Direct Signal Research Articles

Quantitative magnetooptical analysis using indicator films for the detection of magnetic field distributions, temperature, and electrical currents

The accurate characterization of local magnetic fields and temperature is vital for the design of electronic systems. To meet this imperative, we present a novel non-contact approach for simultaneous quantitative magnetic field imaging and temperature sensing using magnetooptics and a bismuth-doped yttrium iron garnet film with out-of-plane anisotropy. For the direct signal quantification, a Stokes polarization camera is employed in a conventional magnetooptical microscope. The magnetization in the garnet is modulated with an external magnetic field to continuously image the Faraday rotation at four distinct points along the saturating magnetization loop. The method enables sensing of the magnetooptical signal in saturation, the magnetooptical susceptibility, the temperature, and self-calibrated driftfree imaging of the out-of-plane magnetic field component. A spatial resolution of magnetic field in the micrometer range with millisecond exposure time is demonstrated. The method is verified by analyzing the stray magnetic field distribution of electrical current in a wire simultaneously to the Joule heating induced by the applied current.

Supercharged fluorescent proteins detect lanthanides via direct antennae signaling

A sustainable operation for harvesting metals in the lanthanide series is needed to meet the rising demand for rare earth elements across diverse global industries. However, existing methods are limited in their capacity for detection and capture at environmentally and industrially relevant lanthanide concentrations. Supercharged fluorescent proteins have solvent-exposed, negatively charged residues that potentially create multiple direct chelation pockets for free lanthanide cations. Here, we demonstrate that negatively supercharged proteins can bind and quantitatively report concentrations of lanthanides via an underutilized lanthanide-to-chromophore pathway of energy transfer. The top-performing sensors detect lanthanides in the micromolar to millimolar range and remain unperturbed by environmentally significant concentrations of competing metals. As a demonstration of the versatility and adaptability of this energy transfer method, we show proximity and signal transmission between the lanthanides and a supramolecular assembly of supercharged proteins, paving the way for the detection of lanthanides via programmable protein oligomers and materials.

Long range juxtacrine signalling through cadherin for collective cell orientation

Many life phenomena, such as development, morphogenesis, tissue remodelling, and wound healing, are often driven by orderly and directional migration of collective cells. However, when cells are randomly oriented or localized disorder exists in orderly oriented collective cells, cell migration cannot occur in an orderly manner although various motion modes such as global rotation and local swirling and/or various motion patterns such as radial pattern and chiral pattern often occur. Therefore, it is important to control cell orientation to ensure the orderly migration of collective cells. Here, we show that it is not force transmission, but juxtacrine signalling through cadherin that plays a critical role in the orientation of collective cells. Surprisingly, juxtacrine signalling for cell orientation reached cells on a plastic dish that were not directly subjected to mechanical stimulation, up to 7 mm away from the actuator. The present study suggests that even weak mechanical stimulation is transmitted in a long range without force transmission through juxtacrine signalling. The long range juxtacrine signalling might play an important role in various life phenomena. Statement of SignificanceJuxtacrine signalling is direct cell-cell contact-dependent signalling, which plays a crucial role in cell behaviors such as mechanosensing, mechanotransduction and collective cell behaviors, however, there is not enough understanding about juxtacrine signalling. The present study has demonstrated that juxtacrine signalling for collective cell orientation is transmitted over a long range through cadherin. To the best of our knowledge, this is the first report of long range juxtacrine signalling. This finding may lead to the elucidation of various life phenomena such as development, morphogenesis, tissue remodelling, and wound healing.

Fluid mediated communication among flexible micro-posts in chemically reactive solutions.

