In the flow past elongated rectangular cylinders at moderate Reynolds numbers, vortices shedding from the leading- and trailing-edge corners are frequency locked by the impinging leading-edge vortex ...instability. The present work investigates how the chord-based Strouhal number varies with the aspect ratio of the cylinder at a Reynolds number (based on the cylinder thickness and the free-stream velocity) of $Re=400$, i.e. when locking is strong. Several two-dimensional, nonlinear simulations are run for rectangular and D-shaped cylinders, with the aspect ratio ranging from $1$ to $11$, and a global linear stability analysis of the flow is performed. The shedding frequency observed in the nonlinear simulations is predicted fairly well by the eigenfrequency of the leading eigenmode. The inspection of the structural sensitivity confirms the central role of the trailing-edge vortex shedding in the frequency locking, as already assumed by other authors. Surprisingly, however, the stepwise increase of the Strouhal number with the aspect ratio reported by several previous works is not fully reproduced. Indeed, with increasing aspect ratio, two distinct flow behaviours are observed, associated with two flow configurations where the interaction between the leading- and trailing-edge vortices is different. These two configurations are fully characterised, and the mechanism of selection of the flow configuration is discussed. Lastly, for aspect ratios close to the jump between two consecutive shedding modes, the Strouhal number is found to present hysteresis, implying the existence of multiple stable configurations. Continuing the lower shedding-mode branch by increasing the aspect ratio, we found that the periodic configuration loses stability via a Neimark–Sacker bifurcation leading to different Arnold tongues. This hysteresis can explain, at least partially, the significant scatter of existing experimental and numerical data.
The primary instability of the flow past rectangular cylinders is studied to comprehensively describe the influence of the aspect ratio $AR$ and of rounding the leading- and/or trailing-edge corners. ...Aspect ratios ranging between $0.25$ and $30$ are considered. We show that the critical Reynolds number ($\textit {Re}_c$) corresponding to the primary instability increases with the aspect ratio, starting from $\textit {Re}_c \approx 34.8$ for $AR=0.25$ to a value of $\textit {Re}_c \approx 140$ for $AR = 30$. The unstable mode and its dependence on the aspect ratio are described. We find that positioning a small circular cylinder in the flow modifies the instability in a way strongly depending on the aspect ratio. The rounded corners affect the primary instability in a way that depends on both the aspect ratio and the curvature radius. For small $AR$, rounding the leading-edge corners has always a stabilising effect, whereas rounding the trailing-edge corners is destabilising, although for large curvature radii only. For intermediate $AR$, instead, rounding the leading-edge corners has a stabilising effect limited to small curvature radii only, while for $AR \geqslant 5$ it has always a destabilising effect. In contrast, for $AR \geqslant 2$ rounding the trailing-edge corners consistently increases $\textit {Re}_c$. Interestingly, when all the corners are rounded, the flow becomes more stable, at all aspect ratios. An explanation for the stabilising and destabilising effect of the rounded corners is provided.
A scaling law to predict the onset of the primary Hopf instability in the steady flow past two-dimensional symmetric bluff bodies is proposed. It uses a measure of the spatial extent of the ...separation bubble as the length scale and the largest reverse-flow speed within it as the velocity scale. The ensuing Reynolds number, evaluated at the onset of the primary Hopf bifurcation, collapses quite nicely for bodies of different shape and aspect ratio even when a small angle of attack perturbs the symmetry; its relative variation is one order of magnitude smaller than that of the usual Reynolds number defined with the free-stream velocity and the cross-stream body size. With the new scaling, it can be roughly assessed whether the steady flow past a two-dimensional bluff body is absolutely and globally unstable to two-dimensional perturbations without a computationally expensive stability analysis: only the inspection of the base flow is required. More importantly, the scaling provides an insight into the flow mechanism that produces the instability.
We introduce a new finite-difference solver for the incompressible Navier–Stokes equations that exploits the direction-splitting method proposed by Guermond and Minev in 2010, but is formulated on a ...co-located grid. The main ingredients of the new solver are: i) the direction-splitting approach adopted for both the momentum and the pressure equations; and ii) the co-located grid approach. The solver is parallelised by the Schur-complement method, and achieves very high performance levels on thousands of processors. Several test cases are proposed to assess the accuracy and efficiency of the method.
•First direction-splitting Navier–Stokes solver using co-located grids.•No explicit stabilisation term has to be added to the equations to avoid checkerboard modes.•Very simple, massively parallel solver, requires the solution of tridiagonal linear systems only.•Very fast: computing time well below 10−6 seconds per time step per grid node in 3D for 1000 processing cores.•Accurate: tested on several test cases ranging from manufactured solutions to driven cavity to fluid-dynamic stability also with immersed boundaries.
Since the pioneering studies of Fleckenstein and co-workers, L-Type Calcium Channel (LTCC) blockers have attracted large interest due to their effectiveness in treating several cardiovascular ...diseases. Medicinal chemists achieved high potency and tissue selectivity by decorating the 1-4-DHP nucleus, the most studied scaffold among LTCC blockers. Nowadays it is clear that the 1,4-DHP nucleus is a privileged scaffold since, when appropriately substituted, it can selectively modulate diverse receptors, channels and enzymes. Therefore, the 1,4-DHP scaffold could be used to treat various diseases by a single-ligand multi-target approach. In this review, we describe the structure-activity relationships of 1,4-DHPs at ion channels, G-protein coupled receptors, and outline the potential for future therapeutic applications.
