• Biomolecules & Therapeutics
• /
• v.32 no.4
• /
• pp.481-491
• /
• 2024

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (M^pro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in M^pro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the M^pro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC₅₀ values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

• The Journal of the Institute of Internet, Broadcasting and Communication
• /
• v.16 no.4
• /
• pp.73-80
• /
• 2016

Multiplayer Online Games(MOG) using the Internet are typically organized based on a CS(client-server) or P2P(peer-to-peer) architecture. We then propose a method that combines a P2P architecture with a CS architecture in order to utilize their advantages. Most MOGs use a primary-copy replication approach that provides strong consistency control over an object. For each object and character there exists an authoritative copy, called primary copy and all other copies are secondary copies or replicas. Any update to the object has to be first performed on the primary copy. In the proposed hybrid architecture, primary copies may reside on the server or be held by clients. In this architecture, load balancing between a server and clients can be achieved by reducing the number of objects maintained by the server. Games consist of various types of actions with different consistency requirements. A multi-level approach to game consistency is sensible as it provides the best trade-off between consistency and performance. The performance for the hybrid game architecture with the primary-copy model is evaluated through simulation experiments and analysis in this paper.

• The KIPS Transactions:PartD
• /
• v.11D no.2
• /
• pp.351-360
• /
• 2004

Most mobile agents are migrated to many mobile agent systems by the sequential node migration method. However. in this case, if some problems such as host's fault or obstacle etc. happened, mobile agent falls infinity walt or orphan states. Therefore, it is difficult to get an expectation effect as use of other distribution technologies because the required time for networking between nodes increases. And so, many researches have been performed to solve this problems. However, most of methods decide node migration based on passive routing table or detour hosts which have some problems. Actually, the researches for reducing the total required time for networking are insufficient yet. In this paper, to reduce the required time for networking of mobile agent we design an active routing table based on the information of implemented objects which are registered in the meta-table of naming agent. And also, for user's keyword, we propose an replication model that replicates many agent object according to the information and number of object references corresponding to meta-table. Replicated objects are migrated to mobile agent systems in parallel and it provides minimized required time for networking.

• Journal of Microbiology and Biotechnology
• /
• v.29 no.8
• /
• pp.1230-1239
• /
• 2019

Scutellaria baicalensis Georgi has been widely used in China for treatment of various diseases. This study investigated the effect of Scutellaria baicalensis Georgi extracts (SBE) against Coxsackievirus B3 (CVB3)-induced myocarditis in vitro and in vivo. In vitro, Hela cells and primary myocardial cells were infected with CVB3 and treated with SBE ($50-800{\mu}g/ml$) and ribavirin ($200{\mu}M$) for 48 h and then determined by CCK8 assay. Real-time PCR and western blotting assays were performed. In vivo, a myocarditis model was induced in male BALB/c mice by injecting CVB3 suspension intraperitoneally for three times, followed by treatment with SBE (400 and 200 mg/kg) and ribavirin (100 mg/kg) for 28 days. SBE ameliorated the cytotoxicity of CVB3 in Hela cells, especially at $400{\mu}g/ml$ (39.93% vs 65.67%, p < 0.05) without influencing cell growth and also significantly reduced CVB3 replication in primary myocardial cells. The levels of AKT, ERK, and p38 were increased after CVB3 infection. SBE could downregulate the expressions of AKT and p38. In vivo, the mortality rate from CVB3 reached to 66.67%, while 10.00% and 23.33% of this came after 400 and 200 mg/kg SBE treatment, respectively (p < 0.05). The CVB3 replication was obviously reduced after SBE administration from day 5. Similarly, the levels of AKT, ERK, and p38 mRNAs and proteins were increased, and SBE suppressed the expression of AKT and p38. Our study indicates that SBE is a promising potent antiviral agent against CVB3-induced myocarditis by inhibition of virus replication via depressing AKT and p38 expressions.

• Journal of Information Technology Applications and Management
• /
• v.10 no.1
• /
• pp.71-89
• /
• 2003

This paper firstly introduces a classification model for designing the architecture of backup centers in terms of business continuity management. We propose that the replication solution, the level of disaster recovery, and the outsourcing style as three important factors that help explain the architecture of backup centers. We provide the details of each factor of the model and apply them to the real world cases of backup centers in Korea. We conclude that the model is well fitted to many cases of currently available backup centers and can provide backup center architects with a well classified architecture model with specific guidelines.

