The evolution of energy in flow driven by rising bubbles

We investigate by direct numerical simulations the flow that rising bubbles cause in an originally quiescent fluid. We employ the Eulerian-Lagrangian method with two-way coupling and periodic boundary conditions. In order to be able to treat up to 288000 bubbles, the following approximations and simplifications had to be introduced: (i) The bubbles were treated as point-particles, thus (ii) disregarding the near-field interactions among them, and (iii) effective force models for the lift and the drag forces were used. In particular, the lift coefficient was assumed to be 1/2, independent of the bubble Reynolds number and the local flow field. The results suggest that large scale motions are generated, owing to an inverse energy cascade from the small to the large scales. However, as the Taylor-Reynolds number is only in the range of 1, the corresponding scaling of the energy spectrum with an exponent of -5/3 cannot develop over a pronounced range. In the long term, the property of local energy transfer, characteristic of real turbulence, is lost and the input of energy equals the viscous dissipation at all scales. Due to the lack of strong vortices the bubbles spread rather uniformly in the flow. The mechanism for uniform spreading is as follows: Rising bubbles induce a velocity field behind them that acts on the following bubbles. Owing to the shear, those bubbles experience a lift force which make them spread to the left or right, thus preventing the formation of vertical bubble clusters and therefore of efficient forcing. Indeed, when the lift is artifically put to zero in the simulations, the flow is forced much more efficiently and a more pronounced energy accumulates at large scales is achieved.Comment: 9 pages, 7 figure

Journey of candidates who were unmatched in the Canadian Residency Matching Service (CaRMS): A phenomenological study

Background: Each year, a number of medical students are unmatched in the Canadian Residency Matching Service (CaRMs) match. There is little information on the experiences of unmatched candidates. This study seeks to explore the experiences of applicants who were unmatched in the first iteration of their CaRMS applications Methods: We interviewed 15 participants who were previously unmatched, using a semi-structured interview guide to ask them of their experiences on the following domains: the overall unmatched experience; circumstances leading to their unmatched status; resources employed; barriers experienced; recommendations; and, their eventual career outcomes. We independently identified major themes from field notes to code the data using a phenomenology approach. Results: Our participants universally reported negative emotions, concerns regarding privacy and confidentiality breaches, and stigma faced (real or perceived). Systemic challenges included: lack of information, pressures faced from undergraduate medical education, and logistical issues such as financial challenges, licensing and scheduling issues. The utility of peer support differed for individual participants, but all those who had support from other unmatched candidates felt that to be useful. Conclusions: Our participants reported significant challenges faced after being unmatched. Based on these experiences, we identified four major recommendations to support candidates through their unmatched journey

Entanglement distribution for a practical quantum-dot-based quantum processor architecture

We propose a quantum dot (QD) architecture for enabling universal quantum information processing. Quantum registers, consisting of arrays of vertically stacked self-assembled semiconductor QDs, are connected by chains of in-plane self-assembled dots. We propose an entanglement distributor, a device for producing and distributing maximally entangled qubits on demand, communicated through in-plane dot chains. This enables the transmission of entanglement to spatially separated register stacks, providing a resource for the realization of a sizeable quantum processor built from coupled register stacks of practical size. Our entanglement distributor could be integrated into many of the present proposals for self-assembled QD-based quantum computation (QC). Our device exploits the properties of simple, relatively short, spin-chains and does not require microcavities. Utilizing the properties of self-assembled QDs, after distribution the entanglement can be mapped into relatively long-lived spin qubits and purified, providing a flexible, distributed, off-line resource. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft

Continuum elasticity theory of edge excitations in a two-dimensional electron liquid with finite range interactions

We make use of continuum elasticity theory to investigate the collective modes that propagate along the edge of a two-dimensional electron liquid or crystal in a magnetic field. An exact solution of the equations of motion is obtained with the following simplifying assumptions: (i) The system is {\it macroscopically} homogeneous and isotropic in the half-plane delimited by the edge (ii) The electron-electron interaction is of finite range due to screening by external electrodes (iii) The system is nearly incompressible. At sufficiently small wave vector $q$ we find a universal dispersion curve $\omega \sim q$ independent of the shear modulus. At larger wave vectors the dispersion can change its form in a manner dependent on the comparison of various length scales. We obtain analytical formulas for the dispersion and damping of the modes in various physical regimes.Comment: 3 figure

