Switching Structure Research Articles

Fluorescence DNA Switch for Highly Sensitive Detection of miRNA Amplified by Duplex-Specific Nuclease.

DNA is a type of promising material for the construction of sensors owing to its sequence programmability to control the formation of certain structures. MicroRNA (miRNA) can be applied as promising biomarkers for the diagnosis of a range of diseases. Herein, a novel fluorescent sensing strategy for miRNA is proposed combining duplex-specific nuclease (DSN)-mediated amplification and dumbbell DNA structural switch. Gold nanoparticles (AuNPs) are employed, which provide a 3D reaction interface. They also act as effective fluorescence quenchers. The proposed sensor exhibits high sensitivity (sub-femtomolar level) with a wide dynamic range. In addition, excellent selectivity to distinguish homology sequences is achieved. It also performs satisfactorily in biological samples. Overall, this fluorescent sensor provides a powerful tool for the analysis of miRNA levels and can be applied for related biological studies and clinical diagnosis.

Experimental demonstration of a transmitter with a 50° divergence angle, 50 Mbps rate, and 476 mW optical power for underwater wireless optical communication based on an engineered diffuser.

In practical application of underwater wireless optical communication (UWOC), the transmitter should have a larger divergence angle to make it easier to establish a communication link, besides high modulated rate and high optical power. Laser diodes (LD) are suitable to design such transmitter, thanks to their simpler structure and much faster switching speed. However, it is difficult to implement for widespread use in ocean engineering because of its quite small divergence angle. For this, we present a simple way to enlarge the divergence angle for an LD transmitter based on an engineered diffuser in this paper. First, we design a blue LD transmitter that has 476 mW output power, 50 Mbps rate, and 50° divergence angle. Then, using such transmitter, we establish a UWOC system in a large experimental tank with 13.3 m communication distance and about 0.26m-1 attenuation coefficient of water. The results show that if the deviation of the transmitting direction is up to ±25∘, the communication system is workable. Emission light from the transmitter could cover a 42.5% solid angle of the hemisphere space. The combination performances of speed, angular coverage, and optical power are suitable for ocean engineering. Also, it implies that a light field could be designed by using a suitable engineered diffuser for UWOC. The method presented in this paper is simple and pragmatic, which is useful to reduce the difficulty in establishing communication links and is easy to popularize.

From Water to Land: The Structural Construction and Molecular Switches in Lungs during Metamorphosis of Microhyla fissipes.

Simple SummaryThe functionalization of lungs is a necessity for most anurans to breathe on land. Previous studies have focused on the morphological and physiological functions of amphibian lungs, while the microstructural changes and molecular mechanisms that underpin the functional maturation of lungs remain under-researched. We used integrated histology and transcriptomics to study the critical cytological and molecular events associated with lung maturation in Microhyla fissipes. The results illuminated the molecular processes and their coordination in lung development, providing an insight into the transition of amphibians from aquatic to terrestrial life stages.Most anurans must undergo metamorphosis to adapt to terrestrial life. This process enhances the air-breathing ability of the lungs to cope with the change in oxygen medium from water to air. Revealing the structural construction and molecular switches of lung organogenesis is essential to understanding the realization of the air-breathing function. In this study, histology and transcriptomics were conducted in combination to explore these issues in Microhyla fissipes’ lungs during metamorphosis. During the pro-metamorphic phase, histological structural improvement of the alveolar wall is accompanied by robust substrate metabolism and protein turnover. The lungs, at the metamorphic climax phase, are characterized by an increased number of cilia in the alveolar epithelial cells and collagenous fibers in the connective tissues, corresponding to the transcriptional upregulation of cilia and extracellular matrix-related genes. Post-metamorphic lungs strengthen their contracting function, as suggested by the thickened muscle layer and the upregulated expression of genes involved in muscle contraction. The blood–gas barrier is fully developed in adult lungs, the transcriptional features of which are tissue growth and regulation of differentiation and immunity. Importantly, significant transcriptional switches of pulmonary surfactant protein and hemoglobin facilitate air breathing. Our results illuminated four key steps of lung development for amphibians to transition from water to land.

Cotranscriptional RNA strand exchange underlies the gene regulation mechanism in a purine-sensing transcriptional riboswitch.

