Functional Switch Research Articles

Multimode Design and Analysis of an Integrated Leg-Arm Quadruped Robot with Deployable Characteristics

To improve locomotion and operation integration, this paper presents an integrated leg-arm quadruped robot (ILQR) that has a reconfigurable joint. First, the reconfigurable joint is designed and assembled at the end of the leg-arm chain. When the robot performs a task, reconfigurable configuration and mode switching can be achieved using this joint. In contrast from traditional quadruped robots, this robot can stack in a designated area to optimize the occupied volume in a nonworking state. Kinematics modeling and dynamics modeling are established to evaluate the mechanical properties for multiple modes. All working modes of the robot are classified, which can be defined as deployable mode, locomotion mode and operation mode. Based on the stability margin and mechanical modeling, switching analysis and evaluation between each mode is carried out. Finally, the prototype experimental results verify the function realization and switching stability of multimode and provide a design method to integrate and perform multimode for quadruped robots with deployable characteristics.

Quasiparticles-mediated thermal diode effect in Weyl Josephson junctions

We theoretically show quasiparticles-driven thermal diode effect (TDE) in an inversion symmetry-broken Weyl superconductor (WSC)-Weyl semimetal (WSM)-WSC Josephson junction. A Zeeman field perpendicular to the WSM region of the thermally-biased Weyl Josephson junction (WJJ) induces an asymmetry between the forward and reverse thermal currents, which is responsible for the TDE. Most interestingly, we show that the sign and magnitude of the thermal diode rectification coefficient is highly tunable by the superconducting phase difference and external Zeeman field, and also strongly depends on the junction length. The tunability of the rectification, particularly, the sign changing behavior associated with higher rectification enhances the potential of our WJJ thermal diode to use as functional switching components in thermal devices.

Broadband intelligent programmable metasurface with polarization-modulated self-adaptive electromagnetic functionality switching

Programmable metasurfaces have received a great deal of attention due to their ability to dynamically manipulate electromagnetic (EM) waves. Despite the rapid growth, most of the existing metasurfaces require manual control to switch among different functionalities, which poses severe limitations on practical applications. Here, we put forth an intelligent metasurface that has self-adaptive EM functionality switching in broadband without human participation. It is equipped with polarization discrimination antennas (PDAs) and feedback components to automatically adjust functionalities for the different incident polarization information. The PDA module can first perceive the polarization of incident EM waves, e.g., linear or circular polarization, and then provide the feedback signal to the controlling platform for switching the EM functionality. As exemplary demonstrations, a series of functionalities in the 9–22 GHz band has been realized, including beam scanning for x-polarization, specular reflection for y-polarization, diffuse scattering for left-handed circular polarization (LCP), and vortex beam generation for right-handed circular polarization (RCP) waves. Experiments verify the good self-adaptive reaction capability of the intelligent metasurface and are in good agreement with the designs. Our strategy provides an avenue toward future unmanned devices that are consistent with the ambient environment.

Dynamic modulation of nodulation factor receptor levels by phosphorylation-mediated functional switch of a RING-type E3 ligase during legume nodulation

The precise control of receptor levels is crucial for initiating cellular signaling transduction in response to specific ligands; however, such mechanisms regulating nodulation factor (NF) receptor (NFR)-mediated perception of NFs to establish symbiosis remain unclear. In this study, we unveil the pivotal role of the NFR-interacting RING-type E3 ligase 1 (NIRE1) in regulating NFR1/NFR5 homeostasis to optimize rhizobial infection and nodule development in Lotus japonicus. We demonstrated that NIRE1 has a dual function in this regulatory process. It associates with both NFR1 and NFR5, facilitating their degradation through K48-linked polyubiquitination before rhizobial inoculation. However, following rhizobial inoculation, NFR1 phosphorylates NIRE1 at a conserved residue, Tyr-109, inducing a functional switch in NIRE1, which enables NIRE1 to mediate K63-linked polyubiquitination, thereby stabilizing NFR1/NFR5 in infected root cells. The introduction of phospho-dead NIRE1Y109F leads to delayed nodule development, underscoring the significance of phosphorylation at Tyr-109 in orchestrating symbiotic processes. Conversely, expression of the phospho-mimic NIRE1Y109E results in the formation of spontaneous nodules in L. japonicus, further emphasizing the critical role of the phosphorylation-dependent functional switch in NIRE1. In summary, these findings uncover a fine-tuned symbiotic mechanism that a single E3 ligase could undergo a phosphorylation-dependent functional switch to dynamically and precisely regulate NF receptor protein levels.

