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This paper presents three-dimensional (3D) direct numerical simulations (DNS) of flow past a circular cylinder over a range of Reynolds number ( $Re$ ) up to 300. The gradual wake transition process from mode A* (i.e. mode A with large-scale vortex dislocations) to mode B is well captured over a range of $Re$ from 230 to 260. The mode swapping process is investigated in detail with the aid of numerical flow visualization. It is found that the mode B structures in the transition process are developed based on the streamwise vortices of mode A or A* which destabilize the braid shear layer region. For each case within the transition range, the transient mode swapping process consists of dislocation and non-dislocation cycles. With the increase of $Re$ , it becomes more difficult to trigger dislocations from the pure mode A structure and form a dislocation cycle, and each dislocation stage becomes shorter in duration, resulting in a continuous decrease in the probability of occurrence of mode A* and a continuous increase in the probability of occurrence of mode B. The occurrence of mode A* results in a relatively strong flow three-dimensionality. A critical condition is confirmed at approximately $Re=265{-}270$ , where the weakest flow three-dimensionality is observed, marking a transition from the disappearance of mode A* to the emergence of increasingly disordered mode B structures.

The purpose of this study was to explore the effect of microRNA-6071 (miR-6071) on glioblastoma (GBM) and its potential mechanisms. In this study, the expressions of miR-6071 and UL16 binding protein 2 (ULBP2) were measured by qRT-RCR in GBM tissues and cells. The prognostic values of miR-6071 and ULBP2 were evaluated by Kaplan-Meier methods using the data obtained from The Cancer Genome Atlas (TCGA) database. The cell clones, proliferation, apoptosis, migration and invasion in GBM cells were detected by colony formation assay, EdU assay, flow cytometry, wound-healing assay and transwell assay. The targeting relationship between miR-6071 and ULBP2 was predicted by Targetscan 7.2 and further verified by dual-luciferase reporter gene assay. Moreover, the expressions of Bax, caspase-3, Bcl-2, matrix metalloproteinases 2 (MMP-2), MMP-9, phosphatidylinositol 3'-kinase (PI3K), p-PI3K, protein kinase B (AKT), p-AKT, mammalian target of rapamycin (mTOR) and p-mTOR were measured by Western blot. miR-6071 was lowly expressed and ULBP2 was highly expressed in GBM tissues and cells. miR-6071 significantly repressed the proliferation, migration and invasion, and promoted apoptosis in GBM cells. Moreover, miR-6071 also inhibited the activation of PI3K/AKT/mTOR pathway in GBM cells. Additionally, miR-6071 has been shown to negatively regulate ULBP2 expression. We also confirmed that ULBP2 could reverse the effects of miR-6071 on GBM cells through regulating PI3K/AKT/mTOR pathway. Our study demonstrated that miR-6071 could suppress cell proliferation, migration and invasion, as well as promote apoptosis through the inhibition of PI3K/Akt/mTOR pathway by binding to ULBP2 in GBM.

Background Postoperative pain (POP) is a severe acute pain encountered in patients suffering from an operation, and is less than adequately controlled by the currently available analgesics. Phosphatidylinositol 3-kinase (PI3K) has been reported to have an important role in neuropathic and inflammatory pain. Our previous research revealed that pre-surgical inhibition of spinal PI3K alleviated the pain behavior induced by plantar incision in mice. The aim of this study was to clarify whether post-surgical inhibition of PI3K would attenuate the POP and the underlying mechanisms. Methods A POP model was established by plantar incision in Kunming mice. A behavioral test was performed to determine mechanical allodynia, thermal hyperalgesia, and cumulative pain scores. The spinal Fos was detected by immunohistochemistry. The spinal expression of protein kinase B (Akt) or phosphorylated Akt (pAkt) was explored using western blot. The cellular location of pAkt was determined by immunofluorescence. Results Post-surgical inhibition of PI3K attenuated mechanical allodynia, thermal hyperalgesia, and cumulative pain scores induced by plantar incision significantly in male mice, and mildly in female mice. Post-surgical inhibition of PI3K attenuated the expression of spinal Fos in male mice. Plantar incision induced a time-dependent expression of spinal pAkt in male mice, which was primarily expressed in the spinal dorsal horn, and localized with the neuron and microglia’s marker. Post-surgical inhibition of PI3K attenuated the activation of Akt induced by plantar incision in male mice as well. Conclusions We concluded that post-surgical inhibition of PI3K could attenuate the pain-related behaviors induced by plantar incision, by suppressing the activation of spinal Akt in male mice. This finding might be used in clinical studies to reach a better understanding of POP mechanisms and optimal treatment.