RNA folds cotranscriptionally to traverse out-of-equilibrium intermediate structures that are important for RNA function in the context of gene regulation. To investigate this process, here we study the structure and function of the Bacillus subtilis yxjA purine riboswitch, a transcriptional riboswitch that downregulates a nucleoside transporter in response to binding guanine. Although the aptamer and expression platform domain sequences of the yxjA riboswitch do not completely overlap, we hypothesized that a strand exchange process triggers its structural switching in response to ligand binding. In vivo fluorescence assays, structural chemical probing data and experimentally informed secondary structure modeling suggest the presence of a nascent intermediate central helix. The formation of this central helix in the absence of ligand appears to compete with both the aptamer's P1 helix and the expression platform's transcriptional terminator. All-atom molecular dynamics simulations support the hypothesis that ligand binding stabilizes the aptamer P1 helix against central helix strand invasion, thus allowing the terminator to form. These results present a potential model mechanism to explain how ligand binding can induce downstream conformational changes by influencing local strand displacement processes of intermediate folds that could be at play in multiple riboswitch classes.

A highly selective naphthalene-fluorophore salamo-based chemosensor for sequential identification of Cu2+ and S2− ions in water applications

Two new fluorescent chemical sensors, H4L and its L-Cu2+ complex, are reported for the selective detection of Cu2+ and S2− ions in DMF solution, respectively. In the fluorescent switch structure of chemical sensor H4L, the binding of Cu2+ ions in the receptor part leads to the coordination between the completely deprotonated ligand (L)4− unit and Cu2+, resulting in fluorescence quenching. S2− was added to the L-Cu2+ complex to turn on the fluorescence of the L-Cu2+ complex. The chemical sensor H4L and its L-Cu2+ complex can possess obvious selectivities for common cations and anions in the micro molar concentration range, so as to quantitatively detect Cu2+ and S2− ions. The interaction of S2− ions with the chemical sensor L-Cu2+ was investigated by fluorescence time response measurement, whereas high-resolution mass spectrometry, and fluorescent titration substantiated the stoichiometry between L-Cu2+ and S2− ions. The crystal structure of the L-Cu2+ complex, [Cu2(L)]·2CHCl3 has been determined by X-ray crystallographic analysis. Density Functional Theory (DFT) calculations were performed in order to show the structures and electronic properties of H4L and its L-Cu2+ complex.

Discovery of a large-scale, cell-state-responsive allosteric switch in the 7SK RNA using DANCE-MaP

7SK is a conserved noncoding RNA that regulates transcription by sequestering the transcription factor P-TEFb. 7SK function entails complex changes in RNA structure, but characterizing RNA dynamics in cells remains an unsolved challenge. We developed a single-molecule chemical probing strategy, DANCE-MaP (deconvolution and annotation of ribonucleic conformational ensembles), that defines per-nucleotide reactivity, direct base pairing interactions, tertiary interactions, and thermodynamic populations for each state in RNA structural ensembles from a single experiment. DANCE-MaP reveals that 7SK RNA encodes a large-scale structural switch that couples dissolution of the P-TEFb binding site to structural remodeling at distal release factor binding sites. The 7SK structural equilibrium shifts in response to cell growth and stress and can be targeted to modulate expression of P-TEFbresponsive genes. Our study reveals that RNA structural dynamics underlie 7SK function as an integrator of diverse cellular signals to control transcription and establishes the power of DANCE-MaP to define RNA dynamics in cells.

Role of an in-plane ferromagnet in a T-type structure for field-free magnetization switching

Deterministic magnetization switching driven by current-induced spin–orbit torque (SOT) without an external magnetic field has potential applications in magnetic random access memory. Here, we realized the field-free magnetization switching in a T-type structure (CoFeB/W/CoFeB), where the two CoFeB layers have perpendicular magnetic anisotropy and in-plane magnetic anisotropy (IMA), respectively. We discovered that the direction of symmetry-breaking field is parallel to the magnetization of the bottom CoFeB (IMA), which cannot be explained by a stray field of this layer. In addition, by placing a 2.5-nm thick insulating layer of MgO between the bottom CoFeB and W layer (CoFeB/MgO/W/CoFeB) to block the interlayer exchange coupling and the spin current from the bottom CoFeB, the field-free SOT switching was still achieved, primarily due to the Néel orange-peel effect in our devices. By using micromagnetic simulations, the roughness of angstrom magnitude was introduced into the model to calculate the symmetry-breaking field, finding a qualitative agreement with experiments. Moreover, we obtained the spin Hall angle of CoFeB (θSH = −0.024) by the current-induced hysteresis loop shift method, and the contribution of the effective efficiency χ from the bottom CoFeB was accounted for about 26% of the total in the current-induced SOT switching process. These results indicated that an in-plane ferromagnet layer in the T-type structure provides not only the symmetry-breaking field but also spin current for the field-free SOT magnetization switching.

