Direct Mechanical Coupling Research Articles

Structural basis of mRNA decay by the human exosome-ribosome supercomplex.

The interplay between translation and mRNA decay is widespread in human cells1-3. In quality-control pathways, exonucleolytic degradation of mRNA associated with translating ribosomes is mediated largelyby the cytoplasmic exosome4-9, which includes the exoribonuclease complex EXO10 and the helicase complex SKI238 (refs. 10-16). The helicase can extract mRNA from the ribosome and is expected to transfer it to the exoribonuclease core through a bridging factor, HBS1L3 (also known as SKI7), but the mechanisms of this molecular handover remain unclear7,17,18. Here we reveal how human EXO10 is recruited by HBS1L3 (SKI7) to an active ribosome-bound SKI238 complex. We show that rather than a sequential handover, a direct physical coupling mechanism takes place, which culminates in the formation of a cytoplasmic exosome-ribosome supercomplex. Capturing the structure during active decay reveals a continuous path in which an RNA substrate threads from the 80S ribosome through the SKI2 helicase into the exoribonuclease active site of the cytoplasmic exosome complex. The SKI3 subunit of the complex directly binds to HBS1L3 (SKI7) and also engages a surface of the 40S subunit, establishing a recognition platform in collided disomes. Exosome and ribosome thus work together as a single structural and functional unit in co-translational mRNA decay, coordinating their activities in a transient supercomplex.

Biomimetic Synchronization in Biciliated Robots.

Direct mechanical coupling is known to be critical for establishing synchronization among cilia. However, the actual role of the connections is still elusive-partly because controlled experiments in living samples are challenging. Here, we employ an artificial ciliary system to address this issue. Two cilia are formed by chains of self-propelling robots and anchored to a shared base so that they are purely mechanically coupled. The system mimics biological ciliary beating but allows fine control over the beating dynamics. With different schemes of mechanical coupling, artificial cilia exhibit rich motility patterns. Particularly, their synchronous beating display two distinct modes-analogous to those observed in C. reinhardtii, the biciliated model organism for studying synchronization. Close examination suggests that the system evolves towards the most dissipative mode. Using this guideline in both simulations and experiments, we are able to direct the system into a desired state by altering the modes' respective dissipation. Our results have significant implications in understanding the synchronization of cilia.

Magnetic Force Dilatometry for Operando Coin Cell Electrochemical Dilation Measurements

Operando characterization of the physical and chemical changes occurring within batteries during electrochemical cycling has become a powerful tool for next generation technology development. In particular, a better understanding of the expansion (dilation) behavior of active materials during charge/discharge is critical for mitigating performance degradation, particularly for high expansion materials like Li or Si. However, current dilatometry devices rely on direct mechanical coupling or line-of-sight measurements with pouch- or custom-cells, which prohibits their use in the most common and accessible research battery format: coin cells. To this end, we propose a novel magnetic force dilatometry (MFD) technique for operando electrochemical dilation measurements. Our custom low-cost dilatometer utilizes magnetic force sensing for contactless expansion measurements via facile replacement of the austenitic spacer with a ferritic spacer within a coin cell. To validate this setup, we demonstrate operando electrochemical dilatometry of a LiNi0.6Mn0.2Co0.2O2 (NMC622) || Li metal full cell in a CR2032 format. Our MFD accurately captures cell expansion/contraction with sensitivities of less than 0.1 μm, and reliability for over hundreds of hours and cycles. This new MFD method is expected to increase the accessibility of electrochemical dilatometry by eliminating the need for pouch cells or other specialized cell expansion measurement configurations.

Gas-particle-heat dynamic coupling simulation in directed energy deposition

Powder flow can affect the temperature variations in directed energy deposition (DED). However, the direct coupling mechanism remains unknown. To solve this problem, the heat and mass transfer in additive manufacturing was simulated using dynamic coupling. The interactions between the multiphase flow and heat transfer were established. A comparison with experiment shows that the accuracy of the predictions of the numerical simulation regarding powder size distributions and temperature increases is higher than 95 %. The average temperature increase of the metal powders with different weight functions was highly consistent in the simulation process. As the powder size increases, the average temperature of the powder on the printing plane decreases. This was the reason for the formation of a deeper melt pool in the case of smaller particles in the experiment. The different curvatures between the particle surface and melt pool surface lead to a decreased energy absorption efficiency in DED. The relationship between the powder features and the melt pool size was studied. A decrease in the powder flow rate increased the temperature, leading to a larger melt depth.

