• BMB Reports
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• v.44 no.1
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• pp.34-39
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• 2011

Resistance to PAI-1 is a factor which confers clinical benefits in thrombolytic therapy. The only US FDA approved PAI-1 resistant drug is Tenecteplase$^{(R)}$. Deletion variants of t-PA have the advantage of fewer disulfide bonds in addition to higher plasma half lives. A new variant was developed by deletion of the first three domains in t-PA in addition to substitution of KHRR 128-131 amino acids with AAAA in truncated t-PA. The specific activity of this new variant, $570\;IU/{\mu}g$, was found to be similar to those found in full length t-PA (Alteplase$^{(R)}$), $580\;IU/{\mu}g$. A 65% and 85% residual activity after inhibition by rPAI-1 was observed for full length and truncated-mutant form, respectively. This new variant as the first PAI-1 resistant truncated t-PA may offer more advantages in clinical conditions in which high PAI-1 levels makes the thrombolytic system prone to re-occlusion.

• Journal of Microbiology
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• v.41 no.2
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• pp.129-136
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• 2003

The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMPI) exhibits considerable sequence heterogeneity among EBV isolates. Seven distinct EBV strains have been defined based on sequence polymorphisms in the LMPI gene, which are designated China 1, China 2, China 3, Alaskan, Mediterranean, NC, and the B95-8 strains. In this study, we analyzed a 30-bp deletion and sequence variations in the carboxy-terminal region of the LMPl gene in 12 EBV isolates from spontaneous lym-phoblastoid cell lines derived from individuals with non-EBV associated cancers in Korea. Eleven of the 12 isolates showed a 30-bp deletion spanning LMPI amino acids 342 to 353, suggesting a high prevalence of the LMPI 30-bp deletion variant among EBV isolates in Korea. In addition, all 12 isolates had a 15-bp common deletion in the 33-bp repeat region and multiple base-pair changes relative to the prototype B95-8 EBV strain along with variations in the number of the 33-bp repeats. The bp changes at positions 168746, 168694, 168687, 168395, 168357, 168355, 168631, 168320, 168308, 168295, and 168225 were highly conserved among the isolates. Comparative analysis of sequence change patterns in the LMPI carboxy-terminal coding region identified nine 30-bp deletion variants as China 1, two deletion variants as a possible interstrain between the Alaskan and China 1 strains, and a single undeleted variant as a possible variant of the Alaskan strain. These results suggest the predominance of the China 1 EBV strain in the Korean population.

• Journal of Korean Society of Industrial and Systems Engineering
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• v.38 no.3
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• pp.136-148
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• 2015

We analyzed the effect of three different types of inventory systems for saving the total cost using simulation on the system where multiple depots and many retailers disperse on the limited area. Three types of inventory systems are single echelon system with inventory exchange and two-echelon system and the variant two-echelon system. Variant two echelon system is the two-echelon system where the inventory transshipmentsare allowed on every two stage inventory echelons. Inventories kept on every retailer are commonly used for all retailers when certain retailer has stock-out. And when all retailers are stock-out, inventories kept on every depot are commonly used for the retailers whose assigned depots are stock-out. These all three systems are simulated with the constraint of service level on wide range of parameter settings. Simulation results show that cost saving effect appear clear for single echelon system and two-echelon system when shortage cost portion and transportation cost portion becomes large respectively irrespective of depot number. Variant two echelon system seems to be superior to two other systems when transportationcost portion becomes very small. But this superiority is not proved in terms of statistics. So we may conclude that the variant two echelon system may be useless with the higher administrative efforts due to frequent inventory exchange. Also we note that the traditional two echelon system becomes inferior to two other systems in terms of statistics when service level becomes high or when demand variance becomes very large. And inventory integration effect that cost becomes saved when depot number decrease, diminishes when transportation cost or stock-out cost increases irrespective of inventory systems.

• Journal of the Korean Vacuum Society
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• v.22 no.4
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• pp.211-217
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• 2013

Two types of organic thin film solar cell devices with bulk hetero-junction (BHJ) structure were fabricated on plastic substrates using conjugated polymers of $PCDTBT:PC_{71}BM$ and $PTB7:PC_{71}BM$ blended as active channel layer. Time-variant characteristics of the organic thin film solar cell devices were investigated: short circuit current density ($J_{SC}$); open circuit voltage ($V_{OC}$); ; fill factor (FF); power conversion efficiency (PCE, ŋ). All the performance parameters were degraded by progress of the measurement time, while $V_{OC}$ showed the most drastic decrease with time. Possible factors to cause the time-variant alteration of performance parameters were discussed to be clarified.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.577-583
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• 2019