Joining of single-core ex-situ MgB2/Fe wires by termination architecture

The development of reliable jointing technique is of great importance for the future of applied superconductivity, especially for superconducting magnets working in persistent mode. Superconducting joints with termination architecture between single-core not reacted ex-situ MgB2/Fe wires were manufactured and tested. I-V characteristics of joints were measured at 4.2 K and 20 K for variable external fields and compared with I-V of joined wire. The ratio of joints critical current to that of parent conductors (Ic-joint/Ic-wire) has been evaluated and discussed. It was found that Ic-joint with termination architecture may be even larger than Ic-wire at high external field, but decreasing for lower fields. Ic-joint/Ic-wire = 0.8 was measured for the best joint at 20 K and low external field 1.5 T, which is promising for functional persistent switch.

Spatially resolved work-function manipulation of azobenzene-functionalized self-assembled monolayers by optical stimulation

Strongly differing static dipole moments of the trans and cis isomers of photochromic azobenzene allow for optical switching of the work function of azobenzene-functionalized self-assembled monolayers (SAMs). We apply these properties in a fundamental experiment to manipulate the area size of the switched SAM. Azobenzene molecules were excited by ultraviolet laser illumination, and the transient isomerization profile of the SAM was spatially resolved recording photoemission electron microscopy images. Thereby, we demonstrate the spatial tuning of the SAM's work function and discuss the role of the laser spot profile in generating sharp edges or gradual changes of the work function.

Abstract 3114: Time Course Multi-omics Approach Investigating Gene Expression Regulation During Vascular Smooth Muscle Cell Phenotypic Transitioning

Coronary artery disease (CAD) is the leading cause of death in the United States. There is a need for novel therapeutic targets that prevent life-threatening consequences directly associated with plaque accumulation in the vascular wall—the underlying cause of CAD. During the progression of atherosclerosis, vascular smooth muscle cells (VSMCs) transdifferentiate from a contractile to a synthetic phenotype that can either promote fibrous cap stability (fibroblast-like) or contribute to inflammation and plaque accumulation (macrophage or osteoblast-like).The molecular mechanisms driving the functional phenotypic switching of VSMCs are not fully understood and represent a unique opportunity for discovering new treatments directly targeting plaque formation in the vascular wall. We measured gene expression regulation during VSMC dedifferentiation using time-course chromatin remodeling (ATACseq) and nascent transcription data (PROseq). We stimulated VSMCs from three healthy heart transplant donors with PDGF-BB for 0, 4, 8, 12, and 16 hours and performed sequencing in duplicate for each donor at each time point for a total of 30 PROseq and 30 ATACseq libraries. We identified 231,315 regions of accessible chromatin (peaks) in the ATACseq data and 12,954 genes in the PROseq data across the five time points. Likelihood ratio testing detected 13,285 peaks and 7,438 genes with time-dynamic changes in read counts representing six patterns of variable accessibility and nascent transcription following PDGF-BB stimulation: gradual increase/decrease (I/D), immediate I/D, and transient I/D. Transcription factor binding site (TFBS) motif enrichment of dynamic peaks revealed 31 TFs unique to one time dynamic. We identified 157 genes directly downstream of peaks enriched for the 31 TFBSs sharing similar time-specific fold changes. THAP1 binding site motifs had the highest number of cis-regulatory connections (596) and downstream genes (80). Our results capture the first ever time-course ATACseq and PROseq analysis conducted in human VSMCs and provide the ability to predict regulatory edges between TFs and genes in order to map the regulatory cascading events occurring during VSMC switching from a contractile to a synthetic state.