Abstract 16610: A New Left Ventricle Vortex Formation Time for Clinical Assessment of Diastolic Filling Efficiency Based on Direct Mechanical Ventricular-Vascular Coupling: Evaluation in Heart-Failure and Healthy Cohort

Introduction: The mechanical coupling of the left ventricle (LV) and aorta creates the apical motion of the atrioventricular plane (AVP), resembling a piston-cylinder system, impacting early diastolic filling (J Am Heart Assoc. 2017;6:e004903). Furthermore, several clinical studies have suggested the vortex formation time (VFT) as an indicator of LV diastolic function (Eur. Heart J. Cardiovasc. Imaging. 2012;13(5):385-93). However, conflicting results exist in previous clinical studies, potentially due to deviations from the original fluid dynamics definition of VFT in a piston-in-cylinder setting. In this study, we propose a new VFT approach to assess LV diastolic filling performance based on direct mechanical ventricular-vascular coupling. Methods: Cardiac MRI was used on 69 healthy individuals and 19 heart failure (HF) patients. The clinical cohort (37% women) had a mean age of 46 [± 17.5] years and BMI of 24.8 [±4.5]. LV valvular diseases were excluded. VFT was assessed using the original L/D definition, where L represents ascending aortic recoil motion (piston displacement) and D represents the mitral valve orifice. Aortic displacement was measured on the three and four-chamber MRI scans by tracing the AVP. Mitral valve orifice was determined as the average of commissure distance (short-axis images) and the leaflet tip distance (three-chamber view). Results: The new VFT approach yielded a mean[± std.] of 4.73[±0.89] for the healthy group, and considerably lower values (3.24±0.83) for the patients with HF (figure 1). Conclusions: The proposed VFT based on the mechanical ventricular-vascular coupling and original fluid dynamic formulation, demonstrates a theoretical optimal value of approximately 4 in healthy individuals, while significantly lower in HF. This novel VFT has the potential to address existing discrepancies regarding the clinical significance of VFT and establish it as a promising indicator of left ventricular filling efficiency.

Insight into the Mechanism for Catalytic Activity of the Oxygen/Hydrogen Evolution Reaction on a Dual-Site Catalyst

The dual-site catalysts consisting of two adjacent single-atom sites on graphene have exhibited promising catalytic activity of the electrochemical oxygen/hydrogen evolution reaction (OER/HER). However, the electrochemical mechanisms of the OER/HER on dual-site catalysts have still been ambiguous. In this work, we employed density functional theory calculations to study the catalytic activity of the OER/HER with a O-O (H-H) direct coupling mechanism on dual-site catalysts. Specifically, these element steps should be classified into two categories: a step evolving proton-coupled electron transfer (PCET step) that needs to be driven by electrode potential and a step without PCET (non-PCET step) that occurs naturally under mild conditions. Our calculated results show that both the maximal free energy change (ΔGMax) contributed by the PCET step and the activity barrier (Ea) of the non-PCET step must be examined to evaluate the catalytic activity of the OER/HER on the dual site. Importantly, it is a basically inevitable negative relationship between ΔGMax and Ea, which would play a critical role in guiding the rational design of effective dual-site catalysts for electrochemical reactions.

Theory of radial oscillations in metal nanoparticles driven by optically induced electron density gradients.

We provide a microscopic approach to describe the onset of radial oscillation of a silver nanoparticle. Using the Heisenberg equation of motion framework, we find that the coupled ultrafast dynamics of coherently excited electron occupation and the coherent phonon amplitude initiate periodic size oscillations of the nanoparticle. Compared to the established interpretation of experiments, our results show a more direct coupling mechanism between the field intensity and coherent phonons. This interaction triggers a size oscillation via an optically induced electron density gradient occurring directly with the optical excitation. This source is more efficient than the incoherent heating process currently discussed in the literature and well-describes the early onset of the oscillations in recent experiments.

