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In the recent defence industries, it is required to develop the small and low cost embedded systems for guided missiles. According to the characteristics of guided missiles, the mission is conducted with multiple phases, which include a squib activation phase. By considering the unexpected squib activation, the squib system should be disabled after the launch of a guided missile. Therefore, the squib system needs to include the functions of the safe ignition and status check. This paper presents the squib ignition and status check circuits design for the compact embedded systems in guided missiles. Validation results show that for the functions of the squib ignition and status check, the presented circuits design performs well. The designed circuits also were implemented with various electronic devices and validated by the ground and flight tests.

Since the concept of Manned-UnManned Teaming(MUM-T) and Unmanned Aircraft System(UAS) can efficiently respond to rapidly changing battle space, many studies are being conducted as key components of the mosaic warfare environment. In this paper, we propose a rule-based AI engagement model based on Basic Fighter Maneuver(BFM) capable of Within-Visual-Range(WVR) air-to-air combat and a simulation environment in which human pilots can participate. In order to develop a rule-based AI engagement model that can pilot a fighter with a 6-DOF dynamics model, tactical manuals and human pilot experience were configured as knowledge specifications and modeled as a behavior tree structure. Based on this, we improved the shortcomings of existing air combat models. The proposed model not only showed a 100 % winning rate in engagement with human pilots, but also visualized decision-making processes such as tactical situations and maneuvering behaviors in real time. We expect that the results of this research will serve as a basis for development of various AI-based engagement models and simulators for human pilot training and embedded software test platform for fighter.

For last two decades, the demand for precisely engineered three-dimensional structures has increased continuously for the developments of biomaterials. With the recent advances in micro- and nano-fabrication techniques, various devices with complex surface geometries have been devised and produced in the pharmaceutical and medical fields for various biomedical applications including drug delivery and biosensors. These advanced biomaterials have been designed to mimic the natural environments of tissues more closely and to enhance the performance for their corresponding biomedical applications. One of the important aspects in the rational design of biomaterials is how to configure the surface of the biomedical devices for better control of the chemical and physical properties of the bioactive surfaces without compromising their bulk characteristics. In this viewpoint, it of critical importance to secure a versatile method to modify the surface of various biomedical devices. Recently, a vapor phase method, termed initiated chemical vapor deposition (iCVD) has emerged as damage-free method highly beneficial for the conformal deposition of various functional polymer films onto many kinds of micro- and nano-structured surfaces without restrictions on the substrate material or geometry, which is not trivial to achieve by conventional solution-based surface functionalization methods. With proper structural design, the functional polymer thin film via iCVD can impart required functionality to the biomaterial surfaces while maintaining the fine structure thereon. We believe the iCVD technique can be not only a valuable approach towards fundamental cell-material studies, but also of great importance as a platform technology to extend to other prospective biomaterial designs and material interface modifications for biomedical applications.

Rechargeable batteries based on MnO2/Zn aqueous chemistry have emerged as a viable alternative to Li-ion batteries (LIB), owing to their low material cost, high safety, sustainable redox chemistry, and remarkable electrochemical performance with an energy density comparable to LIBs. However, the reaction mechanism, particularly the detailed electrochemical process that leads to MnO2 deposition during the charge process, remains elusive to date despite a decade of intensive research. In this study, we utilized various structural analysis methods, including in situ Raman spectroscopy, on simulated discharged electrodes to demonstrate that the charging reaction consists of two reaction steps. These steps involve the precipitation of highly defective phyllomanganates with heavy Zn sorption in the interlayer, followed by the coincidental extraction of zinc and incorporation of manganese into vacancies in MnO6 sheets, which lead to the production of phyllomanganates with much reduced Zn content. This study sheds light on the reaction mechanism of MnO2/Zn batteries and opens new opportunities for improving their performance to commercial levels.

