Browse Articles

HIL co-simulation of an optimal hybrid fractional-order type-2 fuzzy PID regulator based on dSPACE for quadruple tank system

Bipartite binding of the intrinsically disordered scaffold protein JIP1 to the kinase JNK1

Scaffold proteins are key players in many signaling pathways where they ensure spatial and temporal control of molecular interactions by simultaneous tethering of multiple signaling components. The protein JIP1 acts as a scaffold within the c-Jun N-terminal kinase (JNK) signaling pathway by assembling three kinases, MLK3, MKK7, and JNK, into a macromolecular complex that enables their specific activation. The recruitment of these kinases depends on the 450-amino acid intrinsically disordered tail of JIP1, however, the structural details of this tail and the molecular mechanisms by which it binds kinases have remained elusive. Here, we provide an atomic resolution structural description of the JIP1 tail, and we study its interaction with the kinase JNK1. Using NMR spectroscopy, we show that JNK1 not only engages with the well-known docking site motif (D-motif) of JIP1, but also interacts with a noncanonical F-motif. We determine the crystal structure of the JIP1–JNK1 complex at 2.35 Å resolution revealing a bipartite binding mode of JIP1. Our work provides insights into the sequence determinants of F-motifs suggesting that these motifs may be more prevalent in JNK substrates than previously recognized. More broadly, our study highlights the power of NMR spectroscopy in uncovering kinase interaction motifs within disordered scaffold proteins, and it paves the way for atomic-resolution interaction studies of JIP1 with its multitude of interaction partners.

A new method based on binary mixture concept for prediction of ionic liquids critical properties using molecular dynamics simulation

Policy options for the drug pricing conundrum

Current proposals aimed at reducing U.S. pharmaceutical prices would have immediate benefits (particularly for low-income and elderly populations), but could dramatically reduce firms’ investment in potentially highly welfare-improving Research and Development (R&D). The United States subsidizes the worldwide pharmaceutical market: U.S. drug prices are more than 250% of those in other Organization for Economic Co-operation and Development (OECD) countries. If each drug had a single international price across the highest-income OECD countries and total pharmaceutical firm profits were held fixed: U.S. prices would fall by half; every other country’s prices would increase (by 28 to over 300%); and R&D incentives would be maintained. We propose a potential lever for the U.S. government to influence worldwide drug pricing: access to the Medicare market.

Theoretical investigation of parallel 63NiO/GaP heterojunction nuclear battery with graphene layer and its time-related performance

Abstract Betavoltaic (BV) batteries are regarded as appealing power sources due to their high energy densities and long lifetimes. However, the low efficiency and maximum output power density of conventional BV batteries due to the self-absorption effect of radioactive sources, which consist of separate beta-radioactive sources and semiconductor absorbers, limit their applications. In this work, we optimized and compared six 63NiO-related heterojunction nuclear batteries utilizing Monte Carlo software Geant4 and finite element analysis software COMSOL Multiphysics. The 63NiO-related heterojunction nuclear batteries integrate beta-radioactive sources and semiconductor absorbers to overcome the shortcomings of conventional BV batteries. Furthermore, we proposed a parallel connection structure utilizing graphene electrode layer to connect two 63NiO/GaP heterojunctions based on the optimal one from the six heterojunctions in order to maximize the maximum output power density. The total energy conversion efficiency is 2.68% and the maximum output power density is $$5236.2\hbox { nW}\cdot \hbox {cm}^{-2}$$ of the parallel connection nuclear battery. Finally, we investigated the time-related performance of the parallel connection structure nuclear battery within 200 years. It shows that the maximum output power density decreases from $$5236.2\hbox { nW}\cdot \hbox {cm}^{-2}$$ in the beginning to $$1330.5\hbox { nW}\cdot \hbox {cm}^{-2}$$ at 200 years.

