Standard approaches to determining the impacts of sea level rise (SLR) on storm surge flooding employ numerical models reflecting present conditions with modified sea states for a given SLR scenario. ...In this study, we advance this paradigm by adjusting the model framework so that it reflects not only a change in sea state but also variations to the landscape (morphologic changes and urbanization of coastal cities). We utilize a numerical model of the Mississippi and Alabama coast to simulate the response of hurricane storm surge to changes in sea level, land use/land cover, and land surface elevation for past (1960), present (2005), and future (2050) conditions. The results show that the storm surge response to SLR is dynamic and sensitive to changes in the landscape. We introduce a new modeling framework that includes modification of the landscape when producing storm surge models for future conditions.
Key Points
Storm surge response to climate change impacts is dynamic
A framework for constructing dynamic assessments of SLR is developed
In this work we propose a new combined TCAD radiation damage modelling scheme, featuring both bulk and surface radiation damage effects, for the analysis of silicon detectors aimed at the High ...Luminosity LHC. In particular, a surface damage model has been developed by introducing the relevant parameters (N OX , N IT ) extracted from experimental measurements carried out on p-type substrate test structures after gamma irradiations at doses in the range 10-500 Mrad(Si). An extended bulk model, by considering impact ionization and deep-level cross-sections variation, was included as well. The model has been validated through the comparison of the simulation findings with experimental measurements carried out at very high fluences (2 × 10 16 1 MeV equivalent n/cm 2 ) thus fostering the application of this TCAD approach for the design and optimization of the new generation of silicon detectors to be used in future HEP experiments.
The intestinal tract hosts the gut microbiota (GM), actively shaping health. Bile acids(BAs) are both digestive and signaling molecules acting as hormones via the activation of farnesoid X receptor ...(FXR). Obstruction of bile flow initiates a cascade of pathological events ultimately leading to intestinal mucosal injury. Administration of BAs in models of obstructed bile flow counteracts these detrimental effects. Objective of this study was to investigate the effects of the novel FXR agonist 3α, 7α, 11β-Trihydroxy-6α-ethyl-5β-cholan-24-oic Acid (TC-100) on intestinal mucosa integrity and cecal microbiome composition after surgical bile duct ligation (BDL), a rodent model causing bile flow obstruction.
Pharmacological FXR activation was accomplished by daily oral gavage with TC-100 for 5 days. 2 days after treatment initiation, BDL was performed. BAs measurement was carried out and the 16S rDNA (V5-V6 hyper-variable regions) extracted from the cecal content was sequenced.
TC-100 activates Fxr in the gut-liver axis and this translated into a significant reduction of serum and bile BA pool size with a shift to a more hydrophilic composition, while signs of intestinal mucosal damage were prevented. Firmicutes:Bacteroidota ratio progressively increased from Sham Operated (SO) mice to TC-100-treated mice. LEfSe analysis showed that Verrucomicrobia, and particularly Akkermansia muciniphila (Amuc) increasingly recognized for improving gut homeostasis and immune functions, were strongly associated to TC-100-treated mice. Intriguingly, Amuc abundance was also negatively associated to cholic acid levels.
Collectively, these data indicate that intestinal FXR activation by TC-100 prevents early signs of intestinal mucosal damage by modulating BA homeostasis and GM composition.
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•BDL cause lack of BAs flow in the gut and impairs intestinal homeostasis.•TC-100 is a novel semi-synthetic BA and a specific Farnesoid X Receptor activator.•TC-100 treatment in BDL mice preserves the gut barrier integrity via FXR activation.•TC-100 treatment in BDL mice promotes eubiosis with an enrichment in Amuc.•Amuc abundance negatively correlates with the levels of the hydrophobic BA CA.
Nanodiamonds are a novel class of nanomaterials which have raised much attention for application in biomedical field, as they combine the possibility of being produced on large scale using relatively ...inexpensive synthetic processes, of being fluorescent as a consequence of the presence of nitrogen vacancies, of having their surfaces functionalized, and of having good biocompatibility. Among other applications, we mainly focus on drug delivery, including cell interaction, targeting, cancer therapy, gene and protein delivery. In addition, nanodiamonds for bone and dental implants and for antibacterial use is discussed. Techniques for detection and imaging of nanodiamonds in biological tissues are also reviewed, including electron microscopy, fluorescence microscopy, Raman mapping, atomic force microscopy, thermal imaging, magnetic resonance imaging, and positron emission tomography, either in vitro, in vivo, or ex vivo. Toxicological aspects related to the use of nanodiamonds are also discussed. Finally, patents, preclinical and clinical trials based on the use of nanodiamonds for biomedical applications are reviewed.
In this work we propose the application of an enhanced radiation damage model based on the introduction of deep level traps/recombination centers suitable for device level numerical simulation of ...silicon detectors at very high fluences (e.g. 2.0×1016 1MeV equivalent neutrons/cm2). We present the comparison between simulation results and experimental data for p-type substrate structures in different operating conditions (temperature and biasing voltages) for fluences up to 2.2×1016 neutrons/cm2. The good agreement between simulation findings and experimental measurements fosters the application of this modeling scheme to the optimization of the next silicon detectors to be used at HL-LHC.