Human mitochondria contain a circular genome that encodes 13 subunits of the oxidative phosphorylation system. In addition to their role as powerhouses of the cells, mitochondria are also involved in innate immunity as the mitochondrial genome generates long double-stranded RNAs (dsRNAs) that can activate the dsRNA-sensing pattern recognition receptors. Recent evidence shows that these mitochondrial dsRNAs (mt-dsRNAs) are closely associated with the pathogenesis of human diseases that accompany inflammation and aberrant immune activation, such as Huntington’s disease, osteoarthritis, and autoimmune Sjögren’s syndrome. Yet, small chemicals that can protect cells from a mt-dsRNA-mediated immune response remain largely unexplored. Here, we investigate the potential of resveratrol (RES), a plant-derived polyphenol with antioxidant properties, on suppressing mt-dsRNA-mediated immune activation. We show that RES can revert the downstream response to immunogenic stressors that elevate mitochondrial RNA expressions, such as stimulation by exogenous dsRNAs or inhibition of ATP synthase. Through high-throughput sequencing, we find that RES can regulate mt-dsRNA expression, interferon response, and other cellular responses induced by these stressors. Notably, RES treatment fails to counter the effect of an endoplasmic reticulum stressor that does not affect the expression of mitochondrial RNAs. Overall, our study demonstrates the potential usage of RES to alleviate the mt-dsRNA-mediated immunogenic stress response.

For efficient therapeutic use of human mesenchymal stem cells (hMSCs), maximizing their self-renewal performance and multipotency must be fully retained. However, conventional trypsin-based cell passaging methods are known to damage the attached cells to be detached because of the inherent corrosive nature of trypsin, and continuous passaging substantially degrades the self-renewal and differentiation capacity of hMSCs. Therefore, it is imperative to secure a damage-free passaging method that supports cell growth as well as their stem cell function. Here, an enzyme-free cell detachment method using a poly(ethylene glycol dimethacrylate) (pEGDMA)-coated surface is developed, which allows for reduced integrin-dependent cell adhesion. Cell detachment can be facilitated simply by treating the plated cells on the pEGDMA surface with Ca

Despite the essential roles of natural killer (NK) cells in cancer treatment, the physical barrier and biological cues of the tumor microenvironment (TME) may induce NK cell dysfunction, causing their poor infiltration into tumors. The currently available two-dimensional (2D) cancer-NK co-culture systems hardly represent the characteristics of TME and are not suitable for tracking the infiltration of immune cells and assessing the efficacy of immunotherapy. This study aims to monitor NK-mediated cancer cell killing using a polymer thin film-based, 3D assay platform that contains highly tumorigenic cancer spheroids. A poly(cyclohexyl methacrylate) (pCHMA)-coated surface enables the generation of tumorigenic spheroids from pancreatic cancer patient-derived cancer cells, showing considerable amounts of extracellular matrix (ECM) proteins and cancer stem cell (CSC)-like characteristics. The 3D spheroid-based assay platform allows rapid discovery of a therapeutic agent for synergistic NK-mediated cytotoxicity through imaging-based high-content screening. In detail, the small molecule C19, known as a multi-epithelial-mesenchymal transition pathway inhibitor, is shown to enhance NK activation and infiltration

