3,376 research outputs found

    Impacts of storm chronology on the morphological changes of the Formby beach and dune system, UK

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    Impacts of storm chronology within a storm cluster on beach/dune erosion are investigated by applying the state-of-the-art numerical model XBeach to the Sefton coast, northwest England. Six temporal storm clusters of different storm chronologies were formulated using three storms observed during the 2013/2014 winter. The storm power values of these three events nearly halve from the first to second event and from the second to third event. Cross-shore profile evolution was simulated in response to the tide, surge and wave forcing during these storms. The model was first calibrated against the available post-storm survey profiles. Cumulative impacts of beach/dune erosion during each storm cluster were simulated by using the post-storm profile of an event as the pre-storm profile for each subsequent event. For the largest event the water levels caused noticeable retreat of the dune toe due to the high water elevation. For the other events the greatest evolution occurs over the bar formations (erosion) and within the corresponding troughs (deposition) of the upper-beach profile. The sequence of events impacting the size of this ridge–runnel feature is important as it consequently changes the resilience of the system to the most extreme event that causes dune retreat. The highest erosion during each single storm event was always observed when that storm initialised the storm cluster. The most severe storm always resulted in the most erosion during each cluster, no matter when it occurred within the chronology, although the erosion volume due to this storm was reduced when it was not the primary event. The greatest cumulative cluster erosion occurred with increasing storm severity; however, the variability in cumulative cluster impact over a beach/dune cross section due to storm chronology is minimal. Initial storm impact can act to enhance or reduce the system resilience to subsequent impact, but overall the cumulative impact is controlled by the magnitude and number of the storms. This model application provides inter-survey information about morphological response to repeated storm impact. This will inform local managers of the potential beach response and dune vulnerability to variable storm configurations

    Modelling Extreme Wave Overtopping at Aberystwyth Promenade

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    The work presents a methodology to assess the coastal impacts during a storm event which caused significant damage along the promenade at Aberystwyth, Wales on the 3 January 2014. Overtopping was analysed in detail for a section of promenade by downscaling offshore wave conditions to force a surf zone hydrodynamic model, NEWRANS. Overtopping discharges are computed and were in qualitative agreement with published discharges for the level of damage observed along the promenade. Peak storm conditions were observed to arrive just before and during high tide at Aberystwyth, which in addition to a storm surge and wave-setup, contributed to the damage observed. A high frequency of overtopping occurs during peak high tide, with overtopping also occurring in the hour leading up to and following high tide. Finally, comparisons to design methods for the estimation of overtopping discharge were made. Current empirical formulae underestimated the peak overtopping event at high tide. The methodology applied is generic and applicable to any location

    RNF168 cooperates with RNF8 to mediate FOXM1 ubiquitination and degradation in breast cancer epirubicin treatment

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    The forkhead box M1 (FOXM1) transcription factor has a central role in genotoxic agent response in breast cancer. FOXM1 is regulated at the post-translational level upon DNA damage, but the key mechanism involved remained enigmatic. RNF168 is a ubiquitination E3-ligase involved in DNA damage response. Western blot and gene promoter-reporter analyses showed that the expression level and transcriptional activity of FOXM1 reduced upon RNF168 overexpression and increased with RNF168 depletion by siRNA, suggesting that RNF168 negatively regulates FOXM1 expression. Co-immunoprecipitation studies in MCF-7 cells revealed that RNF168 interacted with FOXM1 and that upon epirubicin treatment FOXM1 downregulation was associated with an increase in RNF168 binding and conjugation to the protein degradation-associated K48-linked polyubiquitin chains. Consistently, RNF168 overexpression resulted in an increase in turnover of FOXM1 in MCF-7 cells treated with the protein synthesis inhibitor cycloheximide. Conversely, RNF168, knockdown significantly enhanced the half-life of FOXM1 in both absence and presence of epirubicin. Using a SUMOylation-defective FOXM1-5x(K>R) mutant, we demonstrated that SUMOylation is required for the recruitment of RNF168 to mediate FOXM1 degradation. In addition, clonogenic assays also showed that RNF168 mediates epirubicin action through targeting FOXM1, as RNF168 could synergise with epirubicin to repress clonal formation in wild-type but not in FOXM1-deficient mouse embryo fibroblasts (MEFs). The physiological relevance of RNF168-mediated FOXM1 repression is further emphasized by the significant inverse correlation between FOXM1 and RNF168 expression in breast cancer patient samples. Moreover, we also obtained evidence that RNF8 recruits RNF168 to FOXM1 upon epirubicin treatment and cooperates with RNF168 to catalyse FOXM1 ubiquitination and degradation. Collectively, these data suggest that RNF168 cooperates with RNF8 to mediate the ubiquitination and degradation of SUMOylated FOXM1 in breast cancer genotoxic response

    Two-dimensional reduced-physics model to describe historic morphodynamic behaviour of an estuary inlet