Tunable multifunctional terahertz metasurface based on an indium antimonide medium

Active adjustable terahertz multifunctional devices are crucial for the application of terahertz technology. In this paper, we propose a composite metasurface structure based on an indium antimonide metal octagonal pattern, which achieves different functional switching by controlling the phase state of indium antimonide material under different ambient temperatures. When indium antimonide exhibits in the dielectric state, by stacking and encoding the unit cell, the designed metasurface has the functions of two-beam splitting beam superposition, vortex beam and quarter beam superposition, and dual vortex beam superposition for circularly polarized and linearly polarized wave incidence. When indium antimonide appears in the metallic state, the encoding metasurface alters the modulation function of incident circularly polarized and linearly polarized terahertz waves. This terahertz metasurface provides a new approach for the design of multifunctional devices that can flexibly regulate terahertz wave metasurfaces.

Transcriptomics analysis of long non-coding RNAs in smooth muscle cells from patients with peripheral artery disease and diabetes mellitus

Diabetes mellitus (DM) is a significant risk factor for peripheral arterial disease (PAD), and PAD is an independent predictor of cardiovascular disorders (CVDs). Growing evidence suggests that long non-coding RNAs (lncRNAs) significantly contribute to disease development and underlying complications, particularly affecting smooth muscle cells (SMCs). So far, no study has focused on transcriptome analysis of lncRNAs in PAD patients with and without DM. Tissue samples were obtained from our Vascular Biobank. Due to the sample’s heterogeneity, expression analysis of lncRNAs in whole tissue detected only ACTA2-AS1 with a 4.9-fold increase in PAD patients with DM. In contrast, transcriptomics of SMCs revealed 28 lncRNAs significantly differentially expressed between PAD with and without DM (FDR < 0.1). Sixteen lncRNAs were of unknown function, six were described in cancer, one connected with macrophages polarisation, and four were associated with CVDs, mainly with SMC function and phenotypic switch (NEAT1, MIR100HG, HIF1A-AS3, and MRI29B2CHG). The enrichment analysis detected additional lncRNAs H19, CARMN, FTX, and MEG3 linked with DM. Our study revealed several lncRNAs in diabetic PAD patients associated with the physiological function of SMCs. These lncRNAs might serve as potential therapeutic targets to improve the function of SMCs within the diseased tissue and, thus, the clinical outcome.

Comparison of the Backbone Dynamics of Dehaloperoxidase-Hemoglobin Isoenzymes.

Dehaloperoxidase (DHP) is a multifunctional hemeprotein with a functional switch generally regulated by the chemical class of the substrate. Its two isoforms, DHP-A and DHP-B, differ by only five amino acids and have an almost identical protein fold. However, the catalytic efficiency of DHP-B for oxidation by a peroxidase mechanism ranges from 2- to 6-fold greater than that of DHP-A depending on the conditions. X-ray crystallography has shown that many substrates and ligands have nearly identical binding in the two isoenzymes, suggesting that the difference in catalytic efficiency could be due to differences in the conformational dynamics. We compared the backbone dynamics of the DHP isoenzymes at pH 7 through heteronuclear relaxation dynamics at 11.75, 16.45, and 19.97 T in combination with four 300 ns MD simulations. While the overall dynamics of the isoenzymes are similar, there are specific local differences in functional regions of each protein. In DHP-A, Phe35 undergoes a slow chemical exchange between two conformational states likely coupled to a swinging motion of Tyr34. Moreover, Asn37 undergoes fast chemical exchange in DHP-A. Given that Phe35 and Asn37 are adjacent to Tyr34 and Tyr38, it is possible that their dynamics modulate the formation and migration of the active tyrosyl radicals in DHP-A at pH 7. Another significant difference is that both distal and proximal histidines have a 15-18% smaller S2 value in DHP-B, thus their greater flexibility could account for the higher catalytic activity. The distal histidine grants substrate access to the distal pocket. The greater flexibility of the proximal histidine could also accelerate H2O2 activation at the heme Fe by increased coupling of an amino acid charge relay to stabilize the ferryl Fe(IV) oxidation state in a Poulos-Kraut "push-pull"-type peroxidase mechanism.

