Dependence on aspect ratio of symmetry breaking for oscillating foils: Implications for flapping flight

Using two-dimensional direct numerical simulations, we investigate the flow in a fluid of kinematic viscosity ${\it\nu}$ and density ${\it\rho}$ around elliptical foils of density ${\it\rho}_{s}$ with major axis $c$ and minor axis $b$ for three different aspect ratios: $AR=b/c=1$ (a circle); $AR=0.5$; and $AR=0.1$. The vertical location of these foils $y_{s}(t)=A\sin (2{\rm\pi}f_{0}t)$ oscillates with amplitude $A$ and frequency $f_{0}$ in two distinct ways: ‘pure’ oscillation, where the foils are constrained to remain in place; and ‘flying’ oscillation, where horizontal motion is allowed. We simulate the flow for a range of the two appropriate control parameters, the non-dimensional amplitude, or Keulegan–Carpenter number $KC=2{\rm\pi}A/c$, and the non-dimensional frequency, or Stokes number ${\it\beta}=f_{0}c^{2}/{\it\nu}$. We observe three distinct patterns of asymmetry, labelled ‘S-type’ for synchronous asymmetry, ‘$\text{QP}_{\text{H}}$-type’ and ‘$\text{QP}_{\text{L}}$-type’ for quasi-periodic asymmetry at sufficiently high and sufficiently low (i.e. $AR=0.1$) aspect ratios, respectively. These patterns are separated at the critical locus in $KC$–${\it\beta}$ space by a ‘freezing point’ where the two incommensurate frequencies of the QP-type flows combine, and we show that this freezing point tends to occur at smaller values of $KC$ as $AR$ decreases. We find for the smallest aspect ratio case ($AR=0.1$) that the transition to asymmetry, for all values of $KC$, occurs for a critical value of an ‘amplitude’ Stokes number ${\it\beta}_{A}={\it\beta}(KC)^{2}=4{\rm\pi}^{2}f_{0}A^{2}/{\it\nu}\simeq 3$. The $\text{QP}_{\text{L}}$-type asymmetry for $AR=0.1$ is qualitatively different in physical and mathematical structure from the $\text{QP}_{\text{H}}$-type asymmetry at higher aspect ratio. The flows at the two ends of the ellipse become essentially decoupled from each other for the $\text{QP}_{\text{L}}$-type asymmetry, the two frequencies in the horizontal force signature being close to the primary frequency, rather than twice the primary frequency as in the $\text{QP}_{\text{H}}$-type asymmetry. Furthermore, the associated coefficients arising from a Floquet stability analysis close to the critical thresholds are profoundly different for low aspect ratio foils. Freedom to move slightly suppresses the transition to S-type asymmetry, and for certain parameters, if a purely oscillating foil subject to S-type asymmetry is released to move, flow symmetry is rapidly recovered due to the negative feedback of small horizontal foil motion. Conversely, for the ‘higher’ aspect ratios, the transition to $\text{QP}_{\text{H}}$-type asymmetry is encouraged when the foil is allowed to move, with strong positive feedback occurring between the shed vortices from successive oscillation cycles. For $AR=0.1$, freedom to move significantly encourages the onset of asymmetry, but the newly observed ‘primary’ $\text{QP}_{\text{L}}$-type asymmetry found for pure oscillation no longer occurs when the foil flies, with S-type asymmetry leading ultimately to locomotion at a constant speed occurring all along the transition boundary for all values of $KC$ and ${\it\beta}$.This is the author accepted manuscript. The final version is available from Cambridge University Press via http://dx.doi.org/10.1017/jfm.2015.66

Instabilities of interacting vortex rings generated by an oscillating disk.

