Functional Switch Research Articles

Over-voltage and cross-conduction hard switching stress on schottky gate-type p-GaN HEMT in half-bridge operation. Experimental and physical approaches

The GaN HEMT power device emerges as a promising wide-bandgap component for obtaining ultra-compact and very high efficiency power converters. Nevertheless, its long-time switching operation capability in high overload regimes near or just above its maximum ratings remains unknown. The physical degradation mechanisms specific to GaN HEMT as well as the associated electrical signatures must now be established and better understood. In this article a stress protocol is proposed combining or not functional drain-source over-voltage switching and transient low dead-time cross-conduction stresses. A no-loaded Half Bridge (HB) is used. All stress parameters studied have been associated to electric changes such as drain-source, gate-source leakage currents, and threshold voltage drifts of intrinsic values and even some physical degradation by LIT compound analysis. After analysis, it appears that both the electric field and the current are very stressful for the devices and lead to current leakage caused by physical degradation. The aging observed might be generated from the injection of hot electrons and located depending upon the drain voltage value which influences the depletion region and thus the electric field peak.

Vanadium dioxide thin films-assisted terahertz meta-surface for simultaneous absorption, polarization conversion bi-functional switching, and wavefront operation

Actively switchable metasurfaces are extremely useful for achieving a multifunctional integrated platform. The proposed design enables functional switching through the temperature-induced phase transition features of vanadium dioxide (VO2). The hypothesized metasurface can be considered a broadband absorber when VO2 is in the metallic phase, with an absorption rate approaching 90% in the frequency spectrum of 1.41–2.69 THz, according to numerical simulations. When VO2 is in the insulating phase, the proposed metasurface acts as a half-wave plate with more than 80% polarization conversion rate (PCR) in the frequency range of 0.71–2.72 THz. Furthermore, the dynamic modulation of absorbance and PCR can be achieved when the VO2 conductivity varies within a specific range. Finally, by changing the opening angle of the gold split-ring resonator to introduce an abrupt phase at the interface, the composed metacell can perform arbitrary manipulation of reflected beams in the 1.0–2.2 THz broadband range; we also design 1D and 2D focusing metalenses. Both have good subwavelength focusing characteristics. Therefore, the proposed metasurface can be effectively applied in sixth-generation communication systems, terahertz imaging, and other technologies.

Technical research on test method of the socket and switch of temperature monitoring alarm function

The emergence of sockets and switches with fire protection monitoring and alarm functions had realized the forward detection of the fire risk monitoring gateway, which had played an important role in preventing the occurrence of electrical fires. In 2014, the national standard GB31252 “Fire Monitoring and Alarm Sockets and Switches” was promulgated and implemented, which detailed the product functions, performance and test methods of fire protection monitoring and alarm sockets and switches. This article is based on the difficulty of accurately controlling the heating process when measuring the temperature alarm value of the socket and switch. A new type of simulated temperature alarm test method was designed, and a detection device for the temperature test of the fire monitoring alarm socket and switch was developed. And the testing device was tested and verified. The test results show that the testing device designed in this paper can meet the technical requirements of the temperature part test in GB31252-2014.

Regulatory changes associated with the head to trunk developmental transition

BackgroundDevelopment of vertebrate embryos is characterized by early formation of the anterior tissues followed by the sequential extension of the axis at their posterior end to build the trunk and tail structures, first by the activity of the primitive streak and then of the tail bud. Embryological, molecular and genetic data indicate that head and trunk development are significantly different, suggesting that the transition into the trunk formation stage involves major changes in regulatory gene networks.ResultsWe explored those regulatory changes by generating differential interaction networks and chromatin accessibility profiles from the posterior epiblast region of mouse embryos at embryonic day (E)7.5 and E8.5. We observed changes in various cell processes, including several signaling pathways, ubiquitination machinery, ion dynamics and metabolic processes involving lipids that could contribute to the functional switch in the progenitor region of the embryo. We further explored the functional impact of changes observed in Wnt signaling associated processes, revealing a switch in the functional relevance of Wnt molecule palmitoleoylation, essential during gastrulation but becoming differentially required for the control of axial extension and progenitor differentiation processes during trunk formation. We also found substantial changes in chromatin accessibility at the two developmental stages, mostly mapping to intergenic regions and presenting differential footprinting profiles to several key transcription factors, indicating a significant switch in the regulatory elements controlling head or trunk development. Those chromatin changes are largely independent of retinoic acid, despite the key role of this factor in the transition to trunk development. We also tested the functional relevance of potential enhancers identified in the accessibility assays that reproduced the expression profiles of genes involved in the transition. Deletion of these regions by genome editing had limited effect on the expression of those genes, suggesting the existence of redundant enhancers that guarantee robust expression patterns.ConclusionsThis work provides a global view of the regulatory changes controlling the switch into the axial extension phase of vertebrate embryonic development. It also revealed mechanisms by which the cellular context influences the activity of regulatory factors, channeling them to implement one of several possible biological outputs.