•Development of an enhanced TCAD radiation damage model.•Simulations of silicon detector behavior at very high fluences (e.g. 2×1016 n/cm2).•Application in different operating conditions (temperature and biasing voltages).•Validation through comparison with experimental data for p-type substrate devices.
New anti-telomere strategies represent important goals for the development of selective cancer therapies. In this study, we reported that uncapped telomeres, resulting from pharmacological ...stabilization of quadruplex DNA by RHPS4 (3,11-difluoro-6,8,13-trimethyl-8H-quino4,3,2-klacridinium methosulfate), trigger specific recruitment and activation of poly-adenosine diphosphate (ADP) ribose polymerase I (PARP1) at the telomeres, forming several ADP-ribose polymers that co-localize with the telomeric repeat binding factor 1 protein and are inhibited by selective PARP(s) inhibitors or PARP1-specific small interfering RNAs. The knockdown of PARP1 prevents repairing of RHPS4-induced telomere DNA breaks, leading to increases in chromosome abnormalities and eventually to the inhibition of tumor cell growth both in vitro and in xenografts. More interestingly, the integration of a TOPO1 inhibitor on the combination treatment proved to have a high therapeutic efficacy ensuing a complete regression of the tumor as well as a significant increase in overall survival and cure of mice even when treatments started at a very late stage of tumor growth. Overall, this work reveals the unexplored link between the PARP1 and G-quadruplex ligands and demonstrates the excellent efficacy of a multi-component strategy based on the use of PARP inhibitors in telomere-based therapy.
The DC-coupled resistive silicon detectors (DC-RSD) are the evolution of the AC-coupled RSD (RSD) design, both based on the low-gain avalanche diode (LGAD) technology. The DC-RSD design concept ...intends to address a few known issues present in RSDs (e.g., baseline fluctuation and long tail-bipolar signals) while maintaining their advantages (e.g., signal spreading and 100% fill factor). The simulation of DC-RSD presents several unique challenges linked to the complex nature of its design and the large pixel size. The defining feature of DC-RSD, charge sharing over distances that can be as large as a millimeter, represents a formidable challenge for technology CAD (TCAD), the standard simulation tool. To circumvent this problem, we have developed a mixed-mode approach to the DC-RSD simulation, which exploits a combination of two simulation tools: TCAD and SPICE. Thanks to this hybrid approach, it has been possible to demonstrate that, according to the simulation, the key features of the RSD-excellent timing and spatial resolutions (few tens of picoseconds and few microns)-are maintained in the DC-RSD design. In this work, we present the developed models and methodology, mainly showing the results of device-level numerical simulation, which have been obtained with the state-of-the-art Synopsys Sentaurus TCAD suite of tools. Such results will provide all the necessary information for the first batch of DC-RSD produced by the Fondazione Bruno Kessler (FBK) foundry in Trento, Italy.
This work outlines a dynamic modeling framework to examine the effects of global climate change, and sea level rise (SLR) in particular, on tropical cyclone‐driven storm surge inundation. The ...methodology, applied across the northern Gulf of Mexico, adapts a present day large‐domain, high resolution, tide, wind‐wave, and hurricane storm surge model to characterize the potential outlook of the coastal landscape under four SLR scenarios for the year 2100. The modifications include shoreline and barrier island morphology, marsh migration, and land use land cover change. Hydrodynamics of 10 historic hurricanes were simulated through each of the five model configurations (present day and four SLR scenarios). Under SLR, the total inundated land area increased by 87% and developed and agricultural lands by 138% and 189%, respectively. Peak surge increased by as much as 1 m above the applied SLR in some areas, and other regions were subject to a reduction in peak surge, with respect to the applied SLR, indicating a nonlinear response. Analysis of time‐series water surface elevation suggests the interaction between SLR and storm surge is nonlinear in time; SLR increased the time of inundation and caused an earlier arrival of the peak surge, which cannot be addressed using a static (“bathtub”) modeling framework. This work supports the paradigm shift to using a dynamic modeling framework to examine the effects of global climate change on coastal inundation. The outcomes have broad implications and ultimately support a better holistic understanding of the coastal system and aid restoration and long‐term coastal sustainability.
Key Points
A dynamic storm surge modeling framework is presented
Shoreline morphology, marsh migration and LULC is incorporated into the storm surge model
Storm surge under sea level rise is highly dynamic
Abstract
The sample preparation is one of the fundamental steps to obtain a successful correlative microscopy experiment, and for non-conductive materials the deposition of a thin metal coating is ...often mandatory for a good SEM observation. Nevertheless, in case of correlative experiment, where AFM and Raman spectroscopy are involved in the workflow, this deposition will have a direct influence on both the analysis. In this paper, an investigation about the most common conductive materials used in SEM sample preparation, such as chromium, graphite and gold, and their behaviour in the construction of correlative microscopy workflow is proposed, showing in our results, that chromium is the best choice for this type of combined analysis.
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