPa and elastic stability at 20 and 50\,GPa, key ingredients for long-lived metastable behaviour at moderate pressures.
%
These results highlight YSbH as a benchmark case illustrating the balance between high- performance and limited thermodynamic stability in ternary hydrides, and underscore the importance of combined dynamic, thermodynamic, kinetic and elastic stability analyses for guiding experimental synthesis of metastable superconductors
