• Journal of Microbiology and Biotechnology
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• 제24권4호
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• pp.577-583
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• 2014

Three major classes of retroviral restriction factors (APOBEC3G, Tetherin, and TRIM5${\alpha}$) have been identified in mammals. Restriction factors are cellular proteins that are able to limit viral replication by targeting specific steps of the viral life cycle. To evaluate which restriction factor is the most effective to inhibit the replication of porcine endogenous retroviruses (PERVs), the antiviral activity of each restriction factor was compared. In pseudotype assay, the antiviral activity of human tetherin against PERV pseudotype was slightly weaker than that of human APOBEC3G (hA3G). A combination of tetherin and hA3G was more potent than each individual restriction factor. We questioned whether a combination of tetherin and hA3G could also inhibit the spreading replication of PERV. In agreement with the pseudotype assay, two restriction factors inhibit infectious PERV replication in a spreading infection. In this study, hA3G could strongly inhibit the replication of PERV, but tetherin modestly restricted it. Based on these results, we concluded that a combination of tetherin and hA3G is the most effective way to restrict PERV. A combination of different restriction factors will encourage the development of a new approach to treat retroviral disease.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.1-15
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• 2023

Autophagy is a process of eliminating damaged or unnecessary proteins and organelles, thereby maintaining intracellular homeostasis. Deregulation of autophagy is associated with several diseases including cancer. Contradictory dual roles of autophagy have been well established in cancer. Cytoprotective mechanism of autophagy has been extensively investigated for overcoming resistance to cancer therapies including radiotherapy, targeted therapy, immunotherapy, and chemotherapy. Selective autophagy inhibitors that directly target autophagic process have been developed for cancer treatment. Efficacies of autophagy inhibitors have been tested in various pre-clinical cancer animal models. Combination therapies of autophagy inhibitors with chemotherapeutics are being evaluated in clinal trials. In this review, we will focus on genetical and pharmacological perturbations of autophagy-related proteins in different steps of autophagic process and their therapeutic benefits. We will also summarize combination therapies of autophagy inhibitors with chemotherapies and their outcomes in pre-clinical and clinical studies. Understanding of current knowledge of development, progress, and application of cytoprotective autophagy inhibitors in combination therapies will open new possibilities for overcoming drug resistance and improving clinical outcomes.

• The Korean Journal of Physiology and Pharmacology
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• 제27권3호
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• pp.221-230
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• 2023

Diabetic kidney disease is one of the most serious complications of diabetes. Although diabetic kidney disease can be effectively controlled through strict blood glucose management and corresponding symptomatic treatment, these therapies cannot reduce its incidence in diabetic patients. The sodium-glucose cotransporter 2 (SGLT2) inhibitors and the traditional Chinese herb "Gegen" have been widely used in diabetes-related therapy. However, it remains unclear whether the combined use of these two kinds of medicines contributes to an increased curative effect on diabetic kidney disease. In this study, we examined this issue by evaluating the efficacy of the combination of puerarin, an active ingredient of Gegen, and canagliflozin, an SGLT2 inhibitor for a 12-week intervention using a mouse model of diabetes. The results indicated that the combination of puerarin and canagliflozin was superior to canagliflozin alone in improving the metabolic and renal function parameters of diabetic mice. Our findings suggested that the renoprotective effect of combined puerarin and canagliflozin in diabetic mice was achieved by reducing renal lipid accumulation. This study provides a new strategy for the clinical prevention and treatment of diabetic kidney disease. The puerarin and SGLT2 inhibitor combination therapy at the initial stage of diabetes may effectively delay the occurrence of diabetic kidney injury, and significantly alleviate the burden of renal lipotoxicity.

• Journal of Digestive Cancer Research
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• 제10권1호
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• pp.22-30
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• 2022

Immune checkpoint inhibition has been established as a new treatment option for various types of carcinoma, and many clinical trials are being actively conducted as a treatment for advanced or metastatic gastric cancer, either as a monotherapy with an immune checkpoint inhibitor or as a combination therapy with standard chemotherapy. In the CheckMate-649 clinical trial to confirm the efficacy of the combination of nivolumab and chemotherapy (FP) in advanced gastric cancer and gastroesophageal junction cancer, nivolumab group showed improvement in overall survival in programmed death ligand 1-positive cancer patients compared with placebo group. Also, the combination therapy of pembrolizumab, trastuzumab and chemotherapy (FP) in first-line treatment was tested through the KEYNOTE-811 trial. The pembrolizumab group showed 22.7% of improvement in objective response rate compared with placebo group. Accordingly, the combination of nivolumab/pembrolizumab with standard chemotherapy was approved for the first-line treatment. In KEYNOTE-059 trials for patients with progressive disease after at least two lines of chemotherapy, pembrolizumab monotherapy showed improvement in objective response rate and overall survival, and the use of pembrolizumab was approved for the third-line or more treatment. In this article, we review the result of clinical trials related to immune checkpoint inhibitors that have been recently introduced in the treatment of gastric cancer.

