Search

The variational Riemann problem (VRP) is defined as the first variation of the solution to Riemann''s initial-value problem, also known as the problem of breakup of an arbitrary discontinuity in a gas, when the initial data undergo small variations. We show that the solution to the VRP can be analytically obtained, provided that the solution to the baseline Riemann problem is known. This solution describes the interaction of two abutting parcels of small disturbances against the background of a given base flow and therefore can be efficiently implemented in numerical methods for aeroacoustics. When the spatial distribution of disturbances and base flow parameters are given at a time moment at mesh points of a computational grid, one can exactly determine the disturbance evolution for a short lapse of time by solving the VRP at mesh interfaces. This can then be applied to update disturbance values to a new time moment by using the standard finite-volume scheme. In other words, the VRP can be used in computational aeroacoustics in the similar way to the Riemann problem used in Godunov-type methods for computational fluid dynamics. The present paper elaborates on this idea and adopts the solution to the VRP as a building block for a finite-volume Godunov-type method for aeroacoustics. [Copyright &y& Elsevier]

Neutrophil-to-lymphocyte ratio (NLR) has been recognized as a marker of systemic inflammation with a prognostic impact in patients with various cancers, including breast cancer. The aim of this study was to investigate the relationships between the preoperative NLR and breast cancer prognosis in the patients before and after menopausal age, and its relationship with other prognostic factors. A total of 1868 patients with clinical Stage I-III primary breast cancer were enrolled. The associations between clinicopathological factors and the preoperative NLR were analyzed, and relapse-free survival (RFS) and overall survival (OS) were estimated. Statistical analyses stratified by the menopausal status revealed that a high NLR was significantly associated with worse RFS (P < 0.001) and OS (P = 0.001) in postmenopausal patients, but not in premenopausal patients. Although the postmenopausal patients with relapsed cancer tended to have higher NLR levels than those without relapse (P = 0.079), NLR levels of premenopausal patients with relapsed cancer were significantly lower than that of relapse-free patients (P = 0.024). In postmenopausal patients, a high NLR was only associated with worse RFS in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer (P < 0.001), in those managed without adjuvant chemotherapy (P = 0.003); this association was not observed in patients who received adjuvant chemotherapy. The preoperative NLR can be a useful prognostic marker, especially in postmenopausal breast cancer patients. The relationships between the NLR and breast cancer prognosis may be more evident when patients are assessed according to their menopausal status. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurologic disorder characterized by the accumulation of extracellular deposits of amyloid-β (Aβ) fibrils in the brain of patients. The key etiologic agent in Alzheimer's disease is not known; however oligomeric Aβ appears detrimental to neuronal functions and increases Aβ fibrils deposition. Previous research has shown that curcumin, a phenolic pigment of turmeric, has an effect on Aβ assemblies, although the mechanism remains unclear. In this study, we demonstrate that curcumin disassembles pentameric oligomers made from synthetic Aβ42 peptides (pentameric oAβ42), using atomic force microscopy imaging followed by Gaussian analysis. Since curcumin shows keto-enol structural isomerism (tautomerism), the effect of keto-enol tautomerism on its disassembly was investigated. We have found that curcumin derivatives capable of keto-enol tautomerization also disassemble pentameric oAβ42, while, a curcumin derivative incapable of tautomerization did not affect the integrity of pentameric oAβ42. These experimental findings indicate that keto-enol tautomerism plays an essential role in the disassembly. We propose a mechanism for oAβ42 disassembly by curcumin based on molecular dynamics calculations of the tautomerism. When curcumin and its derivatives bind to the hydrophobic regions of oAβ42, the keto-form changes predominantly to the enol-form; this transition is associated with structural (twisting, planarization and rigidification) and potential energy changes that give curcumin enough force to act as a torsion molecular-spring that eventually disassembles pentameric oAβ42. This proposed mechanism sheds new light on keto-enol tautomerism as a relevant chemical feature for designing such novel therapeutic drugs that target protein aggregation. • AFM and Gaussian analysis quantify the Aβ42 oligomerization and disassembly. • Curcumins capable of keto-enol tautomerism can disassemble pentameric Aβ42 oligomers. • MD analysis supports that tautomerism acts like a spring and disassembles oligomers. [ABSTRACT FROM AUTHOR]