We propose a natural model to probe in a controlled fashion the instability of interacting vortex rings shed from the edge of an oblate spheroid disk of major diameter c, undergoing oscillations of frequency f_{0} and amplitude A. We perform a Floquet stability analysis to determine the characteristics of the instability modes, which depend strongly on the azimuthal (integer) wave number m. We vary two key control parameters, the Keulegan-Carpenter number K_{C}=2πA/c and the Stokes number β=f_{0}c^{2}/ν, where ν is the kinematic viscosity of the fluid. We observe two distinct flow regimes. First, for sufficiently small β, and hence low frequency of oscillation corresponding to relatively weak interaction between sequentially shedding vortex rings, symmetry breaking occurs directly to a single unstable mode with m=1. Second, for sufficiently large yet fixed values of β, corresponding to a higher oscillation frequency and hence stronger ring-ring interaction, the onset of asymmetry is predicted to occur due to two branches of high m instabilities as the amplitude is increased, with m=1 structures being dominant only for sufficiently large values of K_{C}. These two branches can be distinguished by the phase properties of the vortical structures above and below the disk. The region in (K_{C},β) parameter space where these two high m instability branches arise can be described accurately in terms of naturally defined Reynolds numbers, using appropriately chosen characteristic length scales. We subsequently carry out direct numerical simulations of the fully three-dimensional flow to verify the principal characteristics of the Floquet analysis, in particular demonstrating that high wave-number symmetry-breaking generically occurs when vortex rings sequentially interact sufficiently strongly.This research is supported by the National Natural Science Foundation of China (Grant No. 11272283) and the Public Projects of Zhejiang Province (Grant No. 2015C31126).This is the author accepted manuscript. The final version is available from the American Physical Society via http://dx.doi.org/10.1103/PhysRevE.94.03310

Ubiquitination and proteosome-dependent degradation of the activated form of human liver-enriched transcription factor CREB-H regulated by protein kinase A

Poster Presentation - Theme 1: Cell biologyCREB-H is a membrane-bound bZIP transcription factor which is mainly expressed in liver and small intestine. CREB-H plays important roles in the regulation of lipid metabolism, iron metabolism, gluconeogenesis and acute phase response. CREB-H is proteolytically activated by regulated intramembrane proteolysis to generate a C-terminal truncated form known as ...postprin

β-TrCP-mediated ubiquitination and degradation of liver-enriched transcription factor CREB-H

CREB-H is an endoplasmic reticulum-resident bZIP transcription factor which critically regulates lipid homeostasis and gluconeogenesis in the liver. CREB-H is proteolytically activated by regulated intramembrane proteolysis to generate a C-terminally truncated form known as CREB-H-ΔTC, which translocates to the nucleus to activate target gene expression. CREB-H-ΔTC is a fast turnover protein but the mechanism governing its destruction was not well understood. In this study, we report on β-TrCP-dependent ubiquitination and proteasomal degradation of CREB-H-ΔTC. The degradation of CREB-H-ΔTC was mediated by lysine 48-linked polyubiquitination and could be inhibited by proteasome inhibitor. CREB-H-ΔTC physically interacted with β-TrCP, a substrate recognition subunit of the SCFβ-TrCP E3 ubiquitin ligase. Forced expression of β-TrCP increased the polyubiquitination and decreased the stability of CREB-H-ΔTC, whereas knockdown of β-TrCP had the opposite effect. An evolutionarily conserved sequence, SDSGIS, was identified in CREB-H-ΔTC, which functioned as the β-TrCP-binding motif. CREB-H-ΔTC lacking this motif was stabilized and resistant to β-TrCP-induced polyubiquitination. This motif was a phosphodegron and its phosphorylation was required for β-TrCP recognition. Furthermore, two inhibitory phosphorylation sites close to the phosphodegron were identified. Taken together, our work revealed a new intracellular signaling pathway that controls ubiquitination and degradation of the active form of CREB-H transcription factor.published_or_final_versio

Combination of angiotensin converting enzyme inhibitor and irbesartan for the treatment of heart failure

published_or_final_versio

Demagnetization of Quantum Dot Nuclear Spins: Breakdown of the Nuclear Spin Temperature Approach

The physics of interacting nuclear spins arranged in a crystalline lattice is typically described using a thermodynamic framework: a variety of experimental studies in bulk solid-state systems have proven the concept of a spin temperature to be not only correct but also vital for the understanding of experimental observations. Using demagnetization experiments we demonstrate that the mesoscopic nuclear spin ensemble of a quantum dot (QD) can in general not be described by a spin temperature. We associate the observed deviations from a thermal spin state with the presence of strong quadrupolar interactions within the QD that cause significant anharmonicity in the spectrum of the nuclear spins. Strain-induced, inhomogeneous quadrupolar shifts also lead to a complete suppression of angular momentum exchange between the nuclear spin ensemble and its environment, resulting in nuclear spin relaxation times exceeding an hour. Remarkably, the position dependent axes of quadrupolar interactions render magnetic field sweeps inherently non-adiabatic, thereby causing an irreversible loss of nuclear spin polarization.Comment: 15 pages, 3 figure

