146 research outputs found

    Simulation of the December 2017 Flood on the Enza River using a 2D SWE code Coupled with a Levee Breach Erosion Model

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    The levee breach that occurred on the Enza River (Italy) on December 12th 2017 and the resulting flood are simulated with a GPU-accelerated 2D SWE code, where a simple erosion model was implemented to describe the breach evolution in detail

    Implicit iterative particle shifting for meshless numerical schemes using kernel basis functions

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    A novel particle shifting technique (PST) for meshless numerical methods is presented. The proposed methodology uses an implicit iterative particle shifting (IIPS) technique aiming to reduce the spatial particle’ anisotropy, which is associated with the discretization error in meshless numerical schemes based on kernel basis functions. The algorithm controls the particle spatial distribution through an implicit minimization problem, related to the particle concentration gradient and therefore, to the particles’ anisotropy. This results in accurate particle distributions, to demonstrate the effectiveness of the proposed method, the IIPS algorithm is tested within a smoothed particle hydrodynamics (SPH) framework, with static and kinematic cases, by examining the particle distributions and the corresponding spatial accuracy. Further, the computational cost of the proposed methodology is reported and it is shown that it introduces minimal overhead. Moreover, the simulations of the Taylor–Green vortex (TGV), employing a weakly-compressible SPH Navier–Stokes solver, confirmed the superior accuracy of the IIPS in comparison to existing explicit shifting approaches, in simulating internal flows

    Antidepressant-like effects of pharmacological inhibition of FAAH activity in socially isolated female rats

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    Pharmacological inhibition of the enzyme fatty acid amide hydrolase (FAAH), which terminates signaling of the endocannabinoid N-arachidonoylethanolamine (or anandamide, AEA), exerts favourable effects in rodent models of stress-related depression. Yet although depression seems to be more common among women than men and in spite of some evidence of sex differences in treatment efficacy, preclinical development of FAAH inhibitors for the pharmacotherapy of stress-related depression has been predominantly conducted in male animals. Here, adult female rats were exposed to six weeks of social isolation and, starting from the second week, treated with the FAAH inhibitor URB694 (0.3 mg/kg/day, i.p.) or vehicle. Compared to pair-housed females, socially isolated female rats treated with vehicle developed behavioral (mild anhedonia, passive stress coping) and physiological (reduced body weight gain, elevated plasma corticosterone levels) alterations. Moreover, prolonged social isolation provoked a reduction in brain-derived neurotrophic factor (BDNF) and AEA levels within the hippocampus. Together, these changes are indicative of an increased risk of developing a depressive-like state. Conversely, pharmacological inhibition of FAAH activity with URB694 restored both AEA and BDNF levels within the hippocampus of socially isolated rats and prevented the development of behavioral and physiological alterations. These results suggest a potential interplay between AEA-mediated signaling and hippocampal BDNF in the pathogenesis of depression-relevant behaviors and physiological alterations and antidepressant action of FAAH inhibition in socially isolated female rats

    Colonic metastasis from breast carcinoma detection by CESM and PET/CT: A case report

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    Introduction: Metastatic spread in invasive lobular carcinoma (ILC) of breast mainly occurs in bones, gynecological organs, peritoneum, retroperitoneum, and gastrointestinal (GI) tract. Metastases to the GI tract may arise many years after initial diagnosis and can affect the tract from the tongue to the anus, stomach being the most commonly involved site. Clinical presentations are predominantly nonspecific, and rarely asymptomatic. CEA, CA 15-3, and CA 19-9 may be informative for symptomatic patients who have had a previous history of breast cancer. Case presentation: We introduce the case of asymptomatic colonic metastasis from breast carcinoma in a 67-year-old woman followed-up for Luminal A ILC. Diagnosis was performed through positron emission tomography/computed tomography (PET/CT) scan and contrast-enhancement spectral mammography (CESM), steering endoscopist to spot the involved intestinal tract and in ruling out further dissemination in the breast parenchyma. Conclusion: In colonic metastases, tumor markers might not be totally reliable. In asymptomatic cases, clinical conditions might be underappreciated, missing local or distant recurrence. CT and PET/CT scan might be useful in diagnosing small volume diseases, and steering endoscopist toward GI metastasis originating from the breast. CESM represents a tolerable and feasible tool that rules out multicentricity and multifocality of breast localization. Moreover, particular patients could tolerate it better than magnetic resonance imaging (MRI)