Highly sensitive fluorescence-based mercury(II) DNA sensor enhanced by silver(I) activation

Mercury exposure constitutes an acute risk to human health and the environment. Driven by the requirement to monitor trace-level mercury, we report a highly sensitive mercury(II) DNA sensor enhanced by silver(I) activation, followed by mercury(II)-specific oligonucleotides (MSO) molecular configuration switch and mercury(II)-modulated FRET. Activating the MSO strands with silver(I), mismatched cytosine–silver(I)–cytosine bridges induce individual MSO strands to fold readily in response to mercury(II) resulting in enhanced fluorescence signal. The structural switches were studied by 2D 1H–1H NOESY and TOCSY NMR spectroscopy, and 260 nm absorbance. The signal decreases with increasing mercury(II) concentration from 100 pM to 0.1 mM. The approach affords outstanding mercury(II) selectivity over other environmentally associated metals. Furthermore, the methodology was deployed for detection of mercury(II) in spiked pond waters with 97.9–100.6% recovery. The simple and feasible format has great potential for developing a cost effective and useful tool for environmental monitoring.

РАЗРАБОТКА И ПРИМЕНЕНИЕ НЕЙРОСЕТЕВЫХ МОДЕЛЕЙ В АВТОМАТИЗАЦИИ УПРАВЛЕНИЯ ОБОРУДОВАНИЕМ И ТЕХНОЛОГИЧЕСКИМИ ПРОЦЕССАМИ

Models of equipment and technological processes based on neural networks with a commutator structure are developed. The article proposes to use neural network models in automated control systems (ACS). Neural network models make it possible to implement automated control systems with a flexible programmable switching structure, quickly connect and disconnect new technological equipment, change the operation order in technological processes, and adapt the system to changing conditions and the external environment. The object of study is ACS. The method is modelling. The aim is to reduce the cost of developing and using automated control systems.

When to Preprocess? Keeping Information Fresh for Computing-Enable Internet of Things

Age of information (AoI), a notion that measures the information freshness, is an essential performance measure for time-critical applications in Internet of Things (IoT). With the surge of computing resources at the IoT devices, it is possible to preprocess the information packets that contain the status update before sending them to the destination so as to alleviate the transmission burden. However, the additional time and energy expenditure induced by computing also make the optimal updating a non-trivial problem. In this paper, we consider a time-critical IoT system, where the IoT device is capable of preprocessing the status update before the transmission. Particularly, we aim to jointly design the preprocessing and transmission so that the weighted sum of the average AoI of the destination and the energy consumption of the IoT device is minimized. Due to the heterogeneity in transmission and computation capacities, the durations of distinct actions of the IoT device are non-uniform. Therefore, we formulate the status updating problem as an infinite horizon average cost semi-Markov decision process (SMDP) and then transform it into a discrete-time Markov decision process. We demonstrate that the optimal policy is of threshold type with respect to the AoI. Equipped with this, a structure-aware relative policy iteration algorithm is proposed to obtain the optimal policy of the SMDP. Our analysis shows that preprocessing is more beneficial in regimes of high AoIs, given it can reduce the time required for updates. We further prove the switching structure of the optimal policy in a special scenario, where the status updates are transmitted over a reliable channel, and derive the optimal threshold. Finally, simulation results demonstrate the efficacy of preprocessing and show that the proposed policy outperforms two baseline policies.

Supramolecular Core-Shell Nanoassemblies with Tumor Microenvironment-Triggered Size and Structure Switch for Improved Photothermal Therapy.