High Step-Up Current-Fed Diode-Clamped Resonant Converter for Overloaded Fuel-Cell Vehicles

We propose a high step-up current-fed diode-clamped resonant converter for overloaded fuel-cell vehicles. The electric motor is able to demand short-time peak torque during sudden acceleration phase or long-time excessive torque when the fuel-cell vehicles are overloaded. Then, the conventional converter suffers from a high current spike at the secondary-side switches. The proposed converter incorporates diode-clamped cell on the secondary side, and therefore does not have the high current spike, but retains the benefits of the conventional converter such as high step-up function, ripple-free characteristic, and soft switching capability. When the output power is over its maximum nominal value, the secondary-side switches are switched off with complete zero-voltage-switching (ZVS) and the secondary-side diodes are off with zero-current-switching (ZCS). As a result, the proposed converter exhibits high efficiency and long-term operation under the nominal power and even at peak power. Furthermore, we have analyzed voltage gain, ZVS/ZCS region, and current/voltage stress on the active power components when the output power is over its maximum nominal value, which is different from those when the output power is in its nominal range. The theoretical analysis of the proposed converter is presented, then validated using a laboratory-built prototype.

An intermediate state allows influenza polymerase to switch smoothly between transcription and replication cycles.

Influenza polymerase (FluPol) transcribes viral mRNA at the beginning of the viral life cycle and initiates genome replication after viral protein synthesis. However, it remains poorly understood how FluPol switches between its transcription and replication states, especially given that the structural bases of these two functions are fundamentally different. Here we propose a mechanism by which FluPol achieves functional switching between these two states through a previously unstudied conformation, termed an 'intermediate state'. Using cryo-electron microscopy, we obtained a structure of the intermediate state of H5N1 FluPol at 3.7 Å, which is characterized by a blocked cap-binding domain and a contracted core region. Structural analysis results suggest that the intermediate state may allow FluPol to transition smoothly into either the transcription or replication state. Furthermore, we show that the formation of the intermediate state is required for both the transcription and replication activities of FluPol, leading us to conclude that the transcription and replication cycles of FluPol are regulated via this intermediate state.

Protein oxidation increases SAMHD1 binding ssDNA via its regulatory site.

SAMHD1 dNTP hydrolase activity places it at the crossroad of several important biological pathways, such as viral restriction, cell cycle regulation, and innate immunity. Recently, a dNTPase independent function for SAMHD1 in homologous recombination (HR) of DNA double-strand breaks has been identified. SAMHD1 function and activity is regulated by several post-translational modifications, including protein oxidation. Here, we showed that oxidation of SAMHD1 increases ssDNA binding affinity and occurs in a cell cycle-dependent manner during S phase consistent with a role in HR. We determined the structure of oxidized SAMHD1 in complex with ssDNA. The enzyme binds ssDNA at the regulatory sites at the dimer interface. We propose a mechanism that oxidation of SAMHD1 acts as a functional switch to toggle between dNTPase activity and DNA binding.