Abstract 7253: Oncolytic virus therapy with two-factor authentication shows robust safety and efficacy in liver cancer

Abstract Background: Humane Genomics is pioneering multi-factored authenticated oncolytic virotherapy (OVT) using glycoprotein receptor matching and aptazyme technology to positively control replication in cytoplasm. Using VSV as a platform the OVTs show excellent safety and remain highly lytic. Sindbis virus glycoprotein was mutated to eliminate natural infectivity and retargeted to GPC3 with a codon optimized nanobody. An aptazyme was used to regulate viral replication. As far as we are aware, this was the first report of a functional ON switch using a cancer biomarker. Methods: 293T cells were used for virus rescue and titration by TCID50. Identity was confirmed by Nanopore sequencing. We evaluated safety on off-target SK-Hep-1 and NCI-H28 cell lines, and efficacy on target HepG2 and patient derived HB17 cells. Cell health and GFP was measured at multiple timepoints up to 72 hours. Results: Safety testing of HGI498 on SK-Hep-1 (GPC3 negative) and NCI-H28 (GPC3 negative, biomarker negative) showed no virus induced cell cytopathic effects in a range of 0.01 ≤ MOI ≤1. HGI498’s efficacy testing on HepG2 and HB17 showed tumor cytotoxicity at MOI 0.01 (p&amp;lt;0.001). Endpoint dilution assay showed a 159-fold and 316-fold difference between off-target NCI-H28 and on-target HepG2 and HB17, respectively. We incorporated an optimized aptazyme with the GPC3 targeted glycoprotein (HGI572), which was similarly rescued, titered, and evaluated for selectivity. HGI572 demonstrated approximately 1000-fold higher titer on target HepG2 and HB17 cells than off-target cells. Initial in vivo MTD study shows that both HGI498 and HGI572 are well tolerated, and are currently being investigated in vivo for efficacy on Hep3B in NSG mice. HGI498 has shown no seroprevalence (in vitro) and is stable at cryostorage for a minimum of 11 months. Conclusion: We have successfully engineered a two-factor authentication enabled OVT to address an unmet need for a therapy for liver cancer. As far as we are aware, this is the first report of an ON switch using a cancer protein to control viral replication, and the ON/OFF control is the highest to date. Citation Format: Chad M. Moles, Peter Weijmarshausen, Rupsa Basu, Brenda Ho, Manal Farhat, Taylor Flaat, Bruce F. Smith, Michael Whitt, Sarah E. Woodfield, Sanjeev A. Vasudevan. Oncolytic virus therapy with two-factor authentication shows robust safety and efficacy in liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7253.

Vanadium dioxide-based terahertz metasurface device with switchable broadband absorption and beam steering functions

A simple terahertz (THz) metasurface device with dual functionalities of broadband absorption and beam steering is proposed in this paper. The device exploits the phase change properties of vanadium dioxide (VO2), transitioning between its insulating state and metallic states to achieve functional switching. In the metallic state, the device exhibits broadband absorption, surpassing 90% absorption in the 1.03–2.07 THz range. The absorption function maintains exceptional performance across a wide range of incident angles and possesses polarization insensitive properties. In the insulating state of VO2, the metasurface converts into a THz reflective beam steering device. By employing phase coding, 1-bit coding metasurfaces based on phase gradients are designed, enabling dual-beam and four-beam reflection. Building upon this foundation, 2-bit coding metasurfaces facilitate anomalous reflection of a single beam in distinct directions. Consequently, the device not only toggles between broadband absorption and beam steering but also satisfies the design criteria for 3-bit coding metasurfaces. The modulation characteristics of this device serve as a valuable design reference for multifunctional THz devices in diverse scenarios.

Twisted moiré conductive thermal metasurface

Extensive investigations on the moiré magic angle in twisted bilayer graphene have unlocked the emerging field—twistronics. Recently, its optics analogue, namely opto-twistronics, further expands the potential universal applicability of twistronics. However, since heat diffusion neither possesses the dispersion like photons nor carries the band structure as electrons, the real magic angle in electrons or photons is ill-defined for heat diffusion, making it elusive to understand or design any thermal analogue of magic angle. Here, we introduce and experimentally validate the twisted thermotics in a twisted diffusion system by judiciously tailoring thermal coupling, in which twisting an analog thermal magic angle would result in the function switching from cloaking to concentration. Our work provides insights for the tunable heat diffusion control, and opens up an unexpected branch for twistronics -- twisted thermotics, paving the way towards field manipulation in twisted configurations including but not limited to fluids.