Cortical maps, which are indicative of cognitive status, are shaped by the organism’s experience. Previous mapping tools, such as penetrating electrodes and imaging techniques, are limited in their ability to be used to assess high-resolution brain maps largely owing to their invasiveness and poor spatiotemporal resolution, respectively. In this study, we developed a flexible graphene-based multichannel electrode array for electrocorticography (ECoG) recording, which enabled us to assess cortical maps in a time- and labor-efficient manner. The flexible electrode array, formed by chemical vapor deposition (CVD)-grown graphene, provided low impedance and electrical noise because a good interface between the graphene and brain tissue was created, which improved the detectability of neural signals. Furthermore, cortical map remodeling was induced upon electrical stimulation at the cortical surface through a subset of graphene spots. This result demonstrated the macroscale plasticity of cortical maps, suggesting perceptual enhancement via electrical rehabilitation at the cortical surface. The spatial organization of neural networks representing sensorimotor behavior and cognition has been mapped by flexible devices placed on the cortex, the outer layer of the brain. Sensory messages from each part of the body are processed in a specific area in the brain and maps of the cortex can help understand these areas. A person’s cortical map is shaped by their early development and experiences. Study of such maps can help identify and treat sensory disorders. Existing techniques for brain mapping require placement of penetrating electrodes which is time-consuming and risks brain damage. Minseok Lee from City University of Hong Kong and colleagues made arrays of electrodes using graphene membranes and constructed sensory maps of rats and mice by placing these arrays directly on the cortical surface. The timely and continuous measurement of cortical maps is required for studying the nature and plasticity of brain maps. In this work, we developed the multichannel graphene array that enables high-resolution brain mapping, facilitating rapid and repetitive assessments of brain maps. The advanced graphene array with intervening thru-hole enables large-scale mapping simultaneously in the surface and deep of cortical areas, also improving conformality for better detection of electrocorticography signals. In a subset of the graphene array, cortical surface stimulation can remodel cortical maps, therein enhancing cortical plasticity. This technology provides potential therapeutic applications for various brain disorders by correcting brain maps.

The aggregation of mesenchymal stem cells (MSCs) into three-dimensional (3D) spheroids has emerged as a promising therapeutic candidate for the treatment of a variety of diseases. In spite of the numerous 3D culture methods suggested recently for MSC spheroid generation, it is still elusive to fully reflect real stem cell niches; this effort majorly suffers from a lack of cell-extracellular matrix (ECM) interactions within the 3D spheroids. In this study, we develop a simple but versatile method for generating human MSC (hMSC) spheroids by culturing the cells on a functional polymer film surface, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4). Interestingly, the pV4D4-coated surface allows a dynamic cell adhesion to the polymer surface while developing the formation of 3D spheroids. The corresponding mechanotransduction promotes the expression of the endogenous ECM and, in turn, results in a remarkable improvement in self-renewal abilities, pro-angiogenic potency, and multilineage differentiation capabilities. This observation highlights the significance of our method compared to the conventional spheroid-generating methods in terms of recreating the ECM-rich microenvironment. We believe the developed surface can serve as a versatile but reliable method for stem cell-based tissue engineering and regenerative medicine.

Galvanic couple-assisted dissolution of Mg metal in an ethereal solution containing tris(2H-hexafluoroisopropyl)borate was utilized to prepare an efficient Al-compatible electrolyte for rechargeable Mg batteries. The electrolyte exhibited conditioning-free Mg deposition, high oxidative stability (3.5 V VS. Mg/Mg2+), and a superb electrochemical performance with various cathodes on an Al current collector.

The cerebellum coordinates voluntary movements for balanced motor activity in a normal gravity condition. It remains unknown how hypergravity is associated with cerebellum-dependent motor behaviors and Purkinje cell’s activities. In order to investigate the relationship between gravity and cerebellar physiology, we measured AMPA-mediated fast currents and mGluR1-mediated slow currents of cerebellar Purkinje cells along with cerebellum-dependent behaviors such as the footprint and irregular ladder under a hypergravity condition. We found abnormal animal behaviors in the footprint and irregular ladder tests under hypergravity. They are correlated with decreased AMPA and mGluR1-mediated synaptic currents of Purkinje cells. These results indicate that gravity regulates the activity of Purkinje cells, thereby modulating cerebellum-dependent motor outputs.

