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Regulation of genetic activity in single cells and tissues is pivotal to determine key cellular functions in current biomedicine, yet the conventional biochemical activators lack spatiotemporal precision due to the diffusion-mediated slow kinetics and nonselectivity. Here, we describe a magnetogenetic method for target-specific activation of a clustered regularly interspaced short palindromic repeats (CRISPR) system for the regulation of intracellular proteins. We used magnetomechanical force generated by the magnetic nanostructure to activate pre-encoded Piezo1, the mechanosensitive ion channel, on the target cell. The activated Piezo1 further triggers the intracellular Ca

The rapid increase in collateral omics and phenotypic data has enabled data-driven studies for the fast discovery of cancer targets and biomarkers. Thus, it is necessary to develop convenient tools for general oncologists and cancer scientists to carry out customized data mining without computational expertise. For this purpose, we developed innovative software that enables user-driven analyses assisted by knowledge-based smart systems. Publicly available data on mutations, gene expression, patient survival, immune score, drug screening and RNAi screening were integrated from the TCGA, GDSC, CCLE, NCI, and DepMap databases. The optimal selection of samples and other filtering options were guided by the smart function of the software for data mining and visualization on Kaplan-Meier plots, box plots and scatter plots of publication quality. We implemented unique algorithms for both data mining and visualization, thus simplifying and accelerating user-driven discovery activities on large multiomics datasets. The present Q-omics software program (v0.95) is available at http://qomics.sookmyung.ac.kr.

Accurate channel estimation is essential to achieve the performance gains promised by the use of reconfigurable intelligent surfaces (RISs) in wireless communications. In the uplink of multi-user orthogonal frequency division multiple access (OFDMA) systems, synchronization errors such as carrier frequency offsets (CFOs) can significantly degrade the channel estimation performance. This becomes more critical in RIS-aided communications, as even a small channel estimation error leads to a significant performance loss. Motivated by this, we propose a joint CFO and channel estimation method for RIS-aided multi-user massive multiple-input multiple-output (MIMO) systems. Our proposed pilot structure allows accurate estimation of the CFOs without multi-user interference (MUI), using the same pilot resources for both CFO estimation and channel estimation. For joint estimation of multiple users' CFOs, a correlation-based approach is devised using the received signals at all BS antennas. Using least-squares (LS) estimation with the obtained CFO values, the channels of all users are jointly estimated. For optimization of the RIS phase shifts at the data transmission stage, we propose a projected gradient method (PGM). Simulation results demonstrate that the proposed method provides an improvement in the normalized mean-square error (NMSE) of channel estimation as well as in the bit error rate (BER) performance., Comment: 11 pages, 12 figures, this manuscript has been submitted

Osteoarthritis (OA) is the most common form of arthritis. It is characterized by progressive destruction of articular cartilage and the development of chronic pain and constitutes a considerable socioeconomic burden. Currently, pharmacological treatments mostly aim to relieve the OA symptoms associated with inflammation and pain. However, with increasing understanding of OA pathology, several potential therapeutic targets have been identified, enabling the development of disease-modifying OA drugs (DMOADs). By targeting inflammatory cytokines, matrix-degrading enzymes, the Wnt pathway, and OA-associated pain, DMOADs successfully modulate the degenerative changes in osteoarthritic cartilage. Moreover, regenerative approaches aim to counterbalance the loss of cartilage matrix by stimulating chondrogenesis in endogenous stem cells and matrix anabolism in chondrocytes. Emerging strategies include the development of senolytic drugs or RNA therapeutics to eliminate the cellular or molecular sources of factors driving OA. This review describes the current developmental status of DMOADs and the corresponding results from preclinical and clinical trials and discusses the potential of emerging therapeutic approaches to treat OA., Osteoarthritis: moving from symptom relief towards disease control Researchers are exploring several promising avenues to develop treatments for osteoarthritis that control or reverse its progress, rather than simply relieving the symptoms of inflammation and pain. These new opportunities are emerging from increased understanding of the molec_reular mechanisms underlying the onset and progression of osteoarthritis. Seung-Baik Kang, Jin-Hong Kim and colleagues at Seoul National University, South Korea, review the current status and future directions of disease-modifying strategies that are already showing promise in clinical trials. They discuss approaches aimed at restricting the damage to joint cartilage by controlling the inflammatory signaling molecules, enzyme actions and molecular pathways that cause cartilage to degenerate. They also consider treatments that could stimulate the active regeneration of damaged cartilage. They conclude that some approaches will soon be ready to move into general clinical use.

