Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations.

The capsaicin receptor transient receptor potential vanilloid (TRPV)1 is a highly heat-sensitive ion channel. Although chemical activation and heat activation of TRPV1 elicit similar pungent, painful sensation, the molecular mechanism underlying synergistic activation remains mysterious. In particular, where the temperature sensor is located and whether heat and capsaicin share a common activation pathway are debated. To address these fundamental issues, we searched for channel mutations that selectively affected one form of activation. We found that deletion of the first 10 amino acids of the pore turret significantly reduced the heat response amplitude and shifted the heat activation threshold, whereas capsaicin activation remained unchanged. Removing larger portions of the turret disrupted channel function. Introducing an artificial sequence to replace the deleted region restored sensitive capsaicin activation in these nonfunctional channels. The heat activation, however, remained significantly impaired, with the current exhibiting diminishing heat sensitivity to a level indistinguishable from that of a voltage-gated potassium channel, Kv7.4. Our results demonstrate that heat and capsaicin activation of TRPV1 are structurally and mechanistically distinct processes, and the pore turret is an indispensible channel structure involved in the heat activation process but is not part of the capsaicin activation pathway. Synergistic effect of heat and capsaicin on TRPV1 activation may originate from convergence of the two pathways on a common activation gate

Drag reduction of ship airflow using steady Coanda effect

This paper studies the steady Coanda effect for reducing the aerodynamic drag of the Chalmers ship model (CSM) using Large Eddy Simulation (LES) with Wall-Adapting Local-Eddy Viscosity (WALE) model. The flow control mechanism is explored, and the analysis of energy efficiency is conducted to evaluate the net benefit of the flow control. Validating the numerical methods, the predicted aerodynamic drag of the ship and pressure coefficients distribution on the baseline CSM agree well with the experimental measurements and the maximum discrepancy is 4.2%. In creating the flow control models, the hanger base of the baseline CSM is modified with a Coanda surface and two different sizes of jet-blowing slots, 1%h (hanger height) and 2%h, respectively. A drag reduction of 5.34% is achieved by the 1%h slot-size case. The 2%h slot-size case further increases the drag reduction to 6.22% but has doubled power consumption. It is found that vectoring vorticity towards the low-speed area on deck is effective for enhancing the energization. Finally, the analysis of energy efficiency indicates that the net benefit is achieved in both flow control cases, and the case with the 1%h slot size is 11.9% more efficient due to a stronger Coanda effect

Large eddy simulation of ship airflow control with steady Coanda effect

This paper numerically studies the steady Coanda effect for drag reduction and airwake manipulations on the Chalmers ship model (CSM) using large eddy simulation with wall-adapting local-eddy viscosity model. Numerical methods are validated by experimental data acquired from the baseline CSM. In creating the flow control model, the hanger base of the baseline CSM is modified with Coanda surfaces and injection slots along its roof edge and two side edges. Four representative cases are studied: a no-jet case and three cases with the same momentum coefficient of the jet flow activated at different locations (roof, sides, and combined). The results show that the four cases have various performances in drag reduction and vortex structures on the deck. They are also different in mean and turbulent quantities as well as POD (proper orthogonal decomposition) modes in their airwake. It is found that the roof-jet has a stronger Coanda effect and is more vectored toward the low-speed area (LSA) on the deck than the side-jets that detach earlier from the Coanda surface. The energization process is, therefore, different where the roof-jet is more effective that directly brings high momentum to LSA and side-jets manipulate shear layers for mixing enhancement. The cases with roof-jet achieve better mitigation of flow re-circulation and higher recovery of streamwise velocity with lower turbulent fluctuation in the airwake. POD analysis suggests that the roof-jet can stabilize the wake

LookinGood^{\pi}: Real-time Person-independent Neural Re-rendering for High-quality Human Performance Capture