Propagation Delay and Power Dissipation Analysis for a 2-Bit SRAM Using Multi-State SWS Inverter

This paper presents a study on the propagation delay and power dissipation of a 2-bit static random-access memory (SRAM) with two cross-coupled multi-state spatial wave function switching (SWS) CMOS inverters. The proposed SRAM design utilizes the advantages of the CMOS-SWS inverter, such as its small area, low power consumption, and high speed. The 2-bit SRAM circuit simulations were carried out in Cadence to analyze the power dissipation and propagation delay. An Analog Behavioral Model (ABM) and the Berkeley Short-channel IGFET Model (BSIM4.6) in 0.18-μm technology were combined to create this model. The analysis of the propagation delay shows that the multi-state CMOS-SWS SRAM significantly reduces the delay compared to other multi-state 6T SRAM memories. Additionally, the analysis of the power dissipation shows that the multi-state SWS-SRAM is comparable to conventional SRAMs. These results demonstrate the potential of multi-state SWS-SRAM for improving the performance of memory circuits and provide valuable insights for future design optimization.

Janus coding acoustic metasurface with reflection symmetry breaking

Coding metasurfaces with efficient procedures and simple elements have enabled a large number of novel functions in a digital manner. Designs combining coding and functional integration will undoubtedly enhance the efficiency and space utilization of compact systems. Here, we theoretically propose and numerically and experimentally demonstrate an all-passive reflective Janus coding acoustic metasurface, allowing two-faced direction-dependent coding in a decoupled manner. Exquisitely designed double-layer variable-pitch helical structures with smoothly varying acoustic impedance are used to obtain bianisotropic reflection phase responses, which can also be switched to bi-isotropic responses by changing the boundary conditions. The switchable Janus coding metasurface based on the phase state transitions can be programed to achieve switchable functions on one side without affecting the other side. For instance, the asymmetric and symmetric two-faced focusing and unidirectional switching of functions with coding metasurfaces are numerically and experimentally illustrated. We reveal the inherent essence of the structure-caused asymmetric responses and further pave a flexible way to obtain two-faced, independent wavefront operations and functional switching, which exhibit excellent potential for acoustic applications.

Conformational switching and flexibility in cobalamin-dependent methionine synthase studied by small-angle X-ray scattering and cryoelectron microscopy

Cobalamin-dependent methionine synthase (MetH) catalyzes the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate (CH3-H4folate) using the unique chemistry of its cofactor. In doing so, MetH links the cycling of S-adenosylmethionine with the folate cycle in one-carbon metabolism. Extensive biochemical and structural studies on Escherichia coliMetH have shown that this flexible, multidomain enzyme adopts two major conformations to prevent a futile cycle of methionine production and consumption. However, as MetH is highly dynamic as well as both a photosensitive and oxygen-sensitive metalloenzyme, it poses special challenges for structural studies, and existing structures have necessarily come from a "divide and conquer" approach. In this study, we investigate E. coli MetH and a thermophilic homolog from Thermus filiformis using small-angle X-ray scattering (SAXS), single-particle cryoelectron microscopy (cryo-EM), and extensive analysis of the AlphaFold2 database to present a structural description of the full-length MetH in its entirety. Using SAXS, we describe a common resting-state conformation shared by both active and inactive oxidation states of MetH and the roles of CH3-H4folate and flavodoxin in initiating turnover and reactivation. By combining SAXS with a 3.6-Å cryo-EM structure of the T. filiformis MetH, we show that the resting-state conformation consists of a stable arrangement of the catalytic domains that is linked to a highly mobile reactivation domain. Finally, by combining AlphaFold2-guided sequence analysis and our experimental findings, we propose a general model for functional switching in MetH.

Achieving Photonic Spin Hall Effect, Spin-Selective Absorption, and Beam Deflection with a Vanadium Dioxide Metasurface.

Metasurface-based research with phase-change materials has been a prominent and rapidly developing research field that has drawn considerable attention in recent years. In this paper, we proposed a kind of tunable metasurface based on the simplest metal-insulator-metal structure, which can be realized by the mutual transformation of insulating and metallic states of vanadium dioxide (VO2) and can realize the functional switching of photonic spin Hall effect (PSHE), absorption and beam deflection at the same terahertz frequency. When VO2 is insulating, combined with the geometric phase, the metasurface can realize PSHE. A normal incident linear polarized wave will be split into two spin-polarized reflection beams traveling in two off-normal directions. When VO2 is in the metal state, the designed metasurface can be used as a wave absorber and a deflector, which will completely absorb LCP waves, while the reflected amplitude of RCP waves is 0.828 and deflects. Our design only consists of one layer of artificial structure with two materials and is easy to realize in the experiment compared with the metasurface of a multi-layer structure, which can provide new ideas for the research of tunable multifunctional metasurface.