Increased multi-level omics data has enabled data-driven studies on cancer drugs, targets and biomarkers. Thus, it is necessary to develop comprehensive tools for oncologists and cancer scientists to carry out extensive data mining without computational expertise. For this purpose, we have developed innovative software that enables user-driven analyses on cancer omics data, assisted by knowledge-based smart systems. Publicly available multi-level omics data of mutations, gene/protein expression, patient survival, immune score (tumor infiltrating cells), drug screening and RNAi (shRNA and CRISPR) screenings on patient samples and cell lines, were integrated from the TCGA, GDSC, CCLE, NCI and DepMap databases. Q-omics provides user-friendly interface for calculation and visualization of cross-associated data pairs retrieved from integrated datasets. The optimal selection of samples, datasets and/or other filtering options is guided by knowledge-bases of the software for the quick and easy finding of significant associations between data pairs. Furthermore, implemented smart algorithms prioritize significant hits based on consensus scoring methods. Consensus scoring using multiple statistical tests with varied sample (or lineage) selection, enriches noise-free, robust cross-associated pairs in the hit list. We believe that Q-omics provide simple but powerful tools for all areas of oncology and cancer research. The latest version of Q-omics software is available at http://qomics.sookmyung.ac.kr. Citation Format: Sukjoon Yoon, Euna Jeong, Sumin Jeong, Jieun Lee, Youngju Kim. Q-omics: smart software for assisting oncology and cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5035.

Accurate channel estimation is essential for achieving the performance gains offered by reconfigurable intelligent surface (RIS)-aided wireless communications. A variety of channel estimation methods have been proposed for such systems; however, none of the existing methods takes into account the effect of synchronization errors such as carrier frequency offset (CFO). In general, CFO can significantly degrade channel estimation performance of orthogonal frequency division multiplexing (OFDM) systems. Motivated by this, we investigate the effect of CFO on channel estimation for RIS-aided OFDM systems. Furthermore, we propose a joint CFO and channel impulse response (CIR) estimation method for these systems. Simulation results demonstrate the effectiveness of our proposed method, and also demonstrate that the use of time-domain rather than frequency-domain estimation in this context results in an improvement in the mean-squared error (MSE) performance of channel estimation as well as a significantly lower overall computational complexity., Comment: 5 pages, 5 figures, this manuscript has been submitted to IEEE WCL and accepted (Digital Object Identifier:10.1109/LWC.2021.3124049)

Carrier frequency offset (CFO) can significantly influence the performance of multiple-input multiple-output (MIMO) systems if not estimated and corrected. Most of the existing synchronization techniques are designed for MIMO systems with collocated antennas, where the same frequency error is experienced by the received signal at each antenna. In contrast, for MIMO systems with distributed antennas, the received signals at different receive antennas suffer from different frequency errors. This makes synchronization of such systems computationally complex, especially as the number of receive antennas grows large, i.e. massive MIMO. In this paper, we study the problem of CFO estimation for distributed massive MIMO and cell-free massive MIMO. In particular, we evaluate the performance of distributed large-scale MIMO systems with both collaborative and non-collaborative CFO estimation techniques based on the maximum likelihood (ML) criterion. These optimal CFO estimation results can then serve as benchmarks on the achievable estimation performance of practical collaborative and non-collaborative CFO estimation techniques for distributed MIMO systems. The proposed ML-based CFO estimation methods are tailored to work with periodic pilot sequences. We also show how exploiting the relationships which exist between the CFOs to be estimated can substantially reduce the computational load of CFO estimation in the collaborative approach.