Reduction of Nitric Oxide to Nitrous Oxide in Flavodiiron Proteins: Catalytic Mechanism and Plausible Intermediates

The flavin dependent nonheme diiron proteins comprise a family of enzymes, which can act as scavengers for both molecular oxygen and nitric oxide. The reduction of nitric oxide to nitrous oxide and water in flavodiiron proteins (FDPs) has been studied both experimentally and computationally, but the reaction mechanism is far from well understood. From experiments, it is known that two NO molecules can bind to the reduced active site, forming an observable diferrous dinitrosyl complex. A main question has been whether nitrous oxide can be formed directly from the diferrous dinitrosyl complex or if further reduction and/or protonation is needed to make this step feasible. Experiments have shown that nitrous oxide can be formed in a deflavinated form of the enzyme, indicating that further reduction is not needed. In the present study, hybrid density functional theory calculations are performed on a cluster model of the Thermotoga maritima FDP active site. We show that nitric oxide can be reduced to nitrous oxide and water using a direct coupling mechanism, i.e., without further additions to the reduced active site. The diferrous dinitrosyl complex can form an unstable N–N bridging hyponitrite intermediate, which can rotate into an N–O bond bridging hyponitrite with a low barrier. From this intermediate, the N–O bond cleavage leading to release of nitrous oxide is energetically feasible. An energy profile for the entire catalytic cycle of such a direct coupling mechanism is presented, and it is shown that the suggested mechanism agrees with data on FDP variants. Finally, an energy profile for the entire process starting with the fully reduced enzyme turning over four NO equivalents is constructed. This energy profile suggests explanations to experimentally observed states, such as the dihydroxyl form of the fully oxidized diferric state, and the difference with respect to returning to the original oxidized state after NO reduction between the flavinated and the deflavinated form of the enzyme.

Abstract 959: Non-junctional connexin43 complexing with microtubules promotes epithelial-mesenchymal transition

Abstract Epithelial-mesenchymal transition (EMT) is a normal process of embryonic development, stem cell differentiation, and wound healing. During EMT, epithelial cells lose apical-basal polarity, remodel intercellular junctions, and acquire migratory and invasive abilities as they become mesenchymal. Pathologically, EMT has been demonstrated to contribute to intravasation of metastatic tumor cells into the vasculature. Among the activators of EMT, TGF-β has been shown to be most prevalent and is sufficient for experimental induction of EMT. Gap junctions, comprising connexin proteins, allow direct mechanical and metabolic coupling between adjacent cells, and represent a major intercellular structure altered during EMT. Connexin43 (Cx43) is a gap junction protein that has been implicated as both a tumor suppressor and enhancer depending on cancer stage. Our previous work revealed that despite losses in Cx43 gap junctions during EMT, mRNA and cytosolic levels of Cx43 protein increased. Such a shift of Cx43 to cytoplasmic pools has previously been observed in cancer progression and research suggests that non-junctional Cx43 can regulate the cytoskeleton, including microtubule stability. The C-terminus of Cx43 encompasses a tubulin binding domain which, while implicated in Cx43 trafficking, remains functionally poorly understood. We have identified a tumorigenic role for non-junctional Cx43 through its interaction with microtubules in glioma cancer stem cells. This led us to hypothesize that increased cytosolic Cx43 during EMT promotes Cx43-microtubule interaction to facilitate mobility and invasion of metastatic cancer cells. Using several independent TGF-β-induced EMT models, we observe increased complexing of Cx43 and microtubules during EMT by super-resolution microscopy. To study the role of Cx43 interaction with microtubules during EMT, we generated Cx43 harboring mutations in the tubulin binding domain which were ectopically expressed by adenoviral transduction in Cx43 knockout CRISPR/Cas9 epithelial cells. We find these Cx43 mutants fail to interact with microtubules compared to wild-type Cx43. Turning to TGF-β-induced EMT, ablation of the Cx43/microtubules interaction with these mutants is sufficient to decrease expression of mesenchymal markers and inhibit cell migration. We are currently investigating the effects of disrupting Cx43/microtubule complexing in vivo with a breast cancer mouse model to further elucidate effects on tumor progression and metastasis. Given the complex relationship between connexins and cancer progression, our findings support targeting this pathological ‘non-junctional’ Cx43 population specifically to limit metastatic disease, as Cx43 gap junction function is critical to normal tissue function and contributes to tumor suppression. Citation Format: Aryo Sorayya, Christina Wheeler, Stacie Deaver, Kenneth Young, Michael Zeitz, James Smyth, Samy Lamouille. Non-junctional connexin43 complexing with microtubules promotes epithelial-mesenchymal transition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 959.