• Journal of KIISE:Computing Practices and Letters
• /
• v.16 no.7
• /
• pp.759-767
• /
• 2010

RT-eCos 3.0 is a micro-sized embedded real-time kernel that has been developed based on the open source eCos 3.0 to support the basic task model of the well-known distributed real-time object model, TMO(Time-Triggered Message-triggered Object). In this paper, the design and implementation techniques of the RMMC(Real-time Multicast & Memory replication Channel) that is a standard distributed IPC model of the TMO is described based on the RT-eCos 3.0. And the support technique of the global time for using the same time in a distributed environment using the RMMC is also described. The developed global time based RMMC supports highly abstracted distributed IPC environment in a wide area distributed computing environment with the RT-eCos 3.0.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1996.04a
• /
• pp.80-104
• /
• 1996

The development of routine techniques for the isolation and in vitro maintenance of conducting airway epithelial cells in a differentiated state provides an ideal model to study the factors involved in the regulation of the expression of mucocilicary differentiation. Several key factors and conditions have been identified. These factors and conditions include the use of biphasic culture technique to achieve mucociliary differentiation and the use of such stimulators, the thickness of collagen gel substratum, the calcium level, and vitamin A, and such inhibitors, the growth factors EGF and insulin, and steroid hormones, for mucous cell differentiation. Using the defined culture medium, the life cycle of the mucous cell population in vitro was investigated. It was demonstrated that the majority of the mucous cell population in primary cultures is not involved in DNA replication. However, the mucous cell type is capable of self-renewal in culture and this reproduction is vitamin A dependent. furthermore, differentiation from non-mucous cell type to mucous cell type can be demonstrated by adding back a positive regulator such as vitamin A to the “starved” culture. Cell kinetics data suggest that vitamin A-dependent mucous cell differentiation in culture is a DNA replication-independent process and the process is inhibited by TGF-${\beta}$1.

• Journal of Korean Society of Industrial and Systems Engineering
• /
• v.21 no.46
• /
• pp.33-49
• /
• 1998

In order to improve the performance of relational databases, one has to reduce the number of disk accesses necessary to transfer data from disk to main memory. The paper proposes to reduce the number of disk I/O accesses by vertically partitioning relation into fragments and allowing attribute replication to fragments if necessary. When zero-one integer programming model is solved by the branch-and-bound method, it requires much computing time to solve a large sized problem. Therefore, heuristic solutions using genetic algorithm(GA) are presented. GA in this paper adapts a few ideas which are different from traditional genetic algorithms, for examples, a rank-based sharing fitness function, elitism and so on. In order to improve performance of GA, a set of optimal parameter levels is determined by the experiment and makes use of it. As relations are vertically partitioned allowing attribute replications and saved in disk, an attribute replicating vertical partition method by GA can attain less access cost than non-attribute-replication one and require less computing time than the branch-and-bound method in large-sized problems. Also, it can acquire a good solution similar to the optimum solution in small-sized problem.

• Journal of the Korean Society of Safety
• /
• v.20 no.3 s.71
• /
• pp.34-41
• /
• 2005

For assessing residual lift of the steam pipe in fossil power plants, inspections and analysis are usually focused on the critical locations such as butt welds, elbows, Y-piece and T-piece of the steam pipes. In predicting the residual life of T-piece, determination of local stress near welds considering system load as well as internal pressure is not a simple problem. In this study, stress analysis of a T-piece pipe was conducted using a three-dimensional model which represents the T-piece of a domestic fossil power station. Elastic and elastic-creep analysis showed the maximum stress level and its location. Residual creep rupture life was also calculated using the stress analysis results. It was argued that the calculated life is reasonably same as the measured one. The stress analysis results also support life prediction methodology based on in-field replication technique.

• Journal of the Korea Institute of Information and Communication Engineering
• /
• v.17 no.5
• /
• pp.1129-1137
• /
• 2013

Cloud storage system that cloud computing providers provides large amounts of data storage and processing of cloud computing is a key component. Large vendors (such as Facebook, YouTube, Google) in the mass sending of data through the network quickly and easily share photos, videos, documents, etc. from heterogeneous devices, such as tablets, smartphones, and the data that is stored in the cloud storage using was approached. At time, growth and development of the globally data, the cloud storage business model emerging is getting. Analysis new network storage cloud storage services concepts and technologies, including data manipulation, storage virtualization, data replication and duplication, security, cloud computing core.