Background Neurofilaments (Nf) are a series of highly specific scaffolding proteins of neurons. Neurofilament light chains (Nf‐L) and the heavy one (Nf‐H) are subunits of Nf, and they are recognized as potent productions of neural damage. The concentrations of Nf aggrandized significantly in neurological disease including neuromyelitis optica, multiple sclerosis, and Alzheimer's disease. However, whether Nf in cerebrospinal fluid (CSF) elevated in anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis is unclear. Here, we aimed to detect whether CSF Nf is altered in NMDAR and whether changes in CSF Nf can serve as an objective and effective biomarker to evaluate disease severity and prognosis. Methods We collected 24 anti‐NMDAR encephalitis patients, 11 viral meningoencephalitis/encephalitis (VM) patients, and 21 controls in this study. CSF Nf‐L, Nf‐H, and cytokine levels (IL‐1β, IL‐6, and IL‐17A) were determined by enzyme‐linked immunosorbent assay (ELISA) and compared between groups. We evaluated patients’ clinical outcomes or prognosis according to modified Rankin scale (mRS) score. Results Compared with controls, both CSF Nf‐L and Nf‐H levels were significantly increased in anti‐NMDAR encephalitis patients. While compared with VM patients, only Nf‐L were increased in anti‐NMDAR encephalitis patients. Moreover, CSF Nf‐L were positively correlated with concentration of cytokines (IL‐1β, IL‐17A) and mRS scores in anti‐NMDAR encephalitis patients. After treatment, both CSF Nf‐L and Nf‐H levels decreased. Furthermore, the Nf‐L during follow‐up positively correlated with 3‐month mRS scores, and ΔNf‐L positively correlated with ΔmRS. Conclusions Briefly, CSF Nf‐L levels notably increased in anti‐NMDAR encephalitis patients in acute phase and positively correlated with disease severity. It could be considered as a useful indicator for clinical outcomes and prognosis. CSF Nf‐L and Nf‐H were significantly increased in NMDAR patients. After treatment, both CSF Nf‐L and Nf‐H levels decreased. Nf‐L at acute stage was positively related with max mRS score. Furthermore, the Nf‐L during follow‐up was still positively correlated with 3‐month mRS scores and ΔNf‐L positively correlated with ΔmRS scores.

IntroductionThere is an emerging need for the offshore renewable industry to have their own bespoke design guidelines because the associated projects and offshore facilities differ in fundamental ways to oil and gas facilities. Offshore renewable energy (ORE) facilities have already surpassed the numbers of installed facilities in the oil and gas industry by an order of magnitude and demand is forecast to continue growing exponentially. In addition ORE facilities often have different response characteristics and limit states or failure modes as well as profoundly different risk and consequence profiles given they are generally uncrewed and do not contain explosive hydrocarbon fluids which might be released into the environment. Therefore, the purpose of this paper is to advocate for licensing bodies and regulators (such as the various national PEL 114 committees) to challenge the process of automatic adoption of oil and gas design processes, while pushing for offshore renewables to be treated differently, when appropriate, with more relevant and applicable guidance.MethodsTo support this argument we present new bespoke design guidance developed for subsea cables based on specific modes of cable behaviour, which often differ from pipelines. We also show worked examples from recent project experience. The results from on-bottom stability analyses of a set of cables are compared between conventional oil and gas guidance following DNV-RP-F109 versus the stability using cable-optimised approaches.ResultsThe outcomes from the ‘conventional’ oil and gas results are not simply biased compared to cable-optimised design methods, with a trend of being either conservative or unconservative. Instead, the results of the two methods are very poorly correlated. This shows that the oil and gas approach isn't simply biased when applied to cables, but is instead unreliable because it doesn't capture the underlying failure conditions. These analytical comparisons are supported by field observation - the ocean doesn't lie, and makes short work of any anthropogenic structures which are designed with inadequate appreciation of the real world conditions.DiscussionTo support the rapid growth of ORE, we should therefore actively pursue opportunities to rewrite the design rules and standards, so that they better support the specific requirements of ORE infrastructure, rather than legacy oil and gas structures. With more appropriate design practices, we can accelerate the roll out of ORE to meet net zero, and mitigate the climate crisis.

