A gravel-sand bifurcation:a simple model and the stability of the equilibrium states

A river bifurcation, can be found in, for instance, a river delta, in braided or anabranching reaches, and in manmade side channels in restored river reaches. Depending on the partitioning of water and sediment over the bifurcating branches, the bifurcation develops toward (a) a stable state with two downstream branches or (b) a state in which the water discharge in one of the branches continues to increase at the expense of the other branch (Wang et al., 1995). This may lead to excessive deposition in the latter branch that eventually silts up. For navigation, flood safety, and river restoration purposes, it is important to assess and develop tools to predict such long-term behavior of the bifurcation. A first and highly schematized one-dimensional model describing (the development towards) the equilibrium states of two bifurcating branches was developed by Wang et al (1995). The use of a one-dimensional model implies the need for a nodal point relation that describes the partitioning of sediment over the bifurcating branches. Wang et al (1995) introduce a nodal point relation as a function of the partitioning of the water discharge. They simplify their nodal point relation to the following form: s*=q*k , where s* denotes the ratio of the sediment discharges per unit width in the bifurcating branches, q* denotes the ratio of the water discharges per unit width in the bifurcating branches, and k is a constant. The Wang et al. (1995) model is limited to conditions with unisize sediment and application of the Engelund & Hansen (1967) sediment transport relation. They assume the same constant base level for the two bifurcating branches, and constant water and sediment discharges in the upstream channel. A mathematical stability analysis is conducted to predict the stability of the equilibrium states. Depending on the exponent k they find a stable equilibrium state with two downstream branches or a stable state with one branch only (i.e. the other branch has silted up). Here we extend the Wang et al. (1995) model to conditions with gravel and sand and study the stability of the equilibrium states

A Framework to Evaluate the SDG Contribution of Fluvial Nature-Based Solutions

Nature-based solutions (NBSs) are measures reflecting the ‘cooperation with nature’ approach: mitigating fluvial flood risk while being cost-effective, resource-efficient, and providing numerous environmental, social, and economic benefits. Since 2015, the United Nations (UN) 2030 Agenda has provided UN member states with goals, targets, and indicators to facilitate an integrated approach focusing on economic, environmental, and social improvements simultaneously. The aim of this study is to evaluate the contribution of fluvial NBSs to the UN 2030 Agenda, using all its components: Sustainable Development Goals (SDGs), targets, and indicators. We propose a four-step framework with inputs from the UN 2030 Agenda, scientific literature, and case studies. The framework provides a set of fluvial flooding indicators that are linked to SDG indicators of the UN 2030 Agenda. Finally, the fluvial flooding indicators are tested by applying them to a case study, the Eddleston Water Project, aiming to examine its contribution to the UN 2030 Agenda. This reveals that the Eddleston Water Project contributes to 9 SDGs and 33 SDG targets from environmental, economic, societal, policy, and technical perspectives. Our framework aims to enhance the systematic considerations of the SDG indicators, adjust their notion to the system of interest, and thereby enhance the link between the sustainability performance of NBSs and the UN 2030 AgendaRivers, Ports, Waterways and Dredging Engineerin

Vascular E-selectin expression correlates with CD8 lymphocyte infiltration and improved outcome in Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-linked skin cancer. While CD8 lymphocyte infiltration into the tumor is strongly correlated with improved survival, these cells are absent or sparse in most MCCs. We investigated whether specific mechanisms of T-cell migration may be commonly disrupted in MCC tumors with poor CD8 lymphocyte infiltration. Intratumoral vascular E-selectin, critical for T-cell entry into skin, was downregulated in the majority (52%) of MCCs (n=56), and its loss was associated with poor intratumoral CD8 lymphocyte infiltration (p<0.05; n=45). Importantly, survival was improved in MCC patients whose tumors had higher vascular E-selectin expression (p<0.05). Local nitric oxide (NO) production is one mechanism of E-selectin downregulation and it can be tracked by quantifying nitrotyrosine, a stable biomarker of NO-induced reactive nitrogen species (RNS). Indeed, increasing levels of nitrotyrosine within MCC tumors were associated with low E-selectin expression (p<0.05; n=45) and decreased CD8 lymphocyte infiltration (p<0.05, n=45). These data suggest that one mechanism of immune evasion in MCC may be restriction of T cell entry into the tumor. Existing therapeutic agents that modulate E-selectin expression and/or RNS generation may restore T cell entry and could potentially synergize with other immune-stimulating therapies