Human cytochrome P450 2C9 is a highly polymorphic enzyme that is required for drug and xenobiotic metabolism. Here, we studied eleven P450 2C9 genetic variants-including three novel variants F69S, L310V, and Q324X-that were clinically identified in Korean patients. P450 2C9 variant enzymes were expressed in Escherichia coli and their bicistronic membrane fractions were prepared The CO-binding spectra were obtained for nine enzyme variants, indicating P450 holoenzymes, but not for the M02 (L90P) variant. The M11 (Q324X) variant could not be expressed due to an early nonsense mutation. LC-MS/MS analysis was performed to measure the catalytic activities of the P450 2C9 variants, using diclofenac as a substrate. Steady-state kinetic analysis revealed that the catalytic efficiency of all nine P450 2C9 variants was lower than that of the wild type P450 2C9 enzyme. The M05 (R150L) and M06 (P279T) variants showed high $k_{cat}$ values; however, their $K_m$ values were also high. As the M01 (F69S), M03 (R124Q), M04 (R125H), M08 (I359L), M09 (I359T), and M10 (A477T) variants exhibited higher $K_m$ and lower $k_{cat}$ values than that of the wild type enzyme, their catalytic efficiency decreased by approximately 50-fold compared to the wild type enzyme. Furthermore, the novel variant M07 (L310V) showed lower $k_{cat}$ and $K_m$ values than the wild type enzyme, which resulted in its decreased (80%) catalytic efficiency. The X-ray crystal structure of P450 2C9 revealed the presence of mutations in the residues surrounding the substrate-binding cavity. Functional characterization of these genetic variants can help understand the pharmacogenetic outcomes.

• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.320-332
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• 2018

Background: This study was performed to clarify the effect of SLCO1B1 T521C on statin-induced myotoxicity. Methods: The PubMed, Embase, Ovid, and Cochrane Library databases were searched for all published studies between database inception and April 2018. Using Review Manager 5, the pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were determined to assess the effect of SLCO1B1 T521C on statin-induced myotoxicity by using different genetic models. Results: Eleven observational studies and one randomized controlled trial were included in the meta-analysis. The pooled analysis showed that the incidence of statin-induced myotoxicity was significantly associated with the SLCO1B1 521C variant allele. Among patients using statins, the incidence of myotoxicity was higher in those carrying the 521TC or 521CC variant than in those carrying the 521TT variant in the dominant model (TC + CC vs TT, OR: 1.57; 95% CI: 1.20, 2.05; p = 0.001). The 521TC genotype was associated with a higher risk of myotoxicity than the 521TT genotype (OR: 1.42; 95% CI: 1.09, 1.86; p = 0.009). Furthermore, the incidence of myotoxicity was higher in 521CC carriers than in 521TC carriers (OR: 1.40; 95% CI: 1.06, 1.83; p = 0.02) and noticeably higher in 521CC carriers than in 521TT carriers (OR: 2.26; 95% CI: 1.23, 4.17; p = 0.009). Conclusion: The identification of individuals with the SLCO1B1 521C variant allele prior to the initiation of statin therapy might be useful to predict the risk of toxicity development, determine the individual dose, and prevent myotoxicity.

• BMB Reports
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• v.55 no.7
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• pp.348-353
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• 2022

Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes to tumorigenic activity in highly malignant gastric cancer through dissociation from the tumor repressor, HDAC5. NRP/B mRNA expression is significantly higher in the human gastric cancer tissues than in the normal tissues. Further, high levels of both the NRP/B splice variant and Lgr5, but not the full-length protein, are found in highly tumorigenic gastric tumor cells, but not in non-tumorigenic cells. The loss of NRP/B markedly inhibits cell migration and invasion, which reduces tumor formation in vivo. Importantly, the inhibition of alternative splicing increases the levels of NRP/B-1 mRNA and protein in AGS cells. The ectopic expression of full-length NRP/B exhibits tumor-suppressive activity, whereas NRP/B-2 induces the noninvasive human gastric cancer cells tumorigenesis. The splice variant NRP/B-2 which loses the capacity to interact with tumor repressors promoted oncogenic activity, suggesting that the BTB/POZ domain in the N-terminus has a crucial role in the suppression of gastric cancer. Therefore, the regulation of alternative splicing of the NRP/B gene is a potential novel target for the treatment of gastrointestinal cancer.