Hypertension has become the leading risk factor for worldwide cardiovascular diseases. Conventional pharmacological treatment, after both dietary and lifestyle changes, is generally proposed. In this ...review, we present the antihypertensive properties of phytocomplexes from thirteen plants, long ago widely employed in ethnomedicines and, in recent years, increasingly evaluated for their activity in vitro and in vivo, also in humans, in comparison with synthetic drugs acting on the same systems. Here, we focus on the demonstrated or proposed mechanisms of action of such phytocomplexes and of their constituents proven to exert cardiovascular effects. Almost seventy phytochemicals are described and scientifically sound pertinent literature, published up to now, is summarized. The review emphasizes the therapeutic potential of these natural substances in the treatment of the ‘high normal blood pressure’ or ‘stage 1 hypertension’, so-named according to the most recent European and U.S. guidelines, and as a supplementation in more advanced stages of hypertension, however needing further validation by clinical trial intensification.
Display omitted
•Antihypertensive properties of phytocomplexes from 13 plants are presented.•Almost 70 constituents with proved antihypertensive action are individuated from such complexes.•Selection has been made on the criterion of available evidences of in vitro, in vivo and clinical effectiveness.•Their potential in high-normal BP treatment and as a supplementation in hypertension is discussed.
It is generally assumed that the neuropathology of sporadic (late-onset or nonfamilial) Alzheimer's disease (AD) is driven by the overproduction and spreading of first Amyloid-βx-42 (Aβ42) and later ...hyperphosphorylated (hp)-Tau oligomeric "infectious seeds". Hitherto, only neurons were held to make and spread both oligomer types; astrocytes would just remove debris. However, we have recently shown that exogenous fibrillar or soluble Aβ peptides specifically bind and activate the Ca(2+)-sensing receptors (CaSRs) of untransformed human cortical adult astrocytes and postnatal neurons cultured in vitro driving them to produce, accrue, and secrete surplus endogenous Aβ42. While the Aβ-exposed neurons start dying, astrocytes survive and keep oversecreting Aβ42, nitric oxide (NO), and vascular endothelial growth factor (VEGF)-A. Thus astrocytes help neurons' demise. Moreover, we have found that a highly selective allosteric CaSR agonist ("calcimimetic"), NPS R-568, mimics the just mentioned neurotoxic actions triggered by Aβ●CaSR signaling. Contrariwise, and most important, NPS 2143, a highly selective allosteric CaSR antagonist ("calcilytic"), fully suppresses all the Aβ●CaSR signaling-driven noxious actions. Altogether our findings suggest that the progression of AD neuropathology is promoted by unceasingly repeating cycles of accruing exogenous Aβ42 oligomers interacting with the CaSRs of swelling numbers of astrocyte-neuron teams thereby recruiting them to overrelease additional Aβ42 oligomers, VEGF-A, and NO. Calcilytics would beneficially break such Aβ/CaSR-driven vicious cycles and hence halt or at least slow the otherwise unstoppable spreading of AD neuropathology.
In a bacterium like Helicobacter pylori, which is characterized by a recombinant population structure, the associated presence of genes encoding virulence factors might be considered an expression of ...a selective advantage conferred to strains with certain genotypes and, therefore, a potentially useful tool for predicting the clinical outcome of infections. However, differences in the geographical and ethnic prevalence of the H. pylori virulence-associated genotypes can affect their clinical predictive value and need to be considered in advance. In this study we carried out such an evaluation in a group of patients living in Sicily, the largest and most populous island in the Mediterranean Sea. cagA, vacA, babA2, hopQ, oipA, sabA, and hopZ were the H. pylori virulence-associated genes assayed; their presence, expression status or allelic homologs were detected in H. pylori DNA samples and/or isolated strains, obtained by gastric biopsy from 90 Sicilian patients with chronic gastritis, inactive (n = 37), active (n = 26), or active with peptic ulcer (n = 27). Genotypes cagA ⁺, vacAs1, vacAm1, babA2 ⁺, and hopQ I, I/II were identified in 51.8, 80.4, 35.2, 47.3, and 67.7% of the different samples respectively. Only these genotypes were associated with each other and with the active form of chronic gastritis, irrespective of the presence of a peptic ulcer. In our isolates their prevalence was more similar to values observed in the north of Italy and France than to those observed in Spain or other Mediterranean countries that are closer and climatically more similar to western Sicily.
Cerebral aneurysms are a multi-factorial disease with severe consequences. A core part of the European project @neurIST was the physical characterization of aneurysms to find candidate risk factors ...associated with aneurysm rupture. The project investigated measures based on morphological, haemodynamic and aneurysm wall structure analyses for more than 300 cases of ruptured and unruptured aneurysms, extracting descriptors suitable for statistical studies. This paper deals with the unique challenges associated with this task, and the implemented solutions. The consistency of results required by the subsequent statistical analyses, given the heterogeneous image data sources and multiple human operators, was met by a highly automated toolchain combined with training. A testimonial of the successful automation is the positive evaluation of the toolchain by over 260 clinicians during various hands-on workshops. The specification of the analyses required thorough investigations of modelling and processing choices, discussed in a detailed analysis protocol. Finally, an abstract data model governing the management of the simulation-related data provides a framework for data provenance and supports future use of data and toolchain. This is achieved by enabling the easy modification of the modelling approaches and solution details through abstract problem descriptions, removing the need of repetition of manual processing work.
PDF