Although the dendritic cell (DC)-based modulation of immune responses has emerged as a promising therapeutic strategy for tumors, infections, and autoimmune diseases, basic research and therapeutic applications of DCs are hampered by expensive growth factors and sophisticated culture procedures. Furthermore, the platform to drive the differentiation of a certain DC subset without any additional biochemical manipulations has not yet been developed. Here, five types of polymer films with different hydrophobicity via an initiated chemical vapor deposition (iCVD) process to modulate the interactions related to cell-substrate adhesion are introduced. Especially, poly(cyclohexyl methacrylate) (pCHMA) substantially enhances the expansion and differentiation of conventional type 1 DCs (cDC1s), the prime DC subset for antigen cross-presentation, and CD8

Background Langerhans cells (LCs) are dendritic cells that reside in the epidermis and local inflammation results in an increased differentiation of monocyte-derived LCs. Only few studies have investigated on the role of LCs in psoriasis-like dermatitis model, but the results are variable and the exact role of LCs in psoriasis model remains to be elucidated. Objective To explore the functional role of resident (rLCs) and monocyte-derived LCs (mLCs) in imiquimod (IMQ)-induced psoriasis-like inflammation using human Langerin-diphtheria toxin subunit A (huLang-DTA) mice. Methods 5% IMQ cream was topically applied on the skins. Clinical and histopathological features were evaluated. Psoriasis-related gene expression was analyzed by quantitative polymerase chain reaction. The production of psoriasis-related cytokines including IL-17A and IL-22 by T cells were assessed by flow cytometry from the lesional skins. Results huLang-DTA mice showed a common depletion of both rLCs and mLCs in the IMQ-treated skins. huLang-DTA mice had a reduced IMQ-induced psoriasis-like inflammation featuring erythema, scale, and thickness compared with wild-type mice. Psoriatic lesions from huLang-DTA mice had a decreased level of Il23a and accordingly demonstrated an attenuated cytokine production of IL-17A and IL-22 from γδlow T cells. mLCs revealed a significantly greater level of IL-23 expression compared to rLCs in response to topical IMQ treatment. Conclusion Although both rLCs and mLCs are involved in the development of IMQ-induced psoriasis-like dermatitis, inflammation-induced mLCs present a superior capacity for producing IL-23 in this murine experimental model of psoriasis.

Conventional dendritic cells (cDCs) are composed of heterogeneous subsets commonly arising from dendritic cell (DC)−committed progenitors. A population of CD301b-expressing DCs has recently been identified in non-lymphoid barrier tissues such as skin. However, whether CD301b + DCs in the skin represent an ontogenetically unique subpopulation of migratory cDCs has not been fully addressed. Here, we demonstrated that CD301b + dermal DCs were distinct subpopulation of FMS-like tyrosine kinase 3 ligand (FLT3L)−dependent CD11b + cDC2 lineage, which required an additional GM-CSF cue for the adequate development. Although the majority of lymphoid-resident cDC2 lacked CD301b expression, dermal migratory cDC2 contained a substantial fraction of CD301b + subset. Similar to CD301b − population, CD301b + dermal DC development was closely regulated by FLT3 signaling, suggesting their common origin from FLT3L-responsive cDC progenitors. However, FLT3L-driven cDC progenitor culture was not sufficient, but additional GM-CSF treatment was required to produce CD301b + cDC2. In vivo development of CD301b + cDC2 was significantly augmented by exogenous GM-CSF, while the repopulation of CD301b + dermal cDC2 was abrogated by GM-CSF neutralization. Functionally, CD301b + cDC2 was capable of producing a high level of IL-23, and the depletion of CD301b + cDC2 effectively prevented IL-17−mediated psoriasiform dermatitis. Therefore, our findings highlight the differentiation program of a distinct CD301b + dermal cDC2 subset in the skin and its involvement in psoriatic inflammation.