Photothermal therapy (PTT) is demonstrated to be an effective methodology for cancer treatment. However, the relatively low photothermal conversion efficiency, limited tumor accumulation, and penetration still remain to be challenging issues that hinder the clinical application of PTT. Herein, the core-shell hierarchical nanostructures induced by host-guest interaction between water-soluble pillar[5]arene (WP5) and polyethylene glycol-modified aniline tetramer (TAPEG) are constructed. The pH-responsive performance endows the core-shell nanostructures with size switchable property, with an average diameter of 200nm in the neutral pH and 60nm in the acidic microenvironment, which facilitates not only tumor accumulation but also tumor penetration. Moreover, the structure switch of WP5⊃TAPEG under acidic microenvironment and the dual mechanism regulated extending of п conjugate, inclusion in the hydrophobic cavity of WP5 and the dense distribution in the core-shell structured assemblies, dramatically enhance the absorption in the near-infrared-II region and, further, the photothermal conversion efficiency (60.2%). The as-designed intelligent nanoplatform is demonstrated for improved antitumor efficacy via PTT.

Glycosphingolipids in human embryonic stem cells and breast cancer stem cells, and potential cancer therapy strategies based on their structures and functions.

Expression profiles of glycosphingolipids (GSLs) in human embryonic stem cell (hESC) lines and their differentiated embryoid body (EB) outgrowth cells, consisting of three germ layers, were surveyed systematically. Several globo- and lacto-series GSLs were identified in undifferentiated hESCs and during differentiation of hESCs to EB outgrowth cells, and core structure switching of these GSLs to gangliosides was observed. Such switching was attributable to altered expression of key glycosyltransferases (GTs) in GSL biosynthetic pathways, reflecting the unique stage-specific transitions and mechanisms characteristic of the differentiation process. Lineage-specific differentiation of hESCs was associated with further GSL alterations. During differentiation of undifferentiated hESCs to neural progenitor cells, core structure switching from globo- and lacto-series to primarily gangliosides (particularly GD3) was again observed. During differentiation to endodermal cells, alterations of GSL profiles were distinct from those in differentiation to EB outgrowth or neural progenitor cells, with high expression of Gb4Cer and low expression of stage-specific embryonic antigen (SSEA)-3, -4, or GD3 in endodermal cells. Again, such profile changes resulted from alterations of key GTs in GSL biosynthetic pathways. Novel glycan structures identified on hESCs and their differentiated counterparts presumably play functional roles in hESCs and related cancer or cancer stem cells, and will be useful as surface biomarkers. We also examined GSL expression profiles in breast cancer stem cells (CSCs), using a model of epithelial-mesenchymal transition (EMT)-induced human breast CSCs. We found that GD2 and GD3, together with their common upstream GTs, GD3 synthase (GD3S) and GD2/GM2 synthase, maintained stem cell phenotype in breast CSCs. Subsequent studies showed that GD3 was associated with epidermal growth factor receptor (EGFR), and activated EGFR signaling in breast CSCs and breast cancer cell lines. GD3S knockdown enhanced cytotoxicity of gefitinib (an EGFR kinase inhibitor) in resistant MDA-MB468 cells, both in vitro and in vivo. Our findings indicate that GD3S contributes to gefitinib resistance in EGFR-positive breast cancer cells, and is a potentially useful therapeutic target in drug-resistant breast cancers.

Ultrafast, Light, Soft Martensitic Materials

AbstractMartensitic transformations are well documented in metals and alloys where the atoms connected via metallic bonds rearrange concertedly and rapidly; however, due to the metal atoms, these materials are inherently very dense and add significant weight and bulkiness to actuating devices. Here, remarkably rapid lattice switching of molecular martensitic materials is reported where the rate of structural transformation exceeds other phase transitions several orders of magnitude. With a determined speed in the range of 0.3–0.6 m s−1, the new phase advances throughout the crystal about ten thousand times faster relative to spin‐crossover transitions, and about hundred to hundred thousand times faster than other common structural phase transitions. Macroscopic crystals of these materials respond by rapid expansion or contraction of about 0.02 m s−1 for unrestrained crystals and 0.02–0.03 m s−1 for clamped crystals. Monte–Carlo simulation of the spatiotemporal profile of the transition and of the local distribution of elastic and kinetic energies induced by domain growth reveals the critical role of the dynamic phase boundary and the lattice edges in the structure switching. Within a broader context, this study indicates that the martensitic organic crystals are prospective lightweight substitutes of metals for ultrafast and clean energy transduction.

