MiR-29 and MiR-140 Regulate TRAIL-induced Drug Tolerance in Lung Cancer

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has chemotherapeutic potential as a regulator of an extrinsic apoptotic ligand, but its effect as a drug is limited by innate and acquired resistance. Recent findings suggest that an intermediate drug tolerance could mediate acquired resistance, which has made the main obstacle for limited utility of TRAIL as an anti-cancer therapeutics. We propose miRNA-dependent epigenetic modification drives the drug tolerant state in TRAIL-induced drug tolerant (TDT). Transcriptomic analysis revealed miR-29 target gene activation in TDT cells, showing oncogenic signature in lung cancer. Also, the restored TRAIL-sensitivity was associated with miR-29ac and 140-5p expressions, which is known as tumor suppressor by suppressing oncogenic protein RSK2 (p90 ribosomal S6 kinase), further confirmed in patient samples. Moreover, we extended this finding into 119 lung cancer cell lines from public data set, suggesting a significant correlation between TRAIL-sensitivity and RSK2 mRNA expression. Finally, we found that increased RSK2 mRNA is responsible for NF-κB activation, which we previously showed as a key determinant in both innate and acquired TRAIL-resistance. Our findings support further investigation of miR-29ac and -140-5p inhibition to maintain TRAIL-sensitivity and improve the durability of response to TRAIL in lung cancer

Recoverable Random Numbers in an Internet of Things Operating System

Over the past decade, several security issues with Linux Random Number Generator (LRNG) on PCs and Androids have emerged. The main problem involves the process of entropy harvesting, particularly at boot time. An entropy source in the input pool of LRNG is not transferred into the non-blocking output pool if the entropy counter of the input pool is less than 192 bits out of 4098 bits. Because the entropy estimation of LRNG is highly conservative, the process may require more than one minute for starting the transfer. Furthermore, the design principle of the estimation algorithm is not only heuristic but also unclear. Recently, Google released an Internet of Things (IoT) operating system called Brillo based on the Linux kernel. We analyze the behavior of the random number generator in Brillo, which inherits that of LRNG. In the results, we identify two features that enable recovery of random numbers. With these features, we demonstrate that random numbers of 700 bytes at boot time can be recovered with the success probability of 90% by using time complexity for 5.20 × 2 40 trials. Therefore, the entropy of random numbers of 700 bytes is merely about 43 bits. Since the initial random numbers are supposed to be used for sensitive security parameters, such as stack canary and key derivation, our observation can be applied to practical attacks against cryptosystem

End-to-End Post-Quantum Cryptography Encryption Protocol for Video Conferencing System Based on Government Public Key Infrastructure

Owing to the expansion of non-face-to-face activities, security issues in video conferencing systems are becoming more critical. In this paper, we focus on the end-to-end encryption (E2EE) function among the security services of video conferencing systems. First, the E2EE-related protocols of Zoom and Secure Frame (SFrame), which are representative video conferencing systems, are thoroughly investigated, and the two systems are compared and analyzed from the overall viewpoint. Next, the E2EE protocol in a Government Public Key Infrastructure (GPKI)-based video conferencing system, in which the user authentication mechanism is fundamentally different from those used in commercial sector systems such as Zoom and SFrame, is considered. In particular, among E2EE-related protocols, we propose a detailed mechanism in which the post-quantum cryptography (PQC) key encapsulation mechanism (KEM) is applied to the user key exchange process. Since the session key is not disclosed to the central server, even in futuristic quantum computers, the proposed mechanism, which includes the PQC KEM, still satisfies the E2EE security requirements in the quantum environment. Moreover, our GPKI-based mechanism induces the effect of enhancing the security level of the next-generation video conferencing systems up to a quantum-safe level

Blue Transparent OLEDs with High Stability and Transmittance for Modulating Sleep Disorders

Abstract Optoelectronics devices utilizing organic light‐emitting diodes (OLEDs) are emerging as new platforms for healthcare applications. In particular, wearable optoelectronics such as visual stimulus systems offer a distinctive advantage to intervene in and improve sleep disorders. In this study, two improvements are proposed for transparent OLEDs (TrOLEDs) that will be critical for visual applications. First, zinc sulfide with high surface energy and a high refractive index is explored as a seed and capping layer. An ultra‐thin silver cathode of 8 nm is demonstrated to be feasible in TrOLEDs, and luminous transmittance of 91% is achieved. Second, in general, achieving the operational stability of TrOLEDs with high transmittance is challenging due to the vulnerability of thin electrodes. By introducing a doping process to the electron transport layer, a lifetime comparable to that of control OLEDs with thick cathodes (>90%) is secured. Last, a preclinical model using blue light is proposed to modulate sleep patterns. Melanopsin is stimulated at the highest level of sleep desire, reducing non‐rapid eye movement sleep duration in mice by up to 14%. Based on these results, the proposed TrOLEDs are promising candidates for modulating sleep disorders such as insomnia and narcolepsy–cataplexy with the convenience of wearable form factors

An efficient simulation environment and simulation techniques for Bluetooth device design

Validation of an System-on-Chip (SoC) design with networking capability needs global simulation of the whole system including the network as well as the SoC design itself. Especially, it is needed to validate the interoperability of SoCs from different vendors. In this paper, we propose a simulation environment and simulation techniques for efficient validation of such SoC designs and apply them to networked Bluetooth SoC designs. The environment enables two types of simulation. One is modular enough to include the simulation of other vendors' Bluetooth devices and the other is optimized to achieve fast simulation in developing in-house Bluetooth devices. Especially, the former is scalable in that it keeps the constant simulation runtime despite the increase of the number of Bluetooth devices. Since multiple simulators are involved, the global simulation is still slow. Thus, the simulation efforts need to be minimized to shorten the design cycle. We present two simulation techniques, a concept called grouped message for reduction in simulation runtime and a system debug scenario called fix–modify–restart for reduction in the number of simulation runs. The former is to reduce inter-process communication overhead between simulators in the global simulation. The latter is to reduce repeated simulation runs in the conventional design cycle. Experimental results show the scalability of the presented simulation environment, reduction in simulation efforts by two simulation techniques.This research was supported by GCT Inc. and grand No. 20015-302-03-2 from the Basic Research program of th Korea Science & Engineering Foundation(KOSEF)

Salt Triggers the Simple Coacervation of an Underwater Adhesive When Cations Meet Aromatic pi Electrons in Seawater

Adhesive systems in many marine organisms are postulated to form complex coacervates (liquid liquid phase separation) through a process involving oppositely charged polyelectrolytes. Despite this ubiquitous speculation, most well characterized mussel adhesive proteins are cationic and polyphenolic, and the pursuit of the negatively charged proteins required for bulk complex coacervation formation internally remains elusive. In this study, we provide a clue for unraveling this paradox by showing the bulky fluid/fluid separation of a single cationic recombinant mussel foot protein, rmfp-1, with no additional anionic proteins or artificial molecules, that is triggered by a strong cation-pi interaction in natural seawater conditions. With the similar condition of salt concentration at seawater level (>0.7 M), the electrostatic repulsion between positively charged residues of mfp-1 is screened significantly, whereas the strong cation-pi interaction remains unaffected, which leads to the macroscopic phase separation (i.e., bulky coacervate formation). The single polyelectrolyte coacervate shows interesting mechanical properties including low friction, which facilitates the secretion process of the mussel. Our findings reveal that the cation-pi interaction modulated by salt is a key mechanism in the mussel adhesion process, providing new insights into the basic understanding of wet adhesion, self-assembly processes, and biological phenomena that are mediated by strong short-range attractive forces in water