Abstract
Human skin is a self-healing mechanosensory system that detects various mechanical contact forces efficiently through three-dimensional innervations. Here, we propose a biomimetic ...artificially innervated foam by embedding three-dimensional electrodes within a new low-modulus self-healing foam material. The foam material is synthesized from a one-step self-foaming process. By tuning the concentration of conductive metal particles in the foam at near-percolation, we demonstrate that it can operate as a piezo-impedance sensor in both piezoresistive and piezocapacitive sensing modes without the need for an encapsulation layer. The sensor is sensitive to an object’s contact force directions as well as to human proximity. Moreover, the foam material self-heals autonomously with immediate function restoration despite mechanical damage. It further recovers from mechanical bifurcations with gentle heating (70 °C). We anticipate that this material will be useful as damage robust human-machine interfaces.
Temporary cardiac pacemakers used in periods of need during surgical recovery involve percutaneous leads and externalized hardware that carry risks of infection, constrain patient mobility and may ...damage the heart during lead removal. Here we report a leadless, battery-free, fully implantable cardiac pacemaker for postoperative control of cardiac rate and rhythm that undergoes complete dissolution and clearance by natural biological processes after a defined operating timeframe. We show that these devices provide effective pacing of hearts of various sizes in mouse, rat, rabbit, canine and human cardiac models, with tailored geometries and operation timescales, powered by wireless energy transfer. This approach overcomes key disadvantages of traditional temporary pacing devices and may serve as the basis for the next generation of postoperative temporary pacing technology.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
This study investigates the interconnected influence of socio-demographics, behavioral, economic, and technical factors associated with electric vehicle (EV) adoption interest and the influence of ...vehicle-to-grid mobility on preferences. Using hierarchical regression analysis, we examine the impacts of six dimensions relating to socio-demographic, technical, economic, and behavioral factors in a survey (n = 4885) across Denmark, Finland, Iceland, Norway, and Sweden. Our results show that younger males, with higher income, a higher number of children, and who had experiences with EVs, and generally hold sustainability values are positively related to potential EV adoption. Among electric mobility attributes, vehicle-to-grid capability and charging time are determined to be the influential predictors. Adding vehicle-to-grid capability can foster EV adoption in our analysis, considering it can add a revenue stream for EV owners. Individuals continue to use specific knowledge of conventional fuel vehicles when considering EVs and their attributes. Among all of our factors, the fuel economy, financial savings, and environmental value were the strongest predictors. In comparison, the driving range was ranked less critical to former EV owners than to a conventional car and current EV owners. Battery life was ranked more important to conventional fuel vehicle owners than current and former EV owners. Finally, former EV owners considered vehicle-to-grid to be more important than current EV and conventional car owners, implying that vehicle-to-grid could be the marginal incentive that would be the “tipping point.”
•Investigates socio-demographics, behavioral, economic and technical factors associated with electric vehicles.•Analyzes a survey distributed to 4885 participants across seventeen cities in the five Nordic countries.•Younger males, with higher income, more children, and experience with EVs are related to potential EV adoption.•Fuel economy and financial savings and environmental value were the strongest predictors.•Adding vehicle-to-grid capability to electric mobility attributes can foster EV adoption.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The interferon-induced transmembrane (IFITM) proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, ...specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection.
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•IFITMs inhibit HIV-1 cell-to-cell infection and impair viral infectivity•IFITMs specifically interact with HIV-1 Env and inhibit Env processing•IFITM incorporation into HIV-1 virions does not correlate with inhibition•IFITM inhibition of primate lentiviruses is virus-strain specific
Yu et al. show that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 Env glycoprotein to inhibit infection. IFITM proteins interact with HIV-1 Env and impair its processing and incorporation into virions. The effects of IFITMs on HIV-1, HIV-2, and SIVs are virus-strain dependent.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Axons in the mammalian CNS fail to regenerate after injury. Here we show that if the activity of mouse retinal ganglion cells (RGCs) is increased by visual stimulation or using chemogenetics, their ...axons regenerate. We also show that if enhancement of neural activity is combined with elevation of the cell-growth-promoting pathway involving mammalian target of rapamycin (mTOR), RGC axons regenerate long distances and re-innervate the brain. Analysis of genetically labeled RGCs revealed that this regrowth can be target specific: RGC axons navigated back to their correct visual targets and avoided targets incorrect for their function. Moreover, these regenerated connections were successful in partially rescuing a subset of visual behaviors. Our findings indicate that combining neural activity with activation of mTOR can serve as powerful tool for enhancing axon regeneration, and they highlight the remarkable capacity of CNS neurons to re-establish accurate circuit connections in adulthood.