A Single-Magnetic Bidirectional Integrated Equalizer Using Multi-Winding Transformer and Voltage Multiplier for Hybrid Energy Storage System

A single-magnetic bidirectional integrated equalizer using the multi-winding transformer and voltage multiplier for the hybrid energy storage system is proposed. The multi-winding transformer and voltage multiplier, driven by the current ripple of the inductor in the bidirectional buck-boost converter, are used for the battery string and supercapacitor string voltage balance, respectively. Compared to the previous balance circuits, for the schedule of the proposed equalizer, only one winding and one diode are used for each battery. Meanwhile, one capacitor and two diodes are used for each supercapacitor, simplifying the balance circuit. This method has the advantages of low cost, suitable for cells with different voltage levels, multiplexed converter switches, and extremely simple structure. It does not have any active switch for the voltage balancing function. A prototype for four supercapacitor cells and four batteries is set up. The results show that the proposed circuit balances the HESS when the DC-DC converter works, which verifies the theoretical analysis.

The CD40 agonist HERA-CD40L results in enhanced activation of antigen presenting cells, promoting an anti-tumor effect alone and in combination with radiotherapy.

The ability to modulate and enhance the anti-tumor immune responses is critical in developing novel therapies in cancer. The Tumor Necrosis Factor (TNF) Receptor Super Family (TNFRSF) are potentially excellent targets for modulation which result in specific anti-tumor immune responses. CD40 is a member of the TNFRSF and several clinical therapies are under development. CD40 signaling plays a pivotal role in regulating the immune system from B cell responses to myeloid cell driven activation of T cells. The CD40 signaling axis is well characterized and here we compare next generation HERA-Ligands to conventional monoclonal antibody based immune modulation for the treatment of cancer. HERA-CD40L is a novel molecule that targets CD40 mediated signal transduction and demonstrates a clear mode of action in generating an activated receptor complex via recruitment of TRAFs, cIAP1, and HOIP, leading to TRAF2 phosphorylation and ultimately resulting in the enhanced activation of key inflammatory/survival pathway and transcription factors such asNFkB, AKT, p38, ERK1/2, JNK, and STAT1 in dendritic cells. Furthermore, HERA-CD40L demonstrated a strong modulation of the tumor microenvironment (TME) via the increase in intratumoral CD8+ T cells and the functional switch from pro-tumor macrophages (TAMs) to anti-tumor macrophages that together results in a significant reduction of tumor growth in a CT26 mouse model. Furthermore, radiotherapy which may have an immunosuppressive modulation of the TME, was shown to have an immunostimulatory effect in combination with HERA-CD40L. Radiotherapy in combination with HERA-CD40L treatment resulted in an increase in detected intratumoral CD4+/8+ T cells compared to RT alone and, additionally, the repolarization of TAMs was also observed, resulting in an inhibition of tumor growth in a TRAMP-C1 mouse model. Taken together, HERA-CD40L resulted in activating signal transduction mechanisms in dendritic cells, resulting in an increase in intratumoral T cells and manipulation of the TME to be pro-inflammatory, repolarizing M2 macrophages to M1, enhancing tumor control.

