IRAK4 is a member of IL-1 receptor (IL-1R)–associated kinase (IRAK) family and has been shown to play an essential role in Toll-like receptor (TLR)–mediated signaling. We recently generated IRAK4 kinase-inactive knock-in mice to examine the role of kinase activity of IRAK4 in TLR-mediated signaling pathways. The IRAK4 kinase–inactive knock-in mice were completely resistant to lipopolysaccharide (LPS)- and CpG-induced shock, due to impaired TLR-mediated induction of proinflammatory cytokines and chemokines. Although inactivation of IRAK4 kinase activity did not affect the levels of TLR/IL-1R–mediated nuclear factor κB activation, a reduction of LPS-, R848-, and IL-1–mediated mRNA stability contributed to the reduced cytokine and chemokine production in bone marrow–derived macrophages from IRAK4 kinase–inactive knock-in mice. Both TLR7- and TLR9-mediated type I interferon production was abolished in plasmacytoid dendritic cells isolated from IRAK4 knock-in mice. In addition, influenza virus–induced production of interferons in plasmacytoid DCs was also dependent on IRAK4 kinase activity. Collectively, our results indicate that IRAK4 kinase activity plays a critical role in TLR-dependent immune responses.
If a three-dimensional physical electronic system emulating synapse networks could be built, that would be a significant step toward neuromorphic computing. However, the fabrication complexity of complementary metal-oxide-semiconductor architectures impedes the achievement of three-dimensional interconnectivity, high-device density, or flexibility. Here we report flexible three-dimensional artificial chemical synapse networks, in which two-terminal memristive devices, namely, electronic synapses (e-synapses), are connected by vertically stacking crossbar electrodes. The e-synapses resemble the key features of biological synapses: unilateral connection, long-term potentiation/depression, a spike-timing-dependent plasticity learning rule, paired-pulse facilitation, and ultralow-power consumption. The three-dimensional artificial synapse networks enable a direct emulation of correlated learning and trainable memory capability with strong tolerances to input faults and variations, which shows the feasibility of using them in futuristic electronic devices and can provide a physical platform for the realization of smart memories and machine learning and for operation of the complex algorithms involving hierarchical neural networks.
White-light-emitting diodes are fabricated by using 375nm emitting InGaN chip with Sr3MgSi2O8:Eu2+ (blue and yellow) or Sr3MgSi2O8:Eu2+, Mn2+ (blue, yellow, and red). At a color temperature of 5892K, the color coordinates are x=0.32, y=0.33, and the color rendering index is 84%; at a color temperature of 4494K, the color coordinates are x=0.35, y=0.33, and the color rendering index is 92%. The blue (470nm) and yellow (570nm) emission bands are originated from Eu2+ ions, while the red (680) emission band is originated from Mn2+ ions in Sr3MgSi2O8 host. The energy transfer among three bands occurs due to the spectral overlap between emission and absorption bands. It is confirmed by the faster decay time of the energy donor. Our white-light-emitting diodes show higher color reproducibility, higher color stability on forward-bias current, and excellent color rendering index in comparison with a commercial YAG:Ce3+-based white-light-emitting diode.
Perovskite materials have exhibited promising potential for universal applications including backlighting, color conversion, and anticounterfeiting labels fabricated using solution processes. However, owing to the tendency of those materials to have uncontrollable morphologies and to form large crystals, they cannot be utilized in discontinuous microminiaturization, which is crucial for practical optoelectronic applications. In this research, combining the effects of adding polyvinylpyrrolidone (PVP), precisely controlling the inkjet printing technique, and using a postprocessing procedure, we were able to fabricate in situ crystallized perovskite–PVP nanocomposite microarrays with perfect morphologies. The viscosity of the perovskite precursor increased with the addition of PVP, eliminating the outward capillary flow that induces the coffee-ring effect. In addition, because of the presence of metallic bonds with the CO groups in PVP and the spatial confinement of such a polymer, we were able to fabricate regulated CsPbBr3 nanocrystals capped with PVP and with a uniform size distribution. The as-printed patterns showed excellent homogeneity on a macroscale and high reproducibility on a microscale; furthermore, those patterns were invisible in the ambient environment, compatible with flexible substrates, and cost-efficient to produce, indicating that this technique holds promising potential for applications such as anticounterfeiting labels.