• The Journal of Internal Korean Medicine
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• v.43 no.5
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• pp.864-873
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• 2022

Objective: The purpose of this case study was to report the symptom improvement effect of integrative Korean medicine treatment based on Pyongsim Solution: Cheonwangbosim-dan in a patient with variant angina and asthma symptoms. Methods: This 68-year-old male patient was treated with Pyongsim Solution, Gamihyangsayukgunja-tang, Gwakhyangjunggi-san, acupuncture, pharmacopuncture, and cupping therapy for 24 days. The European Quality of Life-5 Dimensions-5 Levels profile, Numerical Rating Scale score, and pulse rate per minute were measured on admission, at two weeks of hospitalization, and upon discharge to assess the clinical outcomes. Results: After treatment, the "mobility" dimension profile of the European Quality of Life-5 Dimensions-5 Levels changed from 1 to 1, "self-care" changed from 1 to 1, "usual activity" changed from 3 to 2, "pain/discomfort" changed from 4 to 3, and "anxiety/depression" changed from 3 to 2. The Numerical Rating Scale score for chest pain decreased from 7 to 5, chest tightness decreased from 6 to 4, sleep disturbance decreased from 6 to 3, polydipsia decreased from 5 to 3, and stomach discomfort decreased from 5 to 3. All the profiles of these five dimensions were unchanged for 11 days in the period between the two weeks of hospitalization and discharge. There were also no changes in the profiles of either "mobility" or "self-care" throughout the entire 24-day hospitalization period. Conclusion: This case report shows that integrative Korean medicine treatment based on Pyongsim Solution can improve the symptoms of patients with variant angina and mild intermittent asthma, suggesting that Pyongsim Solution could be an important herbal medication for treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6403-6409
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• 2013

Purpose: Biallelic germline variants of the 8-hydroxyguanine (8-OG) repair gene MYH have been associated with colorectal neoplasms that display somatic $G:C{\rightarrow}T:A$ transversions. However, the effect of single germline variants has not been widely studied, prompting the present investigation of monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC) in a Chinese population. Patients and Methods: Between January 2006 and December 2012, 400 cases of sporadic CRC and 600 age- and sex-matched normal blood donors were screened randomly for 7 potentially pathogenic germline MYH exons using genetic testing technology. Variants of heterozygosity at the MYH locus were assessed in both sporadic cancer patients and healthy controls. Univariate and multivariate analyses were performed to determine risk factors for cancer onset. Results: Five monoallelic single nucleotide polymorphisms (SNPs) were identified in the 7 exon regions of MYH, which were detected in 75 (18.75%) of 400 CRC patients as well as 42 (7%) of 600 normal controls. The region of exon 1 proved to be a linked polymorphic region for the first time, a triple linked variant including exon 1-316 $G{\rightarrow}A$, exon 1-292 $G{\rightarrow}A$ and intron 1+11 $C{\rightarrow}T$, being identified in 13 CRC patients and 2 normal blood donors. A variant of base replacement, intron 10-2 $A{\rightarrow}G$, was identified in the exon 10 region in 21 cases and 7 controls, while a similar type of variant in the exon 13 region, intron 13+12 $C{\rightarrow}T$, was identified in 8 cases and 6 controls. Not the only but a newly missense variant in the present study, p. V463E (Exon 14+74 $T{\rightarrow}A$), was identified in exon 14 in 6 patients and 1 normal control. In exon 16, nt. 1678-80 del GTT with loss of heterozygosity (LOH) was identified in 27 CRC cases and 26 controls. There was no Y165C in exon 7 or G382D in exon 14, the hot-spot variants which have been reported most frequently in Caucasian studies. After univariate analysis and multivariate analysis, the linked variant in exon 1 region (p=0.002), intron 10-2 $A{\rightarrow}G$ (p=0.004) and p. V463E (p=0.036) in the MYH gene were selected as 3 independent risk factors for CRC. Conclusions: According to these results, the linked variant in Exon 1 region, Intron 10-2 $A{\rightarrow}G$ of base replacement and p. V463E of missense variant, the 3 heterozygosity variants of MYH gene in a Chinese population, may relate to the susceptibility to sporadic CRC. Lack of the hot-spot variants of Caucasians in the present study may due to the ethnic difference in MYH gene.

• Journal of the Institute of Electronics Engineers of Korea SD
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• v.43 no.12 s.354
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• pp.89-101
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• 2006

Frequency-variant transmission line parameters are determined. Then the signal transient characterizations of frequency-dependent multi-coupled lines are investigated. With the proposed method, an accurate signal integrity degradation such as signal ringing (overshoot, undershoot) and crosstalk noises relevant to the switching patterns of signals, rising / falling time(tr, tf) and line lengths is investigated. It is shown that there may be approximately 26% discrepancy of signal transients and 260% difference of crosstalk noises between the constant RLC model and frequency-variant RLC model in on-chip global interconnects while those of package lines are 11% and 70%, respectively.