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Despite the high prevalence of heart failure in the western world, there are few effective treatments. Fibulin-3 is a protein involved in extracellular matrix (ECM) structural integrity, however its role in the heart is unknown. We have demonstrated, using single cell RNA-seq, that fibulin-3 was highly expressed in quiescent murine cardiac fibroblasts, with expression highest prior to injury and late post-infarct (from ~ day-28 to week-8). In humans, fibulin-3 was upregulated in left ventricular tissue and plasma of heart failure patients. Fibulin-3 knockout (Efemp1-/-) and wildtype mice were subjected to experimental myocardial infarction. Fibulin-3 deletion resulted in significantly higher rate of cardiac rupture days 3-6 post-infarct, indicating a weak and poorly formed scar, with severe ventricular remodelling in surviving mice at day-28 post-infarct. Fibulin-3 knockout mice demonstrated less collagen deposition at day-3 post-infarct, with abnormal collagen fibre-alignment. RNA-seq on day-3 infarct tissue revealed upregulation of ECM degradation and inflammatory genes, but downregulation of ECM assembly/structure/organisation genes in fibulin-3 knockout mice. GSEA pathway analysis showed enrichment of inflammatory pathways and a depletion of ECM organisation pathways. Fibulin-3 originates from cardiac fibroblasts, is upregulated in human heart failure, and is necessary for correct ECM organisation/structural integrity of fibrotic tissue to prevent cardiac rupture post-infarct.

Endothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient changes in metabolic gene signatures. Trajectory analysis reveals that the majority of endothelial cells 3 to 7 days after myocardial infarction acquire a transient state, characterized by mesenchymal gene expression, which returns to baseline 14 days after injury. Lineage tracing, using the Cdh5-CreERT2;mT/mG mice followed by single cell RNA sequencing, confirms the transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures of endothelial cells during early and late states after injury. These data suggest that endothelial cells undergo a transient mes-enchymal activation concomitant with a metabolic adaptation within the first days after myocardial infarction but do not acquire a long-term mesenchymal fate. This mesenchymal activation may facilitate endothelial cell migration and clonal expansion to regenerate the vascular network.

http://archive.org/details/theconstructiono1094516052, NA, NA

Patrick Robbins of Missoula, Montana, discusses his family history and how they came to be in the United States, eventually leading to Butte, Montana. He remembers his growing up in Butte, the traditions, character and customs of the community, and his experiences beyond the city., https://scholarworks.umt.edu/gathering/1066/thumbnail.jpg

With the advent of the hovercraft and hydrofoil, high-speed, overwater travel has become a practical proposition. Nevertheless, there would appear to be an upper limit to the speed of these craft imposed by, on the one hand, the intake momentum drag of the hovercraft and, on the other, the drag of the submerged foils of the hydrofoil- One method proposed for reducing these drags employs aerodynamic lifting surfaces to off-load the cushion or hydrodynamic lifting systems. These surfaces, which are referred to as 'ground-effect wings', fall into two main categories, namely 'open' and 'closed'. The latter type is defined as that which mays in theory, be designed for zero induced drag; the former type is that which may not. By employing the linearized lifting-surface theory the minimum induced drag of an open configuration, consisting of a planar wing with end plates, is determined. The results of this theory are in agreement with experiment in predicting that the effect of end plates is to reduce the induced drag. However, the indications of the experiments are that the reduction in induced drag is somewhat greater than the theoretical prediction. There is evidence that this is due to the tendency of the end plates to suppress harmful non-linear effects such as edge separations at the tips of the wing and the sidewash at the wing. A theoretical and experimental study of the lift and induced drag of a closed configuration, comprised of a substantially planar wing with end plates and not designed ab initio for zero induced drag, is

With the advent of the hovercraft and hydrofoil, high-speed, overwater travel has become a practical proposition. Nevertheless, there would appear to be an upper limit to the speed of these craft imposed by, on the one hand, the intake momentum drag of the hovercraft and, on the other, the drag of the submerged foils of the hydrofoil- One method proposed for reducing these drags employs aerodynamic lifting surfaces to off-load the cushion or hydrodynamic lifting systems. These surfaces, which are referred to as 'ground-effect wings', fall into two main categories, namely 'open' and 'closed'. The latter type is defined as that which mays in theory, be designed for zero induced drag; the former type is that which may not. By employing the linearized lifting-surface theory the minimum induced drag of an open configuration, consisting of a planar wing with end plates, is determined. The results of this theory are in agreement with experiment in predicting that the effect of end plates is to reduce the induced drag. However, the indications of the experiments are that the reduction in induced drag is somewhat greater than the theoretical prediction. There is evidence that this is due to the tendency of the end plates to suppress harmful non-linear effects such as edge separations at the tips of the wing and the sidewash at the wing. A theoretical and experimental study of the lift and induced drag of a closed configuration, comprised of a substantially planar wing with end plates and not designed ab initio for zero induced drag, is