Engineering Site 228 of Streptomyces coelicolor Laccase for Optimizing Catalytic Activity.

Malachite green (MG) poses a formidable threat to ecosystems and human health. Laccase emerges as a promising candidate for MG degradation, prompting an investigation into the catalytic activity modulation of a small laccase (SLAC) from Streptomyces coelicolor, with a focus on amino acid position 228. Through saturation mutagenesis, five mutants with a 50% increase in the specific activity were generated. Characterization revealed notable properties, Km of E228F was 8.8% of the wild type (WT), and E288T exhibited a 133% kcat compared to WT. Structural analyses indicated improved hydrophobicity and electrostatic potential on the mutants' surfaces, with the stable E228F-ABTS complex exhibiting reduced flexibility, possibly contributing to the observed decrease in turnover rate. Mutants demonstrated enhanced MG decolorization, particularly E228G. Site 228 acts as a crucial functional control switch, suggesting its potential role in SLAC engineering. This study provides insights into laccase modulation and offers promising avenues for enzymatic bioremediation applications.

Effect of indoline substitution on ring opening in 6-nitro BIPS spiropyran derivatives

Spiropyrans constitute an important class of photoswitchable compound that have been studied in a variety of applications, including nanomaterials and biological sensing. However, many reported spiropyrans are impractical for these contexts due to a low quantum yield of switching, particularly in the ring opening direction. In this work, we report a series of spiropyrans substituted at the 5-indoline position of 6-NO2-BIPS, as a means to understand the electronic effects of substitution at this position on photochromism. Analysis of 1H NMR spectra reveals that switching is greatest for the spiropyran with the most electron donating group at the 5-position. These findings inform the design of new spiropyran derivatives with improved switching to facilitate their use as functional switches.

The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons

Stalled ribosomes at the endoplasmic reticulum (ER) are covalently modified with the ubiquitin-like protein UFM1 on the 60S ribosomal subunit protein RPL26 (also known as uL24)1,2. This modification, which is known as UFMylation, is orchestrated by the UFM1 ribosome E3 ligase (UREL) complex, comprising UFL1, UFBP1 and CDK5RAP3 (ref. 3). However, the catalytic mechanism of UREL and the functional consequences of UFMylation are unclear. Here we present cryo-electron microscopy structures of UREL bound to 60S ribosomes, revealing the basis of its substrate specificity. UREL wraps around the 60S subunit to form a C-shaped clamp architecture that blocks the tRNA-binding sites at one end, and the peptide exit tunnel at the other. A UFL1 loop inserts into and remodels the peptidyl transferase centre. These features of UREL suggest a crucial function for UFMylation in the release and recycling of stalled or terminated ribosomes from the ER membrane. In the absence of functional UREL, 60S–SEC61 translocon complexes accumulate at the ER membrane, demonstrating that UFMylation is necessary for releasing SEC61 from 60S subunits. Notably, this release is facilitated by a functional switch of UREL from a ‘writer’ to a ‘reader’ module that recognizes its product—UFMylated 60S ribosomes. Collectively, we identify a fundamental role for UREL in dissociating 60S subunits from the SEC61 translocon and the basis for UFMylation in regulating protein homeostasis at the ER.

Signaling from RAS to RAF: The Molecules and Their Mechanisms.