Communication in biological systems typically involves enzymatic reactions that occur within fluids confined between the soft, elastic walls of bio-channels and chambers. Through the inherent transformation of chemical to mechanical energy, the fluids can be driven to flow within the confined domains. Through fluid-structure interactions, the confining walls in turn are deformed by and affect this fluid flow. Imbuing synthetic materials with analogous feedback among chemo-mechanical, hydrodynamic and fluid-structure interactions could enable materials to perform self-driven communication and self-regulation. Herein, we develop computational models to determine how chemo-hydro-mechanical feedback affects interactions in biomimetic arrays of chemically active and passive micro-posts anchored in fluid-filled chambers. Once activated, the enzymatic reactions trigger the latter feedback, which generates a surprising variety of long-range, cooperative motion, including self-oscillations and non-reciprocal interactions, which are vital for propagating coherent, directional signals over net distances in fluids. In particular, the array propagates a distinct message; each post interprets the message; and the system responds with a specific mode of organized, collective behavior. This level of autonomous remote control is relatively rare in synthetic systems, particularly as this system operates without external electronics or power sources and only requires the addition of chemical reactants to function.

A TDLAS gas detection method based on digital signal modulation

This research presents a novel TDLAS gas concentration detection method based on digital modulation. The method inherits the advantage of a simple system structure from Direct Absorption Spectroscopy, as well as the excellent sensitivity of Wavelength Modulation Spectroscopy. A low-frequency sawtooth wave is employed to drive the laser, resulting in a digital direct absorption spectrum signal. By constructing a cosine modulation sequence in the time domain and performing linear interpolation on the direct absorption spectrum, it successfully converts to a wavelength-modulated absorption spectrum and simultaneously generates a digital reference signal at double the frequency. Ultimately, phase-locked amplification technology can be used to calculate the amplitude of the second harmonic. Since both the modulation and reference signals are generated digitally, they ensure a strict frequency-doubling relationship and phase correlation, which not only reduces the complexity of the hardware system but also effectively minimizes system errors. Because digital technology generates both the modulation and reference signals, it ensures that they have the same phase and a strict frequency-doubling relationship. Experimental results demonstrate that, when fitted by a cubic polynomial, the second harmonic amplitude and the gas concentration have a correlation coefficient (R2) as high as 0.99999 and a root mean square error as low as 0.0011. This proves the method's great accuracy and reliability in practical applications.

A metabolic dysfunction-associated steatotic liver acinus biomimetic induces pancreatic islet dysfunction in a coupled microphysiology system

Preclinical and clinical studies suggest that lipid-induced hepatic insulin resistance is a primary defect that predisposes to dysfunction in islets, implicating a perturbed liver-pancreas axis underlying the comorbidity of T2DM and MASLD. To investigate this hypothesis, we developed a human biomimetic microphysiological system (MPS) coupling our vascularized liver acinus MPS (vLAMPS) with pancreatic islet MPS (PANIS) enabling MASLD progression and islet dysfunction to be assessed. The modular design of this system (vLAMPS-PANIS) allows intra-organ and inter-organ dysregulation to be deconvoluted. When compared to normal fasting (NF) conditions, under early metabolic syndrome (EMS) conditions, the standalone vLAMPS exhibited characteristics of early stage MASLD, while no significant differences were observed in the standalone PANIS. In contrast, with EMS, the coupled vLAMPS-PANIS exhibited a perturbed islet-specific secretome and a significantly dysregulated glucose stimulated insulin secretion response implicating direct signaling from the dysregulated liver acinus to the islets. Correlations between several pairs of a vLAMPS-derived and a PANIS-derived factors were significantly altered under EMS, as compared to NF conditions, mechanistically connecting MASLD and T2DM associated hepatic-factors with islet-derived GLP-1 synthesis and regulation. Since vLAMPS-PANIS is compatible with patient-specific iPSCs, this platform represents an important step towards addressing patient heterogeneity, identifying disease mechanisms, and advancing precision medicine.

Highly robust electronic skin for object recognition of robot hand based on carbon nanomaterials and SEBS

When robot hands work in a complex environment, they not only need to sense the objects in contact but also need to respond to remote events before physical contact. In this way, robot hands can make predictions, to better adapt to the complex environment. In this paper, we have designed a flexible sensor array, which integrates a piezoresistive sensor and a capacitive sensor for detecting pressure and proximity direction and distance signals simultaneously. Piezoresistive sensors can detect pressure signals in real-time, and capacitive sensors detect pressure and proximity signals. The sensors are arranged in a patterned array and installed on the robot hand to help the robot hand detect the distance and direction of approaching objects, as well as the shape and size of the grasped objects. To avoid mechanical mismatch, piezoresistive sensors and capacitive sensors are fabricated with the same flexible materials. In addition, after extreme pressure tests, the sensors can still work normally, to ensure that the robot hands can work normally after collision. We also combined the detected signal with machine learning, so that the robot can accurately identify objects of different shapes. In the fruit recognition test, the recognition accuracy reached 90 %.