    Accuracy and reproducibility of contrast-enhanced mammography in the assessment of response to neoadjuvant chemotherapy in breast cancer patients with calcifications in the tumor bed

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    This study aimed to evaluate contrast-enhanced mammography (CEM) accuracy and reproducibility in the detection and measurement of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with calcifications, using surgical specimen pathology as the reference. Pre-and post-NAC CEM images of 36 consecutive BC patients receiving NAC in 2012–2020, with calcifications in the tumor bed at diagnosis, were retrospectively reviewed by two radiologists; described were absence/presence and size of residual disease based on contrast enhancement (CE) only and CE plus calcifications. Twenty-eight patients (77.8%) had invasive and 5 (13.9%) in situ-only residual disease at surgical specimen pathology. Considering CE plus calcifications instead of CE only, CEM sensitivity for invasive residual tumor increased from 85.7% (95% CI = 67.3–96%) to 96.4% (95% CI = 81.7–99.9% ) and specificity decreased from 5/8 (62.5%; 95% CI = 24.5–91.5%) to 1/8 (14.3%; 95% CI = 0.4–57.9%). For in situ-only residual disease, false negatives decreased from 3 to 0 and false positives increased from 1 to 2. CEM pathology concordance in residual disease measurement increased (R squared from 0.38 to 0.45); inter-reader concordance decreased (R squared from 0.79 to 0.66). Considering CE plus calcifications to evaluate NAC response in BC patients increases sensitivity in detection and accuracy in measurement of residual disease but increases false positives

    DualSPHysics: from fluid dynamics to multiphysics problems

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    DualSPHysics is a weakly compressible smoothed particle hydrodynamics (SPH) Navier–Stokes solver initially conceived to deal with coastal engineering problems, especially those related to wave impact with coastal structures. Since the first release back in 2011, DualSPHysics has shown to be robust and accurate for simulating extreme wave events along with a continuous improvement in efficiency thanks to the exploitation of hardware such as graphics processing units for scientific computing or the coupling with wave propagating models such as SWASH and OceanWave3D. Numerous additional functionalities have also been included in the DualSPHysics package over the last few years which allow the simulation of fluid-driven objects. The use of the discrete element method has allowed the solver to simulate the interaction among different bodies (sliding rocks, for example), which provides a unique tool to analyse debris flows. In addition, the recent coupling with other solvers like Project Chrono or MoorDyn has been a milestone in the development of the solver. Project Chrono allows the simulation of articulated structures with joints, hinges, sliders and springs and MoorDyn allows simulating moored structures. Both functionalities make DualSPHysics especially suited for the simulation of offshore energy harvesting devices. Lately, the present state of maturity of the solver goes beyond single-phase simulations, allowing multi-phase simulations with gas–liquid and a combination of Newtonian and non-Newtonian models expanding further the capabilities and range of applications for the DualSPHysics solver. These advances and functionalities make DualSPHysics an advanced meshless solver with emphasis on free-surface flow modelling

    [18F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma

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    The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [18F]FDG-PET has some limitations and there is a portion of MM patients who are negative. Glutamine (Gln) addiction has been recently described as a typical metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed so far and is investigated in this study in preclinical models. Firstly, we have synthesized enantiopure (2S,4R)-4-fluoroglutamine (4-FGln) and validated it as a Gln transport analogue in human MM cell lines, comparing its uptake with that of 3H-labelled Gln. We then radiosynthesized [18F]4-FGln, tested its uptake in two different in vivo murine MM models, and checked the effect of Bortezomib, a proteasome inhibitor currently used in the treatment of MM. Both [18F]4-FGln and [18F]FDG clearly identified the spleen as site of MM cell colonization in C57BL/6 mice, challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice, subcutaneously injected with human MM JJN3 cells, showed high values of both [18F]4-FGln and [18F]FDG uptake. Bortezomib significantly reduced the uptake of both radiopharmaceuticals in comparison with vehicle at post treatment PET. However, a reduction of glutaminolytic, but not of glycolytic, tumor volume was evident in mice showing the highest response to Bortezomib. Our data indicate that [18F](2S,4R)-4-FGln is a new PET tracer in preclinical MM models, yielding a rationale to design studies in MM patients