생산가능연령인구 감소와 도시기반 시설 노후화로 인한 도시쇠퇴는 지역 불균형 문제와 더불어 다양한 사회문제를 야기하였고 이에 따라 도시재생 정책 마련을 위한 도시쇠퇴 측정 지표에 관한 연구가 최근 활발히 진행되고 있다. 도시쇠퇴 측정을 위해 사용되는 주요 자료는 행정구역이나 집계구 단위로 집계되는 것이 일반적이다. 그러나 행정구역이나 집계구 통계는 집계의 기준이 되는 공간단위의 면적 편차가 크고 불규칙한 모양을 가졌으며, 시간에 따라 경계가 변화하고 축척이 유동적이지 못한 한계를 가지고 있다. 기존 행정구역 혹은 집계구 통계와 달리 정규 격자 단위 데이터는 비정형 집계단위의 문제점을 상쇄할 수 있는 통계 공간단위 유형이라고 할 수 있다. 본 연구는 광주광역시 도시쇠퇴를 주제로 선정하여, 기존 행정구역 단위를 활용한 선행 연구 결과와 격자 변환 데이터를 활용한 결과를 나열하고 비교 분석 하였다. 연구 결과, 기존 행정구역을 활용한 연구와 전체적으로는 비슷한 결과가 도출되었지만 격자 데이터를 활용했을 경우 행정구역 내에서 상이하게 나타나는 도시쇠퇴의 공간적 분포를 확인할 수 있었고, 행정 경계를 가로지르는 상세한 도시쇠퇴 분포를 확인할 수 있었다. 본 연구를 통해 격자기반 데이터의 건물기반 변환방법을 제시함과 동시에 격자단위 데이터의 특징과 활용방안을 제시함으로써 차후 격자기반 데이터 연구에 대한 시사점을 제공할 수 있을 것으로 기대된다.

Many biomedical applications require an efficient combination and localization of multiple discrete light sources (e.g., fluorescence and absorbance imaging). We present a compact 6 channel combiner that couples the output of independent solid-state light sources into a single 400-μm-diameter fiber stub for handheld Internet of Things (IoT) devices. We demonstrate average coupling efficiencies > 80% for each of the 6 laser diodes installed into the prototype. The design supports the use of continuous wave and intensity-modulated laser diodes. This fiber-stub-type beam combiner could be used to construct custom multi-wavelength sources for tissue oximeters, microscopes and molecular imaging technologies. In order to validate its suitability, we applied the developed fiber-stub-type beam combiner to a multi-wavelength light source for a handheld IoT device and demonstrated its feasibility for smart healthcare through a tumor-mimicking silicon phantom.

The development of novel bifunctional electrocatalysts for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is urgently desired for improving the efficiency of overall water splitting but remains a great challenge. Herein, a metal–organic frameworks (MOFs)-derived hybrid nanostructure consisted of multiple transition metal phosphide (NiCoZnP) nanoclusters and hierarchical ultrathin N-doped carbon (NC) nanosheets is successfully synthesized as binder-free bifunctional electrocatalysts for overall water splitting. The ultrafine and monodispersed NiCoZnP nanoclusters with uniform sizes of 3 nm are homogeneously distributed on the ultrathin NC nanosheets, leading to self-supported NiCoZnP/NC nanosheets array on carbon cloth (CC). The NiCoZnP/NC exhibits large surface area and numerous active sites due to the small sizes of NiCoZnP and hierarchical nanostructures of NC. Furthermore, the NiCoZnP/NC nanosheets are directly grown on CC and avoids the usage of binder, which significantly reduces the electrical contact resistance and exhibits superhydrophilic performance. Therefore, the self-supported NiCoZnP/NC nanosheets array demonstrates high HER activity with low overpotential of 74 mV and OER activity with overpotential of 228 mV to reach current density of 10 mA cm−2 in 1.0 M KOH solution, and exhibits remarkable overall water splitting performances with low potential of 1.54 V to drive 10 mA cm−2 and good long-term stability.