On the Prediction Policy for Timely Status Updates in Space-Air-Ground Integrated Transportation Systems

In this paper, we investigate the timeliness of the vehicular status updates in space-air-ground integrated networks (SAGIN) for intelligent transportation systems (ITS). The Age of Information (AoI) is introduced to capture the timeliness of the vehicular status updates. To overcome the inherent end-to-end latency taken by the long-distance communications in SAGIN for ITS, prediction has attracted extensive attention in the existing literature and shown its superiority. Nevertheless, it is not clear whether prediction is beneficial to the AoI. Inspired by the motivation, we first formulate a model of a real-time vehicular communication link with prediction, where the generated update can be predicted and transmitted to the receiver in advance. Then, we derive the explicit expression of the average age and show that the prediction is not always beneficial to the AoI. Instead, prediction is more applicable for the short-distance communications than long-distance communications. Further, to improve the AoI performance, a MDP framework is presented to obtain a switching structure of the optimal prediction policy. The results show the advantage of the optimal prediction policy over the policy of predicting all the time or with no predicting.

On-chip leakage current variation measurement using external-reference-free current-to-time conversion for densely placed MOSFETs

This paper proposes a time-domain leakage current measurement circuit that uses an external-reference-free current-to-time conversion. Our proposed current-to-time converter (CTC) utilizes a dual inverter-based conversion to provide a stable reference. We share the CTC among the devices under test (DUTs) for accurate characterization of variation. Our CTC, along with a tree-based switch structure, allows us to densely place and route the DUT transistors using a cell-based design flow similar to a digital circuit design. We demonstrate our circuit by measuring subthreshold leakage currents of 256 minimum sized nMOSFETs in a 65 nm bulk low-power CMOS process. We could successfully extract the variations in subthreshold coefficient and subthreshold leakage current at different temperatures. Our circuit is also robust to supply voltage fluctuation making the circuit suitable for accurate characterization of MOSFET parameters for subthreshold operation.

Stabilizing nano-Pd on porous Li2TiO3via chemical and electrochemical reduction systems for the electrooxidation of ethylene glycol

The challenge of breaking the C–C bond in ethylene glycol oxidation requires an efficient electrocatalyst. A porous oxide as the promoter boosts the dispersion of noble metal onto the electrocatalyst surface. Porous Li2TiO3 (LT) was synthesized, characterized, and applied as a promoter for palladium nanoparticles. The nano-Pd as a stable and efficient catalyst was stabilized on spinel LT promoter via two different reduction approaches including chemical (NaBH4) and electrochemical (Zn sheet/HCl) systems. Different techniques such X-ray diffraction, Fourier Transform Infrared Spectroscopy, Energy-Dispersive X-Ray Spectroscopy, Differential scanning calorimetry, thermogravimetric analysis, Barrett-Joyner-Halenda test, scanning electron microscopy, and transition electron microscopy were characterization of LT and LT/Pd. The size of the mesopores is between 2 and 19 nm. In comparison with non-promoted Pd, Pd/LT electrocatalyst was shown an excellent efficiency in parameters like electrochemical active surface area and anti-CO poisoning behaviour. The LT increases the removal of intermediates created in the oxidation of ethylene glycol that can poison the surface of Pd catalyst. This is due to the presence of the lattice oxygens in LT structure and Ti switching between its high and low valances. The morphology of as-synthesized electrocatalysts that was probed by FESEM micrographs demonstrates the embedment of nano-Pd onto the surface and into LT cavities. The results showed that the nano-Pd manufactured with the chemical reduction has a smaller size with high dispersion than the electrochemical reduction system. In this study, for the first time, the adsorption isotherms of fuel on the catalyst's surface were determined through the calculations of adsorption and desorption of hydrogen in the different concentrations of ethylene glycol.

Recent Progress of Switching Power Management for Triboelectric Nanogenerators.