Single-cell transcriptional profiling of hearts during cardiac hypertrophy reveals the role of MAMs in cardiomyocyte subtype switching

Pathological cardiac hypertrophy is the main predecessor of heart failure. Its pathology is sophisticated, and its progression is associated with multiple cellular processes. To explore new therapeutic approaches, more precise examination of cardiomyocyte subtypes and involved biological processes is required in response to hypertrophic stimuli. Mitochondria and the endoplasmic reticulum (ER) are two crucial organelles associated with the progression of cardiac hypertrophy and are connected through junctions known as mitochondria-associated endoplasmic reticulum membranes (MAMs). Although MAM genes are altered in cardiac hypertrophy, the importance of MAMs in cardiac hypertrophy and the expression pattern of MAMs in certain cardiac cell types require a comprehensive analysis. In this study, we analyzed the temporal expression of MAM proteins in the process of cardiac hypertrophy and observed that MAM-related proteins preferentially accumulated in cardiomyocytes at the initial stage of cardiac hypertrophy and underwent a gradual decline, which was synchronized with the proportion of two cardiomyocyte subtypes (CM2 and CM3). Meanwhile, these subtypes went through a functional switch during cardiac hypertrophy. Trajectory analysis suggested that there was a differentiation trajectory of cardiomyocyte subtypes from high to low MAM protein expression. Distinct regulon modules across different cardiomyocyte cell types were revealed by transcriptional regulatory network analysis. Furthermore, scWGCNA revealed that MAM-related genes were clustered into a module that correlated with diabetic cardiomyopathy. Altogether, we identified cardiomyocyte subtype transformation and the potential critical transcription factors involved, which may serve as therapeutic targets in combating cardiac hypertrophy.

Elucidation of the Binding Mechanism of Anionic Phospholipids to Antioxidant Protein Peroxiredoxin 2.

Peroxiredoxins (Prxs) belong to a family of ubiquitously expressed peroxidases that detoxify reactive oxygen species. In addition to their enzymatic function, Prxs also function as molecular chaperones. This functional switch is related to their degree of oligomerization. We have previously revealed that Prx2 interacts with anionic phospholipids and that the anionic phospholipid-containing Prx2 oligomer forms a high molecular weight (HMW) complex in a nucleotide-dependent manner. However, the detailed mechanism of the oligomer and HMW complex formation remains unclear. In this study, we investigated the anionic phospholipid binding site in Prx2 using site-directed mutagenesis to understand the mechanism of the oligomer formation. Our findings demonstrated that six binding site residues in Prx2 are important for the binding of anionic phospholipids.

Alleviating the trade-off by site-guided function switch of nitrilase to nitrile hydratase

Catalytic promiscuity makes nitrilase-mediated unnatural reactivity a promising pathway in the production of primary amides. However, during the functional switch of nitrilase, a trade-off between the newly developed hydration activity and relative activity hinders the application of nitrilase in the production of amides. Our previous study showed that the mutant F193N (Mut0) of nitrilase NIT6803 from Synechocystis sp. PCC6803 improved the hydration activity as the amide ratio increased to 73.4%, whereas the relative activity was only 50.1% of that of the wild-type (WT). In this study, we succeeded in alleviating the trade-off of Mut0 through an evolutionary combination of the key identified sites 101, 192, and 201. Inside the active pocket, the co-evolution of residue Q192 was identified by hotspot prediction to correlate with N193, and Q192H exhibited an improved amide ratio of 76.9% with a relative activity of up to 72%. Outside the active pocket, the flexible loop surface residue G101 and homodimer “A” interface residue I201 were identified using sequence alignment-based mutations. Further evolutionary combination of the three key sites yielded the best triple mutant G101K/Q192H/I201M, which had the highest amide ratio of 98.5% and considerably recovered relative activity of 82.6% while retaining only 1.5% of the carboxylic acid ratio. The transition-state analogue sheds light on the basis of the almost identical switch of the reaction pathways, and our results expand the toolbox of nitrilase-catalysed promiscuity for amide formation.

A Collaborative Method on Reversible Lane Clearance and Signal Coordination Control in Associated Intersection

To improve traffic efficiency and utilization of road resources and alleviate traffic congestion caused by imbalance of bidirectional traffic flow, in view of the conversion conditions of reversible lane function, the operating characteristics of associated intersections under dynamic reversible lanes are analysed in terms of capacity, and a reversible lane control model is constructed based on short-term traffic flow prediction. On this basis, the reversible lane segment clearing time and upstream and downstream signal control strategies under different states are studied. The collaborative control model of reversible lane clearing time and signal timing of associated intersections is established to obtain the optimal time for reversible lane function switching. Finally, using Chaoyang Road, Beijing, as an example, the effectiveness of the proposed model is verified by the simulation indexes of average vehicle delay and reversible lane clearing time. The results show that the optimized clearing efficiency exceeds 15% and the optimized average vehicle delay is reduced by more than 10%. Combined with the future traffic state, the traffic capacity and saturation flow are greatly improved, and the intelligent reversible lane control is better achieved.

