The purpose of this paper is to develop cases for the DPRK's use of nuclear weapons. As background, firstly, the deterrence and countermeasure strategies of the United States-ROK alliance in the face ...of the increasingly sophisticated DPRK's nuclear threat is examined. Then, the DPRK's nuclear capabilities and nuclear strategy are investigated, and nuclear use cases are presented in detail based on those strategies. The relative priorities and feasibility of the different DPRK nuclear use cases were analyzed using parameters evaluating their military effect, the potential for US nuclear retaliation, and the level of civilian casualties. Among the expected cases, an attack on the ROK Mobile Corps would seem to be the most probable scenario, since the benefits that the DPRK would gain from such an attack would be high. Within that case, there is a danger of nuclear provocation due to the asymmetry between the DPRK's nuclear possession and ROK's possession of only conventional forces. The importance of the US extended deterrence policy to deter the DPRK's nuclear threat is therefore emphasized, and measures to strengthen the credibility of US extended deterrence are also suggested.
The human skin is an essential organ of the human body for sensing various changes in the external environment, including pressure, temperature, and humidity, as well as for interacting with the ...outside world. Therefore, in the field of soft electronics, the development of the electronic skin (e-skin) that mimics the functions and properties of the human skin is an important research topic. The potential applications of the e-skin technology include wearable electronics, soft robotics, human-machine interfaces (HMIs), and prosthetic devices. Toward such research goals, various technologies are required. Among these, the stretchable electrode technology is a key component for achieving soft, stretchable e-skin and its applications. Therefore, various materials and design strategies for stretchable electrodes have been developed by many research groups. The successful development of stretchable electrodes has resulted in the rapid progress of high-performance stretchable device components such as stretchable sensors and actuators. Moreover, the integration of these device components with stretchable interconnects has yielded an integrated e-skin system, through which interactive human-machine interfacing can be achieved. This paper presents an overview of state-of-the-art technological advances in materials and design strategies for the development of stretchable electrodes. In addition, e-skin systems and their HMI applications based on such stretchable electrodes are briefly reviewed.
The Warburg effect, which originally described increased production of lactate in cancer, is associated with diverse cellular processes such as angiogenesis, hypoxia, polarization of macrophages and ...activation of T cells. This phenomenon is intimately linked to several diseases including neoplasia, sepsis and autoimmune diseases
. Lactate, which is converted from pyruvate in tumour cells, is widely known as an energy source and metabolic by-product. However, its non-metabolic functions in physiology and disease remain unknown. Here we show that lactate-derived lactylation of histone lysine residues serves as an epigenetic modification that directly stimulates gene transcription from chromatin. We identify 28 lactylation sites on core histones in human and mouse cells. Hypoxia and bacterial challenges induce the production of lactate by glycolysis, and this acts as a precursor that stimulates histone lactylation. Using M1 macrophages that have been exposed to bacteria as a model system, we show that histone lactylation has different temporal dynamics from acetylation. In the late phase of M1 macrophage polarization, increased histone lactylation induces homeostatic genes that are involved in wound healing, including Arg1. Collectively, our results suggest that an endogenous 'lactate clock' in bacterially challenged M1 macrophages turns on gene expression to promote homeostasis. Histone lactylation thus represents an opportunity to improve our understanding of the functions of lactate and its role in diverse pathophysiological conditions, including infection and cancer.
Carbon nanotubes (CNTs) are a promising material for use as a flexible electrode in wearable energy devices due to their electrical conductivity, soft mechanical properties, electrochemical activity, ...and large surface area. However, their electrical resistance is higher than that of metals, and deformations such as stretching can lead to deterioration of electrical performances. To address these issues, here a novel stretchable electrode based on laterally combed CNT networks is presented. The increased percolation between combed CNTs provides a high electrical conductivity even under mechanical deformations. Additional nickel electroplating and serpentine electrode designs increase conductivity and deformability further. The resulting stretchable electrode exhibits an excellent sheet resistance, which is comparable to conventional metal film electrodes. The resistance change is minimal even when stretched by ≈100%. Such high conductivity and deformability in addition to intrinsic electrochemically active property of CNTs enable high performance stretchable energy harvesting (wireless charging coil and triboelectric generator) and storage (lithium ion battery and supercapacitor) devices. Monolithic integration of these devices forms a wearable energy supply system, successfully demonstrating its potential as a novel soft power supply module for wearable electronics.