G-Quadruplex Dynamics Contribute To Regulation Of Mitochondrial Gene Expression

Single-stranded DNA or RNA sequences rich in guanine (G) can adopt non-canonical structures known as G-quadruplexes (G4). Mitochondrial DNA (mtDNA) sequences that are predicted to form G4 are enriched on the heavy-strand and have been associated with formation of deletion breakpoints. Increasing evidence supports the ability of mtDNA to form G4 in cancer cells; however, the functional roles of G4 structures in regulating mitochondrial nucleic acid homeostasis in non-cancerous cells remain unclear. Here, we demonstrate by live cell imaging that the G4-ligand RHPS4 localizes primarily to mitochondria at low doses. We find that low doses of RHPS4 do not induce a nuclear DNA damage response but do cause an acute inhibition of mitochondrial transcript elongation, leading to respiratory complex depletion. We also observe that RHPS4 interferes with mtDNA levels or synthesis both in cells and isolated mitochondria. Importantly, a mtDNA variant that increases G4 stability and anti-parallel G4-forming character shows a stronger respiratory defect in response to RHPS4, supporting the conclusion that mitochondrial sensitivity to RHPS4 is G4-mediated. Taken together, our results indicate a direct role for G4 perturbation in mitochondrial genome replication, transcription processivity, and respiratory function in normal cells

Evidence for Extrarenal Production of 1a,25-Dihydroxyvitamin D in Man

Recent studies provide evidence for extrarenal production of 1a,25-dihydroxyvitamin D [1a,25(OH)2D]. To investigate this possibility, serum vitamin D, 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1a,25(OH)2D were measured in eight adult anephric subjects. All were undergoing hemodialysis and three of them were receiving vitamin D, 50,000 or 100,000 U/d. Serum vitamin D was elevated in two of the patients given vitamin D and was abnormally low in the others. Mean serum 25-OHD was increased in patients given vitamin D (94.0±7.6 ng/ml) and was normal in the others (16.4±0.9 ng/ml, P \u3c 0.001). Mean serum 24,25(OH)2D was normal in patients given vitamin D (1.38±0.27 ng/ml) and was low in the others (0.25±0.08 ng/ml, P \u3c 0.001). Serum 24,25(OH)2D correlated significantly with serum 25-OHD (r = 0.848, P \u3c 0.01). Mean serum 1a,25(OH)2D determined by receptor assay was 5.8±1.9 pg/ml in patients who were not given vitamin D and was 14.1±0.6 in those who were given vitamin D (P \u3c 0.001). Serum 1a,25(OH)2D correlated significantly with serum 25-OHD (r = 0.911, P \u3c 0.01). Mean serum 1a,25(OH)2D, measured by bioassay, was 8.3±1.9 pg/ml in patients who were not given vitamin D and was 15.9±2.4 pg/ml in those who were given vitamin D (P \u3c 0.05). There was a significant correlation between the values for serum 1a,25(OH)2D obtained with the two methods (r = 0.728, P \u3c 0.01). The results (a) provide evidence in man for extrarenal production of both 24,25(OH)2D and, by two independent assays, of 1a,25(OH)2D, and (b) indicate that serum values of the two dihydroxy metabolites of vitamin D in anephric subjects vary with the serum concentration of the precursor 25-OHD

Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines

We have synthesized a series of dimers of (+)-(7R,11R)-huprine Y and evaluated their activity against Trypanosoma brucei, Plasmodium falciparum, rat myoblast L6 cells and human acetylcholinesterase (hAChE), and their brain permeability. Most dimers have more potent and selective trypanocidal activity than huprine Y and are brain permeable, but they are devoid of antimalarial activity and remain active against hAChE. Lead optimization will focus on identifying compounds with a more favourable trypanocidal/anticholinesterase activity ratio

The light skin allele of SLC24A5 in South Asians and Europeans shares identity by descent

Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22–28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus.

COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.post-print2.282 K