Can a fully integrated approach enclose the drainage system design and the flood risk analysis?

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Experimental study of uni and bi-directional exchange flows in a large scale rotating trapezoidal channel

International audienceA large-scale experimental study has been conducted at the Coriolis Rotating Platform to investigate the dynamics of uni- and bi-directional exchange flows along a channel with a trapezoidal cross section under the influence of background rotation. High-resolution two-dimensional particle image velocimetry and micro-conductivity probes were used to obtain detailed velocity fields and density profiles of the exchange flow generated across the channel under different parametric conditions. Experimental measurements give new insight into the stratified-flow dynamics dependence on the magnitude of Burger number, defined as the ratio of the Rossby radius to the channel width, such that values lower than 0.5 characterize unsteady exchange flows. The measurements highlight the role that both ambient rotation and net-barotropic forcing have on the geostrophic adjustment of the dense outflowing layer and on the corresponding counter-flowing water layer fluxes. The coupled effect of these two parametric conditions largely affects the transverse velocity distribution and, for the largest net-barotropic flow in the upper fresh water layer, leads to the partial blockage of the lower saline outflow. Moreover, an increase in the mixing layer thickness, associated with larger rotation rates, and due the interface dynamics, is observed, with shear-driven interfacial instabilities analyzed to highlight the influence of both ambient rotation and net-barotropic forcin

BIM for infrastructure: an efficient process to achieve 4D and 5D digital dimensions

Introduction of the Building Information Modeling (BIM) approach in Civil Engineering practices allows a design optimization through both an improved control of all the components of a project and an increased efficiency in the collaboration between all professionals involved. In Italy, major attention is being paid by scientists and professionals on this subject area, especially after the implementation of the national law DM 560/2017. This document will gradually rule the integration of BIM-based procedures for contractors in major public tenders. The present paper aims to propose a methodology for implementing an optimization dynamic model of time (4D) and costs (5D) across different project phases. To achieve this aim, the process relies on several authoring tools and 4D/5D modeling software, capable to incorporate a variety of project data in a unique and shared environment. The most effective methodology to maximize the interoperability between various codes will be presented. In this regard, a dynamic model involving an optimizationoriented approach for both the quantity surveying and the definition of the design management timeline is introduced. It is important to emphasize that these aspects are two of the major issues for the evaluation criteria in a civil engineering project. Also, this bidirectional process allows for a more accurate estimation of project costs as well as to achieve an optimized timeline of construction activities. Finally, it worth reminding that in case of constrained changes during the design phase, a dynamic model permits to effectively reiterate the process with a significant reduction of the overall computational time

The dynamics of bi-directional exchange flows

The global demand for low carbon electricity requires a variety of energy generation approaches, the choice of which is dependent on multiple criteria. Tidal flows have long been identified as a reliable source of energy, with a high degree of predictability. To this end a novel turbine has been developed that could be well suited to energy generation in both tidal flows, or water courses. In this study a Smoothed Particle Hydrodynamics (SPH) model, namely DualSPHysics, is used to predict the behavior of this novel turbine design. Which will be used to guide the design process. The SPH method was chosen as the design of the turbine uses several connected parts, that requires free movement and interactions to properly represent the prototype and was found to be capable of expressing this behavior

Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer

High-risk non-muscle invasive bladder cancer (NMIBC) progresses to metastatic disease in 10–15% of cases, suggesting that micrometastases may be present at first diagnosis. The prediction of risks of progression relies upon EORTC scoring systems, based on clinical and pathological parameters, which do not accurately identify which patients will progress. Aim of the study was to investigate whether the presence of CTC may improve prognostication in a large population of patients with Stage I bladder cancer who were all candidate to conservative surgery. A prospective single center trial was designed to correlate the presence of CTC to local recurrence and progression of disease in high-risk T1G3 bladder cancer. One hundred two patients were found eligible, all candidate to transurethral resection of the tumor followed by endovesical adjuvant immunotherapy with BCG. Median follow-up was 24.3 months (minimum–maximum: 4–36). The FDA-approved CellSearch System was used to enumerate CTC. Kaplan–Meier methods, log-rank test and multivariable Cox proportional hazard analysis was applied to establish the association of circulating tumor cells with time to first recurrence (TFR) and progression-free survival. CTC were detected in 20% of patients and predicted both decreased TFR (log-rank p < 0.001; multivariable adjusted hazard ratio [HR] 2.92 [95% confidence interval: 1.38–6.18], p 5 0.005), and time to progression (log-rank p < 0.001; HR 7.17 [1.89–27.21], p 5 0.004). The present findings provide evidence that CTC analyses can identify patients with Stage I bladder cancer who have already a systemic disease at diagnosis and might, therefore, potentially benefit from systemic treatment

The dynamics of bi-directional exchange flows::implication for morphodynamic change within estuaries and sea straits