The effects of yaw angle on wake characteristics of a stationary square cylinder were investigated in terms of the hydrodynamic forces, the vortex shedding frequency, and the vortical structures using direct numerical simulations (DNS) at a Reynolds number of 1000. In total, four yaw angles, namely, α = 0°, 15°, 30°, and 45°, were considered. The three-dimensional (3D) Navier–Stokes equations were solved directly using the finite volume method in OpenFOAM. It was found that the first-order statistics of the drag coefficient and the Strouhal number satisfied the independence principle (IP) closely. However, the second-order statistics of the drag and lift coefficients deviated apparently from the IP for α ≥ 25°. The iso-surfaces of the spanwise vorticity gradually disorganized and the magnitudes of the spanwise vorticity contour decreased as the yaw angle α was increased from 0° to 45°. By contrast, the streamwise vorticity iso-surfaces were found to become more organized and the magnitudes of the spanwise velocity contour became larger as a result of the increase in yaw angle, indicating the impairment of the quasi-two-dimensionality and the enhancement of the three-dimensionality of the wake flow. Extensive comparisons were also made with previous DNS results for a yawed circular cylinder, and both similarities and differences between these two kinds of cylinder wakes are discussed.

A physical model testing method to determine the hydrodynamic force coefficients of an object is proposed and applied to an articulated concrete mattress placed on a flat surface under steady current condition. The test setup, which comprises of a pulley system that is able to pull the concrete mattress in either direction relative to the flow (e.g., with the flow direction or against the flow direction) and one load cell to measure the force required to pull the mattress, is simple and straightforward. Writing the equations of load balance for two different pulling directions allows the force coefficients to be deduced. The novelty and advantages of the method are that it completely removes the difficulties associated with measuring forces on individual concrete blocks and isolating the mattresses from contacting the solid surface, which were common in conventional test methods for measuring hydrodynamic forces on structures founded on a solid surface. A series of flume tests have been conducted to demonstrate the validity of the proposed method. It is expected that the proposed testing method is applicable to a wide range of structures, bed surfaces and flow conditions.

Three-dimensional (3-D) wake transition for flow past a square cylinder aligned with sides perpendicular and parallel to the approaching flow is investigated using direct numerical simulation. The secondary wake instability, namely a Mode A instability, occurs at a Reynolds number ( $Re$ ) of 165.7. A gradual wake transition from Mode A* (i.e. Mode A with vortex dislocations) to Mode B is observed over a range of $Re$ from 185 to 210, within which the probability of occurrence of vortex dislocations decreases monotonically with increasing $Re$ . The characteristics of the Strouhal–Reynolds number relationship are analysed. At the onset of Mode A*, a sudden drop of the 3-D Strouhal number from its two-dimensional counterpart is observed, which is due to the subcritical nature of the Mode A* instability. A continuous 3-D Strouhal–Reynolds number curve is observed over the mode swapping regime, since Mode A* and Mode B have extremely close vortex shedding frequencies and therefore only a single merged peak is observed in the frequency spectrum. The existence of hysteresis for the Mode A and Mode B wake instabilities is examined. The unconfined Mode A and Mode B wake instabilities are hysteretic and non-hysteretic, respectively. However, a spanwise confined Mode A could be non-hysteretic. It is proposed that the existence of hysteresis at a wake instability can be identified by examining the sudden/gradual variation of the 3-D flow properties at the onset of the wake instability, with sudden and gradual variations corresponding to hysteretic (subcritical) and non-hysteretic (supercritical) flows, respectively.

The Honji instability is studied using direct numerical simulations of sinusoidal oscillatory flow around a circular cylinder. The three-dimensional Navier–Stokes equations are solved by a finite element method at a relatively small value of the Keulegan–Carpenter number KC. The generation and subsequent development of Honji vortices are discussed over a range of frequency parameters by means of flow visualization. It is found that the spacing between Honji vortices is only weakly dependent on the frequency of oscillation, but is strongly correlated to KC because it is the terms within the governing equation containing KC that dominate the three-dimensional features of the flow. An empirical relationship between KC and the spacing between neighbouring vortices is proposed. The three-dimensional steady streaming structure within the vortices is identified and it is found that at high frequencies the steady streaming is two-dimensional although the instantaneous flow structure is itself fully three-dimensional.