Glial cells: an important switch for the vascular function of the central nervous system.

In this review, we first describe the current understanding of glial-mediated vascular function affecting the role of the blood-brain barrier (BBB) in central nervous system (CNS) disorders. BBB, mainly composed of glial and endothelial cells (ECs), is the protective structure that orchestrates the transport of substances, including ions, molecules, and cells from brain vessels into or out of the CNS. Then, we display the multiple communication between glial and vascular function based on angiogenesis, vascular wrapping, and blood perfusion in the brain. Glial can support microvascular ECs to form a blood network connecting to neurons. Astrocytes, microglia, and oligodendrocytes are the common types of glial surrounding the brain vessel. Glial-vessel interaction is required for the permeability and integrity of BBB. Glial cells surrounding the cerebral blood vessels can transmit communication signals to ECs and regulate the activity of vascular endothelial growth factor (VEGF) or Wnt-dependent endothelial angiogenesis mechanism. In addition, these glial cells monitor the blood flow in the brain via Ca2+/K+-dependent pathways. Finally, we provide a potential research direction for the glial-vessel axis in CNS disorders. Microglial activation can trigger astrocyte activation, which suggests that microglia-astrocyte interaction may play a key role in monitoring cerebral blood flow. Thus, microglia-astrocyte interaction can be the key point of follow-up studies focusing on the microglia-blood mechanism. More investigations focus on the mechanism of how oligodendrocyte progenitor cells communicate and interact with ECs. The direct role of oligodendrocytes in modulating vascular function needs to be explored in the future.

KLF5 and p53 comprise an incoherent feed-forward loop directing cell-fate decisions following stress

In response to stress, cells make a critical decision to arrest or undergo apoptosis, mediated in large part by the tumor suppressor p53. Yet the mechanisms of these cell fate decisions remain largely unknown, particularly in normal cells. Here, we define an incoherent feed-forward loop in non-transformed human squamous epithelial cells involving p53 and the zinc-finger transcription factor KLF5 that dictates responses to differing levels of cellular stress from UV irradiation or oxidative stress. In normal unstressed human squamous epithelial cells, KLF5 complexes with SIN3A and HDAC2 repress TP53, allowing cells to proliferate. With moderate stress, this complex is disrupted, and TP53 is induced; KLF5 then acts as a molecular switch for p53 function by transactivating AKT1 and AKT3, which direct cells toward survival. By contrast, severe stress results in KLF5 loss, such that AKT1 and AKT3 are not induced, and cells preferentially undergo apoptosis. Thus, in human squamous epithelial cells, KLF5 gates the response to UV or oxidative stress to determine the p53 output of growth arrest or apoptosis.

The cilium–centrosome axis in coupling cell cycle exit and cell fate

The centrosome is an evolutionarily conserved, ancient organelle whose role in cell division was first described over a century ago. The structure and function of the centrosome as a microtubule-organizing center, and of its extracellular extension - the primary cilium - as a sensory antenna, have since been extensively studied, but the role of the cilium-centrosome axis in cell fate is still emerging. In this Opinion piece, we view cellular quiescence and tissue homeostasis from the vantage point of the cilium-centrosome axis. We focus on a less explored role in the choice between distinct forms of mitotic arrest - reversible quiescence and terminal differentiation, which play distinct roles in tissue homeostasis. We outline evidence implicating the centrosome-basal body switch in stem cell function, including how the cilium-centrosome complex regulates reversible versus irreversible arrest in adult skeletal muscle progenitors. We then highlight exciting new findings in other quiescent cell types that suggest signal-dependent coupling of nuclear and cytoplasmic events to the centrosome-basal body switch. Finally, we propose a framework for involvement of this axis in mitotically inactive cells and identify future avenues for understanding how the cilium-centrosome axis impacts central decisions in tissue homeostasis.