Hydrogeologic and Thermal Effects of Glaciations on the Intracontinental Basins in Central and Northern Europe

We use a fully coupled hydro-thermal model (TH) to quantify changes in the pore pressure and temperature distribution following the Last Glacial Maximum (LGM) in the intracontinental basins in Central and Northern Europe. We demonstrate that even without considering a direct mechanical coupling from the visco-elastic lithosphere rebound, the system is, at present-day, in a state of hydrogeologic and thermal disequilibrium as a result of the past ice sheet dynamics. We find that the local geology exerts an additional control on the subsurface response to imposed glacial loading, as evidenced by a contrasting thermal and pore pressure configuration in time and space. Highest rates of pore pressure dissipation are restricted to crustal domains that underwent substantial glacial loading, while the majority of the sedimentary sub-basins show a prominent signature of hydraulic disequilibrium (overpressure) at present. Groundwater-driven convective cooling and heating during the advance and retreat of the ice cap occurred mainly within sedimentary rocks, domains where thermal equilibration is ongoing. The spatial correlation between modeled pore pressure dissipation rates and postglacial uplift rates is indicative of a complex and transient hydrogeological system structurally connected to the viscous tail of the ongoing isostatic adjustment after the LGM, with important implications for assessing the long-term mechanical stability of this intraplate setting.

Multi-ball rotative nonlinear energy sink for galloping mitigation

Galloping is a destructive type of flow-induced vibration (FIV) affecting engineering structures subjected to wind. In this paper, we introduce a simple, low-cost device able to passively absorb the energy of vibrating structures and reduce the galloping amplitudes. This purely nonlinear energy sink (NES) consists of multiple balls rotating freely in a circular track without direct mechanical coupling with the primary system. We assess the benefit of the proposed NES in mitigating the galloping of a square prism through wind tunnel tests and explain the main factors affecting its behaviour. The NES balls rotate due to dynamic interaction with the prism, exhibiting a way of nonlinear energy absorption, which is enhanced by ball collisions. We test different NES configurations varying the number of NES balls to highlight the number of balls’ effect on shifting the mass centre and changing the dynamics of the NES. Whereas a single ball NES with a mass 8% that of the prism can increase the critical reduced velocity by 68%, a 2 or 3-ball NES of equivalent mass increases this speed by 87%.

A Novel Microstrip Triple Wideband Bandstop Filter Design by Using Adjacent Direct Coupled Dual-Mode Resonators

In this article, a novel triple wideband bandstop filter design is proposed with two adjacent microstrip square loop resonators (MSLR) having different edge lengths. Degenerate modes of the square loop resonators are induced by using direct coupling mechanism. Perturbation and loading elements are located on resonators and used to control reflection zeros between the second and third bands. Even odd mode analysis of a single direct coupled dual-mode resonator is also extracted to elucidate the filter topology. The proposed resonator structure is designed by using a full-wave EM simulator and three different filter responses are obtained from the designed resonator structure. One of the filters is fabricated and, it is observed that measured results are compatible with simulated results.

Thermodynamic investigation of water generating system through HDH desalination and RO powered by organic Rankine cycle

The present study proposed the water generating system through humidification-dehumidification desalination unit and RO powered by organic Rankine cycle to generate both power and drinking water from the waste heat of Naval Ship by using a low-temperature organic Rankine cycle. Waste heat from the naval ship is used in order to run the topping cycle namely the organic Rankine cycle for power generation which operates the RO system for drinking water. A water-heated humidification dehumidification (HDH) desalination unit is also integrated with the organic Rankine cycle system to produce additional freshwater. The mass and energy balance equations are designed to analyze the thermodynamic performance of the cogeneration of the power-water system at the designed conditions. Suitable working fluids for the organic Rankine cycle are chosen on the basis of thermophysical properties i.e. lower boiling point, critical temperature & pressure and global warming potential. Furthermore, the impact of various vital parameters like extraction pressure, vapor extraction ratio, condenser temperature, turbine inlet pressure, etc. on the performance. It was founded that the impact of extraction parameters on the cycle, the net power, total efficiency and water production is 16.74 kW, 42.10% and 75.18 kg h−1 respectively. The extraction ratio variation causes the improvement in the water production and power generation and lower extraction ratio has better results. The RO System used is direct mechanical coupling which uses the power to run the system and produces the water, 2.4L of drinking water is produced using 16.74 kW power, respectively.