Modelling the effects of a random medium on direct and reflected sound signals from a moving source

Randomnesses in acoustic propagation conditions affect the signal at a receiver placed at a distance from the source. Without any reflecting surface the random medium causes fluctuations in amplitude and phase of the received signal. In the presence of a wave reflecting surface, a version of the signal with other fluctuations is added at the receiver, with some amount of correlation between the direct signal and the reflected signal. A method is presented that in a single approach includes the random fluctuations of the received signals and the decorrelation effect for signal pairs. Numerical examples are calculated and validated in terms of mutual coherence functions by comparison with analytical solutions for different conditions of atmospheric turbulence. Exemplifying sounds with different source signals are produced for a moving source.

FGF4 and ascorbic acid enhance the maturation of induced cardiomyocytes by activating JAK2-STAT3 signaling.

Direct cardiac reprogramming represents a novel therapeutic strategy to convert non-cardiac cells such as fibroblasts into cardiomyocytes (CMs). This process involves essential transcription factors, such as Mef2c, Gata4, Tbx5 (MGT), MESP1, and MYOCD (MGTMM). However, the small molecules responsible for inducing immature induced CMs (iCMs) and the signaling mechanisms driving their maturation remain elusive. Our study explored the effects of various small molecules on iCM induction and discovered that the combination of FGF4 and ascorbic acid (FA) enhances CM markers, exhibits organized sarcomere and T-tubule structures, and improves cardiac function. Transcriptome analysis emphasized the importance of ECM-integrin-focal adhesions and the upregulation of the JAK2-STAT3 and TGFB signaling pathways in FA-treated iCMs. Notably, JAK2-STAT3 knockdown affected TGFB signaling and the ECM and downregulated mature CM markers in FA-treated iCMs. Our findings underscore the critical role of the JAK2-STAT3 signaling pathway in activating TGFB signaling and ECM synthesis in directly reprogrammed CMs. Schematic showing FA enhances direct cardiac reprogramming and JAK-STAT3 signaling pathways underlying cardiomyocyte maturation.

Location-biased β-arrestin conformations direct GPCR signaling.

β-arrestins are multifunctional intracellular proteins that regulate the desensitization, internalization and signaling of over 800 different G protein-coupled receptors (GPCRs) and interact with a diverse array of cellular partners1,2. Beyond the plasma membrane, GPCRs can initiate unique signaling cascades from various subcellular locations, a phenomenon known as "location bias"3,4. Here, we investigate how β-arrestins direct location-biased signaling of the angiotensin II type I receptor (AT1R). Using novel bioluminescence resonance energy transfer (BRET) conformational biosensors and extracellular signal-regulated kinase (ERK) activity reporters, we reveal that in response to the endogenous agonist Angiotensin II and the β-arrestin-biased agonist TRV023, β-arrestin 1 and β-arrestin 2 adopt distinct conformations across different subcellular locations, which are intricately linked to differential ERK activation profiles. We also uncover a population of receptor-free catalytically activated β-arrestins in the plasma membrane that exhibits insensitivity to different agonists and promotes ERK activation on the plasma membrane independent of G proteins. These findings deepen our understanding of GPCR signaling complexity and also highlight the nuanced roles of β-arrestins beyond traditional G protein pathways.