    CARACTERIZAÇÃO E AVALIAÇÃO SENSORIAL DE SORVETE COM EXTRATO AQUOSO DE YACON

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    O yacon está sendo considerado um alimento nutracêutico em decorrência dos estudos sobre a diminuição dos níveis de açúcar no sangue após seu consumo repetido por de ser rico em fibras alimentares, especialmente as solúveis ou viscosas, dentre elas inulina e Frutoligossacarídeos (FOS). O crescente aumento da busca no mercado por produtos que apresentem, além de qualidade sensorial e nutricional, benefícios associados à saúde faz com que as pesquisas nesse ramo cresçam. Com isso, o objetivo do trabalho foi elaborar e avaliar um sorvete com extrato aquoso de yacon em diferentes concentrações. Foram elaboradas duas amostras (F1 com adição de 5% de extrato de yacon e F2 com 10%) e realizaram-se análises de composição centesimal (umidade, cinzas, proteínas, lipídeos e carboidratos) e sensoriais (escala hedônica para cor, sabor, textura, aroma e aspecto global), cor e textura instrumental. A composição centesimal não apresentou diferença significativa (p>0,05) para umidade, cinzas e carboidratos. O teor de proteína foi menor para F2 e o teor de lipídeo foi maior para F2. As amostras apresentaram a cor amarela clara com alta luminosidade e não diferiram significativamente na textura expressa em força de compressão. As duas formulações foram sensorialmente aceitas, não apresentando diferença significativa entre si e conferindo um alto índice de aceitação.AbstractYacon is being considered a nutraceutical food due to studies about the decrease of sugar levels in blood after its repeated consumption, and also for being rich in food fibers, specially the soluble or viscous, among them fructooligosaccharides and inulin. The increasing search in the market for products presenting beyond sensory qualities, nutritional and health benefits, makes the researches in this field grows. The goal of this task was to develop an ice cream with aqueous extract of yacon, in different concentrations. It were prepared two samples, (F1 with addition of 5% of yacon extract, and F2 with 10% of it) and were performed centesimal composition analysis (humidity, ashes, protein, lipids, carbohydrates) and sensory analysis (Hedonic scale for color, taste, texture, flavor and global aspect), beyond color and instrumental texture. The centesimal composition showed no significant difference (p> 0.05) for moisture, ash and carbohydrates. The protein content was lower for F2 and lipid content was higher for F2.Samples displayed a clear yellow coloration, with high luminosity and didn’t differ significantly in texture, expressed in compression force. The two formulations were sensory acceptable, showing no significant difference between it and confirming a high acceptance rate

    Benzisothiazolinone Derivatives as Potent Allosteric Monoacylglycerol Lipase Inhibitors That Functionally Mimic Sulfenylation of Regulatory Cysteines

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    We describe a set of benzisothiazolinone (BTZ) derivatives that are potent inhibitors of monoacylglycerol lipase (MGL), the primary degrading enzyme for the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Structure-activity relationship studies evaluated various substitutions on the nitrogen atom and the benzene ring of the BTZ nucleus. Optimized derivatives with nanomolar potency allowed us to investigate the mechanism of MGL inhibition. Site-directed mutagenesis and mass spectrometry experiments showed that BTZs interact in a covalent reversible manner with regulatory cysteines, Cys201 and Cys208, causing a reversible sulfenylation known to modulate MGL activity. Metadynamics simulations revealed that BTZ adducts favor a closed conformation of MGL that occludes substrate recruitment. The BTZ derivative 13 protected neuronal cells from oxidative stimuli and increased 2-AG levels in the mouse brain. The results identify Cys201 and Cys208 as key regulators of MGL function and point to the BTZ scaffold as a useful starting point for the discovery of allosteric MGL inhibitors
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