A new mechanism of direct coupling of laser energy to ions

The well-known schemes (e.g. Brunel mechanism, resonance absorption, heating etc) couple laser energy to the lighter electron species of the plasma. In this work, a fundamentally new mechanism of laser energy absorption directly to the heavier ion species has been proposed. The mechanism relies on the difference between the drifts of electron and ions in the oscillating electric field of the laser and an external magnetic field to create charge density perturbations. The proposed mechanism is verified with the help of particle-in-cell (PIC) simulations using OSIRIS4.0.

Electromechanical coupling in the hyperpolarization-activated K+ channel KAT1.

Voltage-gated potassium (Kv) channels orchestrate electrical signaling and control cell volume by gating in response to either membrane depolarization or hyperpolarization. Yet, while all voltage-sensing domains transduce transmembrane electric field changes by a common mechanism involving the outward or inward translocation of gating charges1–3, the general determinants of channel gating polarity remain poorly understood4. Here, we suggest a molecular mechanism for electromechanical coupling and gating polarity in non-domain-swapped Kv channels based on the cryo-EM structure of KAT1, the hyperpolarization-activated Kv channel from Arabidopsis thaliana. KAT1 displays a depolarized voltage sensor, which interacts with a closed pore domain directly via two interfaces and indirectly via an intercalated phospholipid. Functional evaluation of KAT1 structure-guided mutants at the sensor-pore interfaces suggests a mechanism in which direct interaction between the sensor and C-linker hairpin in the adjacent pore subunit is the primary determinant of gating polarity. We suggest that a ~5–7 Å inward motion of the S4 sensor helix can underlie a direct-coupling mechanism, driving a conformational reorientation of the C-linker and ultimately opening the activation gate formed by the S6 intracellular bundle. This direct-coupling mechanism contrasts with allosteric mechanisms proposed for hyperpolarization-activated cyclic nucleotide-gated (HCN) channels5, and may represent an unexpected link between depolarization and hyperpolarization-activated channels.

Genome scale metabolic modeling reveals the metabolic potential of three Type II methanotrophs of the genus Methylocystis

Genome Scale Metabolic Models (GSMMs) of the recently sequenced Methylocystis hirsuta and two other methanotrophs from the genus Methylocystis have been reconstructed. These organisms are Type II methanotrophs with the ability of accumulating Polyhydroxyalkanoates under nutrient limiting conditions. For the first time, GSMMs have been reconstructed for Type II methanotrophs. These models, combined with experimental biomass and PHB yields of Methylocystis hirsuta, allowed elucidating the methane oxidation mechanism by the enzyme pMMO (particulate methane monooxygenase) in these organisms. In contrast to Type I methanotrophs, which use the “direct coupling mechanism”, Type II methanotrophs appear to use the so called “redox arm mechanism”. The utilization of the “redox arm mechanism”, which involves the coupling between methane oxidation and complex I of the respiratory chain, was confirmed by inhibition of complex I with catechol. Utilization of the “redox arm” mechanism leads to lower biomass yields on methane compared to Type I methanotrophs. However, the ability of Type II methanotrophs to redirect high metabolic carbon fluxes towards acetoacetyl-CoA under nitrogen limiting conditions makes these organisms promising platforms for metabolic engineering.