Stretchable electrodes using a laterally combed carbon nanotube (CNT) network are fabricated by restructuring of vertically aligned CNTs through a lateral‐combing process. Subsequent Ni‐electroplating further enhances the conductivity of the laterally combed CNT network. This novel nanostructure is used as electrically and electrochemically high performance electrodes in wearable energy harvesting (wireless charger and triboelectric generator) and storage (lithium ion battery and supercapacitor) devices.
Protein homo-oligomerization is an important molecular mechanism in many biological processes. Therefore, the ability to control protein homo-oligomerization allows the manipulation and interrogation ...of numerous cellular events. To achieve this, cryptochrome 2 (CRY2) from Arabidopsis thaliana has been recently utilized for blue light-dependent spatiotemporal control of protein homo-oligomerization. However, limited knowledge on molecular characteristics of CRY2 obscures its widespread applications. Here, we identify important determinants for efficient cryptochrome 2 clustering and introduce a new CRY2 module, named ''CRY2clust'', to induce rapid and efficient homo-oligomerization of target proteins by employing diverse fluorescent proteins and an extremely short peptide. Furthermore, we demonstrate advancement and versatility of CRY2clust by comparing against previously reported optogenetic tools. Our work not only expands the optogenetic clustering toolbox but also provides a guideline for designing CRY2-based new optogenetic modules.Cryptochrome 2 (CRY2) from A. thaliana can be used to control light-dependent protein homo-oligomerization, but the molecular mechanism of CRY2 clustering is not known, limiting its application. Here the authors identify determinants of CRY2 clustering and engineer fusion partners to modulate clustering efficiency.
We report the identification of 67 previously undescribed histone modifications, increasing the current number of known histone marks by about 70%. We further investigated one of the marks, lysine ...crotonylation (Kcr), confirming that it represents an evolutionarily-conserved histone posttranslational modification. The unique structure and genomic localization of histone Kcr suggest that it is mechanistically and functionally different from histone lysine acetylation (Kac). Specifically, in both human somatic and mouse male germ cell genomes, histone Kcr marks either active promoters or potential enhancers. In male germinal cells immediately following meiosis, Kcr is enriched on sex chromosomes and specifically marks testis-specific genes, including a significant proportion of X-linked genes that escape sex chromosome inactivation in haploid cells. These results therefore dramatically extend the repertoire of histone PTM sites and designate Kcr as a specific mark of active sex chromosome-linked genes in postmeiotic male germ cells.
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► Identification of 67 novel histone marks including 28 lysine crotonylation sites ► Verification of Kcr as a novel histone mark ► Kcr is a robust indicator of active cellular genes ► Kcr is likely an important histone mark for male germ cell differentiation
This resource identifies new additions to the histone code. Among them, histone crotonlylation emerges as a mark enriched at testis-specific genes that escape sex chromosome inactivation in germ cells.
•PFOS caused developmental neurotoxicity in zebrafish.•PFOS affected neurological function, oxidative stress, and energy metabolism.•Integration of multi-omics was more decisive in exploring toxicity ...mechanisms than individual omics.•Axonal deformation, neuroinflammatory stimulation, and dysregulation of Ca2+ signaling pathways were the signature to explain developmental neurotoxicity.