Complement inhibitor CSMD1 acts as tumor suppressor in human breast cancer

Human CUB and Sushi multiple domains 1 (CSMD1) is a membrane-bound complement inhibitor suggested to act as a putative tumor suppressor gene, since allelic loss of this region encompassing 8p23 including CSMD1 characterizes various malignancies. Here, we assessed the role of CSMD1 as a tumor suppressor gene in the development of breast cancer in vitro and in vivo. We found that human breast tumor tissues expressed CSMD1 at lower levels compared to that in normal mammary tissues. The decreased expression of CSMD1 was linked to a shorter overall survival of breast cancer patients. We also revealed that expression of CSMD1 in human breast cancer cells BT-20 and MDA-MB-231 significantly inhibited their malignant phenotypes, including migration, adhesion and invasion. Conversely, stable silencing of CSMD1 expression in T47D cells enhanced cancer cell migratory, adherent and clonogenic abilities. Moreover, expression of CSMD1 in the highly invasive MDA-MB-231 cells diminished their signaling potential as well as their stem cell-like properties as assessed by measurement of aldehyde dehydrogenase activity. In a xenograft model, expression of CSMD1 blocked the ability of cancer cells to metastasize to secondary sites in vivo, likely via inhibiting local invasion but not the extravasation into distant tissues. Taken together, these findings demonstrate the role of CSMD1 as a tumor suppressor gene in breast cancer

NADPH-oxidase-driven oxygen radical production determines chondrocyte death and partly regulates metalloproteinase-mediated cartilage matrix degradation during interferon-γ-stimulated immune complex arthritis

In previous studies we have found that FcγRI determines chondrocyte death and matrix metalloproteinase (MMP)-mediated cartilage destruction during IFN-γ-regulated immune complex arthritis (ICA). Binding of immune complexes (ICs) to FcγRI leads to the prominent production of oxygen radicals. In the present study we investigated the contribution of NADPH-oxidase-driven oxygen radicals to cartilage destruction by using p47phox(-/- )mice lacking a functional NADPH oxidase complex. Induction of a passive ICA in the knee joints of p47phox(-/- )mice resulted in a significant elevation of joint inflammation at day 3 when compared with wild-type (WT) controls as studied by histology. However, when IFN-γ was overexpressed by injection of adenoviral IFN-γ in the knee joint before ICA induction, a similar influx of inflammatory cells was found at days 3 and 7, comprising mainly macrophages in both mouse strains. Proteoglycan depletion from the cartilage layers of the knee joints in both groups was similar at days 3 and 7. Aggrecan breakdown in cartilage caused by MMPs was further studied by immunolocalisation of MMP-mediated neoepitopes (VDIPEN). VDIPEN expression in the cartilage layers of arthritic knee joints was markedly lower (between 30 and 60%) in IFN-γ-stimulated arthritic p47phox(-/- )mice at day 7 than in WT controls, despite significant upregulation of mRNA levels of various MMPs such as MMP-3, MMP-9, MMP-12 and MMP-13 in synovia and MMP-13 in cartilage layers as measured with quantitative RT-PCR. The latter observation suggests that oxygen radicals are involved in the activation of latent MMPs. Chondrocyte death, determined as the percentage of empty lacunae in articular cartilage, ranged between 20 and 60% at day 3 and between 30 and 80% at day 7 in WT mice, and was completely blocked in p47phox(-/- )mice at both time points. FcγRI mRNA expression was significantly lower, and FcγRII and FcγRIII were higher, in p47phox(-/- )mice than in controls. NADPH-oxidase-driven oxygen radical production determines chondrocyte death and aggravates MMP-mediated cartilage destruction during IFN-γ-stimulated IC-mediated arthritis. Upregulation of FcγRI by oxygen radicals may contribute to cartilage destruction