Environmental and geophysical flows, including dense bottom gravity currents in the ocean and buoyancy-driven exchange flows in marginal seas, are strongly controlled by topographic features. These are known to exert significant influence on both internal mixing and secondary circulations generated by these flows. In such cases, uni-directional or bi-directional exchange flows develop when horizontal density differences and/or pressure gradients are present between adjacent water bodies connected by a submerged channel. The flow dynamics of the dense lower layer depend primarily on the volumetric flux and channel cross-sectional shape, while the stratified interfacial flow mixing characteristics, leading to fluid entrainment/detrainment, are also dependent on the buoyancy flux and motion within the upper (lower density) water mass. For submerged channels that are relatively wide compared to the internal Rossby radius of deformation, Earth rotation effects introduce geostrophic adjustment of these internal fluid motions, which can suppress turbulent mixing generated at the interface and result in the development of Ekman layers that induce secondary, cross-channel circulations, even within straight channels. Moreover, recent studies of dense, gravity currents generated in rotating and non-rotating systems, respectively, indicated that the V-shaped channel topography had a strong influence on both flow distribution and associated interfacial mixing characteristics along the channel. However, such topographic controls on the interfacial mixing and secondary circulations generated by bi-directional exchange flows are not yet fully understood and remain to be investigated thoroughly in the laboratory. Also the effect of mobile bed for bi-directional exchange flows generated in deformable channels along with the physical interactions between the lower dense water flow and the erodible bed sediments will have a strong influence in (re-)shaping the overall channel bed topography (i.e. bed morphodynamics). Consequently, the resulting temporal changes in cross-sectional channel bathymetry (i.e. through erosion and deposition processes) would also be expected to have associated feedbacks on transverse asymmetries in the bi-directional exchange flow structure, as well as on the internal flow stability

Headache prevalence in the population of L’Aquila (Italy) after the 2009 earthquake

Stress induced by the events of daily life is considered a major factor in pathogenesis of primary tension-type headache. Little is known about the impact that could have a more stressful event, like a natural disaster, both in patients with chronic headache, both in people that do not had headache previously. The aim of the present study was to observe the prevalence of headache in the population following the devastating earthquake that affected the province of L’Aquila on April 6, 2009. The study population was conducted in four tent cities (Onna, Bazzano, Tempera-St. Biagio, Paganica). Sanitary access is recorded in the registers of medical triage, in the first 5 weeks, after the April 6, 2009. The prevalence of primary headache presentation was 5.53% (95% CI 4.2–7.1), secondary headache was 2.82% (95% CI 1.9–4.9). Pain intensity, assessed by Numerical Rating Scale score showed a mean value of 7 ± 1.1 (range 4–10). The drugs most used were the NSAIDs (46%) and paracetamol (36%), for impossibility of finding causal drugs. This study shows how more stressful events not only have an important role in determining acute exacerbation of chronic headache, but probably also play a pathogenic role in the emergence of primary headache. Also underlines the lack of diagnostic guidelines or operating protocols to early identify and treat headache in the emergency settings

Clonality analysis of immunoglobulin gene rearrangement by next-generation sequencing in endemic burkitt lymphoma suggests antigen drive activation of bcr as opposed to sporadic burkitt lymphoma

Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. METHODS: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). RESULTS: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. CONCLUSIONS: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development

NOTCH1-mutated chronic lymphocytic leukemia displays high endoplasmic reticulum stress response with druggable potential

IntroductionConstitutive activation of NOTCH1-wild-type (NT1-WT) signaling is associated with poor outcomes in chronic lymphocytic leukemia (CLL), and NOTCH1 mutation (c.7541_7542delCT), which potentiates NOTCH1 signaling, worsens the prognosis. However, the specific mechanisms of NOTCH1 deregulation are still poorly understood. Accumulative evidence mentioned endoplasmic reticulum (ER) stress/unfolded protein response (UPR) as a key targetable pathway in CLL. In this study, we investigated the impact of NOTCH1 deregulation on CLL cell response to ER stress induction, with the aim of identifying new therapeutic opportunities for CLL.MethodsWe performed a bioinformatics analysis of NOTCH1-mutated (NT1-M) and NT1-WT CLL to identify differentially expressed genes (DEGs) using the rank product test. Quantitative real-time polymerase chain reaction (qPCR), Western blotting, cytosolic Ca2+, and annexin V/propidium iodide (PI) assay were used to detect curcumin ER stress induction effects. A median-effect equation was used for drug combination tests. The experimental mouse model Eμ-TCL1 was used to evaluate the impact of ER stress exacerbation by curcumin treatment on the progression of leukemic cells and NOTCH1 signaling.Results and discussionBioinformatics analysis revealed gene enrichment of the components of the ER stress/UPR pathway in NT1-M compared to those in NT1-WT CLL. Ectopic expression of NOTCH1 mutation upregulated the levels of ER stress response markers in the PGA1 CLL cell line. Primary NT1-M CLL was more sensitive to curcumin as documented by a significant perturbation in Ca2+ homeostasis and higher expression of ER stress/UPR markers compared to NT1-WT cells. It was also accompanied by a significantly higher apoptotic response mediated by C/EBP homologous protein (CHOP) expression, caspase 4 cleavage, and downregulation of NOTCH1 signaling in NT1-M CLL cells. Curcumin potentiated the apoptotic effect of venetoclax in NT1-M CLL cells. In Eμ-TCL1 leukemic mice, the administration of curcumin activated ER stress in splenic B cells ex vivo and significantly reduced the percentage of CD19+/CD5+ cells infiltrating the spleen, liver, and bone marrow (BM). These cellular effects were associated with reduced NOTCH1 activity in leukemic cells and resulted in prolonged survival of curcumin-treated mice. Overall, our results indicate that ER stress induction in NT1-M CLL might represent a new therapeutic opportunity for these high-risk CLL patients and improve the therapeutic effect of drugs currently used in CLL