Genesis of oceanic oxide gabbros and gabbronorites during reactive melt migration at transform walls (Doldrums Megatransform System; 7-8°N Mid-Atlantic Ridge)

The Doldrums Megatransform System (~7-8°N, Mid-Atlantic Ridge) shows a complex architecture including four intra-transform ridge segments bounded by five active transform faults. Lower crustal rocks are exposed along the Doldrums and Vernadsky transform walls that bound the northernmost intra-transform ridge segment. The recovered gabbros are characterized by variably evolved chemical compositions, ranging from olivine gabbros to gabbronorites and oxide gabbros, and lack the most primitive gabbroic endmembers (troctolites, dunites). Notably, the numerous recovered gabbronorites show up to 20 vol% of coarse-grained orthopyroxene. Although covariations in mineral and bulk-rock chemical compositions of the olivine and oxide gabbros define trends of crystallization from a common parental melt, the gabbronorites show elevated light over heavy rare earth elements (LREE/HREE) ratios in both bulk-rock and mineral compositions. These features are not consistent with a petrological evolution driven solely by fractional crystallization, which cannot produce the preferential enrichments in highly incompatible elements documented in the orthopyroxene-bearing lithologies. We suggest that gabbronorites crystallized from evolved melts percolating and partly assimilating a pre-existing olivine gabbro matrix. Saturation in orthopyroxene and selective enrichments in LREE relative to M-HREE are both triggered by an increase in assimilated crystal mass, which ranges from negligible in the oxide-gabbros to abundant in the gabbronorites. This melt-rock reaction process has been related to lateral melt migration beneath ridge-transform intersections, where variably evolved melts injected from the peripheral parts of the melting region towards the transform zone may interact with a gabbroic crystal mush to form abundant oxide-bearing gabbronoritic associations

Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms

Intracellular gap (iGap) formation in liver sinusoidal endothelial cells (LSECs) is caused by the destruction of fenestrae and appears under pathological conditions; nevertheless, their role in metastasis of cancer cells to the liver remained unexplored. We elucidated that hepatotoxin-damaged and fibrotic livers gave rise to LSECs-iGap formation, which was positively correlated with increased numbers of metastatic liver foci after intrasplenic injection of Hepa1-6 cells. Hepa1-6 cells induced interleukin-23-dependent tumor necrosis factor-α (TNF-α) secretion by LSECs and triggered LSECs-iGap formation, toward which their processes protruded to transmigrate into the liver parenchyma. TNF-α triggered depolymerization of F-actin and induced matrix metalloproteinase 9 (MMP9), intracellular adhesion molecule 1, and CXCL expression in LSECs. Blocking MMP9 activity by doxycycline or an MMP2/9 inhibitor eliminated LSECs-iGap formation and attenuated liver metastasis of Hepa1-6 cells. Overall, this study revealed that cancer cells induced LSEC-iGap formation via proinflammatory paracrine mechanisms and proposed MMP9 as a favorable target for blocking cancer cell metastasis to the liver

The Central-Bank Balance Sheet as an Instrument of Monetary Policy

While many analyses of monetary policy consider only a target for a short-term nominal interest rate, other dimensions of policy have recently been of greater importance: changes in the supply of bank reserves, changes in the assets acquired by central banks, and changes in the interest rate paid on reserves. We extend a standard New Keynesian model to allow a role for the central bank's balance sheet in equilibrium determination, and consider the connections between these alternative dimensions of policy and traditional interest-rate policy. We distinguish between "quantitative easing" in the strict sense and targeted asset purchases by a central bank, and argue that while the former is likely be ineffective at all times, the latter dimension of policy can be effective when financial markets are sufficiently disrupted. Neither is a perfect substitute for conventional interest-rate policy, but purchases of illiquid assets are particularly likely to improve welfare when the zero lower bound on the policy rate is reached. We also consider optimal policy with regard to the payment of interest on reserves; in our model, this requires that the interest rate on reserves be kept near the target for the policy rate at all times

Heparan Sulfate Proteoglycans Mediate Interstitial Flow Mechanotransduction Regulating MMP-13 Expression and Cell Motility via FAK-ERK in 3D Collagen

Interstitial flow directly affects cells that reside in tissues and regulates tissue physiology and pathology by modulating important cellular processes including proliferation, differentiation, and migration. However, the structures that cells utilize to sense interstitial flow in a 3-dimensional (3D) environment have not yet been elucidated. Previously, we have shown that interstitial flow upregulates matrix metalloproteinase (MMP) expression in rat vascular smooth muscle cells (SMCs) and fibroblasts/myofibroblasts via activation of an ERK1/2-c-Jun pathway, which in turn promotes cell migration in collagen. Herein, we focused on uncovering the flow-induced mechanotransduction mechanism in 3D.Cleavage of rat vascular SMC surface glycocalyx heparan sulfate (HS) chains from proteoglycan (PG) core proteins by heparinase or disruption of HS biosynthesis by silencing N-deacetylase/N-sulfotransferase 1 (NDST1) suppressed interstitial flow-induced ERK1/2 activation, interstitial collagenase (MMP-13) expression, and SMC motility in 3D collagen. Inhibition or knockdown of focal adhesion kinase (FAK) also attenuated or blocked flow-induced ERK1/2 activation, MMP-13 expression, and cell motility. Interstitial flow induced FAK phosphorylation at Tyr925, and this activation was blocked when heparan sulfate proteoglycans (HSPGs) were disrupted. These data suggest that HSPGs mediate interstitial flow-induced mechanotransduction through FAK-ERK. In addition, we show that integrins are crucial for mechanotransduction through HSPGs as they mediate cell spreading and maintain cytoskeletal rigidity.We propose a conceptual mechanotransduction model wherein cell surface glycocalyx HSPGs, in the presence of integrin-mediated cell-matrix adhesions and cytoskeleton organization, sense interstitial flow and activate the FAK-ERK signaling axis, leading to upregulation of MMP expression and cell motility in 3D. This is the first study to describe a flow-induced mechanotransduction mechanism via HSPG-mediated FAK activation in 3D. This study will be of interest in understanding the flow-related mechanobiology in vascular lesion formation, tissue morphogenesis, cancer cell metastasis, and stem cell differentiation in 3D, and also has implications in tissue engineering