A selective dual-signal electrochemical paper-based device using imprinted sensors for voltammetric and impedance analysis of 4-NQO and carcinoembryonic antigen (CEA)

BackgroundCarcinoembryonic Antigen (CEA) and 4-nitroquinoline-N-oxide (4-NQO) are cancer markers that play a crucial role in tumor risk assessment and early cancer diagnosis. Therefore, it is in demand to develop a fast, accurate, simple, and cost-effective method to detect these cancer markers for quick and early stage-cancer diagnosis and treatment. ResultsHerein, we report a dual signaling approach for direct and indirect signal transduction of cancer biomarker binding on molecularly imprinted-electrodes integrated on an ePAD, enabling sensitive and selective quantitative analysis of 4-NQO and CEA. Multiple test zones on a single device based on artificial recognition sites using core-shell Cu-MOF@MIP were developed to create a selective “Dual-signal-ePAD”. An effective and facile imprinting method on a Cu-MOF surface based on the synthesized of 4-VPBA/MAA/TRIM polymer. It resulted in a novel MIP useable as a high-performance sensing tool for the ultrasensitive and specific quantification of the target cancer biomarkers. Multiple tests consisted of voltammetric analysis of 4-NQO via oxidation of the analyte on a WE1, and impedance analysis of CEA via the molecular interaction with the imprinted WE2. SignificanceThe proposed device provides enhanced electrochemical signal amplification due to its high conductivity, electrocatalytic activity, and the target-specific recognition sites for accurate determination of 4-NQO and CEA targets. The Dual-signal-ePAD exhibits good voltammetric and EIS response, oxidation currents of 4-NQO at −0.06 V and RCT of CEA, resulting in high selectivity and sensitivity with a linear response range covering the concentration range of clinical interest for both analytes. Dual-signal ePAD is a good candidate for clinical screening and POCT.

Optimization in Visual Motion Estimation.

Sighted animals use visual signals to discern directional motion in their environment. Motion is not directly detected by visual neurons, and it must instead be computed from light signals that vary over space and time. This makes visual motion estimation a near universal neural computation, and decades of research have revealed much about the algorithms and mechanisms that generate directional signals. The idea that sensory systems are optimized for performance in natural environments has deeply impacted this research. In this article, we review the many ways that optimization has been used to quantitatively model visual motion estimation and reveal its underlying principles. We emphasize that no single optimization theory has dominated the literature. Instead, researchers have adeptly incorporated different computational demands and biological constraints that are pertinent to the specific brain system and animal model under study. The successes and failures of the resulting optimization models have thereby provided insights into how computational demands and biological constraints together shape neural computation.

The Effect of Tissue Inhibitor of Metalloproteinases on Scar Formation after Spinal Cord Injury.

Spinal cord injury (SCI) often results in permanent loss of motor and sensory function. After SCI, the blood-spinal cord barrier (BSCB) is disrupted, causing the infiltration of neutrophils and macrophages, which secrete several kinds of cytokines, as well as matrix metalloproteinases (MMPs). MMPs are proteases capable of degrading various extracellular matrix (ECM) proteins, as well as many non-matrix substrates. The tissue inhibitor of MMPs (TIMP)-1 is significantly upregulated post-SCI and operates via MMP-dependent and MMP-independent pathways. Through the MMP-dependent pathway, TIMP-1 directly reduces inflammation and destruction of the ECM by binding and blocking the catalytic domains of MMPs. Thus, TIMP-1 helps preserve the BSCB and reduces immune cell infiltration. The MMP-independent pathway involves TIMP-1's cytokine-like functions, in which it binds specific TIMP surface receptors. Through receptor binding, TIMP-1 can stimulate the proliferation of several types of cells, including keratinocytes, aortic smooth muscle cells, skin epithelial cells, corneal epithelial cells, and astrocytes. TIMP-1 induces astrocyte proliferation, modulates microglia activation, and increases myelination and neurite extension in the central nervous system (CNS). In addition, TIMP-1 also regulates apoptosis and promotes cell survival through direct signaling. This review provides a comprehensive assessment of TIMP-1, specifically regarding its contribution to inflammation, ECM remodeling, and scar formation after SCI.