Chronic tinnitus, the perception of lifelong constant ringing in ear, is one capital cause of disability in modern society. It is often present with various comorbid factors that severely affect quality of life, including insomnia, deficits in attention, anxiety, and depression. Currently, there are limited therapeutic treatments for alleviation of tinnitus. Tinnitus can involve a shift in neuronal excitation/inhibition (E/I) balance, which is largely modulated by ion channels and receptors. Thus, ongoing research is geared toward pharmaceutical approaches that modulate the function of ion channels and receptors. Here, we propose a seesaw model that delineates how tinnitus-related ion channels and receptors are involved in homeostatic E/I balance of neurons. This review provides a thorough account of our current mechanistic understanding of tinnitus and insight into future direction of drug development.

Paclitaxel failure promotes collateral resistance to EGFR-targeted therapy by adaptive rewiring of the cellular stress response., Secondary drug resistance stems from dynamic clonal evolution during the development of a prior primary resistance. This collateral type of resistance is often a characteristic of cancer recurrence. Yet, mechanisms that drive this collateral resistance and their drug-specific trajectories are still poorly understood. Using resistance selection and small-scale pharmacological screens, we find that cancer cells with primary acquired resistance to the microtubule-stabilizing drug paclitaxel often develop tolerance to epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs), leading to formation of more stable resistant cell populations. We show that paclitaxel-resistant cancer cells follow distinct selection paths under EGFR-TKIs by enriching the stemness program, developing a highly glycolytic adaptive stress response, and rewiring an apoptosis control pathway. Collectively, our work demonstrates the alterations in cellular state stemming from paclitaxel failure that result in collateral resistance to EGFR-TKIs and points to new exploitable vulnerabilities during resistance evolution in the second-line treatment setting.

Cell sheet engineering, a technique utilizing a monolayer cell sheet, has recently emerged as a promising technology for scaffold-free tissue engineering. In contrast to conventional tissue-engineering approaches, the cell sheet technology allows cell harvest as a continuous cell sheet with intact extracellular matrix proteins and cell-cell junction, which facilitates cell transplantation without any other artificial biomaterials. A facile, non-thermoresponsive method is demonstrated for a rapid but highly reliable platform for cell-sheet engineering. The developed method exploits the precise modulation of cell-substrate interactions by controlling the surface energy of the substrate via a series of functional polymer coatings to enable prompt cell sheet harvesting within 100 s. The engineered surface can trigger an intrinsic cellular response upon the depletion of divalent cations, leading to spontaneous cell sheet detachment under physiological conditions (pH 7.4 and 37 °C) in a non-thermoresponsive manner. Additionally, the therapeutic potential of the cell sheet is successfully demonstrated by the transplantation of multilayered cell sheets into mouse models of diabetic wounds and ischemia. These findings highlight the ability of the developed surface for non-thermoresponsive cell sheet engineering to serve as a robust platform for regenerative medicine and provide significant breakthroughs in cell sheet technology.

The association between psoriasis and risk of atherosclerotic cardiovascular disease has not been thoroughly evaluated in a large longitudinal cohort of an Asian population. We conducted a nationwide population-based retrospective cohort study encompassing more than 1.7 million Koreans with a 15-year follow-up period. The period prevalence of psoriasis was 0.33% among the baseline participants (1997-2000). In Cox proportional hazard analyses, the individuals with psoriasis had a higher adjusted hazard ratio (HR) for incidence of overall atherosclerotic cardiovascular disease (HR, 1.18; 95% confidence interval [CI], 1.09-1.27) compared with controls. Subgroup analyses revealed that the risk for myocardial infarction was commonly increased in both sexes with moderate to severe psoriasis (male: HR, 2.09; 95% CI, 1.35-3.24; female: HR, 3.23; 95% CI, 1.34-7.76), whereas the risk for ischemic stroke was specifically increased in female individuals with moderate to severe psoriasis (HR, 2.02; 95% CI, 1.24-3.30). Our data suggest that appropriate medical screening for possible cardiovascular comorbidities is warranted in Asian psoriatic patients according to disease severity and sex.