Direct control of electron spin at an intrinsically chiral surface for highly efficient oxygen reduction reaction

The oxygen reduction reaction (ORR) in acidic media suffers from sluggish kinetics, primarily due to the spin-dependent electron transfer involved. The direct generation of spin-polarized electrons at catalytic surfaces remains elusive, and the underlying mechanisms are still controversial due to the lack of intrinsically chiral catalysts. To address this challenge, we investigate topological homochiral PdGa (TH PdGa) crystals with intrinsically chiral catalytic surfaces for ORR. Through spin-resolved photoemission spectroscopy and theoretical simulations, we show that both structural chirality and spin–orbit coupling are critical for inducing spin polarization at the surface of TH PdGa. As a result, TH PdGa achieves a kinetic current density over 100 times higher than the achiral PdGa (AC PdGa) at 0.85 V versus the reversible hydrogen electrode. This work underscores the pivotal role of spin polarization in enhancing acidic ORR activity and lays the groundwork for the rational design of chiral catalysts for spin-dependent catalysis.

Dynamic assessment of eco-environmental quality in Xiong’an new area, China using WB-RSEI new model

Computational biology predicts metabolic engineering targets for increased production of 103 valuable chemicals in yeast

Development of efficient cell factories that can compete with traditional chemical production processes is complex and generally driven by case-specific strategies, based on the product and microbial host of interest. Despite major advancements in the field of metabolic modeling in recent years, prediction of genetic modifications for increased production remains challenging. Here, we present a computational pipeline that leverages the concept of protein limitations in metabolism for prediction of optimal combinations of gene engineering targets for enhanced chemical bioproduction. We used our pipeline for prediction of engineering targets for 103 different chemicals using Saccharomyces cerevisiae as a host. Furthermore, we identified sets of gene targets predicted for groups of multiple chemicals, suggesting the possibility of rational model-driven design of platform strains for diversified chemical production.

Predictive framework of vegetation resistance in channel flow

Ectopic mouse TMC1 and TMC2 alone form mechanosensitive channels that are potently modulated by TMIE

The mechanotransduction (MT) channel expressed in cochlear and vestibular hair cells converts the mechanical stimulation of sound and head movements into electrochemical signals. Recently, TMC1 and TMC2 (TMC1/2) have been recognized as the pore-forming subunit of the MT channel, but TMC1/2 functional expression in heterologous cells—which is critical for unequivocally identifying them as the bona fide pore-forming subunit of the MT channel—has not been achieved because ectopic TMC1/2 become trapped in the ER. Here, we report that adding a Fyn lipidation tag to mouse TMC1/2 (mTMC1/2) drove their cell-surface expression, and, importantly, full-length mTMC1/2 expressed alone functioned as mechanosensitive channels, underscoring the view that TMC1/2 constitute the sole pore-forming subunit of the MT channel. Moreover, mouse transmembrane inner ear (TMIE) (mTMIE) protein robustly stimulated TMC1/2 channel activity by modulating their gating. Intriguingly, the N-terminal 27 residues of mTMIE were dispensable for regulating TMC1/2 in our in vitro functional assay, whereas, in striking contrast, mutating mTMIE C76C77, the predicted palmitoylation sites, eliminated mTMIE stimulation of mTMC1/2, indicating a crucial role of the palmitoyl group in regulating TMC1/2 gating. mTMC1/2+mTMIE form 18 pS and 24 pS single channels, respectively. mTMC1/2+mTMIE single channels showed biophysical and pharmacological properties similar to those of the MT channel. Our findings provide insights into several fundamental and debated aspects of the function of TMC1/2 and TMIE, and our functional assay of TMC1/2 and TMIE in heterologous cells will facilitate further functional and structural characterization of these proteins and other MT-complex components.

Algorithmic and mathematical modeling for synthetically controlled overlapping

Chiral structural color from microdomes

Artificial chiral-structural-color materials can carry high-dimensional information based on multiple optical degrees of freedom, providing possibilities for advanced optical security and information storage. However, current artificial chiral-structural-color materials are hindered by their specific compositions, fine nanostructures, and single polarization modulation. Here, we found that microdomes made from common polymers have chiral structural colors with broadband tunability and multiple polarization-modulated chirality. The microdome patterns are easily fabricated by ordinary printing techniques and have inhomogeneous spatial distributions of full polarization states and customizable colors. Our chiral-structural-color microdomes (CSCMs) provide a promising roadmap for high-capacity information encryption and high-security anti-counterfeiting. We developed multidimensional tunable structural color displays and achieved encryption with high information capacity. To further highlight the application potential, we constructed contact lenses integrated with CSCMs for identity authentication with 2 32 distinctive cryptograms.

