High-Reynolds-number weakly stratified flow past an obstacle

Published versio

Phosphorylation of Targeting Protein for Xenopus Kinesin-like Protein 2 (TPX2) at Threonine 72 in Spindle Assembly

The human ortholog of the targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a cytoskeletal protein that plays a major role in spindle assembly and is required for mitosis. During spindle morphogenesis, TPX2 cooperates with Aurora A kinase and Eg5 kinesin to regulate microtubule organization. TPX2 displays over 40 putative phosphorylation sites identified from various high-throughput proteomic screenings. In this study, we characterize the phosphorylation of threonine 72 (Thr(72)) in human TPX2, a residue highly conserved across species. We find that Cdk1/2 phosphorylate TPX2 in vitro and in vivo. Using homemade antibodies specific for TPX2 phosphorylated at Thr(72), we show that this phosphorylation is cell cycle-dependent and peaks at M phase. Endogenous TPX2 phosphorylated at Thr(72) does not associate with the mitotic spindle. Furthermore, ectopic GFP-TPX2 T72A preferentially concentrates on the spindle, whereas GFP-TPX2 WT distributes to both spindle and cytosol. The T72A mutant also increases the proportion of cells with multipolar spindles phenotype. This effect is associated with increased Aurora A activity and abnormally elongated spindles, indicative of higher Eg5 activity. In summary, we propose that phosphorylation of Thr(72) regulates TPX2 localization and impacts spindle assembly via Aurora A and Eg5.X11109Ysciescopu

Primary Coenzyme Q10 Deficiency: An Update

Coenzyme Q10 (CoQ10) has a number of vital functions in all cells, both mitochondrial and extra-mitochondrial. In addition to its key role in mitochondrial oxidative phosphorylation, CoQ10 serves as a lipid soluble antioxidant and plays an important role in fatty acid beta-oxidation and pyrimidine and lysosomal metabolism, as well as directly mediating the expression of a number of genes, including those involved in inflammation. Due to the multiplicity of roles in cell function, it is not surprising that a deficiency in CoQ10 has been implicated in the pathogenesis of a wide range of disorders. CoQ10 deficiency is broadly divided into primary and secondary types. Primary CoQ10 deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In man, at least 10 genes are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status. Patients may respond well to oral CoQ10 supplementation, although the condition must be recognised sufficiently early, before irreversible tissue damage has occurred. In this article, we have reviewed clinical studies (up to March 2023) relating to the identification of these deficiencies, and the therapeutic outcomes of CoQ10 supplementation; we have attempted to resolve the disparities between previous review articles regarding the usefulness or otherwise of CoQ10 supplementation in these disorders. In addition, we have highlighted several of the potential problems relating to CoQ10 supplementation in primary CoQ10 deficiency, as well as identifying unresolved issues relating to these disorders that require further research

Mitochondrial Dysfunction and Coenzyme Q10 Supplementation in Post-Viral Fatigue Syndrome: An Overview

Post-viral fatigue syndrome (PVFS) encompasses a wide range of complex neuroimmune disorders of unknown causes characterised by disabling post-exertional fatigue, myalgia and joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. It includes myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS); fibromyalgia (FM); and more recently post-COVID-19 condition (long COVID). To date, there are no definitive clinical case criteria and no FDA-approved pharmacological therapies for PVFS. Given the current lack of effective treatments, there is a need to develop novel therapeutic strategies for these disorders. Mitochondria, the cellular organelles responsible for tissue energy production, have recently garnered attention in research into PVFS due to their crucial role in cellular bioenergetic metabolism in these conditions. The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS, FM, and long COVID. To address this issue, this article aims to critically review the evidence relating to mitochondrial dysfunction in the pathogenesis of these disorders; in particular, it aims to evaluate the effectiveness of coenzyme Q10 supplementation on chronic fatigue and pain symptoms as a novel therapeutic strategy for the treatment of PVFS