We propose LookinGood^{\pi}, a novel neural re-rendering approach that is aimed to (1) improve the rendering quality of the low-quality reconstructed results from human performance capture system in real-time; (2) improve the generalization ability of the neural rendering network on unseen people. Our key idea is to utilize the rendered image of reconstructed geometry as the guidance to assist the prediction of person-specific details from few reference images, thus enhancing the re-rendered result. In light of this, we design a two-branch network. A coarse branch is designed to fix some artifacts (i.e. holes, noise) and obtain a coarse version of the rendered input, while a detail branch is designed to predict "correct" details from the warped references. The guidance of the rendered image is realized by blending features from two branches effectively in the training of the detail branch, which improves both the warping accuracy and the details' fidelity. We demonstrate that our method outperforms state-of-the-art methods at producing high-fidelity images on unseen people

Comparison of flow characteristics behind squareback bluff-bodies with and without wheels

The wake dynamics of two referenced variations of the squareback Windsor model with and without wheels is numerically studied by performing improved delayed detached eddy simulation. Numerical assessments are validated against publicly available experimental data. The focus of this study is on the wake states influenced by the wheels and the thick oncoming floor boundary layer. Results show that the addition of the wheels significantly changes the aerodynamic forces, the underbody flow, and the wake topology. The wake bi-stability is also enhanced with wheels in place due to the increased curvature of lateral shear layers in the near wake. However, the bi-stable behavior is largely suppressed when immersed in a thick boundary layer. These alterations depend on the degree of interaction between the wake recirculation and the bottom flow, and such degree is strongly affected by the underbody flow momentum. The evolution of low-order flow organizations and complementary spectral analysis highlight the differences in the coherent dynamics of the wake. The finding of this present work suggests that the wake bi-stability behind the squareback body can exist not only for a simplified geometry but also for a more realistic car with wheels in real-world upstream conditions

Divalent cations activate TRPV1 through promoting conformational change of the extracellular region

Divalent cations Mg and Ba selectively and directly potentiate transient receptor potential vanilloid type 1 heat activation by lowering the activation threshold into the room temperature range. We found that Mg potentiates channel activation only from the extracellular side; on the intracellular side, Mg inhibits channel current. By dividing the extracellularly accessible region of the channel protein into small segments and perturbing the structure of each segment with sequence replacement mutations, we observed that the S1-S2 linker, the S3-S4 linker, and the pore turret are all required for Mg potentiation. Sequence replacements at these regions substantially reduced or eliminated Mg-induced activation at room temperature while sparing capsaicin activation. Heat activation was affected by many, but not all, of these structural alternations. These observations indicate that extracellular linkers and the turret may interact with each other. Site-directed fluorescence resonance energy transfer measurements further revealed that, like heat, Mg also induces structural changes in the pore turret. Interestingly, turret movement induced by Mg precedes channel activation, suggesting that Mg-induced conformational change in the extracellular region most likely serves as the cause of channel activation instead of a coincidental or accommodating structural adjustment

The effectiveness of Interpersonal Psychotherapy-Adolescent Skills Training for adolescents with depression: a systematic review and meta-analysis

BackgroundInterpersonal Psychotherapy-Adolescent Skills Training (IPT-AST) is a standardized depression prevention program for adolescents conducted in campus settings. The purpose of this review is to examine the randomized controlled trials of IPT-AST for the prevention of adolescent depression in the past 20 years.MethodsA systematic search of relevant electronic databases (PubMed, WOS, Embase, PsycINFO, the Cochrane Library, CNKI and WANFANG DATA) and study reference lists was conducted. Any study investigating the effectiveness of IPT-AST in 12- to 20-year-olds with depressive symptoms was eligible. Synthesis was via narrative summary and meta-analysis.ResultsA total of 6 studies met the inclusion criteria. Meta-analysis results showed a remarkable improvement in patients’ depressive symptoms after IPT-AST intervention (WMD = −5.05, 95% CI = −8.11 to −1.98, p < 0.05, I2 = 77%). Six month follow-up data showed that the intervention outcomes of IPT-AST remained significant (WMD = −3.09, 95% CI: −5.23 to −0.94, p < 0.05, I2 = 57%).ConclusionThis meta-analysis showed that IPT-AST was effective in adolescents with depressive symptoms at post-prevention and at 6-month follow-up. However, these conclusions are cautious, as they are based on a small number of studies and the presence of author duplication. Future studies should use multi-center, large-sample randomized controlled trials to evaluate the efficacy of IPT-AST for preventing depression in adolescents.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023393047