Local uniform stencil (LUST) boundary condition for arbitrary 3-D boundaries in parallel smoothed particle hydrodynamics (SPH) models

Abstract This paper presents the development of a new boundary treatment for free-surface hydrodynamics using the smoothed particle hydrodynamics (SPH) method accelerated with a graphics processing unit (GPU). The new solid boundary formulation uses a local uniform stencil (LUST) of fictitious particles that surround and move with each fluid particle and are only activated when they are located inside a boundary. This addresses the issues currently affecting boundary conditions in SPH, namely the accuracy, robustness and applicability while being amenable to easy parallelization such as on a GPU. In 3-D, the methodology uses triangles to represent the geometry with a ray tracing procedure to identify when the LUST particles are activated. A new correction is proposed to the popular density diffusion term treatment to correct for pressure errors at the boundary. The methodology is applicable to complex arbitrary geometries without the need of special treatments for corners and curvature is presented. The paper presents the results from 2-D and 3-D Poiseuille flows showing convergence rates typical for weakly compressible SPH. Still water in a complex 3-D geometry with a pyramid demonstrates the robustness of the technique with excellent agreement for the pressure distributions. The method is finally applied to the SPHERIC benchmark of a dry-bed dam-break impacting an obstacle showing satisfactory agreement and convergence for a violent flow

Silicon slow-light-based photonic mixer for microwave-frequencyconversion applications

This paper was published in OPTICS LETTERS and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://dx.doi.org/10.1364/OL.37.001721. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law[EN] We describe and demonstrate experimentally a method for photonic mixing of microwave signals by using a silicon electro-optical Mach¿Zehnder modulator enhanced via slow-light propagation. Slow light with a group index of ~11, achieved in a one-dimensional periodic structure, is exploited to improve the upconversion performance of an input frequency signal from 1 to 10.25 GHz. A minimum transmission point is used to successfully demonstrate the upconversion with very low conversion losses of ~7¿¿dB and excellent quality of the received I/Q modulated QPSK signal with an optimum EVM of ~8%.Financial support from FP7-224312 HELIOS project and Generalitat Valenciana under PROMETEO-2010-087 R&D Excellency Program (NANOMET) are acknowledged. F. Y.Gardes, D. J. Thomson, and G. T. Reed are supported by funding received from the UK EPSRC funding body under the grant “UK Silicon Photonics.” The author A. M. Gutiérrez thanks D. Marpaung for his useful help.Gutiérrez Campo, AM.; Brimont, ACJ.; Herrera Llorente, J.; Aamer, M.; Martí Sendra, J.; Thomson, DJ.; Gardes, FY.... (2012). Silicon slow-light-based photonic mixer for microwave-frequencyconversion applications. Optics Letters. 37(10):1721-1723. https://doi.org/10.1364/OL.37.001721S17211723371

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

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

N-(Anilinoethyl)amide Melatonergic Ligands with Improved Water Solubility and Metabolic Stability

The MT2-selective melatonin receptor ligand UCM765 (N-(2-((3-methoxyphenyl)(phenyl)amino)ethyl)acetamide), showed interesting sleep inducing, analgesic and anxiolytic properties in rodents, but suffers from low water solubility and modest metabolic stability. To overcome these limitations, different strategies were investigated, including modification of metabolically liable sites, introduction of hydrophilic substituents and design of more basic derivatives. Thermodynamic solubility, microsomal stability and lipophilicity of new compounds were experimentally evaluated, together with their MT1 and MT2 binding affinities. Introduction of a m-hydroxymethyl substituent on the phenyl ring of UCM765 and replacement of the replacement of the N,N-diphenyl-amino scaffold with a N-methyl-N-phenyl-amino one led to highly soluble compounds with good microsomal stability and receptor binding affinity. Docking studies into the receptor crystal structure provided a rationale for their binding affinity. Pharmacokinetic characterization in rats highlighted higher plasma concentrations for the N-methyl-N-phenyl-amino derivative, consistent with its improved microsomal stability and makes this compound worthy of consideration for further pharmacological investigation

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

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)

Steps towards sustainable solid phase peptide synthesis: use and recovery ofN-octyl pyrrolidone

The investigation of new green biogenic pyrrolidinones as alternative solvents toN,N-dimethylformamide (DMF) for solid phase peptide synthesis (SPPS) led to the identification ofN-octyl pyrrolidone (NOP) as the best candidate. NOP showed good performances in terms of swelling, coupling efficiency and low isomerization generating peptides with very high purity. A mixture of NOP with 20% dimethyl carbonate (DMC) allowed a decrease in solvent viscosity, making the mixture suitable for the automated solid-phase protocol. Aib-enkephalin and linear octreotide were successfully used to test the methodologies. It is worth noting that NOP, DMC and the piperidine used in the deprotection step could be easily recovered by direct distillation from the process waste mixture. The process mass intensity (PMI), being reduced by 63-66%, achieved an outstanding value representing a clear step forward in achieving green SPPS

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

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

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

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

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