Assessment of the sea surface temperature diurnal cycle in CNRM-CM6-1 based on its 1D coupled configuration

A single column version of the CNRM-CM6-1 global climate model has been developed to ease development and validation of the boundary layer physics and air-sea coupling in a simplified environment. This framework is then used to assess the ability of the coupled model to represent the sea surface temperature (SST) diurnal cycle. To this aim, the atmospheric-ocean single column model (AOSCM), called CNRM-CM6-1D, is implemented on a case study derived from the Cindy-Dynamo field campaign over the Indian Ocean, where large diurnal SST variabilities have been well documented. Comparing the AOSCM and its uncoupled components (atmospheric SCM and oceanic SCM, called OSCM) highlights that the impact of coupling in the atmosphere results both from the possibility to take in to account the diurnal variability of SST, not usually available in forcing products, and from the change in mean state SST as simulated by the OSCM, the ocean mean state not being heavily impacted by the coupling. This suggests that coupling feedbacks are more due to advection processes in the 3D model than to the model physics. Additionally, a sub-daily coupling frequency is needed to represent the SST diurnal variability but the choice of the coupling time-step between 15 min and 3 h does not impact much on the diurnal temperature range simulated. The main drawback of a 3-h coupling being to delay the SST diurnal cycle by 5 h in asynchronous coupled models. Overall, the diurnal SST variability is reasonably well represented in the CNRM-CM6-1 with a 1 h coupling time-step and the upper ocean model resolution of 1 m. This framework is shown to be a very valuable tool to develop and validate the boundary layer physics and the coupling interface. It highlights the interest to develop other atmosphere-ocean coupling case studies.

Effective reduction of magnetisation losses in copper-plated multifilament coated conductors using spiral geometry

We wound copper-plated multifilament coated conductors spirally on a round core to decouple filaments electromagnetically under ac transverse magnetic fields and measured their magnetisation losses. Although the coated conductors were plated with copper, which connects all filaments electrically and allows current sharing among them, the spiral geometry decoupled filaments similar to the twist geometry, and the magnetisation loss was reduced effectively by the multifilament structure. The measured magnetisation loss of a 4 mm-wide, 10-filament coated conductor with a 20 μm-thick copper wound spirally on a 3 mm-core was only 7% of that of the same 10-filament coated conductor with a straight shape under an ac transverse magnetic field with an amplitude and frequency of 100 mT and 65.44 Hz, respectively. We separated the measured magnetisation losses into hysteresis and coupling losses and discussed the influence of filament width, copper thickness, and core diameter on both losses. We compared the hysteresis losses with the analytical values given by Brandt and Indenbom and compared the coupling losses with the values calculated using a general expression of coupling loss with the coupling time constants and geometry factors.

The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity

Cyclophosphamide (CYP)-induced cardiotoxicity is a common side effect of cancer treatment. Although it has received significant attention, the related mechanisms of CYP-induced cardiotoxicity remain largely unknown. In this study, we used cell and animal models to investigate the effect of CYP on cardiomyocytes. Our data demonstrated that CYP-induced a prolonged cardiac QT interval and electromechanical coupling time courses accompanied by JPH2 downregulation. Moreover, N6-methyladenosine (m6A) methylation sequencing and RNA sequencing suggested that CYP induced cardiotoxicity by dysregulating calcium signaling. Importantly, our results demonstrated that CYP induced an increase in the m6A level of JPH2 mRNA by upregulating methyltransferases METTL3, leading to the reduction of JPH2 expression levels, as well as increased field potential duration and action potential duration in cardiomyocytes. Our results revealed a novel mechanism for m6A methylation-dependent regulation of JPH2, which provides new strategies for the treatment and prevention of CYP-induced cardiotoxicity.

Stochastic comparison of synchronization in activator- and repressor-based coupled gene oscillators

Inside living cells, proteins or mRNA can show oscillations even without a periodic driving force. Such genetic oscillations are precise timekeepers for cell-cycle regulations, pattern formation during embryonic development in higher animals, and daily cycle maintenance in most organisms. The synchronization between oscillations in adjacent cells happens via intercellular coupling, which is essential for periodic segmentation formation in vertebrates and other biological processes. While molecular mechanisms of generating sustained oscillations are quite well understood, how do simple intercellular coupling produces robust synchronizations are still poorly understood? To address this question, we investigate two models of coupled gene oscillators - activator-based coupled oscillators (ACO) and repressor-based coupled oscillators (RCO) models. In our study, a single autonomous oscillator (that operates in a single cell) is based on a negative feedback, which is delayed by intracellular dynamics of an intermediate species. For the ACO model (RCO), the repressor protein of one cell activates (represses) the production of another protein in the neighbouring cell after a intercellular time delay. We investigate the coupled models in the presence of intrinsic noise due to the inherent stochasticity of the biochemical reactions. We analyze the collective oscillations from stochastic trajectories in the presence and absence of explicit coupling delay and make careful comparison between two models. Our results show no clear synchronizations in the ACO model when the coupling time delay is zero. However, a non-zero coupling delay can lead to anti-phase synchronizations in ACO. Interestingly, the RCO model shows robust in-phase synchronizations in the presence and absence of the coupling time delay. Our results suggest that the naturally occurring intercellular couplings might be based on repression rather than activation where in-phase synchronization is crucial.