Interfacial fracture strength property of micro-scale SiN/Cu components

AbstractThe strength against fracture nucleation from an interface free-edge of silicon-nitride (SiN)/copper (Cu) micro-components is evaluated. A special technique that combines a nano-indenter specimen holder and an environmental transmission electron microscope (E-TEM) is employed. The critical load at the onset of fracture nucleation from a wedge-shaped free-edge (opening angle: 90°) is measured both in a vacuum and in a hydrogen (H2) environment, and the critical stress distribution is evaluated by the finite element method (FEM). It is found that the fracture nucleation is dominated by the near-edge elastic singular stress field that extends about a few tens of nanometers from the edge. The fracture nucleation strength expressed in terms of the stress intensity factor (K) is found to be eminently reduced in a H2 environment

Design and lyophilization of lipid nanoparticles for mRNA vaccine and its robust immune response in mice and nonhuman primates

mRNA and lipid nanoparticles have emerged as powerful systems for the preparation of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The emergence of novel variants or the necessity of cold chain logistics for approved mRNA vaccines undermines the investigation of next-generation systems that could preserve both potency and stability. However, the correlation between lipid nanoparticle composition and activity is not fully explored. Here, we screened a panel of ionizable lipids in vivo and identified lead lipid nanoparticles with a branched-tail lipid structure. Buffer optimization allowed the determination of lyophilization conditions, where lipid nanoparticle-encapsulated mRNA encoding SARS-CoV-2 spike protein could induce robust immunogenicity in mice after 1 month of storage at 5°C and 25°C. Intramuscularly injected lipid nanoparticles distributed in conventional dendritic cells in mouse lymph nodes induced balanced T helper (Th) 1/Th2 responses against SARS-CoV-2 spike protein. In nonhuman primates, two doses of 10 or 100 μg of mRNA induced higher spike-specific binding geometric mean titers than those from a panel of SARS-CoV-2-convalescent human sera. Immunized sera broadly inhibited the viral entry receptor angiotensin-converting enzyme 2 (ACE2) from binding to the spike protein in all six strains tested, including variants of concern. These results could provide useful information for designing next-generation mRNA vaccines

Multiacquisition Variable-Resonance Image Combination Selective Can Improve Image Quality and Reproducibility for Metallic Implants in the Lumbar Spine

The aim of this study is to evaluate how metallic artifacts in the lumbar spine can affect images obtained from magnetic resonance (MR) sequences. We performed a phantom experiment by scanning an agar containing an orthopedic metallic implant using 64-channel multidetector row computed tomography (CT) and a 3-tesla MR unit. We compared the reproducibility in each measurement, enlargement or reduction ratio of the CT and MR measurements, and signal deviation in each voxel from the control. The reproducibility on CT and multiacquisition variable-resonance image combination selective (MAVRIC SL) was good, but that on the other MR sequences showed either fixed bias or proportional bias. The reduction ratios of the distance between the nails were significantly smaller in MAVRIC SL than in the other MR sequences after CT measurements (p<0.001, respectively). MAVRIC SL was able to reduce the metallic artifact, permitting observation of the tissue surrounding the metal with good reproducibility

Time-resolved magnetic resonance angiography as a follow-up method for visceral artery aneurysm treated with coil-embolisation

Purpose: The purpose of this study is to assess the feasibility and usefulness of time-resolved magnetic resonance angiography (TR-MRA) for follow-up of visceral artery aneurysms (VAAs) after embolotherapy. Material and methods: Twenty-one VAAs (11 splenic, six renal, three internal iliac, and one superior pancreaticoduodenal artery aneurysms) in 18 patients (median age, 64 years; range, 36-88 years) previously treated by embolisation with platinum coils, were evaluated. The mean size of the aneurysm was 10.5 cm3 (range, 0.3-132 cm3). Among them, 19 lesions were treated by aneurysmal packing with or without distal-to-proximal embolisation. For the remaining two lesions, distal-to-proximal embolization alone was performed. The mean observation period after embolotherapy was 35 weeks (range, 4-216). All patients underwent TR-MRA following an intravenous bolus injection of gadolinium chelate. Recanalisation was diagnosed when any portion of the aneurysmal sac was enhanced in the arterial phase. Results: On TR-MRA, two lesions were diagnosed as recanalised. They were confirmed by transcatheter arteriography and re-treated by embolotherapy. For the remaining 19 lesions, there were no findings of recanalisation on TR-MRA. Conclusions: TR-MRA appears to be a feasible method for follow-up examination of VAAs treated by embolotherapy

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target