Integrating quantum synchronization in future generation networks

Abstract The advent of Beyond 5G (emerging 6G) technologies represents a significant step forward in telecommunications, offering unprecedented data speeds and connectivity. These advances enable a wide range of applications, from enhanced mobile broadband and the Internet of Things to ultra-reliable low-latency communication and the tactical Internet. Thus, having accurate and dependable time synchronization is of utmost importance and plays a critical role in ensuring that all processes function smoothly and effectively. However, existing standards, such as the precision time protocol, are unreliable due to jitters, datagram losses, and complexity. Increasing the synchronization error from the ideal tens of nanoseconds to hundreds of microseconds is unacceptable in future-generation networks. This work provides a novel way to establish ultraprecise synchronization, which is critical for the growth of converged optical communication networks and the 6G era. We investigate quantum non-linear synchronization (QNS), which explores the interaction between the non-linear dynamics of atomic systems and dissipation to establish a stable limit-cycle state. In this process, atoms confined within optical resonators are subjected to potential fields, and their spatial motion is synchronized by achieving a stable, phase-locked configuration. By introducing photons into the optical resonators and precisely managing the dissipation effects, it is possible to synchronize multiple optical resonators (referred to as nodes), even in systems with more than three interconnected resonators containing non-linear atoms. To transcend the synchronization signal from the optical setup to communication networks, we propose a distinct mechanism that utilizes the exceptional precision of QNS in the optical lattice setup and frequency down-conversion using frequency combs. In addition, it is combined with electronic components such as analog-to-digital converters and field-programmable gate arrays (FPGAs) to create synchronized digital signals that are understandable to communication networks. Our method transforms optical pulses into precisely timed electrical signals that can be analyzed and used in sophisticated network systems. We demonstrated that QNS and dissipation can synchronize a tri-node clock network to the highest precision of thulium atom-based optical lattice clocks. Our work also highlights the practicality of these applications through MATLAB simulations, bridging theoretical principles and real-world solutions with current technology. In our simulations, we utilized an optical signal with a frequency of 263 THz, downconverted to a lower microwave frequency of 100 GHz to achieve subnanosecond-level synchronized signals. The down-converted signal was subjected to white noise and subsequently digitized. The digital signal was then simulated by sampling rate of $$f_s = 100$$ GHz or GSa/s (gigasample per second) and limiting the resolution to $$b = 8$$ bits. Finally, high-frequency noise was removed by implementing low-pass filtration using FPGAs. This study takes an essential step toward meeting the rising demands for rapid and efficient data transfer in the ever-evolving digital communications landscape, enabling faster and more reliable connectivity for future communication networks and the quantum Internet.

O-GalNAc glycans are enriched in neuronal tracts and regulate nodes of Ranvier

Protein O-glycosylation is a critical modification in the brain, as genetic variants in the pathway are associated with common and severe neuropsychiatric phenotypes. However, little is known about the most abundant O-glycans in the mammalian brain, which are N-acetylgalactosamine (O-GalNAc) linked. Here, we determined the spatial localization, protein carriers, and cellular function of O-GalNAc glycans in the mouse brain. We observed striking spatial enrichment of O-GalNAc glycans in neuronal tracts, and specifically at nodes of Ranvier, specialized structures involved in signal propagation in the brain. Glycoproteomic analysis revealed that more than half of the identified O-GalNAc glycans were present on chondroitin sulfate proteoglycans termed lecticans, and display both domain enrichment and regional heterogeneity. Inhibition of O-GalNAc synthesis in neurons reduced binding of Siglec-4, a known regulator of neurite growth, and shortened the length of nodes of Ranvier. This work establishes a function of O-GalNAc glycans in the brain and will inform future studies on their role in development and disease.