Modulation of human cardiac transient outward potassium current by EGFR tyrosine kinase and Src-family kinases

Aims: The human cardiac transient outward K + current Ito (encoded by Kv4.3 or KCND3) plays an important role in phase 1 rapid repolarization of cardiac action potentials in the heart. However, modulation of I to by intracellular signal transduction is not fully understood. The present study was therefore designed to determine whether/how human atrial I to and hKv4.3 channels stably expressed in HEK 293 cells are regulated by protein tyrosine kinases (PTKs). Methods and results: Whole-cell patch voltage-clamp, immunoprecipitation, western blotting, and site-directed mutagenesis approaches were employed in the present study. We found that human atrial I to was inhibited by the broad-spectrum PTK inhibitor genistein, the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556, and the Src-family kinases inhibitor PP2. The inhibitory effect was countered by the protein tyrosine phosphatase inhibitor orthovanadate. In HEK 293 cells stably expressing human KCND3, genistein, AG556, and PP2 significantly reduced the hKv4.3 current, and the reduction was antagonized by orthovanadate. Interestingly, orthovanadate also reversed the reduced tyrosine phosphorylation level of hKv4.3 channels by genistein, AG556, or PP2. Mutagenesis revealed that the hKv4.3 mutant Y136F lost the inhibitory response to AG556, while Y108F lost response to PP2. The double-mutant Y108FY136F hKv4.3 channels showed no response to either AG556 or PP2. Conclusion: Our results demonstrate that human atrial Ito and cloned hKv4.3 channels are modulated by EGFR kinase via phosphorylation of the Y136 residue and by Src-family kinases via phosphorylation of the Y108 residue; tyrosine phosphorylation of the channel may be involved in regulating cardiac electrophysiology. © The Author 2011.postprin

Requirement of CRTC1 coactivator for hepatitis B virus transcription

Transcription of hepatitis B virus (HBV) from the covalently closed circular DNA (cccDNA) template is essential for its replication. Suppressing the level and transcriptional activity of cccDNA might have anti-HBV effect. Although cellular transcription factors, such as CREB, which mediate HBV transcription, have been well described, transcriptional coactivators that facilitate this process are incompletely understood. In this study we showed that CREB-regulated transcriptional coactivator 1 (CRTC1) is required for HBV transcription and replication. The steady-state levels of CRTC1 protein were elevated in HBV-positive hepatoma cells and liver tissues. Ectopic expression of CRTC1 or its homolog CRTC2 or CRTC3 in hepatoma cells stimulated the activity of the preS2/S promoter of HBV, whereas overexpression of a dominant inactive form of CRTC1 inhibited HBV transcription. CRTC1 interacts with CREB and they are mutually required for the recruitment to the preS2/S promoter on cccDNA and for the activation of HBV transcription. Accumulation of pregenomic RNA (pgRNA) and cccDNA was observed when CRTC1 or its homologs were overexpressed, whereas the levels of pgRNA, cccDNA and secreted HBsAg were diminished when CRTC1 was compromised. In addition, HBV transactivator protein HBx stabilized CRTC1 and promoted its activity on HBV transcription. Our work reveals an essential role of CRTC1 coactivator in facilitating and supporting HBV transcription and replication.published_or_final_versio