An impulsive noise filter for rail vibration measurements using a laser Doppler vibrometer on a moving platform

This paper proposes a new impulsive noise (i.e., IN) filter for non-contact rail vibration measurements performed by a laser Doppler vibrometer (i.e., LDV) placed on a moving rail car. The development of the filter is motivated by the fact that such measurements can be contaminated by IN, which is caused by a high level of speckle noise due to the movement of the LDV. Consequently, some portions of the LDV signals can be distorted, leading to missing measurements from some rail segments. The proposed filter consists of two main steps: (i) detecting the signal segments containing the IN (i.e., detection step), and (ii) replacing the detected segments to estimate their IN-free values (i.e., estimation step). The performance of the filter was evaluated on a synthetic signal, which was created by combining a rail vibration signal in the vertical direction (i.e., vibration component) with a speckle noise signal of an LDV placed on a moving platform (i.e., noise component). The reason to use a synthetic signal was to know the vibration and noise components separately. This allowed for the examination of IN’s behavior, which showed that IN manifests itself as artificial peaks as well as high-frequency noise in the proximity of artificial peaks (i.e., artificial fluctuations). Accordingly, the proposed filter was designed to detect and replace both artificial peaks and fluctuations. Qualitative and quantitative evaluations of the filtered synthetic signal showed that the proposed filter exhibited good performance in mitigating the IN.

Connecting genomic and proteomic signatures of amyloid burden in the brain.

Alzheimer's disease (AD) has a high heritable component characteristic of complex diseases, yet many of the genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may be helpful to understand the underlying biology of the disease. We performed a meta-analysis of GWAS of CSF Aβ42 and PET measures combining six independent cohorts (n=2,076). Due to the opposite effect direction of Aβ phenotypes in CSF and PET measures, only genetic signals in the opposite direction were considered for analysis (n=376,599). Polygenic risk scores (PRS) were calculated and evaluated for AD status and amyloid endophenotypes. We then searched the CSF proteome signature of brain amyloidosis using SOMAscan proteomic data (Ace cohort, n=1,008) and connected it with GWAS results of loci modulating amyloidosis. Finally, we compared our results with a large meta-analysis using publicly available datasets in CSF (n=13,409) and PET (n=13,116). This combined approach enabled the identification of overlapping genes and proteins associated with amyloid burden and the assessment of their biological significance using enrichment analyses. After filtering the meta-GWAS, we observed genome-wide significance in the rs429358-APOE locus and nine suggestive hits were annotated. We replicated the APOE loci using the large CSF-PET meta-GWAS and identified multiple AD-associated genes as well as the novel GADL1 locus. Additionally, we found a significant association between the AD PRS and amyloid levels, whereas no significant association was found between any Aβ PRS with AD risk. CSF SOMAscan analysis identified 1,387 FDR-significant proteins associated with CSF Aβ42 levels. The overlap among GWAS loci and proteins associated with amyloid burden was very poor (n=35). The enrichment analysis of overlapping hits strongly suggested several signalling pathways connecting amyloidosis with the anchored component of the plasma membrane, synapse physiology and mental disorders that were replicated in the large CSF-PET meta-analysis. The strategy of combining CSF and PET amyloid endophenotypes GWAS with CSF proteome analyses might be effective for identifying signals associated with the AD pathological process and elucidate causative molecular mechanisms behind the amyloid mobilization in AD.

MSTKernel Net: a rolling bearing intelligent diagnosis framework based on short-time time–frequency convolution

Abstract Monitoring rotating machinery is a key task in modern production processes. The emergence of deep learning technology has significantly improved the performance of intelligent diagnosis systems for such machinery. However, despite the commendable performance of many existing frameworks, they lack transparency, which hinders their interpretability in fault diagnosis based on directional signals. This study addresses this challenge by delving into the fault features present in vibration signals and designing a convolutional module specifically tailored to these characteristics, modularized short time–frequency kernel (MSTKernel). This innovative framework, MSTKernel Network, employs convolutional neural networks for feature extraction, simulating the time–frequency sliding process through convolutional properties while preserving temporal features and enriching fault diagnosis information. Through experimental data testing and visualization of convolutional kernel characteristics, we evaluate the potential of this framework to significantly enhance the fault diagnosis capability of rolling bearings, demonstrating its practicality and effectiveness in real-world applications.