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    Understanding medium to long term morphodynamic change is important for sustainable coastal and estuary management. This paper analyses morphodynamic change of a complex estuary inlet which is subjected to multiple environmental drivers and proposes a reduced physics model to explain the historic medium term morphodynamic change of the inlet. The analysis shows that even though the estuary inlet undergoes multiscale morphological change, the changes that take place over a timescale of several years are more significant and important. The reduced physics model suggests that this simplified modelling approach is able to recognise principal historic morphodynamic trends in the estuary. However, the length and quality of the inlet bathymetry data set limits the applicability of the models and the quality of model outputs

    Analysis of multi-scale morphodynamic behavior of a high energy beach facing the Sea of Japan

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    Monthly cross shore beach profiles measured at the Ogata Wave Observation pier located in Joetsu-Ogata Coast, Niigata Prefecture, Japan, was analysed to investigate multi-scale morphodynamic beach behaviour. The Ogata beach, facing the Sea of Japan, is subjected to high energy wave conditions with that has a strong winter/summer seasonal signature. The measured beach profiles at the beach show very significant variability where cross-shore movement of shoreline position and lowering of the beach at the location of measurements exceed 20 m and 4 m respectively. The shoreline position seems to follow the seasonal variability of incident wave climate where a correlation coefficient of 0.77 was found between monthly averaged incident significant wave height and the measured monthly shoreline position. During the summer months, the beach variability mostly concentrated to in the sub-tidal part of the profile, while a significant amount of upper beach change was observed during the winter months. The beach profile shape was found to rotate between three different beach states in time; (i) concave reflective profile; (ii) profile with sub-tidal berm; and (iii) gentle, dissipative profile. Empirical Orthogonal Function (EOF) analysis of the profiles show that the variability of beach profile shape is dominated by (a) upper shoreface steepening; (b) sub tidal berm development and dissipation; and (c) variability of the overall profile slope, which have some longer than seasonal cyclic signatures. Comparison of temporal EOFs with climate indices such as Southern Oscillation Index and Pacific Decadal Oscillation index shows notable some correlations between profile change and climatic variability in the region. The analysis also shows that the morphological variability of Joetsu-Ogata Coast has similarities and some distinct spatial and temporal differences to beaches of similar kind found elsewhere

    Detailed two-dimensional modelling of a complex bridge arrangement – McKinlay River No. 2 Bridge, Alice Springs to Darwin railway

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    The Alice Springs – Darwin Railway Project involved the construction of 1420 km of new standard gauge track between Alice Springs and Darwin, including the McKinlay River No. 2 Bridge. During the 2006, 2007 and 2008 flood seasons, significant scour occurred around the McKinlay River No. 2 Bridge piers, raising concerns regarding the continuing stability of the structure. The site has complex geometry, with the river approaching the crossing at a significant angle and the remains of the original railway bridge just upstream of the new structure. Owing to the complex arrangement, a detailed 2-D hydrodynamic SOBEK model of the bridge crossing was developed to inform the design of scour protection works at the site. The model was used to analyse a number of options to reduce the potential for scour, and allowed for the scour protection works to be optimised for conditions at the site. The designed protection works were constructed in 2011, and have performed well in several subsequent flow events

    Morphodynamic evolution of an estuary inlet

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    This paper presents the application of a morphodynamic model based on 2D reduced-physics principles to investigate morphology change of a complex estuary inlet system in the United Kingdom. The model combines a simple governing equation with a set of measured bathymetry data in order to model morphology change. The modelling method suggests that this simplified approach is able to recognise principal medium term morphodynamic trends in the estuary. However, the length and quality of the estuary bathymetry data set limits the applicability of the model to inter-annual scale

    SUMOylation inhibits FOXM1 activity and delays mitotic transition

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    The forkhead box transcription factor FOXM1 is an essential effector of G2/M-phase transition, mitosis and the DNA damage response. As such, it is frequently deregulated during tumorigenesis. Here we report that FOXM1 is dynamically modified by SUMO1 but not by SUMO2/3 at multiple sites. We show that FOXM1 SUMOylation is enhanced in MCF-7 breast cancer cells in response to treatment with epirubicin and mitotic inhibitors. Mutation of five consensus conjugation motifs yielded a SUMOylation-deficient mutant FOXM1. Conversely, fusion of the E2 ligase Ubc9 to FOXM1 generated an auto-SUMOylating mutant (FOXM1-Ubc9). Analysis of wild-type FOXM1 and mutants revealed that SUMOylation inhibits FOXM1 activity, promotes translocation to the cytoplasm and enhances APC/Cdh1-mediated ubiquitination and degradation. Further, expression of the SUMOylation-deficient mutant enhanced cell proliferation compared with wild-type FOXM1, whereas the FOXM1-Ubc9 fusion protein resulted in persistent cyclin B1 expression and slowed the time from mitotic entry to exit. In summary, our findings suggest that SUMOylation attenuates FOXM1 activity and causes mitotic delay in cytotoxic drug response
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