Paleoflooding reconstruction from Holocene levee deposits in the Lower Meuse valley, the Netherlands

This study investigates the Holocene levee deposits and paleoflooding history of the Lower Meuse in the Netherlands based on archeological investigations and sedimentary analyses (grain size, end-member modelling, magnetic susceptibility and thermogravimetric analyses). The levee on the left bank in the study area near Ooijen contains a continuous sedimentary record in the NW downstream part. The archeological evidence and sedimentary results, including a grain size based flood energy index (LFEI), indicate that the Lower Meuse experienced a quiescent flooding period and low sedimentation rates during the mid-late Mesolithic when the levee was low and human influence was minor. Deposition during the Mesolithic shows a fining-upward trend and a highly-developed soil containing abundant artefacts. During the Neolithic and Bronze Age, the flooding intensity was low but gradually increased to a moderate level probably because of deforestation and increased runoff. Limited Bronze Age findings may reflect decreased human activity because of the increased flooding. Starting from the Iron Age, the Meuse experienced a generally enhanced flooding regime, which is reflected by erosion and coarsened sedimentation in the Iron Age and Roman Period. The high peak discharges during the Iron Age may have re-opened a low-lying paleochannel near to the levee during the intensified floods. This general increasing trend is interrupted by the lower flooding phase in the early Middle Ages (Dark Ages). From the middle to the late Middle Ages, the floods intensified again. The coarsening deposition and higher sedimentation rates since the Iron Age resulted from increased floods and higher sediment supply by deforestation and soil erosion. The findings of this study agree with a recent paleoflood reconstruction for the Lower Meuse by using a floodplain archive, implying that levee sediment records have potential in paleohydrological studies if the completeness of the record and chronological information is guaranteed

PEGylation Potentiates the Effectiveness of an Antagonistic Peptide That Targets the EphB4 Receptor with Nanomolar Affinity

The EphB4 receptor tyrosine kinase together with its preferred ligand, ephrin-B2, regulates a variety of physiological and pathological processes, including tumor progression, pathological forms of angiogenesis, cardiomyocyte differentiation and bone remodeling. We previously reported the identification of TNYL-RAW, a 15 amino acid-long peptide that binds to the ephrin-binding pocked of EphB4 with low nanomolar affinity and inhibits ephrin-B2 binding. Although ephrin-B2 interacts promiscuously with all the EphB receptors, the TNYL-RAW peptide is remarkably selective and only binds to EphB4. Therefore, this peptide is a useful tool for studying the biological functions of EphB4 and for imaging EphB4-expressing tumors. Furthermore, TNYL-RAW could be useful for treating pathologies involving EphB4-ephrin-B2 interaction. However, the peptide has a very short half-life in cell culture and in the mouse blood circulation due to proteolytic degradation and clearance by the kidneys and reticuloendothelial system. To overcome these limitations, we have modified TNYL-RAW by fusion with the Fc portion of human IgG1, complexation with streptavidin or covalent coupling to a 40 KDa branched polyethylene glycol (PEG) polymer. These modified forms of TNYL-RAW all have greatly increased stability in cell culture, while retaining high binding affinity for EphB4. Furthermore, PEGylation most effectively increases peptide half-life in vivo. Consistent with increased stability, submicromolar concentrations of PEGylated TNYL-RAW effectively impair EphB4 activation by ephrin-B2 in cultured B16 melanoma cells as well as capillary-like tube formation and capillary sprouting in co-cultures of endothelial and epicardial mesothelial cells. Therefore, PEGylated TNYL-RAW may be useful for inhibiting pathological forms of angiogenesis through a novel mechanism involving disruption of EphB4-ephrin-B2 interactions between endothelial cells and supporting perivascular mesenchymal cells. Furthermore, the PEGylated peptide is suitable for other cell culture and in vivo applications requiring prolonged EphB4 receptor targeting

Damping signatures at JUNO, a medium-baseline reactor neutrino oscillation experiment

Abstract We study damping signatures at the Jiangmen Underground Neutrino Observatory (JUNO), a medium-baseline reactor neutrino oscillation experiment. These damping signatures are motivated by various new physics models, including quantum decoherence, nu(3) decay, neutrino absorption, and wave packet decoherence. The phenomenological effects of these models can be characterized by exponential damping factors at the probability level. We assess how well JUNO can constrain these damping parameters and how to disentangle these different damping signatures at JUNO. Compared to current experimental limits, JUNO can significantly improve the limits on tau(3)/m(3) in the nu(3) decay model, the width of the neutrino wave packet sigma(x), and the intrinsic relative dispersion of neutrino momentum sigma(rel)