Rapid microwave-assisted liquid phase conversion of bio-ethanol to n-butanol over a heterogeneous catalyst

A sustainable bio-based fuel industry is dependent on finding efficient technologies for the production of biofuels. A microwave-assisted method to produce bio-butanol from bio-ethanol in liquid phase was investigated using a 2-level factorial design with catalyst type and loading, reaction temperature and reaction time as variables. A combined severity factor (CSF) was used to quantify the combined effect of all reaction conditions on ethanol conversion and butanol selectivity. From the results, it could be qualitatively deduced that the reaction initially followed the Guerbet mechanism for formation of butanol, but gradually shifted toward the direct coupling mechanism as reaction conditions became more severe with 50% of the butanol produced at a CSF of 6, produced through the direct coupling mechanism. The overall reaction order and observed specific reaction rate was determined as 1.54 ± 0.26 and 2.91·10−6 ± 2.36·10−7 g.0.54.L−0.54.s−1 respectively. Both high ethanol conversions (76.6 wt%) and high butanol selectivity (60 wt%) could be obtained in a very short reaction time (60 minutes). The results represent an improvement in reaction time, ethanol conversion and butanol selectivity of 300%, 47% and 16.7% respectively compared to previously reported data. This represents a significant step towards realizing an affordable low-carbon drop-in fuel for a low carbon economy.

Elastomeric Waveguide on-Chip Coupling of an Encapsulated MoS2 Monolayer

We propose a robust photonic platform for encapsulation and addressing of optically active 2D- and nano-materials. Our implementation utilises a monolayer of MoS$_2$ transition metal dichalcogenide embedded in an elastomeric waveguide chip. The structure is manufactured from PDMS using soft-lithography and capable of sustaining a single mode of guided light. We prove that this setup facilitates addressing of the 2D material flake by pumping it with polarised laser light and gathering polarisation-resolved photoluminescence spectra with the extinction ratio of 31, which highlights the potential for selection-rule dependent measurements. Our results demonstrate improved handling of the material and experimental simplification compared to other techniques. Furthermore, inherent elasticity of the host provides an avenue for direct mechanical coupling to embedded materials.

Electroelastic investigation of drying rate in the direct contact ultrasonic fabric dewatering process

Ultrasonic vibrations, used to atomize liquids into a fine mist, are a promising solution for the future of efficient clothes drying technology. The world’s first ultrasonic dryer—demonstrated by researchers at Oak Ridge National Laboratory—successfully applies the scientific principles behind ultrasonic drying, and several working prototypes have been demonstrated. This technology is based on direct mechanical coupling between mesh piezoelectric transducers and wet fabric. During the atomization process, vertical oscillations of a contained liquid, called Faraday excitations, result in the formation of standing waves on the liquid surface. At increasing amplitudes and frequencies of oscillation, wave peaks become extended and form “necks” connecting small secondary droplets to the bulk liquid. When the oscillation reaches an acceleration threshold, the droplet momentum is sufficient to break the surface tension of the neck and enable the droplets to travel away from the liquid. In this work, we investigate the atomization process using an ultrasonic transducer as it pertains to moisture retained within a fabric. An experimentally validated electromechanical analytical-numerical model is proposed. This model bridges the vibrations of a piezoelectric mesh transducer to the critical acceleration needed for fabric drying to occur. Then, the drying rate model is developed, consisting of an initial nonlinear region due to atomization, followed by a linear thermal evaporation region. The models developed identify the influence of key parameters on ultrasonic drying and will aid in improving atomizer design for efficient, timely fabric drying. This study is the first proposed model for the ultrasonic atomization of fabrics saturated with water, applicable to any type of transducer. The results present a non-dimensional equation for the ultrasonic dewatering of fabrics, dependent only on transducer acceleration and the surface area of the cloth. The development of this technology using the proposed physical models will allow for global reductions in electrical demand related to clothes drying.

Transitions in synchronization states of model cilia through basal-connection coupling

Despite evidence for a hydrodynamic origin of flagellar synchronization between different eukaryotic cells, recent experiments have shown that in single multi-flagellated organisms, coordination hinges instead on direct basal body connections. The mechanism by which these connections lead to coordination, however, is currently not understood. Here, we focus on the model biflagellate Chlamydomonas reinhardtii, and propose a minimal model for the synchronization of its two flagella as a result of both hydrodynamic and direct mechanical coupling. A spectrum of different types of coordination can be selected, depending on small changes in the stiffness of intracellular couplings. These include prolonged in-phase and anti-phase synchronization, as well as a range of multi-stable states induced by spontaneous symmetry breaking of the system. Linking synchrony to intracellular stiffness could lead to the use of flagellar dynamics as a probe for the mechanical state of the cell.