Stretchable optoelectronic materials are essential for applications in wearable electronics, human-machine interfaces and soft robots. However, intrinsically stretchable optoelectronic devices such ...as light-emitting capacitors usually require high driving alternating voltages and excitation frequencies to achieve sufficient luminance in ambient lighting conditions. Here, we present a healable, low-field illuminating optoelectronic stretchable (HELIOS) device by introducing a transparent, high permittivity polymeric dielectric material. The HELIOS device turns on at an alternating voltage of 23 V and a frequency below 1 kHz, safe operating conditions for human-machine interactions. We achieved a brightness of 1,460 cd m
at 2.5 V µm
with stable illumination demonstrated up to a maximum of 800% strain. The materials also self-healed mechanically and electronically from punctures or when severed. We further demonstrate various HELIOS light-emitting capacitor devices in environment sensing using optical feedback. Moreover, our devices can be powered wirelessly, potentially enabling applications for untethered damage-resilient soft robots.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Broadly neutralizing antibodies (bNAbs) have been isolated from HIV-1 patients and can potently block infection of a wide spectrum of HIV-1 subtypes. These antibodies define common epitopes shared by ...many viral isolates. While bNAbs potently antagonize infection with cell-free virus, inhibition of HIV-1 transmission from infected to uninfected CD4
T cells through virological synapses (VS) has been found to require greater amounts of antibody. In this study, we examined two well-studied molecular clones and two transmitted/founder (T/F) clones for their sensitivities to a panel of bNAbs in cell-free and cell-to-cell infection assays. We observed resistance of cell-to-cell transmission to antibody neutralization that was reflected not only by reductions of antibody potency but also by decreases in maximum neutralization capacity relative to the levels seen with cell-free infections. BNAbs targeting different epitopes exhibited incomplete neutralization against cell-associated virus with T/F Envs, which was not observed with the cell-free form of the same virus. We further identified the membrane-proximal internal tyrosine-based sorting motif as a determinant that can affect the incomplete neutralization of these T/F clones in cell-to-cell infection. These findings indicate that the signal that affects surface expression and/or internalization of Env from the plasma membrane can modulate the presentation of neutralizing epitopes on infected cells. These results highlight that a fraction of virus can escape from high concentrations of antibody through cell-to-cell infection while remaining sensitive to neutralization in cell-free infection. The ability to fully inhibit cell-to-cell transmission may represent an important consideration in the development of antibodies for treatment or prophylaxis.
In recent years, isolation of new-generation HIV-1 bNAbs has invigorated HIV vaccine research. These bNAbs display remarkable potency and breadth of coverage against cell-free virus; however, they exhibit a diminished ability to block HIV-1 cell-to-cell transmission. The mechanism(s) by which HIV-1 resists neutralization when transmitting through VS remains uncertain. We examined a panel of bNAbs for their ability to neutralize HIV-1 T/F viruses in cell-to-cell infection assays. We found that some antibodies exhibit not only reduced potency but also decreased maximum neutralization capacity or
efficacy against cell-to-cell infection of HIV-1 with T/F Envs compared to cell-free infection of the same virus. We further identified the membrane-proximal internal tyrosine-based sorting motif YXXL as a determinant that can affect the incomplete neutralization phenotype of these T/F clones. When the maximum neutralization capacity falls short of 100%, this can have a major impact on the ability of antibodies to halt viral replication.
HIV-1 infection is enhanced by adhesive structures that form between infected and uninfected T cells called virological synapses (VSs). This mode of transmission results in the frequent ...co-transmission of multiple copies of HIV-1 across the VS, which can reduce sensitivity to antiretroviral drugs. Studying HIV-1 infection of humanized mice, we measured the frequency of co-transmission and the spatiotemporal organization of infected cells as indicators of cell-to-cell transmission in vivo. When inoculating mice with cells co-infected with two viral genotypes, we observed high levels of co-transmission to target cells. Additionally, micro-anatomical clustering of viral genotypes within lymphoid tissue indicates that viral spread is driven by local processes and not a diffuse viral cloud. Intravital splenic imaging reveals that anchored HIV-infected cells induce arrest of interacting, uninfected CD4+ T cells to form Env-dependent cell-cell conjugates. These findings suggest that HIV-1 spread between immune cells can be anatomically localized into infectious clusters.
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•Infected T cells co-transmit multiple HIV-1 copies to T cells in immune tissues•HIV-infected cells can migrate but frequently become anchored within tissues•Clustering of infected cells with the same genotype indicates local viral spread•HIV-1-infected cells slow the migration of uninfected T cells that contact them
The role that cell-to-cell infection plays during HIV-1 spread within lymphoid tissues has been poorly defined. Law et al. find that HIV-infected T cells can form durable cell-cell contacts with other T cells in vivo, leading to clusters of infection that frequently co-transmit multiple viruses per cell.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Continuous monitoring of internal physiological parameters is essential for critical care patients, but currently can only be practically achieved via tethered solutions. Here we report a wireless, ...real-time pressure monitoring system with passive, flexible, millimetre-scale sensors, scaled down to unprecedented dimensions of 1 × 1 × 0.1 cubic millimeters. This level of dimensional scaling is enabled by novel sensor design and detection schemes, which overcome the operating frequency limits of traditional strategies and exhibit insensitivity to lossy tissue environments. We demonstrate the use of this system to capture human pulse waveforms wirelessly in real time as well as to monitor in vivo intracranial pressure continuously in proof-of-concept mice studies using sensors down to 2.5 × 2.5 × 0.1 cubic millimeters. We further introduce printable wireless sensor arrays and show their use in real-time spatial pressure mapping. Looking forward, this technology has broader applications in continuous wireless monitoring of multiple physiological parameters for biomedical research and patient care.
Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in ...electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology.
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