Based on the coupling effect of contact electrification and electrostatic induction, the triboelectric nanogenerator (TENG) as an emerging energy technology can effectively harvest mechanical energy from the ambient environment. However, due to its inherent property of large impedance, the TENG shows high voltage, low current and limited output power, which cannot satisfy the stable power supply requirements of conventional electronics. As the interface unit between the TENG and load devices, the power management circuit can perform significant functions of voltage and impedance conversion for efficient energy supply and storage. Here, a review of the recent progress of switching power management for TENGs is introduced. Firstly, the fundamentals of the TENG are briefly introduced. Secondly, according to the switch types, the existing power management methods are summarized and divided into four categories: travel switch, voltage trigger switch, transistor switch of discrete components and integrated circuit switch. The switch structure and power management principle of each type are reviewed in detail. Finally, the advantages and drawbacks of various switching power management circuits for TENGs are systematically summarized, and the challenges and development of further research are prospected.

Multivalent Engineering of Exosomes with Activatable Aptamer Probes for Specific Regulation and Monitoring of Cell Targeting.

Reconstituting and probing exosome-cell interactions is critical for elucidating exosome-related cell biology and advancing their diagnostic and therapeutic potential. We report here an exosomal engineering strategy to achieve controlled regulation of exosome-cell interactions with activatable sensing capability. The approach relies on membrane-protein directed, programmable DNA self-assembly to construct a DNA polymeric scaffold with multivalent display of structure-switchable aptamer sensing probes on exosome surfaces. The engineered exosomes exhibit enhanced cancer cell targeting ability compared to exosomes modified with monovalent aptamers. Furthermore, the anchored aptamer probes could be activated by specific membrane protein targeting, followed by structural switching to report an output fluorescence signal, thus allowing dynamic monitoring of exosome-cell interactions both in vitro and in vivo. We envision this will provide a complementary tool for specific regulation and monitoring of exosome-cell docking interactions and will advance the development of exosome-based biomedical applications.

Wireless power transfer system based on LCC/LCL-S variable structure with constant output power

In magnetic coupling wireless power transfer system, the relative position of power transfer coils may change during the operating condition. In order to solve the mutual inductance variation caused by the movement of coils, increase the anti-offset capability of the system to achieve constant power output, a variable structure is proposed in this article. Build the mathematic models of LCC-S and LCL-S structures and analyze the expressions of output power and efficiency in two structures. Design the switching condition, the relationship between coupling coefficient at switching point and parameter setting of capacitor array is obtained with the same input voltage and constant output power. The coupling coefficient range is estimated by output open circuit voltage with a small-voltage input, and the controlling strategy is put forward. Analyze the efficiency of variable structure and build the loss model. It is proved that the switching and input harmonic loss can be reduced by using LCC/LCL-S structure, while the transfer efficiency can be improved through the structure switching between two structures. The simulation results show that the variable structure can effectively reduce the variation range of input voltage and decrease the total harmonic distortion (THD) of input voltage by 46.6%, and keep THD of input current small in a wide range of coupling coefficient.

ATP-Responsive Liposomes via Screening of Lipid Switches Designed to Undergo Conformational Changes upon Binding Phosphorylated Metabolites.

Liposomal delivery vehicles can dramatically enhance drug transport. However, their clinical application requires enhanced control over content release at diseased sites. For this reason, triggered release strategies have been explored, although a limited toolbox of stimuli has thus far been developed. Here, we report a novel strategy for stimuli-responsive liposomes that release encapsulated contents in the presence of phosphorylated small molecules. Our formulation efforts culminated in selective cargo release driven by ATP, a universal energy source that is upregulated in diseases such as cancer. Specifically, we developed lipid switches 1a-b bearing two ZnDPA units designed to undergo substantial conformational changes upon ATP binding, thereby disrupting membrane packing and triggering the release of encapsulated contents. Dye leakage assays using the hydrophobic dye Nile red validated that ATP-driven release was selective over 11 similar phosphorylated metabolites, and release of the hydrophilic dye calcein was also achieved. Multiple alternative lipid switch structures were synthesized and studied (1c-d and 2), which provided insights into the structural features that render 1a-b selective toward ATP-driven release. Importantly, analysis of cellular delivery using fluorescence microscopy in conjunction with pharmacological ATP manipulation showed that liposome delivery was specific, as it increased upon intracellular ATP accumulation, and was inhibited by ATP downregulation. Our new approach shows strong prospects for enhancing the selectivity of release and payload delivery to diseased cells driven by metabolites such as ATP, providing an exciting new paradigm for controlled release.