RAF family protein kinases are a key node in the RAS/RAF/MAP kinase pathway, the signaling cascade that controls cellular proliferation, differentiation, and survival in response to engagement of growth factor receptors on the cell surface. Over the past few years, structural and biochemical studies have provided new understanding of RAF autoregulation, RAF activation by RAS and the SHOC2 phosphatase complex, and RAF engagement with HSP90-CDC37 chaperone complexes. These studies have important implications for pharmacologic targeting of the pathway. They reveal RAF in distinct regulatory states and show that the functional RAF switch is an integrated complex of RAF with its substrate (MEK) and a 14-3-3 dimer. Here we review these advances, placing them in the context of decades of investigation of RAF regulation. We explore the insights they provide into aberrant activation of the pathway in cancer and RASopathies (developmental syndromes caused by germline mutations in components of the pathway).

Comparing antipseudomonal effects of honey samples with different geographical and botanical origin

Pseudomonas aeruginosa, resistant to all broad-spectrum antibiotics, is on the World Health Organization's list of first-priority critical pathogens. Using reserve antibiotics, such as colistin, highlights the imperative for safer, more effective alternatives to combat these superbugs.Medical-grade honey, known for its antibacterial properties and efficacy in wound healing, emerges as a promising candidate.This study analyzed eleven honey samples, diverse in geographical, botanical, and entomological origins, for their antipseudomonal activity using the agar well-diffusion method. Zones of inhibition growth were measured in mm. The function switch was used to approximate the zones of inhibition values for antibacterial activity expressed as minimal inhibitory concentrations MIC99, MIC90, and MIC80, the lowest concentration, killing 99 %, 90 %, and 80 % of organisms, respectively. The authenticity and quality of honey samples complied with the European Commission, Codex Alimentarius, and Serbia Rulebook standards for honey. Melissopalynological analysis ensured the botanical authenticity of tested honey samples. A unique aspect of this research is that it included a honey sample from Serbia's Zlatar mountain region, harvested from Apis mellifera carnica bee colonies. The study's findings reveal that wild-type and multidrug-resistant Pseudomonas clinical isolates were susceptible to the tested honey samples. Honeydew honey from Zlatar showed the highest antibacterial activity on both tested bacteria. Honeydew and buckwheat honey from Zlatar yielded larger inhibition zones than manuka honey. Artificial honey showed no antibacterial effect.In conclusion, this research suggests the potential of honey, particularly from Zlatar, as an alternative therapy for treating infected wounds, warranting further investigation into its antimicrobial efficacy.

Gate-Controlled Neuromorphic Functional Transition in an Electrochemical Graphene Transistor.

Neuromorphic devices have attracted significant attention as potential building blocks for the next generation of computing technologies owing to their ability to emulate the functionalities of biological nervous systems. The essential components in artificial neural networks such as synapses and neurons are predominantly implemented by dedicated devices with specific functionalities. In this work, we present a gate-controlled transition of neuromorphic functions between artificial neurons and synapses in monolayer graphene transistors that can be employed as memtransistors or synaptic transistors as required. By harnessing the reliability of reversible electrochemical reactions between carbon atoms and hydrogen ions, we can effectively manipulate the electric conductivity of graphene transistors, resulting in a high on/off resistance ratio, a well-defined set/reset voltage, and a prolonged retention time. Overall, the on-demand switching of neuromorphic functions in a single graphene transistor provides a promising opportunity for developing adaptive neural networks for the upcoming era of artificial intelligence and machine learning.

Enhancing Fault Detection and Classification in Grid-Tied Solar Energy Systems Using Radial Basis Function and Fuzzy Logic-Controlled Data Switch

This study integrates fuzzy logic-controlled data switching and the radial basis function neural network (RBFNN) for fault detection and classification in grid-tied solar energy systems. The fuzzy logic controller filters out invalid sensor data through a data switch, ensuring that the fault detection and classification system receives reliable input. Training data were prepared through data normalization using the z-score function and principal component analysis, thereby reducing data complexity and standardizing the inputs. The resulting RBFNN model exhibited a low mean squared error with a value of 7.67×10-4, indicating its ability to classify faults based on the actual system scenarios. Performance evaluation metrics, including accuracy, precision, recall, and F1-score, were used to assess the effectiveness of the RBFNN model. The model demonstrated high accuracy (96.4%), precision (98.281%), recall (98.013%), and F1-score (98.147%), indicating the suitability and effectiveness of the RBFNN model to identify and classify faults in grid-tied solar energy systems.