With the tremendous advances in technology, gas-sensing devices are being popularly used in many distinct areas, including indoor environments, industries, aviation, and detectors for various toxic domestic gases and vapors. Even though the most popular type of gas sensor, namely, resistive-based gas sensors, have many advantages over other types of gas sensors, their high working temperatures lead to high energy consumption, thereby limiting their practical applications, especially in mobile and portable devices. As possible ways to deal with the high-power consumption of resistance-based sensors, different strategies such as self-heating, MEMS technology, and room-temperature operation using especial morphologies, have been introduced in recent years. In this review, we discuss different types of energy-saving chemisresitive gas sensors and their application in the fields of environmental monitoring. At the end, the review will be concluded by providing a summary, challenges and future perspectives.
The electrical properties of flexible nonvolatile organic bistable devices (OBDs) fabricated with graphene sandwiched between two insulating poly(methyl methacrylate) (PMMA) polymer layers were investigated. Current-voltage (I-V) measurements on the Al/PMMA/graphene/PMMA/indium-tin-oxide/poly(ethylene terephthalate) devices at 300 K showed a current bistability due to the existence of the graphene, indicative of charge storage in the graphene. The maximum ON/OFF ratio of the current bistability for the fabricated OBDs was as large as 1 x 10(7), and the endurance number of ON/OFF switchings was 1.5 x 10(5) cycles, and an ON/OFF ratio of 4.4 x 10(6) was maintained for retention times larger than 1 x 10(5) s. No interference effect was observed for the scaled-down OBDs containing a graphene layer. The memory characteristics of the OBDs maintained similar device efficiencies after bending and were stable during repetitive bendings of the OBDs. The mechanisms for these characteristics of the fabricated OBDs are described on the basis of the I-V results.
Toll-like receptors transduce their signals through the adaptor molecule MyD88 and members of the IL-1R-associated kinase family (IRAK-1, 2, M and 4). IRAK-1 and IRAK-2, known to form Myddosomes with MyD88-IRAK-4, mediate TLR7-induced TAK1-dependent NFjB activation. IRAK-M was previously known to function as a negative regulator that prevents the dissociation of IRAKs from MyD88, thereby inhibiting downstream signalling. However, we now found that IRAK-M was also able to interact with MyD88-IRAK-4 to form IRAK-M Myddosome to mediate TLR7-induced MEKK3-dependent second wave NFjB activation, which is uncoupled from post-transcriptional regulation. As a result, the IRAK-M-dependent pathway only induced expression of genes that are not regulated at the post-transcriptional levels (including inhibitory molecules SOCS1, SHIP1, A20 and IjBa), exerting an overall inhibitory effect on inflammatory response. On the other hand, through interaction with IRAK-2, IRAK-M inhibited TLR7-mediated production of cytokines and chemokines at translational levels. Taken together, IRAK-M mediates TLR7-induced MEKK3-dependent second wave NFjB activation to produce inhibitory molecules as a negative feedback for the pathway, while exerting inhibitory effect on translational control of cytokines and chemokines.
Interleukin-1 (IL-1)-mediated signaling in T cells is essential for T helper 17 (Th17) cell differentiation. We showed here that SIGIRR, a negative regulator of IL-1 receptor and Toll-like receptor signaling, was induced during Th17 cell lineage commitment and governed Th17 cell differentiation and expansion through its inhibitory effects on IL-1 signaling. The absence of SIGIRR in T cells resulted in increased Th17 cell polarization in vivo upon myelin oligodendrocyte glycoprotein (MOG35–55) peptide immunization. Recombinant IL-1 promoted a marked increase in the proliferation of SIGIRR-deficient T cells under an in vitro Th17 cell-polarization condition. Importantly, we detected increased IL-1-induced phosphorylation of JNK and mTOR kinase in SIGIRR-deficient Th17 cells compared to wild-type Th17 cells. IL-1-induced proliferation was abolished in mTOR-deficient Th17 cells, indicating the essential role of mTOR activation. Our results demonstrate an important mechanism by which SIGIRR controls Th17 cell expansion and effector function through the IL-1-induced mTOR signaling pathway.
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