Coupled mechanical oscillations were first observed in paired pendulum clocks in the mid-seventeenth century and were extensively studied for their novel sympathetic oscillation dynamics [1, 2]. In this era of nanotechnologies, coupled oscillations have again emerged as subjects of interest when realized in nanomechanical resonators for both practical applications and fundamental studies [3][4][5][6][7][8][9][10][11]. However, a key obstacle to the further development of this architecture is the ability to coherently manipulate the coupled oscillations. This limitation arises as a consequence of the usually weak coupling between the constituent nanomechanical elements. Here, we report parametrically coupled mechanical resonators in which the coupling strength can be dynamically adjusted by modulating (pumping) the stress in the mechanical elements via a piezoelectric transducer. The parametric control enables the coupling rate between the two resonators to be made so strong that it exceeds their intrinsic energy dissipation rate by more than a factor of four. This ultra-strong coupling can be exploited to coherently transfer phonon populations, namely phonon Rabi oscillations [12,13], between the mechanical resonators via two coupled vibration modes, realizing superposition states of the two modes and their time-domain control. More unexpectedly, the nature of the parametric coupling can also be tuned from a linear first-order interaction to a non-linear higher-order process in which more than one pump phonon mediates the coherent oscillations. This demonstration of multipump phonon mixing echoes multi-wave photon mixing [14] and suggests that concepts from nonlinear optics can also be applied to mechanical systems. Ultimately, the parametric pumping is not only useful for controlling classical oscillations [15] but can also be extended to the quantum regime [12,13,[16][17][18], opening up the prospect of entangling two distinct macroscopic mechanical objects [19,20].The dynamic parametric coupling is developed in GaAs-based paired mechanical beams shown in Fig. 1a, in which the piezoelectric effect is exploited to mediate all-electrical displacement transduction [21]. The frequency response of beam 1 measured by harmonically driving it while the parametric pump is deactivated displays two coupled vibration modes (Fig. 1b), where mode 1 (ω 1 = 2π × 293.93 kHz) is dominated by the vibration of beam 1 while mode 2 (ω 2 = 2π × 294.37 kHz) is dominated by the vibration of beam 2. The amplitude of mode 2 is much smaller than that of mode 1 reflecting the energy exchange due to the structural coupling via the overhang is inefficient because of the eigenfrequency difference between the two beams. This difference can be compensated by activating the parametric pump, which is induced by piezoelectrically modulating the spring constant of beam 1 with the pump frequency ω p at around the frequency difference between the two modes, ∆ω ≡ ω 2 − ω 1 (Fig. 1c).The dynamics of this system can then be expressed by the following e...

Background: Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. The mechanisms remain unclear. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure. Methods and results: The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13). Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks. After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses. Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected. Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation. Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR. In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues. The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin. Conclusions: Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes. Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.

No abstract