• Journal of Biosystems Engineering
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• 제22권4호
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• pp.439-450
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• 1997

Most of Korean feed mill has a pregrind system which was suitable for the processing of less number of ingredients and finished products, and good for the mash type feed product. But industries has been changed in production volume and cost, and also from mash to further processed products such as pelleted and extruded. Therefore, Korea feed industries now should change the process, especially the grinding system from the current pregrind to other grind system, but this change will cost a lot of investment and also loosing current grinding system, and should have production shut down during the construction period. To solve these problems, combined grinding system based on a new model mill has been developed. The combined grind system is combination of pregrind and postgrind system, which has the advantages of those two grind systems, and also which can allow to utilize existing pregrind system continuously without any production interruption due to new postgrind system construction. This newly developed model has been applied to the feed mill expansion project of `B`feed company in 1994, and it was very successful application and showed excellent results as we intended. The new model mill, combined grind system applied can save fixed asset investment because old pregrind system can be used as is, and also can reduce production cost and improve product quality. And the possibility of critical production shut down can be much lowered. Within this new grinding model development, multi-screen combination system has been developed for the better grinding texture quality and safer operation. This new model mill with combined grind system will be applied by most feed manufacturing plant and may enhance their production competitiveness, and the further study and development should be continued.

• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3530-3538
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• 2010

In this study 1-[4-(2-methoxy benzyl)-6-aryl-pyridazin-3(2H)-ylidene] hydrazines were used for the synthesis of new heterocyclic systems such as thiazolidine, phthalazine, pyrazolo, tetrazolo, hydrazide and new pyridazine derivatives to explore the effect of silver nanoparticles on their biological activity efficiency. Structures of the new heterocycles were characterized by the aid of several analytical techniques including; $^1H$-NMR, FTIR and mass spectra. Silver nanoparticles were synthesized by a simple methodology and the formation of silver nanoparticles was confirmed by transmission electron microscopy (TEM) and UV studies. Most of the new prepared heterocycles were evaluated in vitro as new antimicrobial agents. Combination effects of the silver nanoparticles on the antimicrobial activity of the new heterocycles were investigated using the disk diffusion method. Compound 10a exhibited the strongest enhancing effect of silver nanoparticles solution against Aspergillus flavus and Candida albicans.

• 한국영어학회지:영어학
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• 제2권2호
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• pp.149-159
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• 2002

Prepositional stranding (P-Stranding), which was possible only in certain types of constructions in Old English, began to be allowed more freely in the Middle English (ME) period, resulting in many new types of P-Stranding. Although many relevant studies have tried to account for the development of these new P-Stranding types, none of them or no combination of them seem to adequately explain how the new types came into being in ME and why they occurred in the order in which they occurred. In this paper, I explain why the development of new P-Stranding types in Middle English cannot be properly explained by any of the previous studies and then provide an alternative account of the advent of each new type of P-Stranding and the chronology involved on the basis of the displacement of the prepositional object from PP (DPO), a constraint on DPO (DPO), and the subject requirement (SubjR).

• Communications for Statistical Applications and Methods
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• 제31권3호
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• pp.263-277
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• 2024

This paper proposes new parameterizations of the tilted beta binomial distribution, obtained from the combination of the binomial distribution and the tilted beta distribution, where the beta component of the mixture is parameterized as a function of their mean and variance. These new parameterized distributions include as particular cases the beta rectangular binomial and the beta binomial distributions. After that, we propose new linear regression models to deal with overdispersed binomial datasets. These new models are defined from the proposed new parameterization of the tilted beta binomial distribution, and assume regression structures for the mean and variance parameters. These new linear regression models are fitted by applying Bayesian methods and using the OpenBUGS software. The proposed regression models are fitted to a school absenteeism dataset and to the seeds germination rate according to the type seed and root.

• Tuberculosis and Respiratory Diseases
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• 제44권3호
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• pp.525-533
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• 1997

연구배경 : 수술적 절제가 불가능한 폐암환자에서 복합화학요법의 역할이 최근 증대되고 있으나 아직 가장 이상적인 복합화학요법은 확립되지 않고 있다. 두 종류 이상의 항암제를 복합투여시 약제간의 상호작용에 의해 항암효과의 상승 혹은 억제를 보일 수 있으나 이를 예측하기가 어려웠다. 본 연구에서는 MTT 검사를 이용하여 두 약제를 여러 농도에서 복합투여후 살해능의 변화를 관찰하였다. 방 법 : 사람의 폐선암세포인 PC-14를 이용하여 cisplatin, mitomycin C, adriamycin 및 etoposide를 여러 농도에서 단독 또는 두 약제를 복합투여하여 항암효과의 변화를 MTT 검사로 측정하고 두 약제 복합투여시의 상호 작용의 결과를 이원배치법을 이용한 Anova분석을 이용하여 측정하였다. 결 과 : 위의 네종류의 약제는 단독투여시 농도에 비례하는 암세포살해능을 보였고 두 약제를 복합투여시 모든 조합에서 암세포살해능의 상승효과를 보였으며 특히 mitomycin C 와 cisplatin 및 adriamycin과 cisplatin을 복합투여시 상승효과가 강하게 나타났다. 결 론 : 위의 결과로 비소세포폐암의 복합화학요법시 mitomycin C와 cisplatin 혹은 adriamycin과 cisplatin을 같이 사용할 경우 항암효과의 극대화를 얻을 수 있으리라 기대된다. 나아가 이번 연구의 디자인은 복합항암화학요법을 필요로 하는 모든 종류의 암에 적용되어 최대항암효과를 얻을 수 있는 약제선정에 도움의 될 수 있으리라 생각된다.

• 한국CDE학회논문집
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• 제2권4호
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• pp.215-221
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• 1997

A new approach in solving design centering problem is presented. Like most stochastic optimization problems, optimal design centering problems have intrinsic difficulties in multivariate intergration of probability density functions. In order to avoid to avoid those difficulties, genetic algorithm and very coarse Monte Carlo simulation are used in this research. The new algorithm performs robustly while producing improved yields. This result implies that the combination of robust optimization methods and approximated simulation schemes would give promising ways for many stochastic optimizations which are inappropriate for mathematical programming.