Horizontal locomotion of a vertically flapping oblate spheroid

We consider the self-induced motions of three-dimensional oblate spheroids of density \unicode[STIX]{x1D70C}_{s} with varying aspect ratios $AR=b/c\leqslant 1$, where $b$ and $c$ are the spheroids’ centre-pole radius and centre-equator radius, respectively. Vertical motion is imposed on the spheroids such that y_{s}(t)=A\sin (2\unicode[STIX]{x03C0}ft) in a fluid of density \unicode[STIX]{x1D70C} and kinematic viscosity \unicode[STIX]{x1D708}. As in strictly two-dimensional flows, above a critical value $Re_{C}$ of the flapping Reynolds number Re_{A}=2Afc/\unicode[STIX]{x1D708}, the spheroid ultimately propels itself horizontally as a result of fluid–body interactions. For $Re_{A}$ sufficiently above $Re_{C}$, the spheroid rapidly settles into a terminal state of constant, unidirectional velocity, consistent with the prediction of Deng et al. (Phys. Rev. E, vol. 94, 2016, 033107) that, at sufficiently high $Re_{A}$, such oscillating spheroids manifest $m=1$ asymmetric flow, with characteristic vortical structures conducive to providing unidirectional thrust if the spheroid is free to move horizontally. The speed $U$ of propagation increases linearly with the flapping frequency, resulting in a constant Strouhal number $St(AR)=2Af/U$, characterising the locomotive performance of the oblate spheroid, somewhat larger than the equivalent $St$ for two-dimensional spheroids, demonstrating that the three-dimensional flow is less efficient at driving locomotion. $St$ decreases with increasing aspect ratio for both two-dimensional and three-dimensional flows, although the relative disparity (and hence relative inefficiency of three-dimensional motion) decreases. For flows with $Re_{A}\gtrsim Re_{C}$, we observe two distinct types of inherently three-dimensional motion for different aspect ratios. The first, associated with a disk of aspect ratio $AR=0.1$ at $Re_{A}=45$, consists of a ‘stair-step’ trajectory. This trajectory can be understood through consideration of relatively high azimuthal wavenumber instabilities of interacting vortex rings, characterised by in-phase vortical structures above and below an oscillating spheroid, recently calculated using Floquet analysis by Deng et al. (Phys. Rev. E, vol. 94, 2016, 033107). Such ‘in-phase’ instabilities arise in a relatively narrow band of $Re_{A}\gtrsim Re_{C}$, which band shifts to higher Reynolds number as the aspect ratio increases. (Indeed, for horizontally fixed spheroids with aspect ratio $AR=0.2$, Floquet analysis actually predicts stability at $Re_{A}=45$.) For such a spheroid ($AR=0.2$, $Re_{A}=45$, with sufficiently small mass ratio m_{s}/m_{f}=\unicode[STIX]{x1D70C}_{s}V_{s}/(\unicode[STIX]{x1D70C}V_{s}), where $V_{s}$ is the volume of the spheroid) which is free to move horizontally, the second type of three-dimensional motion is observed, initially taking the form of a ‘snaking’ trajectory with long quasi-periodic sweeping oscillations before locking into an approximately elliptical ‘orbit’, apparently manifesting a three-dimensional generalisation of the $QP_{H}$ quasi-periodic symmetry breaking discussed for sufficiently high aspect ratio two-dimensional elliptical foils in Deng &amp; Caulfield (J. Fluid Mech., vol. 787, 2016, pp. 16–49).</jats:p

The finite-temperature chiral transition in QCD with adjoint fermions

We study the nature of the finite-temperature chiral transition in QCD with N_f light quarks in the adjoint representation (aQCD). Renormalization-group arguments show that the transition can be continuous if a stable fixed point exists in the renormalization-group flow of the corresponding three-dimensional Phi^4 theory with a complex 2N_f x 2N_f symmetric matrix field and symmetry-breaking pattern SU(2N_f)->SO(2N_f). This issue is investigated by exploiting two three-dimensional perturbative approaches, the massless minimal-subtraction scheme without epsilon expansion and a massive scheme in which correlation functions are renormalized at zero momentum. We compute the renormalization-group functions in the two schemes to five and six loops respectively, and determine their large-order behavior. The analyses of the series show the presence of a stable three-dimensional fixed point characterized by the symmetry-breaking pattern SU(4)->SO(4). This fixed point does not appear in an epsilon-expansion analysis and therefore does not exist close to four dimensions. The finite-temperature chiral transition in two-flavor aQCD can therefore be continuous; in this case its critical behavior is determined by this new SU(4)/SO(4) universality class. One-flavor aQCD may show a more complex phase diagram with two phase transitions. One of them, if continuous, should belong to the O(3) vector universality class.Comment: 36 page