Double-side debonding detection of honeycomb sandwich structure based on air-coupled ultrasonic guided waves

Abstract In structural health monitoring, fast, non-destructive, and non-contact testing has gradually become an important demand. This paper presents a double-side debonding detection method of honeycomb sandwich structure (HSS) based on the air-coupled guided wave. We analyze the dispersion characteristics and propagation law of guided waves in a honeycomb sandwich structure (HSS) using numerical simulation. Moreover, dispersion compensation was employed to reduce the stacking of signals. Finally, the debonding region was imaged. It realizes debonding detection on both upper and lower skins according to the amplitude changes of the direct wave signal and coda wave signal.

Presubicular VIP expressing interneurons receive facilitating excitation from anterior thalamus

The presubiculum is part of the parahippocampal cortex and plays a fundamental role for orientation in space. Many principal neurons of the presubiculum signal head direction, and show persistent firing when the head of an animal is oriented in a specific preferred direction. GABAergic neurons of the presubiculum control the timing, sensitivity and selectivity of head directional signals from the anterior thalamic nuclei. However, the role of vasoactive intestinal peptide (VIP) expressing interneurons in the presubicular microcircuit has not yet been addressed. Here, we examined the intrinsic properties of VIP interneurons as well as their input connectivity following photostimulation of anterior thalamic axons. We show that presubicular VIP interneurons are more densely distributed in superficial than in deep layers. They are highly excitable. Three groups emerged from the unsupervised cluster analysis of their electrophysiological properties. We demonstrate a frequency dependent recruitment of VIP cells by thalamic afferences and facilitating synaptic input dynamics. Our data provide initial insight into the contribution of VIP interneurons for the integration of thalamic head direction information in the presubiculum.

PhotoSolver: A bidirectional photonic solver for systems of linear equations

Solving systems of linear equations is one of the most fundamental challenges in computing, with ubiquitous applications in science and engineering. Solving large-scale linear equations is particularly challenging, requiring tremendous computing expenses. However, conventional solvers in electronic digital computers face inevitable physical bottlenecks that hinder further advancements in electronic chips. Unlike the electronic architectures, optical computing harnesses the inherent advantages of lights, such as ultimately high speed, negligible energy consumption, and high parallelism, making optical architectures attractive sources for ultra-high speed analog computing. Especially, recent advances in integrated photonic circuits bring exciting new possibilities for high performance computing based on photonic chips. In this work, we propose a bidirectional PhotoSolver using the propagation of optical signals in different directions on a single integrated photonic chip to perform multiple operations in solving systems of linear equations, scalable to solve large-scale systems. Specifically, we propose an in situ approach to iteratively update solutions by performing the forward and backward propagations within a single photonic chip. Furthermore, we propose a partitioning approach to solve large-scale systems using arrays of photonic chips. Numerical experiments demonstrate these capabilities with representative systems of linear equations. By utilizing lights propagating in integrated photonic chips, our PhotoSolvers provide a promising computing architecture to solve large systems of linear equations, with potentials in wide computational applications.

Direct Growth of Vertical Graphene on Fiber Electrodes and Its Application in Alternating Current Line-Filtering Capacitors.

Fiber-shaped electrochemical capacitors (FSECs) have garnered substantial attention to emerging portable, flexible, and wearable electronic devices. However, achieving high electronic and ionic conductivity in fiber electrodes while maintaining a large specific surface area is still a challenge for enhancing the capacitance and rapid response of FSECs. Here, we present an electric-field-assisted cold-wall plasma-enhanced chemical vapor (EFCW-PECVD) method for direct growth of vertical graphene (VG) on fiber electrodes, which is incorporated in the FSECs. The customized reactor mainly consists of two radio frequency coils: one for plasma generation and the other for substrate heating. Precise temperature control can be achieved by adjusting the conductive plates and the applied power. With induction heating, only the substrate is heated to above 500 °C within just 5 min, maintaining a low temperature in the gas phase for the growth of VG with a high quality. Using this method, VG was easily grown on metallic fibers. The VG-coated titanium fibers for FSECs exhibit an ultrahigh rate performance and quick ion transport, enabling the conversion of an alternating current signal to a direct current signal and demonstrating outstanding filtering capabilities.