The Fermi Bubble as a Source of Cosmic Rays in the Energy Range > 10E15 eV

The {\it Fermi} Large Area Telescope has recently discovered two giant gamma-ray bubbles which extend north and south of the Galactic center with diameters and heights of the order of $H\sim 10$ kpc. We suggest that the periodic star capture processes by the Galactic supermassive black hole Sgr A$^*$, with a capture rate of $\tau_{\rm cap}^{-1}\sim 3\times 10^{-5}$ yr$^{-1}$ and an energy release of $W\sim 3\times 10^{52}$ erg per capture, can result in hot plasma injecting into the Galactic halo at a wind velocity of $u\sim 10^8$ cm s$^{-1}$. The periodic injection of hot plasma can produce a series of shocks. Energetic protons in the bubble are re-accelerated when they interact with these shocks. We show that for energy larger than $E> 10^{15}$ eV, the acceleration process can be better described by the stochastic second-order Fermi acceleration. We propose that hadronic cosmic rays (CRs) within the ``knee'' of the observed CR spectrum are produced by Galactic supernova remnants distributed in the Galactic disk. Re-acceleration of these particles in the Fermi Bubble produces CRs beyond the knee. With a mean CR diffusion coefficient in this energy range in the bubble $D_B\sim 3\times 10^{30}$ cm$^2$ s$^{-1}$, we can reproduce the spectral index of the spectrum beyond the knee and within. The conversion efficiency from shock energy of the bubble into CR energy is about 10\%. This model provides a natural explanation of the observed CR flux, spectral indices, and matching of spectra at the knee.Comment: 43 pages, 8 figues, to be published in the Astrophysical Journal; version 2, 45 pages, 8 figures, added references and corrected typo

On the effects of surface morphology on the structure of wall-turbulence

Experiments were conducted in the fully-rough regime on surfaces with large relative roughness (h/δ ≈ 0.1) generated by regularly distributed LEGO™ bricks of uniform height, arranged in different configurations. Measurements were made with high resolution PIV on six different frontal solidities, λF, at fixed plan solidity, λP. Results indicate that the spatial underlying structure of the turbulence across the different surface morphologies is universal in both its shape and orientation in relation to the flow velocity. Harpin packets inclination with respect of the wall is also found to be consistent not only across the different wall surfaces but also when compared to previous studies on smooth walls. Slices of two-point correlations for both streamwise and wall-normal velocity fluctuations and Reynolds shear stresses present a good collapse across the entire y/δ range for all wall morphologies

Closed-loop separation control over a sharp edge ramp using Genetic Programming

We experimentally perform open and closed-loop control of a separating turbulent boundary layer downstream from a sharp edge ramp. The turbulent boundary layer just above the separation point has a Reynolds number $Re_{\theta}\approx 3\,500$ based on momentum thickness. The goal of the control is to mitigate separation and early re-attachment. The forcing employs a spanwise array of active vortex generators. The flow state is monitored with skin-friction sensors downstream of the actuators. The feedback control law is obtained using model-free genetic programming control (GPC) (Gautier et al. 2015). The resulting flow is assessed using the momentum coefficient, pressure distribution and skin friction over the ramp and stereo PIV. The PIV yields vector field statistics, e.g. shear layer growth, the backflow area and vortex region. GPC is benchmarked against the best periodic forcing. While open-loop control achieves separation reduction by locking-on the shedding mode, GPC gives rise to similar benefits by accelerating the shear layer growth. Moreover, GPC uses less actuation energy.Comment: 24 pages, 24 figures, submitted to Experiments in Fluid

Defining the roughness sublayer and its turbulent statistics

The roughness sublayer in a turbulent openchannel flow over a very rough wall is investigated experimentally both within the canopy and above using particle image velocimetry by gaining complete optical access with new methodologies without disturbing the flow. This enabled reliable estimates of the double-averaged mean and turbulence profiles to be obtained by minimizing and quantifying the usual errors introduced by limited temporal and spatial sampling. It is shown, for example, that poor spatial sampling can lead to erroneous vertical profiles in the roughness sublayer. Then, in order to better define and determine the roughness sublayer height, a methodology based on the measured spatial dispersion is proposed which takes into account temporal sampling errors. The results reveal values well below the usual more ad hoc estimates for all statistics. Finally, the doubleaveraged mean and turbulence statistics in the roughness sublayer are discussed