To study the function of arginine vasotocin (AVT) in a specific courtship behavior (body undulation) in male Hynobius leechii, we injected various doses of AVT or an AVT V1a or V2 receptor antagonist into breeding and non-breeding males. After these injections, we placed the males alone or with breeding females in Petri dishes and measured the incidence and frequency of body undulation. Additionally, to test whether AVT modulates the olfactory response of males, we exposed breeding males that were injected with AVT to female odors and measured the same response. Both breeding and non-breeding males intraperitoneally injected with 50 or 100 µg of AVT exhibited body undulation. Additionally, breeding males intraperitoneally injected with 50 or 100 µg of AVT exhibited an increased frequency of body undulation when exposed to female odors. The intraperitoneal injection of 5, 25, or 50 µg of the AVT V1a or V2 receptor antagonist did not significantly decrease the incidence or frequency of body undulation of 100 µg AVT-injected breeding males. However, in a post-hoc experiment, the breeding males that were subcutaneously injected with 100 µg of the AVT V1a receptor antagonist exhibited a significant decrease in the frequency of body undulation, induced by exposure to females. Additionally, a central injection of 1 µg of AVT into the brain induced body undulation in breeding males. Our results show that AVT not only induces a specific courtship behavior in male H. leechii via AVT V1a receptors but also modulates the olfactory response.

Physostigmine, an acetylcholinesterase inhibitor, is known to affect the brain function in various aspects. This study was conducted to test whether physostigmine affects cell proliferation in the telencephalon of zebrafish. BrdU-labeled cells was prominently observed in the ventral zone of the ventral telencephalon of zebrafish. The increased number of BrdU- and proliferating cell nuclear antigen-labeled cells were shown in zebrafish treated with 200μM physostigmine, which was inhibited by pretreatment with 200μM scopolamine. iNOS mRNA expression was increased in the brain of zebrafish treated with 200μM physostigmine. Consistently, aminoguanidine, an iNOS inhibitor, attenuated the increase in the number of BrdU-labeled cells by physostigmine treatment. Zebrafish also showed seizure-like locomotor activity characterized by a rapid and abrupt movement during a 30min treatment with 200μM physostigmine. Neural activity in response to an electrical stimulus was increased in the isolated telencephalon of zebrafish continuously perfused with 200μM physostigmine. None of the number of BrdU-labeled cells, neural activity, or locomotor activity was affected by treatment with 20μM physostigmine. These results suggest that 200μM physostigmine increased neural activity and induced cell proliferation via nitric oxide production in zebrafish.

We consider a two-degree-of-freedom model where the focus is on analyzing the vibrations of a fixed but flexible structure that is struck repeatedly by a second object. The repetitive impacts due to the second mass are driven by a flowing fluid. Morison’s equation is used to model the effect of the fluid on the properties of the structure. The model is developed based on both linearized and quadratic fluid drag forces, both of which are analyzed analytically and simulated numerically. Conservation of linear momentum and the coefficient of restitution are used to characterize the nature of the impacts between the two masses. A resonance condition of the model is analyzed with a Fourier transform. This model is proposed to explain the nature of ice-induced vibrations, without the need for a model of the ice-failure mechanism. The predictions of the model are compared to ice-induced vibrations data that are available in the open literature and found to be in good agreement. Therefore, the use of a repetitive impact model that does not require modeling the ice-failure mechanism can be used to explain some of the observed behavior of ice-induced vibrations.

Introduction of an invasive prey species into an ecosystem may affect an endemic predator's fitness by altering the prey-predator system. Successful adaptation may allow the endemic predator to eat and control the invasive species, while unsuccessful adaptation may result in extinction of the predator. We examine the possible effects of the invasive North American bullfrog (Rana (Lithobates) catesbeiana) on the endemic Red-backed rat snake (Oocatochus rufodorsatus) in South Korea. We do so by comparing the morphology and behavior of adult and hatchling snakes from bullfrog-exposed (Taean) and bullfrog-unexposed (Hongcheon) populations. Among the seven morphological characteristics investigated, relative tail length (tail length/snout-vent length) of both adults and hatchlings from Taean was significantly greater than that of adults and hatchlings from Hongcheon. Also, adult snakes from Taean had a significantly shorter latency of first tongue flick in response to prey compared to adults from Hongcheon. This difference was not observed in hatchlings. In other snake species, a longer relative tail length and shorter latency of first tongue flick are known to improve foraging efficiency, and these characters may be adaptations of O. rufodorsatus to prey on bullfrogs. This study provides preliminary evidence that the presence of an invasive prey species may cause morphological and behavioral changes in an endemic predator.