A viscoplastic model of expanding cylindrical shells subjected to internal explosive detonations

Magnetic flux compression generators rely on the expansion of thin ductile shells to generate magnetic fields. These thin shells are filled with high explosives, which when detonated, cause the shell to expand to over 200% strain at strain-rates on the order of 10{sup 4} s{sup {minus}1}. Experimental data indicate the development and growth of multiple plastic instabilities which appear in a quasi-periodic pattern on the surfaces of the shells. These quasi-periodic instabilities are connected by localized zones of intense shear that are oriented approximately 45{degree} from the outward radial direction. The quasi-periodic instabilities continue to develop and eventually become through-cracks, causing the shell to fragment. A viscoplastic constitutive model is formulated to model the high strain-rate expansion and provide insight into the development of plastic instabilities. The formulation of the viscoplastic constitutive model includes the effects of shock heating and damage in the form of microvoid nucleation, growth, and coalescence in the expanding shell. This model uses the Johnson-Cook strength model with the Mie-Grueneisen equation of state and a modified Gurson yield surface. The constitutive model includes the modifications proposed by Tvergaard and the plastic strain controlled nucleation introduced by Neeleman. The constitutive model is implemented as a user material subroutine into ABAQUS/Explicit, which is a commercially available nonlinear explicit dynamic finite element program. A cylindrical shell is modeled using both axisymmetric and plane strain elements. Two experiments were conducted involving plane wave detonated, explosively filled, copper cylinders. Instability, displacement, and velocity data were recorded using a fast framing camera and a Fabry-Perot interferometer. Good agreement is shown between the numerical results and experimental data. An additional explosively bulged cylinder experiment was also performed and a photomicrograph of an instability is shown to provide a qualitative comparison between the experimental observations and the numerical predictions

A two-component pre-seeded dermal-epidermal scaffold

We have developed a bilayered dermal-epidermal scaffold for application in the treatment of full-thickness skin defects. The dermal component gels in situ and adapts to the lesion shape, delivering human dermal fibroblasts in a matrix of fibrin and cross-linked hyaluronic acid modified with a cell adhesion-promoting peptide. Fibroblasts were able to form a tridimensional matrix due to material features such as tailored mechanical properties, presence of protease-degradable elements and cell-binding ligands. The epidermal component is a robust membrane containing cross-linked hyaluronic acid and poly-l-lysine, on which keratinocytes were able to attach and to form a monolayer. Amine-aldehyde bonding at the interface between the two components allows the formation of a tightly bound composite scaffold. Both parts of the scaffold were designed to provide cell-type-specific cues to allow for cell proliferation and form a construct that mimics the skin environment.D.S.K. acknowledges funding from the Biotechnology Research Endowment from the Department of Anesthesiology at Boston Children's Hospital. I.P.M. acknowledges the Portuguese Foundation for Science and Technology for the grant BD/39396/2007 and the MIT-Portugal Program. D.G. acknowledges the Swiss National Science Foundation for a post-doctoral fellowship (PBGEP3-129111). B.P.T. acknowledges an NIR Ruth L. Kirschstein National Research Service Award (F32GM096546)

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

A viscoplastic model of expanding cylindrical shells subjected to internal explosive detonations

Magnetic flux compression generators rely on the expansion of thin ductile shells to generate magnetic fields. These thin shells are filled with high explosives, which when detonated, cause the shell to expand to over 200% strain at strain-rates on the order of 10{sup 4} s{sup {minus}1}. Experimental data indicate the development and growth of multiple plastic instabilities which appear in a quasi-periodic pattern on the surfaces of the shells. These quasi-periodic instabilities are connected by localized zones of intense shear that are oriented approximately 45{degree} from the outward radial direction. The quasi-periodic instabilities continue to develop and eventually become through-cracks, causing the shell to fragment. A viscoplastic constitutive model is formulated to model the high strain-rate expansion and provide insight into the development of plastic instabilities. The formulation of the viscoplastic constitutive model includes the effects of shock heating and damage in the form of microvoid nucleation, growth, and coalescence in the expanding shell. This model uses the Johnson-Cook strength model with the Mie-Grueneisen equation of state and a modified Gurson yield surface. The constitutive model includes the modifications proposed by Tvergaard and the plastic strain controlled nucleation introduced by Neeleman. The constitutive model is implemented as a user material subroutine into ABAQUS/Explicit, which is a commercially available nonlinear explicit dynamic finite element program. A cylindrical shell is modeled using both axisymmetric and plane strain elements. Two experiments were conducted involving plane wave detonated, explosively filled, copper cylinders. Instability, displacement, and velocity data were recorded using a fast framing camera and a Fabry-Perot interferometer. Good agreement is shown between the numerical results and experimental data. An additional explosively bulged cylinder experiment was also performed and a photomicrograph of an instability is shown to provide a qualitative comparison between the experimental observations and the numerical predictions

Amplification of AML1 in acute lymphoblastic leukemia is associated with a poor outcome

A total of 28 children and nine adults with relapsed T-ALL were analyzed for the configuration of their T-cell receptor (TCR) and TAL1 genes at diagnosis and relapse to evaluate their stability throughout the disease course. A total of 150 clonal TCR and TAL1 gene rearrangements were identified in the 37 patients at diagnosis. In 65% of cases all rearrangements and in 27% of cases most rearrangements found at diagnosis were preserved at relapse. Two children with unusually late T-ALL recurrences displayed completely different TCR gene rearrangement sequences between diagnosis and relapse. This indicates that a proportion of very late T-ALL recurrences might represent second T-ALL. Specifically, 88% of clonal rearrangements identified at diagnosis in truly relapsed T-ALL were preserved at relapse. This is significantly higher as compared to previously studied precursor-B-ALL (~70%). Thus, from biological point of view, immunogenotype of T-ALL is more stable as compared with precursor-B-ALL. The overall stability of TCR gene rearrangements was higher in adult T-ALL (97%) than in childhood T-ALL (86%). Based on the stability of TCR gene rearrangements, we propose a strategy for PCR target selection (TCRD+TAL1 TCRB TCRG), which probably allows reliable minimal residual disease detection in all T-ALL patients