Limited studies on multi-omics have been conducted to comprehensively investigate the molecular mechanism underlying the developmental neurotoxicity of perfluorooctanesulfonic acid (PFOS). In this study, the locomotor behavior of zebrafish larvae was assessed under the exposure to 0.1–20 μM PFOS based on its reported neurobehavioral effect. After the number of zebrafish larvae was optimized for proteomics and metabolomics studies, three kinds of omics (i.e., transcriptomics, proteomics, and metabolomics) were carried out with zebrafish larvae exposed to 0.1, 1, 5, and 10 μM PFOS. More importantly, a data-driven integration of multi-omics was performed to elucidate the toxicity mechanism involved in developmental neurotoxicity. In a concentration-dependent manner, exposure to PFOS provoked hyperactivity and hypoactivity under light and dark conditions, respectively. Individual omics revealed that PFOS exposure caused perturbations in the pathways of neurological function, oxidative stress, and energy metabolism. Integrated omics implied that there were decisive pathways for axonal deformation, neuroinflammatory stimulation, and dysregulation of calcium ion signaling, which are more clearly specified for neurotoxicity. Overall, our findings broaden the molecular understanding of the developmental neurotoxicity of PFOS, for which multi-omics and integrated omics analyses are efficient for discovering the significant molecular pathways related to developmental neurotoxicity in zebrafish.
Hydrogels consist of a cross-linked porous polymer network and water molecules occupying the interspace between the polymer chains. Therefore, hydrogels are soft and moisturized, with mechanical ...structures and physical properties similar to those of human tissue. Such hydrogels have a potential to turn the microscale gap between wearable devices and human skin into a tissue-like space. Here, we present material and device strategies to form a tissue-like, quasi-solid interface between wearable bioelectronics and human skin. The key material is an ultrathin type of functionalized hydrogel that shows unusual features of high mass-permeability and low impedance. The functionalized hydrogel acted as a liquid electrolyte on the skin and formed an extremely conformal and low-impedance interface for wearable electrochemical biosensors and electrical stimulators. Furthermore, its porous structure and ultrathin thickness facilitated the efficient transport of target molecules through the interface. Therefore, this functionalized hydrogel can maximize the performance of various wearable bioelectronics.
Wearable electronic devices are used to perform various electronic functions on the human skin, and their mechanical softness while maintaining high performances is critical. Therefore, there is a ...need to develop novel materials with outstanding softness and high electrical and ionic conductivity for wearable electronics. Here, we present an intrinsically stretchable and conductive nanocomposite based on alginate hydrogels and silver nanowires (AgNWs). The developed nanocomposite was applied to highly conductive soft electrodes that can be used in various wearable electronic devices. The nanocomposite electrode was prepared by cross-linking alginate molecules in the presence of AgNWs, exhibiting higher electrical, ionic conductivity, higher stretchability, and lower modulus than conventional conducting rubbers. By forming a bilayer structure with the nanocomposite and the ultrasoft hydrogel layer, the mechanical properties of the nanocomposite device could be matched to that of the human skin. We used the nanocomposite electrode for fabricating key device components of wearable electronics, such as a wearable antenna and a skin-mountable supercapacitor. Such demonstrations successfully proved the effectiveness of the proposed nanocomposite as a soft conducting material for wearable electronics.
Despite efforts to visualize the spatio-temporal dynamics of single messenger RNAs, the ability to precisely control their function has lagged. This study presents an optogenetic approach for ...manipulating the localization and translation of specific mRNAs by trapping them in clusters. This clustering greatly amplified reporter signals, enabling endogenous RNA-protein interactions to be clearly visualized in single cells. Functionally, this sequestration reduced the ability of mRNAs to access ribosomes, markedly attenuating protein synthesis. A spatio-temporally resolved analysis indicated that sequestration of endogenous β-actin mRNA attenuated cell motility through the regulation of focal-adhesion dynamics. These results suggest a mechanism highlighting the indispensable role of newly synthesized β-actin protein for efficient cell migration. This platform may be broadly applicable for use in investigating the spatio-temporal activities of specific mRNAs in various biological processes.
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