Differential effects of robot’s touch on perceived emotions and the feeling of Kawaii in adults and seniors

Emergent quantum state unveiled by ultrafast collective dynamics in 1 <i>T</i> -TaS ₂

Charge density wave (CDW) material 1 T -TaS 2 was proposed as a quantum spin liquid candidate, on which a cluster Mott insulator comes into being below the transition temperature. We report an experimental ultrafast generation and detection of the coherent amplitude mode (AM) of its CDW state. A salient feature emerges: The coherent CDW mode AM exhibits an unusual T 3.56 temperature dependence below 65 K, in addition to the T 2 temperature dependence observed in the 65 to 200 K range. This behavior suggests the enhancement of in-gap electronic excitations below 65 K and the emergence of a new phase of matter. Consequently, the intriguing quantum state leads to a crossover. Our investigation provides insights into understanding the interplay among various degrees of freedom in quantum materials.

Experience in conversion of symptomatic urethral diverticulum to asymptomatic status through surgery

Critical fragility in sociotechnical systems

Sociotechnical systems, where technological and human elements interact in a goal-oriented manner, provide important functional support to our societies. Here, we draw attention to the underappreciated concept of timeliness—i.e., system elements being available at the right place at the right time—that has been ubiquitously and integrally adopted as a quality standard in the modus operandi of sociotechnical systems. We point out that a variety of incentives, often reinforced by competitive pressures, prompt system operators to myopically optimize for efficiencies, running the risk of inadvertently taking timeliness to the limit of its operational performance, correspondingly making the system critically fragile to perturbations by pushing the entire system toward the proverbial “edge of a cliff.” Invoking a stylized model for operational delays, we identify the limiting operational performance of timeliness, as a true critical point, where the smallest of perturbations can lead to a systemic collapse. Specifically for firm-to-firm production networks, we suggest that the proximity to critical fragility is an important ingredient for understanding the fundamental “excess volatility puzzle” in economics. Further, in generality for optimizing sociotechnical systems, we propose that critical fragility is a crucial aspect in managing the trade-off between efficiency and robustness.

Hardware implementation of visible light communication based multipurpose camouflage spy robot

Abstract The proposed system outlines a novel camouflage-enabled mobile robot designed for various roles that require secure and rapid audio, video, and navigation data transmission and the capabilities to camouflage with any background to aid in remote monitoring. The robot is equipped with a self-sustaining power management and obstacle detection system. The design addresses the challenges of converting operations by integrating state-of-the-art Visible Light Communication Technology for secure and rapid communication. The system’s performance is analyzed using statistical methods and Little’s theorem, providing insights into operational efficiency and transmission reliability.

NOTCH, ERK, and SHH signaling respectively control the fate determination of cortical glia and olfactory bulb interneurons

During cortical development, radial glial cells (neural stem cells) initially are neurogenic, generating intermediate progenitor cells that exclusively produce glutamatergic pyramidal neurons. Next, radial glial cells generate tripotential intermediate progenitor cells (Tri-IPCs) that give rise to cortical astrocytes and oligodendrocytes, and olfactory bulb interneurons. The molecular mechanisms underlying the transition from cortical neurogenesis to gliogenesis, and the subsequent fate determination of cortical astrocytes, oligodendrocytes, and olfactory bulb interneurons, remain unclear. Here, we report that extracellular signal-regulated kinase (ERK) signaling plays a fundamental role in promoting cortical gliogenesis and the generation of Tri-IPCs. Additionally, sonic hedgehog-smoothened-glioma-associated oncogene homolog (SHH-SMO-GLI) activator signaling has an auxiliary function to ERK during these processes. We further demonstrate that, from Tri-IPCs, NOTCH signaling is crucial for the fate determination of astrocytes, while ERK signaling plays a prominent role in oligodendrocyte fate specification, and SHH signaling is required for the fate determination of olfactory bulb interneurons. We provide evidence suggesting that this mechanism is conserved in both mice and humans. Finally, we propose a unifying principle of mammalian cortical gliogenesis.