Specific Syndecan-1 Domains Regulate Mesenchymal Tumor Cell Adhesion, Motility and Migration

Malignant mesothelioma is an asbestos induced cancer that is difficult to diagnose. Several studies have combined biomarkers to improve mesothelioma diagnosis, but with moderate success, and there is a need for new mesothelioma biomarkers. The tumour is often resistant to treatment and most patients will survive less than a year. An indicator of patient survival is the tumours growth pattern, which in turn is influenced by expressed proteoglycans. In this thesis work, we aim to improve the possibilities to diagnose malignant mesothelioma by combining biomarkers and by identifying new ones. We also investigate tumour driving mechanisms with focus on one of these suggested biomarkers, the cell-bound proteoglycan syndecan-1. We were able to construct a diagnostic two-step model based on biomarkers in patient material. By implementing a cut-off level and thereafter focusing on unresolved patients we combined hyaluronan and N-ERC/mesothelin (paper I), which significantly increased the diagnostic accuracy for malignant mesothelioma. To further improve diagnosis, we used mass spectrometry to find new biomarkers. We identified and validated galectin-1, which was excellent in discriminating mesotheliomas from adenocarcinomas (paper II). In the same study, we were also the first to describe aldo-keto reductase 1B10 as a novel prognostic mesothelioma biomarker. Syndecan-1 has been indicated as a marker for carcinomas. In paper I we describe how higher levels of syndecan-1 indicate the presence of a carcinoma over a mesothelioma. This was verified in paper II when syndecan-1 was identified as downregulated in fluids from mesothelioma patients compared to lung cancer patients. Paper III and paper IV focus on this proteoglycan. Malignant cell lines transfected with syndecan-1 and various truncated forms of syndecan-1 affected adhesion and migration, which are key features of cancer invasion (paper III). The results showed a domain- and cell type specific effect on the cells’ motility. Regulating syndecan-1 levels and analysing the global gene expression of mesothelioma cells made it evident that this proteoglycan has a strong influence on transforming growth factor β signalling and several growth factor pathways (paper IV). Links to cell migration and proliferation were furthermore identified, along with glycosaminoglycan modifying enzymes. These results can shed light on the complex role of syndecan-1 in invasion and growth of malignant mesenchymal cells. Taken together, this thesis work describes a complement to conventional mesothelioma diagnosis and identifies novel biomarkers. Furthermore, the potential biomarker syndecan-1 was shown to have an effect on cell motility and proliferation. These results increase our understanding of this aggressive malignancy

Modelling and active control aiming at enhancing the sound transmission loss of thin partition panels

The transport and civil industry research has been aiming at improving vibro-acoustic performance of panel-like structures such as trim panels, glazing windows or separating walls. Focusing on the airborne path, the application of an active control for optimizing the plate acoustic isolation performance is here investigated. A transmission model of an acoustically excited plate is derived in the time domain predicting the plate velocity and its acoustic radiation. The dynamic system is modelled together with the control loop in MATLAB (R) where a suitable control algorithm for enhancing the panel transmission loss performance is developed

Physicochemical Stability, Antioxidant Activity, and Acceptance of Beet and Orange Mixed Juice During Refrigerated Storage

The objective of this study was to mix beet juice and orange juice in two proportions (1:1 and 1:2 v/v), evaluate their physicochemical stability and antioxidant activity during storage (4 °C for 30 days), and evaluate their acceptance by consumers. Beet juice (with or without pasteurization) and pasteurized orange juice were used as controls. The presence of orange juice contributed to the pH, betacyanin, betaxanthin, and antioxidant capacity stabilities during storage, whereas the presence of beet improved the color stability. The mixed juices showed high total phenolic compounds (484–485 µg gallic acid/mL), DPPH scavenging capacity (2083–1930 µg Trolox/mL), and ABTS (1854–1840 µg Trolox/mL), as well as better sensory acceptance than the pasteurized beet juice. However, the mixed juices had a more significant reduction in the ascorbic acid content (completely lost at 15 days of storage) than the pasteurized orange juice (25% reduction at 30 days). The beet and orange mixed juice is an alternative functional beverage that can contribute to an increase in the consumption of beet and orange